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pubmed_354_19604
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INTRODUCTION
Patients with systemic lupus erythematosus (SLE) possessing anti-phospholipid antibodies (aPLs) are often complicated by thrombotic vascular events. aPLs commonly associated with the complications are anti-cardiolipin/β2-glycoprotein I antibodies (aCL/β2GPI) and anti-phosphatidylserine/prothrombin antibodies (aPS/PT). However, the pathological mechanisms leading to thrombosis remain unclear. We explored clinical features of SLE patients with aCL/β2GPI and aPS/PT and investigated thrombogenic effects of their IgG fractions.
MATERIALS AND METHODS
We enrolled 97 SLE patients and 38 healthy control volunteers and performed activated protein C (APC) resistance screening test using their plasma samples. To detect the direct effect of aPLs IgG on APC, we developed an APC sensitivity ratio assay. Effects of aPLs IgG on monocytes were studied by measuring the surface expression of tissue factor (TF) and excretion of TNF-α from peripheral blood mononuclear cell culture.
RESULTS AND CONCLUSION
Thrombotic complications among SLE patients were closely associated with aCL/β2GPI or aPS/PT, with higher prevalence in patients with both antibodies. Addition of aPLs(+)-IgG to the APC sensitivity ratio assay led to significant suppression of the anticoagulant activity of APC. The suppression was more pronounced in double-positive cases. TF expression on monocytes and concentration of TNF-α in culture medium were increased by aPLs, again more pronounced in double-positive cases. These results indicate that the effects of aCL/β2GPI and aPS/PT are synergic both for APC anticoagulant activity and for production of TF and TNF-α from mononuclear cells. These modes of thrombogenic action of aPLs could be an important target for developing specific measures to prevent complications of SLE.
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10.1016/j.thromres.2019.07.006
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pubmed_1082_7211
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Macrophages (M phi s) exhibit variations in their ability to release and metabolize arachidonate (AA) depending on their state of activation, differentiation, and tissue origin. In order to understand these variations on a molecular level, we determined whether differences in AA release and metabolism by murine peritoneal M phi s could be explained in terms of cytosolic phospholipase A2 (cPLA2) and cyclooxygenase (COX) expression. Resident M phi s exhibited greater COX capacity (conversion of exogenous AA to PGE2) but lower phospholipase (PLase) activity (release of endogenous AA) than elicited M phi s. Activation of resident M phi s in vivo with endotoxin increased both their PLase activity and COX capacity. Despite the observed differences in PLase activity, peritoneal M phi s under all conditions expressed similar amounts of cPLA2 mRNA and protein. All M phi s exhibited COX-1 mRNA and protein (i.e., the constitutive isoform of COX), although elicited M phi s exhibited increased mRNA for COX-1 but decreased levels of protein, relative to resident M phi s. Elicited (but not resident) cells also exhibited COX-2 mRNA but not COX-2 protein (i.e., the inducible form of COX). Despite the increased COX capacity of resident cells with in vivo activation, their expression of COX-2 mRNA and protein was equivalent to that of unactivated cells, becoming apparent only after cell adherence in vitro. In sum, there is no simple relationship between the ability of M phi s to release and metabolize AA, and the expression of cPLA2 or COX isoforms. Moreover, adherence appears to be important for the expression of COX-2 by M phi s.
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10.1016/0090-6980(95)00067-k
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pubmed_419_11372
|
BACKGROUND
& Objectives: Spontaneous intracranial hypotension (SIH) is characterized by loss of CSF-volume. We hypothesize that in this situation of low volume, a larger CSF-flow and spinal cord motion at the upper spine can be measured by non-invasive phase-contrast MRI.
METHODS
A prospective, age-, gender- and BMI- matched controlled cohort study on SIH patients presenting with spinal longitudinal extradural fluid collection (SLEC) was conducted November 2021 to February 2022. Adapted cardiac-gated 2D phase-contrast MRI sequences were acquired at segment C2/C3, and C5/C6 for CSF-flow, and spinal cord motion analysis. Data processing was fully automated. CSF-flow and spinal cord motion were analyzed by peak-to-peak-amplitude and total displacement per segment and heartbeat, respectively. Clinical data included: age, height, body mass index, duration of symptoms, Bern score according to Dobrocky et al. 2019, and type of the spinal CSF leak according to Schievink et al. 2016. Groups were compared via Mann-Whitney U-test; multiple linear regression analysis was performed to address possible relations.
RESULTS
20 SIH patients and 40 healthy controls were analyzed; each group consisted of 70% women. 11 SIH patients presented with Type 1 leak, eight with Type 2, and one was indeterminate. CSF flow per heartbeat was increased at C2/C3 (peak-to-peak-amplitude 65.68 ± 18.3 mm/s vs. 42.50 ± 9.8 mm/s, total displacement 14.32 ± 3.5 mm vs. 9.75 ± 2.7 mm, p<0.001, respectively). Craniocaudal spinal cord motion per heartbeat was larger at segment C2/C3 (peak-to-peak-amplitude 7.30 ± 2.4 mm/s vs. 5.82 ± 2.0 mm/s, total displacement 1.01 ± 0.4 mm vs. 0.74 ± 0.4 mm, p=0.006, respectively) and at segment C5/C6 (total displacement 1.41 ± 0.7 mm vs. 0.97 ± 0.4 mm, p=0.021).
DISCUSSION
SLEC-positive SIH patients show higher CSF-flow and higher spinal cord motion at the upper cervical spine. This increased craniocaudal motion of the spinal cord per heartbeat might produce increased mechanic strain on neural tissue and adherent structures which may be a mechanism leading to cranial nerve dysfunction, neck pain and stiffness in SIH. Non-invasive phase-contrast MRI of CSF-flow and spinal cord motion is a promising diagnostic tool in SIH.
GERMAN CLINICAL TRIALS REGISTER, IDENTIFICATION NUMBER
DRKS00017351 CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that non-invasive phase-contrast MRI of the upper spine identifies differences in CSF-flow and spinal cord motion in SIH patients compared to healthy controls.
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10.1212/WNL.0000000000201527
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pubmed_737_9534
|
BACKGROUND
Patients with type-2 diabetes are at risk for treatment- and disease-related complications. Little is known about the interrelation of hypoglycaemia and co-morbid vascular disease (VD), defined as coronary heart disease, stroke and peripheral arterial disease.
HYPOTHESIS
Hypoglycaemia is associated with co-morbid VD in diabetic patients.
METHODS
DiaRegis is a prospective registry that included patients with type-2 diabetes in 2009/2010. Metric variables are displayed as median and quartiles. For the comparison of patients with or without VD Odds Ratios (OR) were determined from univariate analyses and adjusted for differences in patient characteristics (multivariable analysis).
RESULTS
Data on hypoglycaemia and VD within the last 12 months were available for 3741 patients (98.2%) with a median (IQR) age of 65.9 (57.6-72.9) years; 46.7% were female. VD patients (n = 909; 24.3%) were older (70.7 vs 63.9 years; p < 0.0001), less often female (33.6% vs 50.9%; p < 0.0001) and had had diabetes for a longer duration (6.4 vs 5.4 years; p < 0.0001). Mean cholesterol (total, HDL and LDL) was also slightly lower (p < 0.0001). Glycaemic control (HbA1c, fasting and postprandial glucose) was comparable. VD patients received less metformin (80.7 vs 85.2%; p < 0.01) and more sulfonylureas (31.8 vs 27.6%; p < 0.05). There was an increased incidence of symptomatic hypoglycaemia with or without requiring help and with a need for medical assistance. After adjusting a number of baseline variables the rates of symptomatic hypoglycaemias with help remained significantly increased (OR 3.73 (95% CI 1.31-10.65) in patients with VD.
CONCLUSIONS
As hypothesized there is a strong association between the incidence of hypoglycaemia and vascular disease at comparable glycaemic control, which confirms prior randomized controlled trial data suggesting an interrelationship between hypoglycaemia and vascular disease.
|
10.1177/1741826711411104
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pubmed_738_24977
|
DNA methylation is an essential epigenetic modification that significantly regulates gene expression during development and differentiation. In this study, genome-wide methylation analysis of different gonads of the large yellow croaker was performed using whole-genome bisulfite sequencing (WGBS), which has characterized DNA methylation patterns in gonad tissue and identified candidate regions for future studies. Clustering analysis revealed that male and neomale methylation patterns were close compared to female. Based on KEGG pathway analysis of differentially methylated genes, we obtained signaling pathways related to gonadal development. We further investigated the methylation status of previously reported sex determination genes, and found that these genes showed different methylation status in three types of gonads, which may provide important clues to reveal the sex determination genes in the large yellow croaker. Furthermore, combined with transcriptome analysis, we found 7 sex-related genes in three comparison groups where expression negatively correlated with methylation.
|
10.1016/j.gene.2020.144754
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pubmed_820_11539
|
It has been previously shown that wavelet artificial neural networks (WANNs) are able to classify the different states of epileptiform activity and predict the onsets of seizure-like events (SLEs) by offline processing (Ann. Biomed. Eng. 33(6):798-810, 2005) of the electrical data from the in-vitro hippocampal slice model of recurrent spontaneous SLEs. The WANN design entailed the assumption that time-varying frequency information from the biological recordings can be used to estimate the times at which onsets of SLEs would most likely occur in the future. Progressions of different frequency components were captured by the artificial neural network (ANN) using selective frequency inputs from the initial wavelet transform of the biological data. The training of the WANN had been established using 184 SLE episodes in 34 slices from 21 rats offline. Nine of these rats also exhibited periods of interictal bursts (IBs). These IBs were included as part of the training to help distinguish the difference in dynamics of bursting activities between the preictal- and interictal type. In this paper, we present the results of an online processing using WANN on 23 in-vitro rat hippocampal slices from 9 rats having 93 spontaneous SLE episodes generated under low magnesium conditions. Over the test cases, three of the nine rats exhibited over 30 min of IB activities. We demonstrated that the WANN was able to classify the different states, namely, interictal, preictal, ictal, and IB activities with an accuracy of 86.6, 72.6, 84.5, and 69.1%, respectively. Prediction of state transitions into ictal events was achieved using regression of initial "normalized time-to-onset" estimates. The SLE onsets can be estimated up to 36.4 s ahead of their actual occurrences, with a mean error of 14.3 +/- 27.0 s. The prediction errors decreased progressively as the actual time-to-onset decreased and more initial "normalized time-to-onset" estimates were used for the regression procedure.
|
10.1007/s10439-005-9029-9
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pubmed_584_1040
|
We performed 97 uncemented primary total hip arthroplasties in 80 patients having an average age of 50 years. The femoral implant was a titanium stem with a proximal circumferential plasma spray-coating. Three different acetabular components were used: a threaded and partly porous-coated design in 70% of the cases. The average follow-up period was 8 years. 1 stem was revised 9 years after insertion due to a comminuted fracture of the proximal femur, 1 stem was revised 9 years after insertion due to a deep infection. No stem revisions were due to aseptic loosening. 1 femora had areas of distal osteolysis associated with a deep infection, but no signs of proximal loosening. 3 femora had areas of minor proximal osteolysis. 16 acetabular components (14 threaded) had been revised in 13 patients. The average Harris hip score was 91 points at the latest follow-up. We conclude that the uncemented titanium femoral component with a circumferential porous coating performed well in these patients, most of whom were young. As reported previously, aseptic loosening of threaded acetabular components was common.
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pubmed_584_1040
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pubmed_539_249
|
PURPOSE
To determine, using scanning laser polarimetry, whether or not the retinal nerve fiber layer (RNFL) is altered in dementia of the Alzheimer type (DAT).
METHODS
Thirty individuals with mild to moderate DAT and 30 healthy age-matched controls participated in the study. Fundus images were acquired with a Nerve Fiber Analyzer. RNFL thickness measurements were obtained under an ellipse located 1.75 disc diameter from the optic nerve head (ONH) center.
RESULTS
No differences in RNFL thickness were observed between DAT and healthy subjects. The regional distribution of RNFL thickness was similar between the two test groups, with the RNFL being thickest in the superior and inferior retinal segments relative to the nasal and temporal regions.
CONCLUSIONS
Our data indicate that the RNFL is not altered in DAT, at least in the earlier stages of the disease.
|
10.1034/j.1600-0420.2001.079002187.x
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pubmed_353_8422
|
We sought to determine if the histone deacetylase inhibitor (HDI), trichostatin A (TSA), would alter systemic lupus erythematosus (SLE) in NZB/W mice. Fourteen to sixteen-week-old female NZB/W F1 mice were given TSA (1.0mg/kg body weight (BW)) intraperitonealy (i.p.) daily, TSA (1.0mg/kg BW) i.p.+anti-CD25 (250mg/mouse) i.p. every third day, only anti-CD25 (250mg/mouse) i.p., DMSO or isotype IgG. Disease progression was assessed as they aged. Mice were sacrificed at 26 or 38 weeks of age, tissues collected and evaluated. At 36 weeks, TSA-treated animals had decreased anti-double stranded DNA (dsDNA) autoantibodies and decreased protein excretion compared to controls. Spleen size and the percentage of CD4+CD69+ cells were decreased, with an increase in CD4+CD25+ T cells in the TSA-treated mice. Real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis of T cells showed a decrease in IL-6 production but an increase in TGF-beta1 and Foxp3 in the TSA-treated animals. Kidney analysis showed a decrease in IgG and C3 deposition, decrease in pathologic glomerular disease and renal MCP-1, MMP-9, and IL-6 mRNA expression. Anti-CD25-treated mice euthanized at 26 weeks of age showed decreased Foxp3+CD4+CD25+ T cells compared to TSA-treated mice. These data suggest TSA administration modulates lupus-like disease, in part, by increasing T regulatory cells.
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10.1016/j.jaut.2008.04.020
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pubmed_20_20827
|
Heterogeneity is commonplace in all cancer types and at several levels--intrinsic (genetic), epigenetic, positional, and at the population level. The different subpopulations with a tumor mass communicate with each other and influence the behavior of other tumor cells both locally and at a distance. These properties have profound implications regarding the understanding of tumor behavior and how therapies are (or should be) administered. This brief commentary highlights the insightful review of Gloria Heppner and how it has influenced cancer research even three decades after it was published.
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10.1158/0008-5472.CAN-15-3024
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pubmed_894_2158
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Survival of Staphylococcus epidermidis (10(2) organisms/ml) in solutions containing various levels of radioactivity was assessed. Six test preparations contained nonbacteriostatic 0.9% sodium chloride solution; four of these contained technetium Tc 99m pertechnetate (99mTcO-4) in various quantities (80, 250, 500, and 750 mCi). A fifth contained technetium that had decayed to an essentially nonradioactive form, and a sixth contained 0.9% sodium chloride solution only. Each of the six 20-ml solutions was inoculated with 2 ml of single-strength trypticase soy broth (TSB) containing 10(3) organisms/ml. At various times up to 12 hours after inoculation, 1-ml aliquots of each test solution were withdrawn and passed through 0.22-micron filters, thereby preventing further irradiation of the filtered organisms. The filters were incubated in single-strength TSB at 37 degrees C, and samples were examined for turbidity at 24, 48, and 72 hours. After 24 hours, 25 of the 36 sample tubes showed turbidity; after 48 hours, the turbid samples totaled 28. Bacteria in the two nonradioactive solutions remained viable throughout the 12-hour sampling period. Accumulated doses of radiation obtained in the 250-, 500-, and 750-mCi samples inhibited bacterial growth. To be a valid quality-control measure, sterility monitoring of prepared radiopharmaceutical dosage forms may need to be performed concurrently with their preparation.
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pubmed_894_2158
|
pubmed_965_25154
|
Advances in treatment for testicular cancer that include the coadministration of bleomycin, etoposide, and cisplatin (BEP) have brought the cure rate to higher than 90%%. The goal of this study was to elucidate the impact of BEP treatment on gene expression in male germ cells. Brown-Norway rats were treated for 9 wk with vehicle (0x) or BEP at doses equivalent to 0.3x and 0.6x the human dose. At the end of treatment, spermatogenesis was affected, showing altered histology and a decreased sperm count; spermatozoa had a higher number of DNA breaks. After 9 wk of treatment, round spermatids were isolated, and RNA was extracted and probed on Rat230-2.0 Affymetrix arrays. Of the 31 099 probe sets present on the array, 59%% were expressed in control round spermatids. BEP treatment significantly altered the expression of 221 probe sets, with at least a 1.5-fold change compared with controls; 80% were upregulated. We observed a dose-dependent increase in the expression of oxidative stress response genes and no change in the expression of genes involved in DNA repair. BEP upregulated genes were implicated in pathways related to Jun and Junb protooncogenes. Increased mRNA levels of Jun and Junb were confirmed by quantitative RT-PCR; furthermore, JUN protein was increased in elongating spermatids. Thus, BEP exposure triggers an oxidative stress response in round spermatids and induces many pathways that may lead to the survival of damaged cells and production of abnormal sperm.
|
10.1095/biolreprod.108.072108
|
pubmed_556_13031
|
OBJECTIVE
To explore the clinical effect of ultrasound evaluation of fiberoptic bronchoscope (FB) guided tracheotomy, which can provide help for difficult tracheotomy and new operators.
METHODS
The operating protocol was standardized for ultrasound evaluation of FB guided tracheotomy. Ten patients with difficult tracheotomy admitted to the department of critical care medicine of Donge Hospital from October 2019 to January 2020 were enrolled. According to this protocol, FB guided tracheotomy was performed under the ultrasound evaluation, and the amount of blood loss, operation time and related complications during procedures were collected.
RESULTS
The preparation of supplies, personnel, patients and the operation, the process of FB guided tracheotomy under the ultrasound evaluation were standardized. When tracheotomy was preformed for patients with difficult tracheotomy, it was necessary to use ultrasound first to evaluate the neck condition and vascular disorientation of patients, and the tracheotomy plan (tracheotomy site, incision size, and incision depth) was designed, and then the tracheotomy process was monitored under the guidance of FB. Among the 10 patients with difficult tracheotomy, 6 were male and 4 were female; body mass index was (32.2±1.4) kg/m2. Tracheotomy was successfully completed within 10 minutes in all the 10 patients, with less than 5 mL blood loss, and no complications occurred.
CONCLUSIONS
Ultrasound evaluation of FB guided tracheotomy can improve the clinical operations and ensure patient safety.
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10.3760/cma.j.cn121430-20200116-00060
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pubmed_801_21421
|
For the last century T tube drainage of the bile duct has remained standard practice following choledochlithotomy. It vents the biliary tree, provides route for cholangiography and management of residual stones. However, T tubes are associated with significant complications. This retrospective study compared the use of Endonasobiliary drainage tubes and the T tube in 66 patients who underwent open choledocholithotomy for effectiveness and complications. Both groups were statistically comparable. Only 15.15% patients in the Endonasobiliary drainage group, while 45.45% patients in the T tube group developed complications. Severe complications such as biliary peritonitis and intraperitoneal collections were noted only in the T tube group. The Endonasobiliary drainage tube was removed significantly earlier and patients from this group were discharged earlier as compared to those in the T tube. The Endonasobiliary drainage tube is as effective as the T tube in postoperative biliary drainage and allows cholangiograms to be performed. Its use is associated with less complications and it can be removed safely earlier than the T tube. Thus patients have a shorter time with tubes and can be discharged home earlier.
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10.1007/s12262-010-0122-4
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pubmed_330_4667
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The purpose of this research was to identify themes in the daily lives of community-dwelling older adults with chronic health problems. Qualitative descriptive methods based on symbolic interaction were used. Data were generated through unstructured interviews, participant diaries, and researcher logs. Participants were interviewed twice and kept diaries in between. Measures to enhance trustworthiness included bracketing, multiple data sources, repeated interviews, prolonged engagement, an audit trail, participant checking, and consultation with an expert qualitative researcher. Ten older adults 75-98 years of age living in their own homes with at least one self-reported chronic health problem participated in the research. Participants' health problems varied, and they developed strategies to maintain balance in activity, attitude, autonomy, health, and relationships. This research provides a new perspective on living with chronic illness, and the model may provide a framework for rehabilitation nurses who work with older adults.
|
10.1002/j.2048-7940.2010.tb00026.x
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pubmed_137_7002
|
Primacy and recency effects are common benchmarks for models of free recall and episodic memory. In this work, we show that RT distributions carry diagnostic information about how items enter into competition for recall, and how that competition impacts on the dynamics of recall and leads to novel conclusions about the forms of primacy and recency effects. We jointly fit RT distributions and serial position functions for free recall initiation with both a racing diffusion model and the linear ballistic accumulator (LBA: Brown & Heathcote, 2008). The models were fit in a hierarchical Bayesian framework, factorially varying different assumptions of how primacy and recency are generated. Recency functions were either exponential or power law in shape. Primacy was treated either as a strength boost to the early list items so that both primacy and recency items jointly compete to be retrieved; a mixture of primacy and recency gradients reflecting the usage of different retrieval cues; or a primacy-as-recency account in which primacy items are functionally recent due to the contribution of rehearsal. Although serial position curves do not distinguish between these accounts, they make distinct predictions about how RT distributions vary across serial positions. Results from a number of data sets strongly favor an exponential recency function along with a mixture model of primacy and recency gradients. These results suggest that complete RT distributions can provide informative constraints on models of free recall. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
|
10.1037/rev0000149
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pubmed_163_5761
|
BACKGROUND
Lung adenocarcinoma (LUAD) is still one of the primary malignant diseases leading to higher mortality worldwide. It has been previously reported that multiple genes in the CENPA-nucleosome associated complex (NAC) complex in lung cancer can be used as prognostic markers; however, there is lack of comprehensive research on the CENPA-NAC complex.
METHODS
The hub genes of lung cancer were obtained by analyzing multiple gene expression omnibus (GEO) lung cancer datasets. The key genes of the CENPA-NAC complex in the evolution of LUAD were identified according to lung cancer data obtained from The Cancer Genome Atlas (TCGA) database, and the key genes were constructed as a survival prognostic model. The relationship between the model and immune cell infiltration was studied by the Tumor Immune Estimation Resource (TIMER) and single-sample gene set enrichment analysis (ssGSEA) studies.Droplet Digital polymerase chain reaction (ddPCR) was used to verify the effectiveness of the prognostic model to predict survival using clinical samples.
RESULTS
A comprehensive study showed that CENPA, CENPH, CENPM, CENPN and CENPU were key genes in the development and evolution of LUAD. The constructed survival prognosis model was an independent risk factor for LUAD and can be used to assess the survival of LUAD patients. The risk score was closely related to the infiltration of multiple immune cells. The independent cohorts GSE31210 and GSE50081 further confirmed the validity of the prognostic model, and finally, the model was validated with clinical samples.
CONCLUSIONS
In conclusion, the results of the present study showed that CENPA, CENPH, CENPM, CENPN, and CENPU are a group of potential prognostic markers in LUAD. The constructed model has been confirmed to be applicable in the clinical setting in evaluating the survival of patients with LUAD, and providing more evidence on immunotherapy for LUAD.
|
10.1016/j.prp.2021.153680
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pubmed_707_911
|
OBJECTIVE
To observe the effect of ZhuLian's type Ⅱ inhibition needling technique on sex hormones, insulin resistance and ovarian morphology in rats with polycystic ovary syndrome (PCOS), so as to explore its mechanism on regulating endocrine and metabolic dysfunction of PCOS.
METHODS
Twenty-four female SD rats were randomly divided into control, model and ZhuLian acupuncture groups (n=8 in each group). The PCOS model was established by continuous gavage of letrozole combined with high-fat diet. Rats of the ZhuLian acupuncture group were stimulated at "Guanyuan"(CV4) and bilateral "Guilai"(ST29), "Zusanli"(ST36), "Sanyinjiao"(SP6), and "Fenglong"(ST40) by ZhuLian's type Ⅱ inhibition needling technique for 30 min, continuously intervented for 28 days. The body weight was measured before and after modeling and after intervention. The ovarian volume was calculated. HE staining was used to observe the changes of ovarian histology. Plasma levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and fasting insulin (FINS) were measured by ELISA. LH/FSH ratio and insulin resistance index (HOMA-IR) were calculated.
RESULTS
After modeling, the rats' body weight and the ovarian volume were increased (P<0.05), and the ovaries showed polycystic changes in the model group compared with the control group. And the FINS level, HOMA-IR, LH content and LH/FSH ratio were significantly increased (P<0.05), while the FSH level was decreased (P<0.05). After the intervention, the rats' body weight and ovarian volume were decreased (P<0.05), and a small number of preantral follicles and more antral follicles were observed under microscope, and the levels of LH, LH/FSH, FINS and HOMA-IR were significantly decreased (P<0.05), while FSH content was increased (P<0.05) in the ZhuLian acupuncture group than in the model group.
CONCLUSION
ZhuLian's type Ⅱ inhibition needling technique can improve the endocrine and metabolic disorders in PCOS rats, which may be related to the regulation of endocrine system.
|
10.13702/j.1000-0607.20210259
|
pubmed_220_414
|
OBJECTIVES
Growth signaling is instrumental in tumor development. Insight into signaling pathways by molecular and cellular biology has changed the development of new anticancer agents. Outside the field of urology specifically targeted drugs such as imatinib mesylate and gefitinib showed impressive anticancer activity in chronic myeloid leukemia and non-small cell lung cancer, respectively.
METHODS
Literature search of PubMed documented publications and abstracts from meetings.
RESULTS
Preclinical data in prostate cancer shows upregulation of a wide variety of growth factors and their receptors such as PDGF, EGF, IGF, FGF, and VEGF suggesting efficacy of agents targeting these pathways. Here the preclinical evidence and first clinical data on the use of growth signal targeting in prostate cancer is reviewed. Although some anticancer efficacy of signal transduction inhibition monotherapy was reported, combination with chemotherapy and radiotherapy seemed most promising in prostate cancer.
CONCLUSION
So-called smart drugs are small molecules targeted at specific growth signaling pathways. These new drugs will dominate clinical trials in the years to come either as single-drug modality, but more likely as combination treatment.
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10.1016/j.eururo.2003.08.011
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pubmed_809_382
|
The intramolecular and intermolecular perturbation on the electronic state of FAD was investigated by FTIR spectroscopy by using the C=O stretching vibrations as probes in D(2)O solution. Natural and artificial FADs, i.e. 8-CN-, 8-Cl-, 8-H-, 8-OCH(3)-, and 8-NH(2)-FAD labelled by 2-(13)C, (18)O=C(2), or 4,10a-(13)C(2) were used for band assignments. The C(2)=O and C(4)=O stretching vibrations of oxidized FAD were shifted systematically by the substitution at the 8-position, i.e. the stronger the electron-donating ability (NH(2) > OCH(3) > CH(3) > H > Cl > CN) of the substituent, the lower the wavenumber region where both the C(2)=O and C(4)=O bands appear. In contrast, the C(4)=O band of anionic reduced FAD scarcely shifted. The 1,645-cm(-1) band containing C(2)=O stretching vibration shifted to 1,630 cm(-1) in the medium-chain acyl-CoA dehydrogenase (MCAD)-bound state, which can be explained by hydrogen bonds at C(2)=O of the flavin ring. The band was observed at 1,607 cm(-1) in the complex of MCAD with 3-thiaoctanoyl-CoA. The 23 cm(-1) shift was explained by the charge-transfer interaction between oxidized flavin and the anionic acyl-CoA. In the case of electron-transferring flavoprotein, two bands associated with the C(4)=O stretching vibration were obtained at 1,712 and 1,686 cm(-1), providing evidence for the multiple conformations of the protein.
|
10.1093/jb/mvm129
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pubmed_1051_17238
|
MOTIVATION
Polypharmacy is the combined use of drugs for the treatment of diseases. However, it often shows a high risk of side effects. Due to unnecessary interactions of combined drugs, the side effects of polypharmacy increase the risk of disease and even lead to death. Thus, obtaining abundant and comprehensive information on the side effects of polypharmacy is a vital task in the healthcare industry. Early traditional methods employed machine learning techniques to predict side effects. However, they often make costly efforts to extract features of drugs for prediction. Later, several methods based on knowledge graphs are proposed. They are reported to outperform traditional methods. However, they still show limited performance by failing to model complex relations of side effects among drugs.
RESULTS
To resolve the above problems, we propose a novel model by further incorporating complex relations of side effects into knowledge graph embeddings. Our model can translate and transmit multidirectional semantics with fewer parameters, leading to better scalability in large-scale knowledge graphs. Experimental evaluation shows that our model outperforms state-of-the-art models in terms of the average area under the ROC and precision-recall curves.
AVAILABILITY
Code and data are available at: https://github.com/galaxysunwen/MSTE-master.
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10.1093/bioinformatics/btac094
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pubmed_807_10809
|
Piwil2, a member of AGO/PIWI family of proteins, has been reported to be expressed in precancerous stem cells (pCSCs), tumor cell lines and various types of human cancers. However, the significance of piwil2 expression in breast cancer has not been investigated. In this study, archival formalin-fixed, paraffin-embedded breast cancer specimens at various developmental stages were prepared as tissue microarrays (TMAs) and examined for the expressions of piwil2, estrogen receptor (ER), progesterone receptor (PR) and a cell proliferation marker Ki67 by immunohistochemical (IHC) staining and human epidermal growth factor receptor 2 (HER2) by fluorescence in situ hybridization (FISH). The correlation of piwil2 expression with ER, PR and Ki67 were analyzed statistically. The piwil2 was detected in all of breast cancer TMA cores. In contrast, ER, PR, HER2, and Ki67 were detected only in 66.1%, 54.5%, 36.0%, and 47% of the TMA cores, respectively. Piwil2 was expressed in cytoplasm (Cyt), nucleus (N) or both cytoplasm and nucleus (C-N). The N pattern was less observed in breast precancers, whereas all three patterns were observed in invasive and metastatic cancers. While the Cyt pattern was significantly correlated with ER expression (p = 0.002); N pattern was significantly correlated with Ki67 expression (p =0.001). ER and Ki67 expressions were reduced and increased, respectively, with the expression patterns being shifted from Cyt --> C-N --> N. In conclusion, piwil2 is expressed in various stages of breast cancers and has the potential to be used a novel biomarker.
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pubmed_807_10809
|
pubmed_910_21007
|
Kidney injury is a common clinical feature among liver transplantation (LT) candidates that heavily affects prognosis and complicates the surgical decision-making process. Up to 20% of patients undergoing LT demonstrate some degree of renal impairment, and 2% will benefit from a combined liver-kidney transplantation (LKT). We present a case-control study of all patients who underwent LKT and combined liver-dual kidney transplantation (LDKT) from November 2013 to March 2016. For the selection of LDKT candidates, a histological-based algorithm was applied: when evaluating extended criteria donors (ECDs), with any Remuzzi score between 4 and 7, we would consider performing a LDKT instead of a simple LKT. Study groups were similar for recipient variables. In the LDKT group, donor age, donor risk index, and donor body mass index were found to be significantly higher. Biopsies obtained from all pairs of kidney grafts in the LDKT group demonstrated the following Remuzzi scores: 4+4, 4+4, 7+1, 4+5. Despite longer operative times for the LDKT procedure, no differences were observed regarding the main investigated outcome parameters. Overall survival was 100% (LDKT) and 91% (LKT, P > 0.99). This is a preliminary experience which might indicate that LDKT is a safe, feasible, and resource-effective technique. The evaluation of a larger cohort, as well as the experience from other centers, would be needed to clearly identify its role in the ECD era. Liver Transplantation 23:28-34 2017 AASLD.
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10.1002/lt.24472
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pubmed_819_16451
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We report on a male patient aged 38, affected by a syndrome whose characteristic features include onset in early childhood, slow progression, diffuse muscle weakness, mental retardation and cardiomyopathy. Muscle biopsy showed myopathic changes compatible with muscular dystrophy. However, immunostaining for dystrophin as well as 50 and 43 kDa dystrophin-associated glycoproteins (DAGs) was normal. Genetic analysis suggested that direct involvement of the dystrophin gene was highly unlikely. No other family members were affected. Although the clinical picture is reminiscent of Duchenne/Becker muscular dystrophy, the immunologically and genetically documented lack of dystrophin involvement suggests that this particular syndrome is as yet undescribed.
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10.1016/0960-8966(96)00016-8
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pubmed_1136_15846
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Little is known about hypoxia-induced modification of the canal network in the cortical bone despite its involvement in intracortical vascularity and bone blood supply. In this study, we examined the effect of chronic hypoxia on the canal network in postnatal bone. Tibiae were harvested from 4- and 8-week-old rats (hyp-4 and -8, n = 8 each), whose growth was retarded owing to postnatal exposure to hypoxia (12-14% O₂), and from 3- and 4-week-old normoxic rats (cnt-4 and -5, n = 8 each), which were similar in tibial length and cortical cross-sectional area to hyp-4 and -8, respectively. The diaphyseal canals were detected by monochromatic synchrotron radiation CT with a 3.1-μm voxel resolution. The anatomical properties of the canal network were compared between age- or size-matched hypoxic and normoxic groups. The canals were larger in diameter, were more densely distributed and connected, and opened into the marrow cavity with a higher density in hyp-4 than in cnt-4. The canal density and connectivity were also higher in hyp-4 than in cnt-3. The canal diameter, density, and connectivity were smaller in hyp-8 than in cnt-4; however, the densities of endocortical and periosteal canal openings did not differ between hyp-8 and cnt-4. We concluded that chronic hypoxia enhanced the formation of cortical canal networks at the postnatal developmental stage, probably facilitating intra- and transcortical vascularization and bone perfusion accordingly.
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10.1007/s00223-010-9415-7
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pubmed_531_7751
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We report a set of oligonucleotide primers and amplification conditions for the polymerase chain reaction to detect the ctx operon of Vibrio cholerae. The results of this assay on strains of V. cholerae and related organisms were identical with those obtained by the DNA colony hybridization test with the polynucleotide probe. The detection limit of this system was 1 pg of chromosomal DNA or broth culture containing three viable cells. The polymerase chain reaction method could directly detect the ctx operon sequences in rice-water stool samples from patients with cholera.
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10.1128/jcm.29.11.2517-2521.1991
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pubmed_897_4415
|
BACKGROUND
To study the expression of survivin mRNA in non-small cell lung cancer (NSCLC), and to explore its relationship with carcinogenesis, development invasion and metastasis of NSCLC.
METHODS
In situ hybridization was applied to detect survivin mRNA expression in 12 normal bronchial epithelium, 9 dysplasia, 34 NSCLC and 12 metastatic lymph nodes. The relationship between survivin expression and clinicopathological characteristics was analyzed.
RESULTS
In normal bronchial epithelium, dysplasia, NSCLC and metastatic lymph nodes, the positive rate of survivin mRNA expression were 16.67% (2/12), 33.33% (3/9), 61.76% (21/34), and 91.67% (11/12), respectively. There were significant differences in survivin mRNA expression between lung cancer and normal bronchial epithelium ( P < 0.01), as well as between metastatic lymph nodes and normal bronchial epithelium ( P < 0.001). There were remarkably higher survivin mRNA expressions in poor- and moderate-differentiated groups than that in well-differentiated group ( P =0.003, P =0.004). The expression of survivin mRNA was not related to histologic classification and lymph node status ( P > 0.05, P > 0.05).
CONCLUSIONS
Survivin mRNA expression may play an important role in the carcinogenesis and development of NSCLC. It may be a new target in gene therapy of lung cancer through blocking or down-regulating survivin mRNA expression to recover the normal regulation mechanism of apoptosis.
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10.3779/j.issn.1009-3419.2003.04.08
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pubmed_229_18498
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Specialised clinics for the long-term follow-up of survivors from childhood cancer have developed over recent years. The problems encountered among patients who received multiple chemotherapy and radiotherapy can be challenging and require high expertise and close collaboration among different professionals (e.g. oncologists, endocrinologists, radiotherapists, psychologists). Endocrine disorders are often seen, particularly among those who received cranial radiotherapy or gonadotoxic chemotherapy; puberty can be affected and the spectrum of disorders may range from precocious or accelerated puberty to delayed, arrested or even absent pubertal development. Growth impairment can be multifactorial and growth hormone deficiency is an important but probably not the only factor involved. Many questions remain about the optimal management of this group of young patients. In the consensus guidelines that follow the overview an attempt is made to help optimise patients' growth and puberty by suggesting practical clinical approaches to some of the most challenging issues.
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10.1515/jpem-2001-s212
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pubmed_14_17533
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Minimum inhibition concentrations (MICs) were determined for ampicillin, ceftiofur, cephalothin, chloramphenicol, enrofloxacin, gentamicin, lincomycin, lincospectin (lincomycin/spectinomycin), neomycin, premafloxacin, spectinomycin, sulfamethoxazole/trimethoprim, and tetracycline against a total of 180 isolates of Actinobacillus pleuropneumoniae, Escherichia coli, and Salmonella choleraesuis (60 each) clinically isolated from pigs on farms in Taiwan from 1994 to 1996. No more than 3 isolates per farm were used. Ceftiofur had the highest activity in vitro against isolates of A. pleuropneumoniae, E. coli, and S. choleraesuis, with MIC90 values of 0.03, 2, and 1 microg/ml, respectively. Premafloxacin was highly active against isolates of A. pleuropneumoniae, E. coli, and S. choleraesuis, with MIC90 values of 2, 8, and 0.5 microg/ml, respectively, which were lower than those with enrofloxacin (MIC90 8, 32, and 2 microg/ml, respectively). Neomycin was moderately active against A. pleuropneumoniae and E. coli, with MIC90 values of 8 and 64 microg/ml, respectively, but was inactive with S. choleraesuis. Gentamicin showed high activity against A. pleuropneumoniae (MIC90 of 2 microg/ml) but was only moderately active with E. coli and S. choleraesuis (MIC90 of 64 and 32 microg/ml). Cephalothin was highly active against isolates of A. pleuropneumoniae (MIC90 of 1 microg/ml) but was inactive with E. coli (MIC90 of 128 microg/ml). Lincomycin had moderate activity (MIC90 of 32 microg/ml) against A. pleuropneumoniae. Chloramphenicol, lincomycin, and tetracycline were inactive with E. coli and S. choleraesuis (MIC90 > 128 microg/ml). In conclusion, ceftiofur and premafloxacin were highly active against isolates of A. pleuropneumoniae, E. coli, and S. choleraesuis, enrofloxacin and gentamicin were highly to moderately active; cephalothin was highly active against A. pleuropneumoniae and moderately active against S. cholearesuis; chloramphenicol, lincomycin, and tetracycline were active only with A. pleuropneumoniae; neomycin was moderately active against A. pleuropneumoniae and E. coli. The other antimicrobials tested were inactive.
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10.1177/104063870201400210
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pubmed_569_22373
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During senescence, cells express molecules called senescence-associated secretory phenotype (SASP), including growth factors, proinflammatory cytokines, chemokines, and proteases. The SASP induces a chronic low-grade inflammation adjacent to cells and tissues, leading to degenerative diseases. The anti-inflammatory activity of flavonoids was investigated on SASP expression in senescent fibroblasts. Effects of flavonoids on SASP expression such as IL-1α, IL-1β, IL-6, IL-8, GM-CSF, CXCL1, MCP-2 and MMP-3 and signaling molecules were examined in bleomycin-induced senescent BJ cells. In vivo activity of apigenin on SASP suppression was identified in the kidney of aged rats. Among the five naturally-occurring flavonoids initially tested, apigenin and kaempferol strongly inhibited the expression of SASP. These flavonoids inhibited NF-κB p65 activity via the IRAK1/IκBα signaling pathway and expression of IκBζ. Blocking IκBζ expression especially reduced the expression of SASP. A structure-activity relationship study using some synthetic flavones demonstrated that hydroxyl substitutions at C-2',3',4',5 and 7 were important in inhibiting SASP production. Finally, these results were verified by results showing that the oral administration of apigenin significantly reduced elevated levels of SASP and IκBζ mRNA in the kidneys of aged rats. This study is the first to show that certain flavonoids are inhibitors of SASP production, partially related to NF-κB p65 and IκBζ signaling pathway, and may effectively protect or alleviate chronic low-grade inflammation in degenerative diseases such as cardiovascular diseases and late-stage cancer.
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pubmed_569_22373
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pubmed_187_16650
|
OBJECTIVE
To examine whether human papillomavirus (HPV) type 16 is involved in the etiology of vulvar carcinomas.
METHODS
We studied 142 histologically confirmed cases of vulvar intraepithelial neoplasia (VIN) grade 3 and invasive vulvar cancer and 126 community controls. In addition to a detailed questionnaire through which we obtained information on putative risk factors for vulvar cancer, blood samples were collected from participating subjects and tested for the presence of antibodies to HPV-16 virus-like particles. Data were analyzed by logistic regression.
RESULTS
Subjects positive for HPV-16 antibodies were at a 5.3-fold increased risk of vulvar neoplasia (95% confidence interval [CI] 2.5, 11.1), and subjects with high antibody levels were at a 20-fold increased risk of disease (95% CI 5.4, 76.7). A stronger association between HPV-16 seropositivity and disease was observed for VIN grade 3 (odds ratio [OR] 13.4; 95% CI 3.9, 46.5) than for invasive disease (OR 2.9; 95% CI 0.94, 8.7), and for invasive tumors, there was a suggestion that the association was stronger for women diagnosed with squamous carcinoma of basaloid and/or warty types (OR 3.8; 95% CI 0.76, 18.9) than for those diagnosed with keratinizing squamous cell carcinomas (OR 1.6; 95% CI 0.35, 7.4). Number of sexual partners and herpes simplex virus type 2 seropositivity remained as independent risk factors for vulvar neoplasia after control for confounding by HPV-16. The risk associated with HPV-16 seropositivity was higher among smokers (OR 8.5; 95% CI 3.8, 19) than among nonsmokers (OR 3.4; 95% CI 0.85, 13).
CONCLUSION
Our results confirm that HPV is associated with vulvar carcinomas. Findings also suggest the possibility that other sexually transmitted agents might be involved in the etiology of some vulvar tumors and that smoking may be an important cofactor involved in the etiology of HPV-related vulvar tumors. Evaluation of the role of HPV types other than HPV-16 in the etiology of vulvar cancer is needed, and additional efforts aimed at further elucidating the role of smoking and other cofactors in this disease process are warranted.
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10.1016/S0029-7844(97)00467-5
|
pubmed_576_15105
|
PURPOSE
To examine prostate and seminal vesicles position late in the course of radiation therapy and to determine the effect and predictive value of the bladder and rectum on prostate and seminal vesicles positioning.
METHODS AND MATERIALS
Twenty-four patients with localized prostate cancer underwent a computerized tomography scan (CT1) before the start of radiation therapy. After 4-5 weeks of radiation therapy, a second CT scan (CT2) was obtained. All patients were scanned in the supine treatment position with instructions to maintain a full bladder. The prostate, seminal vesicles, bladder, and rectum were contoured. CT2 was aligned via fixed bony anatomy to CT1. The geometrical center and volume of each structure were obtained and directly compared.
RESULTS
The prostate shifted along a diagonal axis extending from an anterior-superior position to a posterior-inferior position. The dominant shift was to a more posterior-inferior position. On average, bladder and rectal volumes decreased to 51% (+/-29%) and 82% (+/-45%) of their pretreatment values, respectively. Multiple regression analysis (MRA) revealed that bladder movement and volume change and upper rectum movement were independently associated with prostate motion (p = 0.016, p = 0. 003, and p = 0.052 respectively).
CONCLUSION
Patients are often instructed to maintain a full bladder during a course of external beam radiation therapy, in the hopes of decreasing bladder and small bowel toxicity. However, our study shows that large bladder volumes late in therapy are strongly associated with posterior prostate displacement. This prostate displacement may result in marginal miss.
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10.1016/s0360-3016(00)00469-7
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pubmed_794_26811
|
Objective
To define the normal values and examine the influence of aging on B81 bone vibrator-induced cervical vestibular-evoked myogenic potentials (B81-cVEMPs) and ocular vestibular-evoked myogenic potentials (B81-oVEMPs).
Methods
Seventy healthy subjects, divided into seven groups according to their ages, were enrolled in this study. The 4-9-, 10-19-, 20-29-, 30-39-, 40-49-, 50-59-, and 60-70-year-old participants were divided into groups I-VII, respectively. B81-cVEMP and B81-oVEMP were recorded in each group.
Results
The B81-cVEMP response rates for groups I-VII were 100, 100, 100, 100, 95, 95, and 75%, respectively, with significant differences only between groups I-VI and group VII (p = 0.047, p < 0.05). The B81-oVEMP response rates for groups I-VII were 100, 100, 100, 100, 70, 65, and 40%, respectively, with significant differences only between groups I-IV and groups V-VII (p = 0.020, p = 0.008, p = 0.000; p < 0.05). The threshold, P13, and N23 latencies of B81-cVEMP positively correlated with age (r = 0.756, p = 0.000; r = 0.357, p = 0.003; r = 0.316, p = 0.009; p < 0.05). The raw amplitudes and corrected amplitudes negatively correlated with age (r = -0.641, p = 0.000; r = -0.609, p = 0.000, p < 0.05). For B81-oVEMP, the corrected amplitudes negatively correlated with age (r = -0.638, p = 0.000, p<0.05), but the threshold and N10 latency positively correlated with age (r = 0.768, p = 0.000; r = 0.334, p = 0.009, p < 0.05). Moreover, the interaural asymmetry ratio did not significantly correlate with age for B81-cVEMP and B81-oVEMP.
Conclusion
As age increased, the B81-cVEMP response rate decreased, the thresholds increased, P13 and N23 latencies were prolonged, and the raw amplitude and corrected amplitude decreased. The B81-oVEMP response rate and corrected amplitude decreased, the thresholds increased, and N10 latency was prolonged with age. These changes are probably due to the occurrence of morphological and functional changes in the vestibular system with aging. Therefore, we suggest establishing different reference values according to different age groups when evaluating the VEMP results in patients with vestibular diseases.
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10.3389/fneur.2022.881682
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pubmed_1110_13043
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Lake et al. proposed a way to build machines that learn as fast as people do. This can be possible only if machines follow the human processes: the perception-action loop. People perceive and act to understand new objects or to promote specific behavior to their partners. In return, the object/person provides information that induces another reaction, and so on.
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10.1017/S0140525X1700022X
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pubmed_836_5076
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The unselective cyclooxygenase (COX) inhibitor S-flurbiprofen and its-in terms of COX-inhibition-"inactive" enantiomer R-flurbiprofen have been previously found to inhibit tumor development and growth in various animal models. The underlying mechanisms are unknown. Here, we show that both R- and S-flurbiprofen reduce survival of three colon cancer cell lines, which differ in the expression of COX-2 (HCT-15, no COX-2; Caco-2, inducible COX-2; and HT-29, constitutive COX-2). The IC50 for S- and R-flurbiprofen ranged from 250 to 450 microM. Both flurbiprofen enantiomers induced apoptosis in all three cell lines as indicated by DNA- and PARP-cleavage. In addition, R- and S-flurbiprofen caused a G1-cell cycle block. The latter was associated with an activation of c-Jun N-terminal kinase (JNK), an increase of the DNA binding activity of the transcription factor AP-1 and down-regulation of cyclin D1 expression. Western blot analysis, as well as supershift experiments, revealed that the AP-1 activation was associated with a change of AP-1 composition toward an increase of JunB. The JNK inhibitor SP600125 antagonized R- and S-flurbiprofen-induced AP-1 DNA binding, suppression of cyclin D1 expression, and the G1-cell cycle block. However, JNK inhibition had no effect on flurbiprofen-induced apoptosis. Hence, the cell cycle arrest is obviously mediated, at least in part, through JNK-activation, whereas R- and S-flurbiprofen-induced apoptosis is largely independent of JNK. Although in vitro effects of R- and S-flurbiprofen were indistinguishable, only R-flurbiprofen inhibited HCT-15 tumor growth in nude mice, suggesting the involvement of additional in vivo targets, which are differently affected by R- and S-flurbiprofen.
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10.1096/fj.02-0919fje
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pubmed_150_20894
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Introduction This study, through a systematic review and meta-analysis, has sought to demonstrate that the opportunity cost is a value to take into account in studies of economic cost in telemedicine, illustrated through the time of the dermatologist's consultation in teledermatology and traditional consultation. Methods Economic evaluation studies have been identified that compare teledermatology and traditional dermatological consultation during the period 1998-2015. We carried out a meta-analysis considering the work cost and the dermatologist's consultation time, analysing their differences. The opportunity cost represented by these differences in the dermatological remote consultation time was subsequently calculated based on the design of a cost/time variable. Results It was not possible to meta-analyse the cost of the dermatologist's consultation due to insufficient standardized complete data. It was possible to carry out a meta-analysis of the consultation time, and three articles were selected (2945 patients). Teledermatology accounts for more time (7.54 min) than conventional consultation ( p < 0.00001) and this difference is an opportunity cost of teledermatology of €29.25 per each remote consultation, with a unitary factor cost/time of 3.88€/minute. Conclusions There is no unanimity in the literature regarding which of the two procedures is cheaper; further studies with the necessary standardized variables are required. In this meta-analysis, teledermatology takes more time than a conventional dermatology consultation, which leads to an opportunity cost, increasing the total cost of consultation. The opportunity cost is a value that should be included in an analysis of economic costs, in the context of an economic assessment, when we evaluate a health activity.
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10.1177/1357633X16660876
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pubmed_900_9722
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Molecular phylogenetic analyses of 113 taxa representing Ascaridida, Rhigonematida, Spirurida and Oxyurida were used to infer a more comprehensive phylogenetic hypothesis for representatives of 'clade III'. The posterior probability of multiple alignment sites was used to exclude or weight characters, yielding datasets that were analysed using maximum parsimony, likelihood, and Bayesian inference methods. Phylogenetic results were robust to differences among inference methods for most high-level taxonomic groups, but some clades were sensitive to treatments of characters reflecting differences in alignment ambiguity. Taxa representing Camallanoidea, Oxyurida, Physalopteroidea, Raphidascarididae, and Skrjabillanidae were monophyletic in all 9 analyses whereas Ascaridida, Ascarididae, Anisakidae, Cosmocercoidea, Habronematoidea, Heterocheilidae, Philometridae, Rhigonematida and Thelazioidea were never monophyletic. Some clades recovered in all trees such as Dracunculoidea and Spirurina included the vast majority of their sampled species, but were non-monophyletic due to the consistent behaviour of one or few 'rogue' taxa. Similarly, 102 of 103 clade III taxa were strongly supported as monophyletic, yet clade III was paraphyletic due to the grouping of Truttaedacnitis truttae with the outgroups. Mapping of host 'habitat' revealed that tissue-dwelling localization of nematode adults has evolved independently at least 3 times, and relationships among Spirurina and Camallanina often reflected tissue predilection rather than taxonomy.
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10.1017/S0031182007002880
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pubmed_1080_2567
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To test whether verapamil protects myocardial high-energy phosphate content during hypoxia by reducing pre-hypoxic cardiac work or secondary to metabolic events that occur during hypoxia, we compared the relation between myocardial performance and high-energy phosphate content during normoxia, hypoxia and reoxygenation using 31P NMR spectroscopy in isolated, isovolumic buffer-perfused rat hearts. Function was reduced either by supplying verapamil or by altering work mechanically. During normoxia, supplying verapamil (10(-6.5) to 10(-5) M) decreased cardiac performance, increased both creatine phosphate content and intracellular pH, but had no effect on ATP content. During hypoxia, supplying verapamil attenuated ATP and creatine phosphate depletion, and during reoxygenation, ATP content was higher in verapamil-supplied hearts. In hearts in which pre-hypoxic performance was reduced mechanically, high-energy phosphate content during hypoxia and reoxygenation was preserved to the same extent as in hearts treated with 10(-6.5) M verapamil. During reoxygenation, neither verapamil-pretreatment nor mechanical reduction of pre-hypoxic performance affected the creatine phosphate content or indices of cardiac performance, expressed as percentage of pre-hypoxic values. Since reducing pre-hypoxic workload, either by supplying 10(-6.5) M verapamil or mechanically, produced indistinguishable effects on ATP and creatine phosphate contents during hypoxia and reoxygenation, we conclude that the primary mechanism of action of verapamil in hypoxic injury in the buffer-perfused rat heart is the reduction of pre-hypoxic energy demand.
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10.1016/0022-2828(89)90693-7
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pubmed_824_14693
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Identification of key amino acids is required for development of efficient cell-penetrating peptides (CPPs) and has tremendous implications in medicine. Extensive research work has enlightened us about the importance of two amino acids, arginine and tryptophan, in cell penetration. Here, we present a top-down approach to show how spatial positions of two tryptophans regulate the cellular entry and nuclear localization. This enables us to develop short, non-toxic tetrapeptides with excellent potential for cell penetration and nuclear localization. Among them, Glu-Thr-Trp-Trp (ETWW) emerges as the most promising. Results suggest that it enters into cancer cells following an endocytic pathway and binds at the major groove of nuclear DNA, where successive tryptophan plays major role. We subsequently show that it is not a P-glycoprotein substrate and is non-toxic to PC12-derived neurons, suggesting its excellent potential as a CPP. Furthermore, its potential as a CPP is validated in multi-cellular 3D cell culture (spheroid) and in in vivo mice model. This study provides major fundamental insights about the positional importance of tryptophan and opens new avenues toward the development of next-generation CPPs and major-groove-specific anticancer drugs.
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10.1021/jacs.7b10254
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pubmed_50_20946
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The in vitro antibacterial activity of some essential oils from Sardinian flora, both alone and in combination with chitosan, was investigated against a strain of Cutibacterium acnes, a bacterium involved in pathogenesis of acne. The composition of the essential oils was determined by gas chromatography and gas chromatography/mass spectrometry. The results of this investigation demonstrated that some of the oils examined, characterised by different chemical profiles, possessed some activity against C. acnes. Interestingly, this antibacterial effect was enhanced by sub-inhibitory concentrations of chitosan. These observations suggest the potential application of this synergy in the development of innovative topical formulations useful in the management of acne.
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10.3390/scipharm86030040
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pubmed_383_6090
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Vitamin C is a powerful antioxidant that has an intricate relationship with cancer and has been studied for more than 60 years. However, the specific mechanisms that allow malignant cells to uptake, metabolize, and compartmentalize vitamin C remain unclear. In normal human cells, two different transporter systems are responsible for its acquisition: glucose transporters (GLUTs) transport the oxidized form of vitamin C (dehydroascorbic acid) and sodium-coupled ascorbic acid transporters (SVCTs) transport the reduced form (ascorbic acid [AA]). In this study, we review the mechanisms described for vitamin C uptake and metabolization in cancer. Several studies performed recently in vivo and in vitro have provided the scientific community a better understanding of the differential capacities of cancer cells to acquire vitamin C: tumors from different origins do not express SVCTs in the plasma membrane and are only able to acquire vitamin C in its oxidized form. Interestingly, cancer cells differentially express a mitochondrial form of SVCT2. Why tumors have reduced AA uptake capacity at the plasma membrane, but develop the capacity of AA transport within mitochondria, remains a mystery. However, it shows that understanding vitamin C physiology in tumor survival might be key to decipher the controversies in its relationship with cancer. A comprehensive analysis of the mechanisms by which cancer cells acquire, compartmentalize, and use vitamin C will allow the design of new therapeutic approaches in human cancer. Antioxid. Redox Signal. 35, 61-74.
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10.1089/ars.2020.8166
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pubmed_344_843
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The effects of benzodiazepines on GABA(A) receptors are dependent largely on the particular α subunit isoform that is present in the receptor pentamer. The inclusion of either the α4 or α6 subunit is generally thought to render the receptor insensitive to classical benzodiazepines. We expressed the rat α4β3γ2L subtype in Xenopus oocytes and observed that both diazepam and flunitrazepam significantly potentiated GABA-gated currents. This potentiation occurred at nanomolar concentrations similar to those seen at the most abundant "diazepam-sensitive" receptor i.e., the α1β2γ2 subtype. In the α4β3γ2L receptor, the effects of diazepam and flunitrazepam were inhibited by nanomolar concentrations of the benzodiazepine site antagonists, Ro15-1788 and ZK93426. The presence of the β3 subunit appears to be important for this modulation since diazepam did not affect GABA responses mediated by recombinant α4β1γ2L or α4β2γ2L receptors. Interestingly, when the α4β3γ2L receptor was expressed in HEK293 cells, diazepam and flunitrazepam displaced the relatively non-selective benzodiazepine site ligand, [(3)H]Ro15-4513, only at high concentrations (>10 μM) demonstrating a lack of high affinity binding for these classical benzodiazepines. Functional studies of the cell-expressed receptors using whole cell recording techniques showed that neither diazepam nor flunitrazepam potentiated GABA-evoked currents although currents were enhanced by nanomolar concentrations of Ro15-4513. These results suggest that the observed benzodiazepine modulation of the α4β3γ2L subtype depends on the expression system used and may be specific for expression in Xenopus oocytes.
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10.1016/j.neuropharm.2010.07.011
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pubmed_122_21701
|
OBJECTIVE
Our study aimed to investigate the interaction between peroxiredoxin 1 (Prx1) and forkhead box O3 (FOXO3) and to explore the role of PI3K/AKT pathway in the development of pancreatic cancer.
MATERIAL AND METHODS
Human pancreatic normal cells HPDE6-C7 and pancreatic cancer cells PANC-1 were randomly divided into control group, Prx1-silencing (si-Prx1) group, Prx1/FOXO3 dual-silencing (si-Prx1/FOXO3) group, and negative control group. Cell proliferation assay, clone formation assay, and cell apoptosis assay were performed to investigate the effects of Prx1 silencing and FOXO3 silencing on the proliferation and apoptosis ability of pancreatic cancer cells. qRT-PCR and Western blot were performed to study the Prx1 and FOXO3 mRNA in the two cells and FOXO3 protein expression in PANC-1 cells.
RESULT
We found Prx1 silencing could inhibit growth and promote apoptosis of PANC-1 cells. And Prx1 silencing could decrease the Prx1 mRNA level and increase FOXO3 mRNA level. To further explore the role of Prx1 in PI3K/AKT, we study the cell proliferation and apoptosis ability after adding the PI3K inhibitor and PI3K activator. We observed that PI3K inhibitor could inhibit tumor cell growth and promote cell apoptosis. And PI3K inhibitor also downregulated Prx1 protein expression.
CONCLUSION
We concluded that the Prx1 silencing inhibited the growth and promoted apoptosis of pancreatic cancer cells via modulation of PI3K/AKT pathway by targeting FOXO3 gene.
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10.2147/CMAR.S177243
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pubmed_939_8095
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Linearly conjugated systems have long served as an archetype of conjugated materials, but suffer from two intrinsic structural problems: potential instability due to intermolecular interactions and the flexibility of the C-C bonds connecting C═C bonds. Efforts to solve these problems have included the insertion of aromatic units as a part of the conjugation and the introduction of carbon bridges to stop the bond rotation. We report here B/N-doped p-arylenevinylene chromophores synthesized through the incorporation of a cyclopenta[c][1,2]azaborole framework as a part of the conjugated system. The ring strain intrinsic to this new skeleton both flattens and rigidifies the conjugation, and the B--N+ dative bond is much easier to form than a C-C bond, which simplifies the synthetic design. The B-N dative bond also reduces the HOMO-LUMO gap, thereby causing a significant redshift of the absorption and emission compared with their all-carbon congeners while retaining high photostability and high fluorescence quantum yield in both solution and film states. A doubly B/N-doped compound showed emission peaks at 540 nm with a small Stokes shift of 20 nm and a fluorescence quantum yield of 98%. The molecules serve as excellent lipophilic fluorescent dyes for live-cell imaging, showing a higher photostability than that of commercially available BODIPY-based dyes.
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10.1021/jacs.0c10337
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pubmed_763_2161
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BACKGROUND
In preclinical testing, ventricular wall injection of hydrogels has been shown to be effective in modulating ventricular remodeling and preserving cardiac function. For some approaches, early-stage clinical trials are under way. The hydrogel delivery method varies, with minimally invasive approaches being preferred. Endocardial injections carry a risk of hydrogel regurgitation into the circulation, and precise injection patterning is a challenge. An epicardial approach with a thermally gelling hydrogel through the subxiphoid pathway overcomes these disadvantages.
METHODS
A relatively stiff, thermally responsive, injectable hydrogel based on N-isopropylacrylamide and N-vinylpyrrolidone (VP gel) was synthesized and characterized. VP gel thermal behavior was tuned to couple with a transepicardial injection robot, incorporating a cooling feature to achieve injectability. Ventricular wall injections of the optimized VP gel have been performed ex vivo and on beating porcine hearts.
RESULTS
Thermal transition temperature, viscosity, and gelling time for the VP gel were manipulated by altering N-vinylpyrrolidone content. The target parameters for cooling in the robotic system were chosen by thermal modeling to support smooth, repeated injections on an ex vivo heart. Injections at predefined locations and depth were confirmed in an infarcted porcine model.
CONCLUSIONS
A coupled thermoresponsive hydrogel and robotic injection system incorporating a temperature-controlled injectate line was capable of targeted injections and amenable to use with a subxiphoid transepicardial approach for hydrogel injection after myocardial infarction. The confirmation of precise location and depth injections would facilitate a patient-specific planning strategy to optimize injection patterning to maximize the mechanical benefits of hydrogel placement.
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10.1016/j.athoracsur.2016.02.082
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pubmed_177_22426
|
Oro-facial dysfunctions (OFD) or oro-facial myofunctional disorders in children lead to severe problems in teeth and jaw position, articulation, chewing and swallowing. The forces of the tongue, the central muscle for articulation, chewing and swallowing are focused on in several studies. In this examination, isometric tongue protrusion forces (TPF) of children with OFD and controls were compared. Thirty participants with OFD and 30 controls were presented a target force level as a straight line on a monitor that they were supposed to match by generating an isometric tongue force for different target levels (0.25 N and 0.5 N). Correlations of the severity of OFD (symptom score) with the capacities of the TPF 0.25 N and 0.5 N were calculated. Statistical differences were obvious in TPF variability and the accuracy, depending on the weight. Tongue contact time, expressed as per cent (TCT, total contact: 100%), was significantly lower in children with OFD (P = .005). Mean and median TPF was not different between groups. The predictive value of TPF for OFD revealed a level of 58.6% for TPF 0.25 N and 74.5% for TPF 0.5 N. Correlations of the severity of OFD were seen for some parameters. Subjects with OFD show significantly lower competencies in accuracy and endurance of tongue protrusion forces. This may have a high impact on phenotyping children with OFD and influence therapeutical approaches.
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10.1111/joor.12598
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pubmed_796_14059
|
The interleukin-2 (IL-2) assay has become a useful tool for examining the cellular immune response. Because of a lack of avian IL-2-dependent cell lines, the avian IL-2 assay in its present state, however, is not currently as powerful as its mammalian counterpart in effectively evaluating levels of IL-2 activity. The use of an avian IL-2 reference standard, Percoll-enriched populations of lymphoblasts, and sample collection times were examined to optimize the assay for comparing levels of IL-2 activity in a large number of birds. The reference standard was effective in accounting for assay-to-assay variance. Percoll-enriched populations of responding lymphoblasts were more sensitive to IL-2 than nonseparated populations of cultured peripheral blood lymphocytes. Levels of IL-2 activity of cells isolated from the same bird did not change within a 1-week period, although differences did approach significance. In addition, levels of IL-2 activity differed between genetically distinct populations.
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10.1016/0165-2427(89)90169-4
|
pubmed_815_6883
|
Phosphate plays a central role in many of the basic processes essential to the cell and organism. In particular, skeletal mineralisation is dependent on the appropriate regulation of phosphate in the body, and any disturbances in phosphate homeostasis can have severe repercussions on the integrity of bone. The kidney regulates the serum levels of phosphate by tubular mechanisms which are not fully understood. Furthermore, the processes involved in regulating renal tubular phosphate reabsorption are complex, and involve a large number of factors. It is not surprising therefore that defects in renal phosphate handling result in a failure of bone mineralisation. There are three well characterised conditions which are associated with renal tubulopathies resulting in a phosphate leak, with consequent bone disease. Two are familial, hypophosphataemic rickets (HYP), and hereditary hypophosphataemic rickets with hypercalciuria (HHRH). The third is acquired via a tumour, oncogenic hypophosphataemic osteomalacia (OHO), and may well have relevance to the inherited hypophosphataemias. Recent advances in molecular genetics are permitting the identification of genes involved in human diseases from their chromosomal location. These approaches are now being applied to the analysis of the hypophosphataemias. The isolation of the genes responsible for the renal tubulopathies will be an important achievement. Ultimately this will help to increase our understanding of the mechanisms involved in the control of phosphate handling in the body.
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10.1007/BF00211008
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pubmed_147_18000
|
Mutations in the RNA binding protein fused in sarcoma/translated in liposarcoma (FUS/TLS) cause amyotrophic lateral sclerosis (ALS). Although ALS-linked mutations in FUS often lead to a cytosolic mislocalization of the protein, the pathogenic mechanisms underlying these mutations remain poorly understood. To gain insight into these mechanisms, we examined the biochemical, cell biological and functional properties of mutant FUS in neurons. Expression of different FUS mutants (R521C, R521H, P525L) in neurons caused axonal defects. A protein interaction screen performed to explain these phenotypes identified numerous FUS interactors including the spinal muscular atrophy (SMA) causing protein survival motor neuron (SMN). Biochemical experiments showed that FUS and SMN interact directly and endogenously, and that this interaction can be regulated by FUS mutations. Immunostaining revealed co-localization of mutant FUS aggregates and SMN in primary neurons. This redistribution of SMN to cytosolic FUS accumulations led to a decrease in axonal SMN. Finally, cell biological experiments showed that overexpression of SMN rescued the axonal defects induced by mutant FUS, suggesting that FUS mutations cause axonal defects through SMN. This study shows that neuronal aggregates formed by mutant FUS protein may aberrantly sequester SMN and concomitantly cause a reduction of SMN levels in the axon, leading to axonal defects. These data provide a functional link between ALS-linked FUS mutations, SMN and neuronal connectivity and support the idea that different motor neuron disorders such as SMA and ALS may be caused, in part, by defects in shared molecular pathways.
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10.1093/hmg/ddt222
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pubmed_251_11652
|
Pyridinoline (Pyr) and deoxypyridinoline (Dpyr) are mature crosslinks which maintain the structure of the collagen fibril. Pentosidine (Pen) is a senescent crosslink and one of the advanced glycation end products. We developed a direct and one-injection method to measure Pyr, Dpyr, and Pen in the hydrolysate of tissues using reversed-phase high-performance liquid chromatography. Using a linear gradient of acetonitrile and a cleaning step, the objective crosslinks were well separated and continuously and automatically assayed. Recovery rates of Pyr, Dpyr, and Pen were 95-116, 94-110, and 92-120%, respectively (n = 5). The intraassay coefficients of variation for Pyr, Dpyr, and Pen were 5.3, 5.8, and 4.3%, respectively (n = 5), and the interassay coefficients of variation for Pyr, Dpyr, and Pen were 3.5, 4.6, and 5.7%, respectively (n = 5). Linear regression analysis showed the linearity (r = 0.999) of calibration line for each Pyr, Dpyr, and Pen. We measured the content of these crosslinks in the tissues from the young and old subjects. There was no difference in the content of Pyr and Dpyr between the young and the old group. On the other hand, the content of Pen in the old group was extremely higher than that in the young group. We demonstrated the direct method for measuring two kinds of major crosslinks which have different characters and believe that this method will be useful in determining the content of these crosslinks in tissues under various conditions.
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10.1006/abio.1995.0002
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pubmed_206_9026
|
One of the topics which forms part of CONRAD project addresses the problems related to the dosimetry of complex-mixed radiation fields at workplaces. This topic was included in work package (WP) 6. WP 6 was established to co-ordinate research activities in two areas:the development of new techniques and the improvement of current techniques for characterisation of complex workplace fields (including high-energy fields and pulsed fields): measurement and calculation of particle energy and direction distributions (Subgroup A); and model improvements for dose assessment of solar particle events (Subgroup B). In both cases in order to aid the research, WP 6 increases the efficiency of resource utilisation, and facilitates the technology transfer to practical application and for the development of standards. This contribution presents a general overview of activities of SG A; specific results related to the benchmark experiment at GSI Darmstadt are presented separately, and will be published in other way. As far as the results acquired in the frame of the SG B activities, these are presented in the meeting held as part of EURADOS AM 2008.
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10.1093/rpd/ncn220
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pubmed_335_14323
|
Cutaneous CD30+ T-cell lymphoproliferative disorders (CD30+ LPD) are the second most common form of cutaneous T-cell lymphoma. CD30+ LPD include lymphomatoid papulosis, primary cutaneous anaplastic large-cell lymphoma, and borderline lesions. Despite expression of CD30 by the neoplastic cells as the hallmark of these disorders, they differ in their clinical presentation and histological features as well as the course, the prognosis, and consecutively in the treatment. Diagnosis of CD30+ LPD and distinction from the broad spectrum of differential diagnoses essentially depends on clinicopathologic correlation as well as the results of staging examinations. Although the histological findings indicate a high-grade lymphoma, CD30+ LPD in most cases have a favorable prognosis. Recent advances in targeted therapy have led to new therapeutic approaches to CD30+ LPDs. This review describes the clinicopathologic features of CD30+ LPDs, their differential diagnoses, the treatment, and the role of CD30 as a diagnostic marker and therapeutic target.
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10.12788/j.sder.2018.001
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pubmed_1140_14667
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Operation Iraqi Freedom was perhaps the last military campaign that will ever utilize the services of a mobile Army surgical hospital (MASH). The Army has now essentially replaced the MASH with combat surgical hospitals (CSH) and forward surgical teams (FST). MASH units were designed as mobile, flexible, forward-deployed military hospitals, providing care for the wounded near the frontlines of the battlefield. These hospitals not only saved thousands of lives during war but also greatly influenced the delivery of trauma and critical care in civilian hospitals. The MASH was made popular by the television series of the 1970s, depicting the 4077th during the Korean War. Although a comical series, these television episodes provided viewers with a glimpse of life in a MASH during time of war. This article chronicles the history of the MASH from its inception during World War II to recent experiences in Operation Iraqi Freedom.
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pubmed_1140_14667
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pubmed_37_5068
|
Novel N-aryltriazole nucleosides were synthesized via Cu-mediated C-N cross-coupling reaction starting with 3-aminotriazole ribonucleoside and various boronic acids. Two of them exhibited potent apoptosis-related antiproliferative activity against the drug-resistant pancreatic cancer cell line MiaPaCa-2, with an increased potency compared to gemcitabine, the reference treatment for pancreatic cancer. A preliminary SAR study suggests that the appended N-aryl moiety and the substituent at its para-position, as well as the ribose sugar component, contribute considerably to the observed antiproliferative activity.
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10.1016/j.bmcl.2010.02.104
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pubmed_260_22963
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A chest X-ray (CXR) is routinely performed after percutaneous dilatational tracheostomy (PDT). The purpose of this study was to evaluate the diagnostic yield of routine CXR following PDT and its impact on patient management and to identify predictors of post-PDT CXR changes. Two-hundred-and-thirty-nine patients who underwent PDT in a 21-bed intensive care unit were included prospectively in the study. The following data were collected: patient demographics, APACHE III scores, pre-PDT FiO2 and PEEP, PDT technique, perioperative complications and the use of bronchoscopic guidance. We compared post-PDT CXR with the last pre-PDT CXR. We documented any post-PDT new radiographic findings including atelectasis, pneumothorax, pneumomediastinum, surgical emphysema, pulmonary infiltrates or tracheostomy tube malposition. We also recorded management modifications based on post-PDT radiographic changes, including increased PEEP, chest physiotherapy, therapeutic bronchoscopy or chest tube insertion. Atelectasis was the only new finding detected on post-PDT CXRs of 24 (10%) patients. The new radiographic findings resulted in a total of 14 modifications of management in 10 (4%) patients including increased PEEP in six, chest physiotherapy in six and bronchoscopy in two patients. Trauma and pre-PDT PEEP >5 cmH2O were independent predictors of post-PDT CXR changes. Routine CXR following PDT has a low diagnostic yield, detecting mainly atelectasis and leading to a change in the management in only a minority ofpatients. Routine CXR after apparently uncomplicated PDT performed by an experienced operator may not be necessary and selective use may improve its diagnostic yield. Further studies are required to validate the safety of selective versus routine post-PDT CXR.
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10.1177/0310057X0703500313
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pubmed_573_19765
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A robust and efficient protocol for the introduction of the dioxolanylethyl moiety onto various aryl and heteroaryl halides has been developed, providing cross-coupling yields up to 93%. Copper-catalyzed borylation of 2-(2-bromoethyl)-1,3-dioxolane with bis(pinacolato)diboron followed by treatment with potassium bifluoride provides the key organotrifluoroborate reagent.
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10.1021/ol400320q
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pubmed_656_2727
|
Non-invasive diagnostic markers are needed to ease the diagnosis of non-alcoholic steatohepatitis (NASH) among patients with non-alcoholic fatty liver disease (NAFLD). The long noncoding RNA (lncRNA) LeXis is related to cholesterol metabolism and hepatic steatosis in mice, and its batch genome conversion in humans is TCONS_00016452. Here, we aimed to evaluate the potential of lncRNA LeXis as a non-invasive diagnostic marker for NASH. We analyzed a total of 44 NAFLD patients whose diagnosis was confirmed by a pathologist through analysis of a percutaneous liver biopsy. The expression of LeXis in the plasma of NAFLD patients with and without NASH was compared using quantitative real-time polymerase chain reaction. The expression of plasma LeXis was significantly higher in patients with NASH than in those with NAFL (8.2 (5.0-14.9); 4.6 (4.0-6.6), p = 0.025). The area under the receiver operating characteristic curve was 0.743 (95% CI 0.590-0.895, p < 0.001), and a sensitivity of 54.3% and specificity of 100% could be achieved for NASH diagnosis. Low LeXis was independently associated with NASH diagnosis in patients with NAFLD (p = 0.0349, odds ratio = 22.19 (5% CI, 1.25-395.22)). Therefore, circulating lncRNA LeXis could be a potential non-invasive diagnostic biomarker for NASH.
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10.3390/life10100230
|
pubmed_996_19878
|
OBJECTIVE
In patients with hypothyroid goitrous Hashimoto's thyroiditis, the recovery from hypothyroidism seems to be due to a spontaneous decrease of antibodies (Ab) to the TSH-receptor (R). In contrast, in patients with Graves' disease made euthyroid by antithyroid drug therapy, the suppression of TSH secretion by thyroid hormone during antithyroid drug treatment decreases the production of Ab to TSH-R. We investigated in patients with initially euthyroid or hypothyroid goitrous Hashimoto's thyroiditis the relationships between thyroid status and the serum TSH-R, peroxidase (TPO) and thyroglobulin (Tg) Ab concentrations in untreated or L-thyroxine (T4) treated patients.
PATIENTS
A prospective study of 174 consecutive patients, referred with goitrous Hashimoto's disease in an initially euthyroid (group I, n = 78) or hypothyroid (group II, n = 96) state. The patients with positive (> or = 7%) TSH-RAb (group I, n = 18; group II, n = 22) were reinvestigated 12 months after the initiation of L-T4 therapy. After which, (1) L-T4 was continued and an evaluation performed 2 months later (i.e. 14 months after L-T4 initiation) in 9 patients of group I and in 11 patients of group II or (2) L-T4 was withdrawn and an evaluation performed 2 months later in 9 patients of group I and in 11 patients of group II.
MEASUREMENTS
Measurements of basal plasma TSH, free T4 (FT4) and total T3 and serum TSH-R, TPO and TgAb.
RESULTS
The prevalence of positive TSH-RAb levels did not differ between group I (23.1%) and group II (22.9%). However, the mean TSH-RAb level in group I (9.4 +/- 0.4%) was lower (P < 0.01) than in group II (11.6 +/- 0.5%). In the patients with positive TSH-R Ab, (1) the prevalences of positive TSH-RAb decreased (P < 0.001) under L-T4 therapy (group I = 22.2%, group II = 21.2%) and increased again (P < 0.01) 2 months after L-T4 cessation (group I = 77.7%, group II = 63.6%) to reach lower levels (group I, P < 0.05; group II, P < 0.01) than those obtained prior to L-T4 treatment. Statistical analysis of TSH levels through the course of the study confirmed these results. (2) In contrast to the variations of the mean TgAb values, the variations of the mean TPOAb levels in each group were in good agreement with those of TSH-RAb through the course of the study. (3) There were significant correlations between some parameters of thyroid status and both TSH-RAb (TSH, r = 0.43, P < 0.001; FT4, r = -0.35, P < 0.01) and TPOAb (TSH, r = 0.42, P < 0.001; FT4, r = -0.31; P < 0.01) levels. In contrast, no correlations were found between thyroid status and TgAb values.
CONCLUSIONS
This study demonstrates that thyroid status can modulate thyroid autoimmunity expression, such as TSH-RAb and TPOAb, in patients with euthyroid or hypothyroid goitrous Hashimoto's thyroiditis. Similar results have been reported in patients with Graves' disease made euthyroid by the administration of thyroid hormone during antithyroid drug treatment.
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10.1111/j.1365-2265.1994.tb02494.x
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pubmed_70_10688
|
OBJECTIVES
Religion and spirituality are increasingly recognized as important in the care of seriously ill patients. This study evaluates religious and spiritual beliefs and practices among pediatric oncology faculty and compares their religiosity and spirituality to the general public.
METHODS
Information was gathered from a sampling frame of all pediatric oncology faculty working in 13 US News and World Report's "honor role" hospitals. These data were compared with the general public (using the General Social Survey), through frequency distributions, descriptive crosstabs, and tests of significance, including chi(2) statistics.
RESULTS
Eighty-five percent of pediatric oncology faculty described themselves as spiritual. In all, 24.3% reported attending religious services 2 to 3 times a month or more in the past year. Twenty-seven percent of pediatric oncologists believed in God with no doubts. In all, 52.7% believed their spiritual or religious beliefs influence interactions with patients and colleagues. Among the general public 40.1% reported attending religious services 2 to 3 times a month or more in the past year (P<0.01) and 60.4% believed in God with no doubts (P<0.001).
CONCLUSIONS
Although many have no traditional religious identity, large fractions of pediatric oncology faculty described themselves as spiritual. This may have implications for the education of pediatric oncologists and the spiritual care of seriously ill children and their families.
|
10.1097/MPH.0b013e31815a0e39
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pubmed_918_6903
|
OBJECTIVE
To analyze factors such as parental supervision and support, as well as the type of education (single-gender education and co-education) and its correlation with the initiation of sexual activity in adolescents.
MATERIALS AND METHODS
Quantitative, descriptive, explanatory cross-sectional study with 522 participants between 12 and 18 years of age. A questionnaire with 26 questions was applied to evaluate some parental practices, the type of education and the initiation of sexual activity. The results were analyzed using the SPSS program version 23. Each participant gave informed consent, and the confidentiality of the data was preserved.
RESULTS
Significant differences were found regarding the onset of sexual activity in adolescents according to the type of education and age; no differences were observed with respect to family type. As the age of the adolescent increases, parents show more support and less supervision, therefore, the likelihood of engaging in sexual intercourse increases. In the context of co-education, a greater number of adolescents who had initiated sexual activity was found.
CONCLUSIONS
This study highlights the importance of parental involvement in the education of children to delay the onset of sexual activity as a healthy practice during adolescence. Less parental supervision and a greater age result in earlier onset of sexual activity in young people. Co-educated teens engage in this activity earlier, although their mothers tend to supervise them more. Family and school are important contexts for fostering healthy life styles in teenagers.
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10.15446/rsap.V20n3.60386
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pubmed_698_4974
|
BACKGROUND
Nutritional safety of protein-restricted diets in patients with chronic renal failure is controversial. In the present study, we have assessed the evolution of nutritional status after initiation of hemodialysis in patients previously treated by a supplemented very low protein diet (SVLPD).
METHODS
Nutritional data were prospectively collected during the first year of hemodialysis from 15 consecutive patients treated with a SVLPD (0.3 g protein/kg/day supplemented with essential amino acids, calcium, iron, and vitamins) and compared to 15 age- and gender-matched end-stage renal disease (ESRD) patients previously on a less-restricted diet (0.90 +/- 0.21 g protein/kg/day) who started hemodialysis during the same period. Dual-energy x-ray absorptiometry (DEXA) was used to assess body composition at 0, 6, and 12 months. Hemodialysis prescriptions, biologic data and 3-day food records were collected every 3 months.
RESULTS
Protein intake was higher than 1.2 g/kg/day in both groups as soon as 3 months after the start of hemodialysis. Albumin and prealbumin increased significantly during the first 6 months in all patients. Body mass index (BMI) increased in all patients (+0.97 +/- 1.31 kg/m2; P < 0.001) reflecting a gain in fat mass in the overall population (+2.36 +/- 2.94 kg/m2; P < 0.001) while lean body mass remained stable overall.
CONCLUSION
Once on hemodialysis, SVLPD patients rapidly increased protein intake. Nutritional status improved in all patients, with a gain in fat mass in all, and a gain in lean body mass in SVLPD men only. These data indicate that treatment with a SVLPD prior to hemodialysis initiation is nutritionally safe.
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10.1046/j.1523-1755.2003.00884.x
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pubmed_677_2598
|
This paper is motivated by a study of physical activity participation habits in African American women with three potential sources of correlation among study outcomes, according to method of assessment, timing of measurement, and intensity of physical activity. To adjust for the multiple sources of correlation in this study, we implement an approach based on generalized estimating equations that models association via a patterned correlation matrix. We present a general algorithm that is relatively straightforward to program, an analysis of our physical activity study, and some asymptotic relative efficiency comparisons between correctly specifying the correlation structure vs ignoring two sources of correlation in the analysis of data from this study. The efficiency comparisons demonstrate that correctly modeling the correlation structure can prevent substantial losses in efficiency in estimation of the regression parameter.
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10.1002/sim.1887
|
pubmed_200_8463
|
OBJECTIVES
Contact granuloma has been associated with voice abuse, laryngopharyngeal reflux, and habitual throat clearing. It has a high propensity for persistence and recurrence. Treatment options included voice therapy and antireflux measures. Surgical excision has been considered in patients who do not respond to medical management. In this research, we aimed to present our experience with botulinum toxin injection only.
STUDYDESIGN
Retrospective case series of a tertiary referral center.
METHODS
Our series consisted of 22 patients, who underwent botulinum toxin injection only as an office procedure to bilateral thyroarytenoid and lateral cricoarytenoid muscles in 2 × 1.25 to 2 × 2.5 U. No other treatment was applied. The cases were followed up for at least 6 months ranging between 6 and 100 months with a mean of 28.
RESULTS
Seventeen cases (77%) were cured of their granuloma. Eleven of the cured cases had grade 2, four cases had grade 1, and two patients had grade 3 granuloma.
CONCLUSIONS
Botulinum toxin A injection only is an efficient treatment modality in contact granuloma, especially for grade 1, 2, and 3 cases, and it can be used as a first-line treatment.
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10.1016/j.jvoice.2015.07.015
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pubmed_565_17430
|
The discrete wavelet transform may be used as a signal-processing tool for visualization and analysis of nonstationary, time-sampled waveforms. The highly desirable property of shift invariance can be obtained at the cost of a moderate increase in computational complexity, and accepting a least-squares inverse (pseudoinverse) in place of a true inverse. A new algorithm for the pseudoinverse of the shift-invariant transform that is easier to implement in array-oriented scripting languages than existing algorithms is presented together with self-contained proofs. Representing only one of the many and varied potential applications, a recorded speech waveform illustrates the benefits of shift invariance with pseudoinvertibility. Visualization shows the glottal modulation of vowel formants and frication noise, revealing secondary glottal pulses and other waveform irregularities. Additionally, performing sound waveform editing operations (i.e., cutting and pasting sections) on the shift-invariant wavelet representation automatically produces quiet, click-free section boundaries in the resulting sound. The capabilities of this wavelet-domain editing technique are demonstrated by changing the rate of a recorded spoken word. Individual pitch periods are repeated to obtain a half-speed result, and alternate individual pitch periods are removed to obtain a double-speed result. The original pitch and formant frequencies are preserved. In informal listening tests, the results are clear and understandable.
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10.1121/1.1869732
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pubmed_110_8776
|
The classic cystinuria is a hereditary disorder characterized by a defective transport of cystine and the dibasic amino acids arginine, lysine and ornithine in the epithelial cells of the renale tubule and the gastrointestinal tract. The excretion patterns of cystine and the dibasic amino acids in 24-hour urine samples from heterozygotes can be used to the differentiation between the genetic subtypes. 120 probands in the age range from 3 to 70 years from 22 families with cystinuria were investigated by thin-layer chromatography and by ion exchange chromatography. In patients with cystinuria the genotype I-I has a frequency of 50%. These results and the distribution of the other subtypes are in accordance with published data. From 98 persons investigated in 22 families with cystinuria 14 run the risk to form cystine stones. Therefore, the knowledge of the subtypes is relevant for practice.
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pubmed_110_8776
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pubmed_609_17728
|
The self assembly of actin and the large number of actin-binding proteins are important in the establishment of cell shape and function during embryogenesis. Thymosin beta4 (Tbeta4) is a small acidic peptide that participates in the regulation of actin polymerization in mammalian cells. In the present work, we report the presence of the mRNA encoding for Tbeta4 in mouse embryonic stem cells and its induction in P1 9 embryonal cells stimulated to differentiate into ectodermal-like (neurons and glia) or mesodermal-like cells (cardiac and skeletal muscle). The induction of Tbeta4, mRNA in P19 cells was confirmed by in situ hybridization analysis of early mouse postimplantation embryos. Noteworthy, we observed an important hybridization signal in several areas of the embryo specially in blood vessels and in heart tissues, suggesting a role for this peptide in angiogenesis. In conclusion, the results presented here demonstrate the expression of Tbeta4 gene during early embryogenesis which immediately suggests an important role for this peptide in developmental processes requiring actin-based functions such as the formation of cardiovascular system.
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10.1016/0167-4781(96)00003-6
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pubmed_543_9210
|
Mandibular condyles in organ culture commonly have been used as a model system for examination of the factors that influence skeletal growth and development. The work reported here complements previously published histological studies by providing quantitative temporal information on growth and matrix accumulation. Condyles maintained for as long as 5 weeks in serum-free and 1% serum-supplemented culture media were found to remain viable and metabolically active as demonstrated by continued dimensional growth as well as cell and matrix accumulation. Growth occurred by a combination of cell proliferation, matrix synthesis and accumulation, and cell hypertrophy (with the latter two mechanisms dominating). Increases in tissue volume correlated directly with increased glycosaminoglycan content; both increased 7-fold over 5 weeks. In comparison with serum-free culture, after 35 days in medium containing 1% serum, glycosaminoglycan content was 24% lower and collagen content was 36% higher, whereas dry weight, condyle length, and DNA content were not significantly different; in addition, histological observation suggested that, for samples cultured with serum, chondrogenic phenotype had been lost from some regions. The temporal behavior for all growth parameters exhibited a transient phase 1-2 weeks in duration followed by a steady-state period in which dimensions and tissue constituents or content increased at a constant or near constant rate. Comparison of the rates of incorporation of [35S]sulfate with glycosaminoglycan content in serum-free cultures suggests that the loss of glycosaminoglycan occurs only initially or is negligible; therefore, under these baseline conditions, cartilage glycosaminoglycan content reflects the biosynthetic rate. The high degree of reproducibility seen during steady-state growth suggests that these data provide reliable baseline information and further supports the notion that this model system is useful for investigation of the effects of specific physical factors on in vitro growth and development.
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10.1002/jor.1100130209
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pubmed_1086_8003
|
Reliable data on stroke incidence and prevalence are essential for calculating the burden of stroke and the planning of prevention and treatment of stroke patients. In the current study we have reviewed the published data from EU countries, Iceland, Norway, and Switzerland, and provide WHO estimates for stroke incidence and prevalence in these countries. Studies on stroke epidemiology published in peer-reviewed journals during the past 10 years were identified using Medline/PubMed searches, and reviewed using the structure of WHO's stroke component of the WHO InfoBase. WHO estimates for stroke incidence and prevalence for each country were calculated from routine mortality statistics. Rates from studies that met the 'ideal' criteria were compared with WHO's estimates. Forty-four incidence studies and 12 prevalence studies were identified. There were several methodological differences that hampered comparisons of data. WHO stroke estimates were in good agreement with results from 'ideal' stroke population studies. According to the WHO estimates the number of stroke events in these selected countries is likely to increase from 1.1 million per year in 2000 to more than 1.5 million per year in 2025 solely because of the demographic changes. Until better and more stroke studies are available, the WHO stroke estimates may provide the best data for understanding the stroke burden in countries where no stroke data currently exists. A standardized protocol for stroke surveillance is recommended.
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10.1111/j.1468-1331.2006.01138.x
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pubmed_742_8233
|
The morphological phase transition between sessile and lenticular shapes of a droplet placed in a nanochannel is observed upon increasing the droplet volume. The phase diagram for this system is discussed within both macroscopic and mesoscopic approaches. On the mesoscopic level, the van der Waals forces are taken into account via the effective interface potential acting between the channel walls and the droplet. We discuss the contact angle dependence on the droplet volume and the distance between the walls; this angle turns out to be smaller than the macroscopic Young's angle. The droplet's presence induces the solvation force acting between the channel walls. It can be either attractive or repulsive, depending on the width of the channel.
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10.1088/0953-8984/26/3/035101
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pubmed_1025_22795
|
Bark beetles that colonize living conifers and their microbial associates encounter constitutive and induced chemical defenses of their host. Monoterpene hydrocarbons comprise a major component of these allelochemicals, and many are antibiotic to insects, fungi, and bacteria. Some bark beetle species exhaust these defenses by killing their host through mass attacks mediated by aggregation pheromones. Others lack adult aggregation pheromones and do not engage in pheromone-mediated mass attacks, but rather have the ability to complete development within live hosts. In the former species, the larvae develop in tissue largely depleted of host terpenes, whereas in the latter exposure to these compounds persists throughout development. A substantial literature exists on how monoterpenes affect bark beetles and their associated fungi, but little is known of how they affect bacteria, which in turn can influence beetle performance in various manners. We tested several bacteria from two bark beetle species for their ability to grow in the presence of a diversity of host monoterpenes. Bacteria were isolated from the mountain pine beetle, Dendroctonus ponderosae Hopkins, which typically kills trees during colonization, and the red turpentine beetle, Dendroctonus valens LeConte, which often lives in their host without causing mortality. Bacteria from D. ponderosae were gram-positive Actinobacteria and Bacilli; one yeast also was tested. Bacteria from D. valens were Actinobacteria, Bacilli, and γ-Proteobacteria. Bacteria from D. valens were more tolerant of monoterpenes than were those from D. ponderosae. Bacteria from D. ponderosae did not grow in the presence of α-pinene and 3-carene, and grew in, but were inhibited by, β-pinene and β-phellandrene. Limonene and myrcene had little inhibitory effect on bacteria from either beetle species. Tolerance to these antibiotic compounds appears to have resulted from adaptation to living in a terpene-rich environment.
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10.1007/s10886-011-9992-6
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pubmed_1084_25166
|
OBJECTIVE
To assess the safety, efficacy, and medium-term durability of bipolar plasmakinetic transurethral resection of the prostate (PK-TURP) for the treatment of bladder outlet obstruction due to benign prostatic hyperplasia in a prospective study.
METHODS
From March 2007 to May 2008, 132 consecutive patients underwent PK-TURP at our institution. All patients were assessed perioperatively and followed up at 1, 3, 6, 12, 18, 24, and 36 months postoperatively. The parameters included the International Prostate Symptom Score, quality of life scores, maximal urinary flow rates, transrectal ultrasonography, postvoid residual urine volume, and serum prostate-specific antigen level.
RESULTS
The mean patient age was 64.55±4.03 years. The prostate volume was 79.66±12.36 g. The operative time was 78.83±17.41 minutes, and the resected weight was 58.12±7.29 g. The catheterization time was 69.00±17.99 hours, and the hospital stay was 117.00±17.99 hours. The decrease in hemoglobin and sodium was 1.55±0.48 g/dL and 1.57±0.38 mmol/L, respectively. A significant improvement occurred in the maximal urinary flow rate (22.34±3.1 mL/s), International Prostate Symptom Score (2.90±1.60), and quality of life (1.12±0.60) at the 3-year follow-up compared with baseline (P<.001). Of the 132 patients, 6 (4.5%) required reoperation.
CONCLUSION
PK-TURP represents an effective surgical intervention for the treatment of bladder outlet obstruction for large prostates. Furthermore, the functional results at 3 years demonstrated durability. Therefore, the PK-TURP technique could play an important role in the surgical treatment of patients with symptomatic benign prostatic hyperplasia with a large prostate gland.
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10.1016/j.urology.2011.08.052
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pubmed_18_16692
|
BACKGROUND AND OBJECTIVES
Clinical trials of acute kidney injury (AKI) use changes in creatinine as outcome metrics. This study investigated how outcome metrics and baseline creatinine affect trial outcome.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
A one-compartment pharmacokinetic model of creatinine change resulting from a decrease in GFR was applied to a population of 10,000 simulated virtual inpatients. Treatment was simulated as an amelioration of GFR decrease by a specified percentage, the treatment efficacy, in 50%. Three categorical and two continuous outcome metrics were calculated and compared. Outcomes were compared for measured and estimated baseline creatinine levels that were back-calculated assuming a GFR of 100 or 75 ml/min.
RESULTS
The continuous metrics, the average value of creatinine and the average value of creatinine relative to baseline decreased approximately linearly with increase in treatment efficacy. The categorical metrics displayed a sigmoidal decrease and erroneously suggested perfect treatment when GFR decrease was ameliorated by only 60 to 80%. Using an estimate of baseline creatinine increased the number of patients who were classified as having AKI.
CONCLUSIONS
When used to determine clinical trial outcome, continuous metrics correctly detected the extent of intervention. At low treatment efficacy, categorical metrics underestimated and at high treatment efficacy overestimated the effect of treatment. These effects were exaggerated when the population contained a high proportion of patients with more severe AKI. An estimated baseline creatinine level will overestimate AKI prevalence compared with a measured baseline value. Clinical trials of AKI should use a continuous outcome metric and a measured baseline and report baseline median and interquartile range.
|
10.2215/CJN.00820209
|
pubmed_362_1804
|
PURPOSE
To investigate the expression of heat shock protein 90α (HSP90α) in patients with lung cancer (LC) and the clinical value of HSP90α and other related markers in the diagnosis of LC.
METHODS
Of 335 patients enrolled in the study cohort, 175 were screened for LC and 160 were healthy (HC). The plasma levels of HSP90α and related markers (CEA, NSE, CYFRA21-1 and ProGRP) were detected in all individuals in the cohort by enzyme-linked immunosorbent assay (ELISA). Groups were divided according to gender (male/female), age (≤60 years/>60 years), types of LC (small-cell carcinoma, squamous carcinoma and adenocarcinoma), staging (I, II, III and IV) and metastasis (metastasis and non-metastasis) separately. Wilcoxon Mann-Whitney test and Kruskal-Wallis test were used to compare statistical differences between two groups/among the multiple groups for each factor of HSP90α. The r-value and Kappa were used to compare HSP90α with related markers, and the receiver operating curve (ROC) was used to evaluate the efficacy of plasma HSP90α in predicting LC.
RESULTS
No statistical difference was found in the plasma level of HSP90α among different age and gender groups (p > 0.05). In the group divided by LC type, staging and metastasis status, there were statistical differences among different groups in HSP90α level (p < 0.05). The levels of HSP90α, CEA, NSE, CYFRA21-1 and ProGRP in LC groups were significantly higher than HC (p < 0.001). R values of HSP90α correlated with other related markers in the diagnosis of LC (p < 0.05). Although HSP90α and other related markers did not fit the satisfactory conformance, in terms of the positive rate of diagnosis, it was statistically differences in the diagnostic positive rate between HSP90α and each marker (p < 0.01). ROC analysis showed that a plasma HSP90α cut-off point of 50.02 ng/ml had an optimal predictive value for LC.
CONCLUSIONS
HSP90α has significant clinical value in early screening and diagnosis of LC. The combined application of HSP90α and related markers can improve the positive rate of early diagnosis of LC effectively.
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10.1002/jcla.24462
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pubmed_607_14400
|
A case of chronic, corticosteroid-responsive arthritis affecting particularly one ankle in a patient with type IV hyperlipoproteinaemia is reported. After gout or inflammatory rheumatism of another nature had been excluded, and following synovial fluid examination and synovial membrane biopsy, a diagnosis of type IV hyperlipoproteinaemia rheumatism was made. At electron microscopy, the synovial membrane showed numerous large spumous cells and a peculiar appearance of the capillary vessels.
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pubmed_607_14400
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pubmed_379_399
|
Of the 10 neuronal nicotinic acetylcholine receptor (AChR) genes identified in chick, five are expressed by ciliary ganglion neurons in vivo (alpha 3, alpha 5, alpha 7, beta 2, and beta 4), and the mRNA levels produced increase during development approximately in parallel with the two major classes of AChRs present. Here we report that when chick ciliary ganglion neurons from 8-day embryos are transferred to dissociated cell culture, they express the same five genes but at much lower levels. The alpha 3 and alpha 7 transcripts, chosen for detailed analysis because they encode subunits segregated between the two AChR species, decrease rapidly in abundance on transfer to culture and, after 1 week, are at levels less than a 20th of those found in vivo for neurons of the same age. Co-culturing the neurons with skeletal myotubes did not increase the levels of AChR transcripts in the neurons. Despite low amounts of mRNA from all five genes, neither class of AChRs was much reduced in culture compared to in vivo. The numbers of AChRs on the cell surface actually increased with time in culture. Several culture conditions known to down-regulate the receptors in culture did not reduce the abundance of the alpha 3 and alpha 7 mRNAs. The results suggest that post-transcriptional controls can play an important role in determining AChR abundance on the neurons.
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10.1002/neu.480251210
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pubmed_1063_9086
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IntroductionData on chronic hepatitis C (HCV) infection prevalence in European prisons are incomplete and impact the public health opportunity that incarceration provides.AimsWe aimed to estimate the seroprevalence of untreated chronic HCV infection and to identify associated risk factors in an Irish male prison.MethodsWe conducted a cross-sectional study involving a researcher-administered questionnaire, review of medical records and HCV serology.ResultsOf 422 prisoners (78.0% of the study population) who participated in the study, 298 (70.6%) completed the questionnaire and 403 (95.5%) were tested for HCV antibodies. Of those tested, 92 (22.8%) were HCV antibody-positive, and of those, 53 (57.6%) were HCV RNA-positive, 23 (25.0%) had spontaneous clearance, 16 (17.4%) had a sustained viral response, 10 (11.0%) were co-infected with HIV and six (6.0%) with HBV. The untreated chronic HCV seroprevalence estimate was 13.1% and the seroprevalence of HCV among prisoners with a history of injecting drug use (IDU) was 79.7%. Risk factors significantly associated with past HCV infection were IDU (p < 0.0001), having received a prison tattoo (p < 0.0001) or a non-sterile community tattoo (p < 0.0001), sharing needles and other drug-taking paraphernalia (p < 0.0001). Small numbers of prisoners had a history of sharing razors (n=10; 3.4%) and toothbrushes (n=3; 1.0%) while incarcerated. On multivariable analysis, history of receiving a non-sterile community tattoo was the only significant risk factor associated with HCV acquisition (after IDU was removed from the model) (p = 0.005, β = 0.468).ConclusionThe level of untreated chronic HCV infection in Irish prisons is high, with IDU the main associated risk.
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10.2807/1560-7917.ES.2019.24.14.1800369
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pubmed_1098_16594
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Despite unprecedented access to information, partisans increasingly disagree about basic facts that are backed by data, posing a serious threat to a democracy that relies on finding common ground based on objective truths. We examine the underpinnings of this phenomenon using drift diffusion modeling (DDM). Partisans (N = 148) completed a sequential sampling task where they evaluated the honesty of Democrat or Republican politicians during a debate based on fact-check scores. We found that partisans required less and weaker evidence to correctly categorize the ingroup as more honest, and were more accurate on trials when the ingroup candidate was more honest, compared to the outgroup. DDM revealed that such tendencies arise from both a prior preference for categorizing the ingroup as more honest (i.e., biased starting point) and more precise accumulation of information favoring the ingroup candidate compared to the outgroup (i.e., biased drift rate). Moreover, individual differences in cognitive reasoning moderated task performance for the most devoted partisans and maintained divergent associations with the DDM parameters. This suggests that partisans may reach biased conclusions via different pathways depending on their depth of cognitive reasoning. These findings provide key insights into the mechanisms driving partisan divides in polarized environments, and can inform interventions that reduce impasse and conflict.
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10.1016/j.cognition.2022.105304
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pubmed_293_1885
|
Mitochondria are ancient organelles that have co-evolved with their cellular hosts, developing a mutually beneficial arrangement. In addition to making energy, mitochondria are multifaceted, being involved in heat production, calcium storage, apoptosis, cell signaling, biosynthesis, and aging. Many of these mitochondrial functions decline with age, and are the basis for many diseases of aging. Despite the vast amount of research dedicated to this subject, the relationship between aging mitochondria and immune function is largely absent from the literature. In this review, three main issues facing the aging immune system are discussed: (1) inflamm-aging; (2) susceptibility to infection and (3) declining T-cell function. These issues are re-evaluated using the lens of mitochondrial dysfunction with aging. With the recent expansion of numerous profiling technologies, there has been a resurgence of interest in the role of metabolism in immunity, with mitochondria taking center stage. Building upon this recent accumulation of knowledge in immunometabolism, this review will advance the hypothesis that the decline in immunity and associated pathologies are partially related to the natural progression of mitochondrial dysfunction with aging.
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10.3390/biology8020026
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pubmed_931_13676
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Women who are obese have higher risks of complications during pregnancy than their non-obese counterparts, reinforcing the need for health professionals to get healthy eating messages across.
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10.7748/ns.21.18.22.s23
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pubmed_680_3095
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Brain imaging genetics provides the foundation for further revealing brain disorder, which combines genetic variation with brain structure or functions. Recently, sparse canonical correlation analysis (SCCA) and multimodality analysis have been widely utilized for imaging genetics. However, SCCA is an unsupervised learning method which ignores the diagnostic information related to the disease. Traditional multimodality analysis cannot distinguish the consistent and specific information from different neuroimaging that are correlated to the genotypic variances. In this paper, we propose the Label-Guided Multi-task Sparse Canonical Correlation Analysis (LGMTSCCA) method to identify the informative features from the single nucleotide polymorphisms (SNPs) and brain regions related to the pathogenesis of Alzheimer's disease (AD). Specifically, LGMTSCCA uses label constraint via inducing diagnostic information to guide the imaging genetic correlation learning. Considering multi-modal imaging genetic correlations, we use the weight decomposition strategy to calculate the correlation weights in consistency and specificity with different parameters. We evaluate the effectiveness of the LGMTSCCA on synthetic and real data sets. The experimental results show LGMTSCCA can achieve superior performances than the existing methods, which has more flexible ability for identifying modality-consistent and modality-specific features.
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10.1109/TBME.2022.3203152
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pubmed_305_1666
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Human organic anion transporter-3 (hOAT3) is richly expressed in the kidney, where it plays critical roles in the secretion, from the blood to urine, of clinically important drugs, such as anti-viral therapeutics, anti-cancer drugs, antibiotics, antihypertensives, and anti-inflammatories. In the current study, we examined the role of dexamethasone in hOAT3 transport activity in the kidney HEK293 cells. Cis-inhibition study showed that dexamethasone exhibited a concentration-dependent inhibition of hOAT3-mediated uptake of estrone sulfate, a prototypical substrate for the transporter, with IC50 value of 49.91 μM. Dixon plot analysis revealed that inhibition by dexamethasone was competitive with a Ki = 47.08 μM. In contrast to the cis-inhibition effect of dexamethasone, prolonged incubation (6 h) of hOAT3-expressing cells with dexamethasone resulted in an upregulation of hOAT3 expression and transport activity, kinetically revealed as an increase in the maximum transport velocity Vmax without meaningful alteration in substrate-binding affinity Km. Such upregulation was abrogated by GSK650394, a specific inhibitor for serum- and glucocorticoid-inducible kinases (sgk). Dexamethasone also enhanced sgk1 phosphorylation. Our study demonstrated that dexamethasone exhibits dual effects on hOAT3: it is a competitive inhibitor for hOAT3-mediated transport, and interestingly, when entering the cells, it stimulates hOAT3 expression and transport activity through sgk1.
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10.1016/j.jphs.2017.12.011
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pubmed_498_18991
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The prognosis for pancreatic ductal adenocarcinoma (PDAC) patients is still dismal. Elucidation of associated genomic alteration may provide effective therapeutic strategies for PDAC treatment. NIMA-related protein kinase 7 is widely expressed in various tumors, including breast cancer, colorectal cancer and lung cancer, and promotes the proliferation of liver cancer cells in vitro and in vivo. We investigated the protein expression level of NEK7 in tumor tissues and adjacent normal tissues using immunohistochemistry of 90 patients with PADC. Meanwhile, the RNA expression level of NEK7 was examined using database-based bioinformatic analysis. Correlation and significance of NEK7 expression with patient clinicopathological features and prognosis were examined. Cell proliferation, cell adhesion, migration and invasion capabilities were measured following downregulation of NEK7 expression. 3D tumor organoids of pancreatic cancer were established and splenic xenografted into nude mice, then liver metastatic ability of NEK7 was evaluated in following 4 weeks. We observed NEK7 expression was upregulated in tumor tissues compared to normal tissues at both RNA and protein levels using bioinformatic analysis and immunohistochemistry analysis in PDAC. NEK7 expression was undetectable in normal pancreatic ducts; NEK7 was overexpressed in primary tumor of PDAC; NEK7 expression was highly correlated with advanced T stage, poorly differentiated histological grade invasive ductal carcinoma, and lymphatic invasion. Meanwhile, patients with higher NEK7 expression accompanied by worse survival outcome. Moreover, NEK7 promoted migration, invasion, adhesion, proliferation and liver metastatic ability of pancreatic cancer cells. Taken together, our data indicate that NEK7 promotes pancreatic cancer progression and it may be a potential marker for PDAC prognosis.
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10.3389/fonc.2021.705797
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pubmed_230_14311
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During the evolution of the Diptera there is a dramatic modification of the embryonic ectoderm, whereby mosquitoes contain separate amnion and serosa lineages while higher flies such as Drosophila melanogaster contain a single amnioserosa. Whole-genome transcriptome assays were performed with isolated serosa from Anopheles gambiae embryos. These assays identified a large number of genes implicated in the production of the larval cuticle. In D. melanogaster, these genes are activated just once during embryogenesis, during late stages where they are used for the production of the larval cuticle. Evidence is presented that the serosal cells secrete a dedicated serosal cuticle, which protects A. gambiae embryos from desiccation. Detailed temporal microarray assays of mosquito gene expression profiles revealed that the cuticular genes display biphasic expression during A. gambiae embryogenesis, first in the serosa of early embryos and then again during late stages as seen in D. melanogaster. We discuss how evolutionary modifications in the well-defined dorsal-ventral patterning network led to the wholesale deployment of the cuticle biosynthesis pathway in early embryos of A. gambiae.
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10.1016/j.ydbio.2009.02.038
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pubmed_659_2443
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The adsorption of Cu(ii), Cd(ii), and Pb(ii) ions onto hydrogels derived from modified galactoglucomannan (GGM) hemicellulose was studied. GGM hemicellulose was modified with methacrylate groups (GGM-MA) to incorporate vinyl groups into the polymeric structure, which reacted later with synthetic monomers such as 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS). The results show that all the synthesized hydrogels were capable of adsorbing contaminating ions with high adsorption efficiency during short periods of time. Furthermore, an increase in the content of GGM-MA generated a hydrogel (H3) with a similar ion adsorption property to the other hydrogels but with a lesser degree of swelling. The H3 hydrogel had an adsorption capacity of 60.0 mg g-1 Cd(ii), 78.9 mg g-1 Cu(ii), and 174.9 mg g-1 Pb(ii) at 25 °C. This result shows that modified GGM hemicelluloses can be employed as renewable adsorbents to remove Cu(ii), Cd(ii), and Pb(ii) ions from aqueous solutions.
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10.1039/d1ra06278f
|
pubmed_851_20035
|
OBJECTIVES
The main objective of this study was to measure the vibrotactile thresholds on the mastoid process and forehead positions using patients with bilateral deafness and to compare the results from the two bone conduction vibrators Radioear B71 and B81.
DESIGN
There is a possibility that the vibrotactile sensation on the skin makes it difficult to discriminate between sound and vibration. The risk is highest for patients who have bone conduction hearing thresholds in proximity to or worse than their vibrotactile thresholds. All measurements were performed similar to regular bone conduction threshold testing using an audiometer-driven bone conduction vibrator and pulsed warble tones, but the patients were instructed to respond only when feeling vibrations of the bone conduction vibrator instead of when hearing sound. Both the posterior forehead position and the mastoid process position on the temporal bone were tested for comparative reasons. In total, 16 patients participated in the study, 31% females and 69% males of age 29 to 77 years. All subjects were cochlear implant recipients, either uni- or bilaterally implanted. They were selected based on their audiogram data showing unmeasurable unaided hearing.
RESULTS
The force level at which the vibrotactile thresholds were reached, increased with frequency from 125 up to 500 Hz, but remained constant for higher frequencies up to 2 kHz. A statistically significant difference was found between the 2 devices at 125 Hz at both the mastoid process and forehead position, where the vibrotactile threshold seem to be more sensitive for B71, possibly due to contribution of distortion components. There was no statistically significant difference in vibrotactile thresholds between the mastoid process and forehead position in absolute values (force level in dB re 1 µN), but in terms of hearing levels (dB HL) there was an average difference of 10 and 9 dB for B71 and B81, respectively.
CONCLUSIONS
The results indicate that the vibrotactile thresholds can be confounded with bone conduction hearing thresholds measurements up to 500 Hz when using a standard audiometer and in particular when measuring on the forehead position.
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10.1097/AUD.0000000000000456
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pubmed_1113_6235
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Zidovudine (ZDV) and lamivudine (3TC) metabolism to triphosphates (TP) is necessary for antiviral activity. The aims of this study were to compare ZDV-TP and 3TC-TP concentrations in adolescents receiving twice daily (BID) and once daily (QD) regimens and to determine the metabolite concentrations of ZDV and 3TC during chronic therapy on a QD regimen. Human immunodeficiency virus-infected patients (12 to 24 years) taking ZDV (600 mg/day) and 3TC (300 mg/day) as part of a highly active antiretroviral therapy regimen received QD and BID regimens of ZDV and 3TC for 7 to 14 days in a crossover design. Serial blood samples were obtained over 24 h on the QD regimen. Intracellular mono-, di-, and triphosphates for ZDV and 3TC were measured. The median ratio of BID/QD for ZDV-TP predose concentrations was 1.28 (95% confidence interval [CI] = 1.00 to 2.45) and for 3TC-TP was 1.12 (95% CI = 0.81 to 1.96). The typical population estimated half-lives (+/- the standard error of the mean) were 9.1 +/- 0.859 h for ZDV-TP and 17.7 +/- 2.8 h for 3TC-TP. Most patients had detectable levels of the TP of ZDV (24 of 27) and 3TC (24 of 25) 24 h after dosing, and half-lives on a QD regimen were similar to previously reported values when the drugs were given BID. Lower, but not significantly different, concentrations of ZDV-TP were demonstrated in the QD regimen compared to the BID regimen (P = 0.056). Although findings were similar between the BID and QD groups, the lower concentrations of ZDV and the number of patients below the level of detection after 24 h suggests that ZDV should continue to be administered BID.
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10.1128/AAC.01626-06
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pubmed_798_8904
|
Postconditioning (PostC) may limit mitochondrial damage and apoptotic signaling. We studied markers of apoptosis and mitochondrial protection in isolated rat hearts, which underwent a) perfusion without ischemia (Sham), b) 30-min ischemia (I) plus 2-hour reperfusion (R), or c) PostC protocol (5 intermittent cycles of 10-s reperfusion and 10-s ischemia immediately after the 30-min ischemia). Markers were studied in cytosolic (CF) and/or mitochondrial (MF) fractions. In CF, while pro-apoptotic factors (cytochrome c and caspase-3) were reduced, the anti-apoptotic markers (Bcl-2 and Pim-1) were increased by PostC, compared to the I/R group. Accordingly, phospho-GSK-3beta and Bcl-2 levels increased in mitochondria of PostC group. Moreover, I/R reduced the level of mitochondrial structural protein (HSP-60) in MF and increased in CF, thus suggesting mitochondrial damage and HSP-60 release in cytosol, which were prevented by PostC. Electron microscopy confirmed that I/R markedly damaged cristae and mitochondrial membranes; damage was markedly reduced by PostC. Finally, total connexin-43 (Cx43) levels were reduced in the CF of the I/R group, whereas phospho-Cx43 level resulted in higher levels in the MF of the I/R group than the Sham group. PostC limited the I/R-induced increase of mitochondrial phospho-Cx43. Data suggest that PostC i) increases the levels of anti-apoptotic markers, including the cardioprotective kinase Pim-1, ii) decreases the pro-apoptotic markers, e.g. cytochrome c, iii) preserves the mitochondrial structure, and iv) limits the migration of phospho-Cx43 to mitochondria.
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10.1016/j.bbabio.2009.03.013
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pubmed_319_24812
|
Mutations in the LMNA gene, which encodes lamin A and C (lamin A/C), cause a diverse spectrum of tissue-selective diseases termed laminopathies. The most prevalent form affects striated muscles as dilated cardiomyopathy with variable skeletal muscle involvement, which includes autosomal Emery-Dreifuss muscular dystrophy. Mechanisms underlying the disease pathogenesis are beginning to be understood and they point toward defects in cell signaling. We therefore assessed putative signaling defects in a mouse model carrying a point mutation in Lmna (Lmna (H222P/H222P) ) that faithfully recapitulates human Emery-Dreifuss muscular dystrophy. We found that AKT-mechanistic target of rapamycin (MTOR) signaling was hyperactivated in hearts of Lmna (H222P/H222P) mice and that reducing MTOR activity by pharmacological intervention ameliorated cardiomyopathy. Given the central role of MTOR in regulating autophagy, we assessed fasting-induced autophagic responses and found that they were impaired in hearts of these mice. Moreover, the improved heart function associated with pharmacological blockade of MTOR was correlated with enhanced autophagy. These findings demonstrated that signaling defects that impair autophagy underlie pathogenesis of dilated cardiomyopathy arising from LMNA mutation.
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10.4161/auto.22403
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pubmed_785_13604
|
While predetermined débitage technologies are recognized beginning with the middle Acheulian, the Middle Paleolithic is usually associated with a sharp increase in their use. A study of scraper-blank technology from three Yabrudian assemblages retrieved from the early part of the Acheulo-Yabrudian complex of Tabun Cave (ca. 415-320 kyr) demonstrates a calculated and preplanned production, even if it does not show the same complexity and elaboration as in the Levallois technology. These scraper dominated assemblages show an organization of production based on an intensive use of predetermination blank technology already in place at the end of the Lower Paleolithic of the Levant. These results provide a novel perspective on the differences and similarities between the Lower and Middle Paleolithic industries. We suggest that there was a change in the paradigm in the way hominins exploited stone tools: in many Middle Paleolithic assemblages the potential of the stone tools for hafting was a central feature, in the Lower Paleolithic ergonometric considerations of manual prehension were central to the design of blanks and tools.
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10.1371/journal.pone.0106293
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pubmed_210_5068
|
PURPOSE
To present surgical methods and outcomes in women with bladder cancer (BCa) requiring correction of neobladder-vaginal fistula (NVF) after radical cystectomy (RC) with ileal orthotopic neobladder (IONB).
MATERIALS AND METHODS
The medical records of 163 women who underwent RC with IONB for BCa between January 2010 and December 2018 were retrospectively reviewed. The presence of NVF was confirmed by cystoscopy and/or voiding cystography. NVF repair was performed using a transvaginal approach, which included circumferential incision of the fistula tract, creation of a plane between the neobladder serosa and the vaginal epithelium, and multi-layered transvaginal closure.
RESULTS
During a median follow-up of 47.9 months, NVF was identified in 12 (8.8%) of the 163 included women. Eight (66.7%) fistulas were located in the proximal anterior vaginal wall and four (33.3%) in the vaginal apex. Median time from RC to NVF repair was 3.4 months (range, 2.1-5.6 months), median NVF size was 6.0 mm (range, 4.0-22.0 mm), and median duration of urethral Foley catheter indwelling was 24.0 days (range, 15.0-43.0 days). Initial repair of NVF was successful in ten (83.3%) patients. Two (16.7%) patients who relapsed retained IONB through the subsequent operation. Two (16.7%) patients developed severe urinary incontinence after NVF repair, requiring anti-incontinence surgery with a synthetic transobturator mid-urethral sling.
CONCLUSION
The transvaginal approach for NVF repair is feasible, yielding successful surgical outcomes. However, women should be counseled about the risks of relapse and urinary incontinence.
|
10.2147/CMAR.S277001
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pubmed_663_18581
|
BACKGROUND
Summarization of gene information in the literature has the potential to help genomics researchers translate basic research into clinical benefits. Gene expression microarrays have been used to study biomarkers for disease and discover novel types of therapeutics and the task of finding information in journal articles on sets of genes is common for translational researchers working with microarray data. However, manually searching and scanning the literature references returned from PubMed is a time-consuming task for scientists. We built and evaluated an automatic summarizer of information on genes studied in microarray experiments. The Gene Information Clustering and Summarization System (GICSS) is a system that integrates two related steps of the microarray data analysis process: functional gene clustering and gene information gathering. The system evaluation was conducted during the process of genomic researchers analyzing their own experimental microarray datasets.
RESULTS
The clusters generated by GICSS were validated by scientists during their microarray analysis process. In addition, presenting sentences in the abstract provided significantly more important information to the users than just showing the title in the default PubMed format.
CONCLUSION
The evaluation results suggest that GICSS can be useful for researchers in genomic area. In addition, the hybrid evaluation method, partway between intrinsic and extrinsic system evaluation, may enable researchers to gauge the true usefulness of the tool for the scientists in their natural analysis workflow and also elicit suggestions for future enhancements.
AVAILABILITY
GICSS can be accessed online at: http://ir.ohsu.edu/jianji/index.html.
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10.1186/1471-2105-10-S2-S5
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pubmed_215_20487
|
PURPOSE
To study the markers of bone turnover in epilepsy patients in the different stages of the pubertal growth before and after the beginning of carbamazepine (CBZ) monotherapy.
METHODS
We have investigated bone turnover in 60 epilepsy patients treated with CBZ. They were stratified according to pubertal stage and compared with a control group of 60 sex- and age-matched healthy children.
RESULTS
After 2 years of therapy, we found higher values of the serum markers of bone formation [bone alkaline phosphatase (bone ALP), osteocalcin (OC), carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP)], and of bone resorption [carboxy-terminal telopeptide of type I collagen (ICTP) and the urinary cross-linked N-telopeptides of type I collagen (NTX)] in patients than in control subjects, in presence of a normal vitamin D metabolism.
CONCLUSIONS
CBZ induces an increase of bone formation and of bone resorption that seems to be independent of the pubertal stage.
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10.1046/j.1528-1157.2002.13002.x
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pubmed_169_11180
|
A review of cerebral phlebothrombosis using material from the pathology departments of the National Institute of Cardiology and the General Hospital in Mexico City is presented. The most frequent causes found were: post partum. Secondary to congenital heart disease and associated with infections. In both institutions the most frequent anatomical find was thrombosis of the superior longitudinal sinus. Isolated venous thrombi in the brain probably takes place more frequently than reported. Hemorrhagic necrosis in brain tissue is the most frequent microscopic finding, associated in variable degrees with edema and anoxic encephalopathy. A description of clinical and angiographic findings is presented.
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pubmed_169_11180
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pubmed_251_13958
|
The production of the cytokines IL-1-alpha, IL-1-beta, IL-2, TNF-alpha, and INF-gamma was measured by a sensitive immunological assay in stimulated whole blood cell cultures from 52 healthy children (33 aged from 1 to 9 years and 19 aged between 10 and 17 years) and 67 healthy adults. When the higher absolute mononuclear cell counts in the peripheral blood samples of the children were taken into account, the relative production of all measured cytokines was lower in the cell cultures of the children than of the adults. In the group of the younger children (< 10 years) the differences were significant for all measured cytokines. In the group of older children (> or = 10 years) the values were higher than in the younger children but lower than in adults. The findings indicate that the cellular immunological competence is or can be reduced in children and adolescents, particularly young children below 10 years of age. There seems to be a gradual development of cytokine production during childhood.
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10.1111/j.1399-3038.1995.tb00278.x
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pubmed_396_14462
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Avian vitellin antibodies (IgY) obtained after immunization with mouse IgG and mouse IgM in the presence or absence of Freund"s complete adjuvant are suited for labelling with FITC or biotin. In FACS analysis the antibodies prove to be excellent tools in detecting mouse monoclonal antibodies of different isotypes. The working dilution (titer of IgY-FITC) is highest when egg preparations of the secondary and tertiary immune response were used. Double staining of two different antigens can be carried out with direct labelled mab (FITC) and indirect labelled mab by IgY-conjugates (biotin). The two antigens can also be detected by double staining of different isotypes (mabs) by hen anti-mouse IgM FITC and hen anti-mouse IgG biotin-streptavidin-phycoerythrin. The staining obtained with IgY is at least as good or even better than that gained with mammalian secondary antibodies.
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pubmed_396_14462
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pubmed_974_19929
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Retinoblastoma is an aggressive eye cancer that develops during infancy and is divided into two clinical types, sporadic and heritable. RB1 has been identified as the only pathological gene responsible for heritable retinoblastoma. Here, we identified 11 RB1 germline mutations in the Han pedigrees of 17 bilateral retinoblastoma patients from China. Four mutations were nonsense mutations, five were splice site mutations, and two resulted in a frame shift due to an insertion or a deletion. Three of the mutations had not been previously reported, and the p.Q344L mutation occurred in two generations of retinoblastoma patients. We investigated phenotypic-genotypic relationships for the novel mutations and showed that these mutations affected the expression, location, and function of the retinoblastoma protein. Abnormal protein localization was observed after transfection of the mutant genes. In addition, changes in the cell cycle distribution and apoptosis rates were observed when the Saos-2 cell line was transfected with plasmids encoding the mutant RB1 genes. Our findings expand the spectrum of known RB1 mutations and will benefit the investigation of RB1 mutation hotspots. Genetic counseling can be offered to families with heritable RB1 mutations.
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10.1007/s13277-014-2851-7
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pubmed_219_619
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It is clinically relevant to understand whether it is safe to recommend to trained overweight/obese people long-distance treks and whether these experiences could have a negative psychological impact or become even dangerous exposing the trekkers to the risk of clinically silent myocardial damage. To answer these questions we have performed a quantitative/qualitative study comparing the changes in mood profiles, personal views, body composition, and plasma troponin levels of 40 overweight/obese subjects with those of 36 healthy normal weight subjects after the participation in a trek of 388 km from the Adriatic to the Tyrrhenian seas trek: the "Step by step…Italy's coast to coast". The results of this study demonstrate that long-distance treks are a safe activity for trained overweight/obese people which should be recommended because they improve mood, health status, and the relationship of participants with themselves and with the regular practice of exercise with effects similar to those obtained by healthy normal weight subjects.
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10.1155/2014/854129
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pubmed_820_6488
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Radical prostatectomy and radiotherapy are the most commonly utilized modalities for managing patients with localized prostate cancer. Each has effects on quality of life that are important in decision making. Long term side effects of these treatment modalities include urinary, bowel and sexual dysfunction, and have been documented. Comparison of the side effects of these different modalities continues to be explored, emphasizing their effects on quality of life (QOL) from the patient's viewpoint. Questionnaires were mailed to 224 eligible patients and a response was elicited in 161 men (72%). The final number of patients who completed all the questionnaires was 151. Of these, 73 (48%) had radical prostatectomy and 78 (52%) had radiotherapy. General well being measures demonstrated a definite advantage favoring men treated with radical prostatectomy. Prostate cancer specific QOL measures were similar among men treated with surgery or radiotherapy. Radiotherapy treated men were slightly more likely to report bowel-related problems than surgically treated men. Urinary QOL measures were no different between treated groups. Surgically treated men reported lower level of sexual function than radiotherapy treated men.
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10.1080/01485010500315925
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pubmed_483_12786
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OBJECTIVES
Patients with systemic lupus erythematosus (SLE) are under increased risk for cardiovascular events (CVE) and mortality. Aortic stiffness, as measured by carotid-femoral pulse wave velocity (cfPWV), has been shown to predict CVE and mortality in the general population. The aim of the present study was to examine the factors associated with cfPWV in patients with SLE and to determine differences of SLE patients in comparison to healthy controls.
METHODS
125 patients with SLE and 104 controls were included. Demographic, medication and cardiovascular risk factor data were collected from all participants. Furthermore, clinical and laboratory SLE associated parameters were documented in the patients' group. All subjects underwent measurements of blood pressure and cfPWV.
RESULTS
Interestingly, only age (β=0.55; p<0.001), mean arterial pressure (MAP) (β=0.29; p<0.001) and estimated glomerular filtration rate (eGFR) (β=-0.20; p=0.033) were associated independently with cfPWV in patients with SLE. Moreover, there was no difference of cfPWV between patients with SLE and controls before (p=0.301) and after adjustment for disparities between the groups (p=0.671).
CONCLUSIONS
Vascular stiffness in patients with SLE seems to be independent from SLE-related factors and from most traditional CVRF and is mainly associated with age, MAP and renal function defined as eGFR. There is an independent correlation between eGFR and cfPWV in a SLE population with a widely normally ranged eGFR. There is no difference of cfPWV between patients with SLE and controls.
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pubmed_483_12786
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pubmed_191_14548
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Human skin fibroblasts were cultured long-term in the presence of ascorbic acid to allow formation of a three-dimensional collagen matrix, and the effects of this on activation of secreted matrix metalloproteinase-2 (MMP-2) were examined. Accumulation of collagen over time correlated with increased levels of both mature MMP-2 and cell-associated membrane type 1-MMP (MT1-MMP), and subsequently increased mRNA levels for MT1-MMP, providing temporal resolution of the "nontranscriptional" and "transcriptional" effects of collagen on MT-1MMP functionality. MMP-2 activation by these cultures was blocked by inhibitors of prolyl-4-hydroxylase, or when fibroblasts derived from the collagen alpha1(I) gene-deficient Mov-13 mouse were used. MMP-2 activation by the Mov-13 fibroblasts was rescued by transfection of a full-length alpha1(I) collagen cDNA, and to our surprise, also by transfection with an alpha1(I) collagen cDNA carrying a mutation at the C-proteinase cleavage, which almost abrogated fibrillogenesis. Although studies with ascorbate-cultured MT1-MMP-/- fibroblasts showed that MT1-MMP played a significant role in the collagen-induced MMP-2 activation, a residual MT1-MMP-independent activation of MMP-2 was seen which resembled the level of MMP-2 activation persisting when wild-type fibroblasts were cultured in the presence of both ascorbic acid and MMP inhibitors. We were also unable to block this residual activation with inhibitors specific for serinyl, aspartyl, or cysteinyl enzymes.
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10.1006/excr.2001.5403
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