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pubmed_201_24728 | Tissue morphogenesis relies on the production of active cellular forces. Understanding how such forces are mechanically converted into cell shape changes is essential to our understanding of morphogenesis. Here, we use myosin II pulsatile activity during Drosophila embryogenesis to study how transient forces generate irreversible cell shape changes. Analyzing the dynamics of junction shortening and elongation resulting from myosin II pulses, we find that long pulses yield less reversible deformations, typically a signature of dissipative mechanics. This is consistent with a simple viscoelastic description, which we use to model individual shortening and elongation events. The model predicts that dissipation typically occurs on the minute timescale, a timescale commensurate with that of force generation by myosin II pulses. We test this estimate by applying time-controlled forces on junctions with optical tweezers. Finally, we show that actin turnover participates in dissipation, as reducing it pharmacologically increases the reversibility of contractile events. Our results argue that active junctional deformation is stabilized by actin-dependent dissipation. Hence, tissue morphogenesis requires coordination between force generation and dissipation. | 10.1016/j.cub.2017.09.005 |
pubmed_810_16063 | Since some drug intervention effects are only experienced by the patient, organizations such as the Food and Drug Administration prefer clinically meaningful outcome measures. Here, we evaluated which symptoms and limitations in daily life are most burdensome to pediatric patients with mitochondrial disorders and their parents, using two questionnaires. In a study of 78 patients, the most burdensome complaints included fatigue, behavior and speech disturbances, epilepsy and muscle weakness and a high degree of limitations in daily activities was found. Importantly, there was a discrepancy between what symptoms metabolic pediatricians estimated would be most burdensome compared to the patients'/caretakers' opinion. To include feasible and relevant outcome measures in intervention studies, the experience and opinions of patients and caretakers should therefore be heard. | pubmed_810_16063 |
pubmed_509_15763 | CONTEXT
Patients with dementia have a lower bispectral index score (BIS) when awake than age-matched healthy controls.
OBJECTIVES
The primary aim was to compare the BIS and the dose of propofol required for induction in patients suffering from cognitive impairment with that in those who had normal cognitive function. This study also evaluated the effects of cognitive impairment in the elderly on anaesthetic agent consumption during surgery and on emergence from anaesthesia.
DESIGN AND SETTING
This randomised controlled study was carried out in a university hospital. Patients over 65 years of age, ASA I-II and scheduled for elective orthopaedic procedures were allocated to one of two groups.
INTERVENTIONS
Patients (n = 92) were allocated according to their Mini Mental State Examination score: 25 or higher (group 1) or 21 or less (group 2). All patients received propofol 0.5 mg kg(-1) following the commencement of a remifentanil infusion at 0.5 μg kg(-1) min(-1). After incremental doses of propofol up to loss of consciousness, a propofol infusion was started at 75 μg kg(-1) min(-1). Propofol and remifentanil infusion doses were adjusted to keep the BIS value between 45 and 60 during surgery.
MAIN OUTCOME MEASURE
MMSE score was evaluated 24 h before and after surgery. The anaesthetic consumption, mean arterial pressure, HR and BIS values of the patients were recorded.
RESULTS
Before surgery, mean Mini Mental State Examination scores were 26.8 ± 1.6 and 16.6 ± 4.2 in group 1 and 2, respectively. These returned to baseline value 24 h after surgery in group 1 (26.6 ± 1.5) and group 2 (15.6 ± 4.3). Before induction, four of 45 patients (8.9%) in group 1 had a BIS value less than 93 compared with 13 of 47 (27.7%) in group 2 (P = 0.02). The mean BIS value was significantly lower in group 2 than in group 1 before induction, during loss of consciousness, 3 and 5 min after discontinuation of the anaesthetic agents and before extubation (P < 0.05). The induction dose of propofol was lower in group 2 than in group 1 (P = 0.02). The eye opening time was significantly longer in group 2 than in group 1 (P = 0.03).
CONCLUSION
The baseline BIS value was lower in patients with cognitive impairment than in those with normal cognitive function. The former received less propofol during induction and eye opening time was longer. On the basis of our findings from the recovery period, we suggest that the recommended target BIS value for adequate anaesthesia in the general population is inappropriate for patients with cognitive impairment. | 10.1097/EJA.0b013e32835475c6 |
pubmed_921_11628 | Despite significant clinical and research efforts aimed at recognizing and managing "difficult" patients, such patients remain a frustrating experience for many clinicians. This is especially true for primary care residents, who are required to see a significant volume of patients with diverse and complex problems, but who may not have adequate training and life experience to enable them to deal with problematic doctor-patient situations. Literature--short stories, poems, and patient narratives--is a little-explored educational tool to help residents in understanding and working with difficult patients. In this report, the authors examine the mechanics of using literature to teach about difficult patients, including structuring the learning environment, establishing learning objectives, identifying teaching resources and appropriate pedagogic methods, and incorporating creative writing assignments. They also present an illustrative progression of a typical literature-based teaching session about a difficult patient. | 10.1097/00001888-200007000-00026 |
pubmed_317_1243 | Inguinoscrotal pain (ISP) is a common complaint that affects almost all age groups. The etiology may be vascular, neurogenic, visceral, muscular or psychological. Most causes of ISP are benign, but Pott's spine as a cause of ISP, when missed, may lead to serious outcomes. | 10.4103/0970-1591.145294 |
pubmed_91_10008 | A partially purified extract of DNA methylases from E. coli K-12 containing DNA-adenine as well as DNA-cytosine methylase activities has been examined with respect to different DNA species as substrates. The results show that the natural content of 6-MAP) in the applied DNA represses the DNA-adenine methylase activity. On the other hand, 5-MC, already present in the substrate does not influence the activity of the DNA-cytosine methylase. DNA from Micrococcus radiodurans, which is completely free of methylated bases served as comparison. Since netropsin preferentially binds to AT-rich regions of DNA, the influence of this oligopeptide antibiotic on the methylation of DNA was investigated. As expected the antibiotic predominantly inhibits adenine methylation of DNA. The degree of inhibition depends on the molar ratio of netropsin to DNA phosphate. | 10.1002/jobm.3630190706 |
pubmed_861_3479 | High body mass index (BMI) has been associated with an increased risk of several cancers. Evidence relating body fatness, especially based on different anthropometric measures, to risk of major cancers in China from prospective cohort studies is lacking. The prospective China Kadoorie Biobank study recruited 0.5 million adults aged 30-79 years from 10 diverse areas across China during 2004-2008, recording 21,474 incident cancers during 8.95 years of follow-up. BMI, body fat percentage (BFP), waist circumference (WC) and waist-to-hip ratio (WHR) were measured at baseline. We assessed the associations of body fatness with 15 major cancers by calculating Cox regression yielded adjusted hazard ratios (HRs). Each 5 kg/m2 increase in BMI was associated with an increased risk of endometrial (HR, 2.01; 95% CI, 1.72-2.35), postmenopausal breast (HR, 1.29; 95% CI, 1.18-1.40), colorectal (HR, 1.17; 95% CI, 1.10-1.25) and cervical (HR, 1.15; 95% CI, 1.03-1.29) cancer, whereas it was associated with a reduced risk of esophageal (HR, 0.73; 95% CI, 0.67-0.79), lung (HR, 0.78; 95% CI, 0.74-0.82), liver (HR, 0.85; 95% CI, 0.79-0.92) and gastric (HR, 0.88; 95% CI, 0.82-0.94) cancer. Significant linear trends of BMI-cancer associations were observed, excluding for lung, gastric and cervical cancer (both overall and nonlinear p < 0.05). The relation between BFP, WC and WHR and the above cancers was similar to that of BMI. Our study indicates that either high or low body fatness contributes to the incidence of different types of cancer in China. | 10.1002/ijc.32394 |
pubmed_50_14685 | BACKGROUND
While most anatomic TSA stems allow some intra-operative adjustments, the default configuration assumes that head offset is directly proportional to stem diameter. Some authors reported that humeral head diameter is proportional to intra-medullary canal width and humeral head offset, but none investigated the direct relationship between head offset and endosteal measurements. The purpose of the study was to determine whether global humeral head offset is proportional to intramedullary canal width at the distal metaphysis and proximal diaphysis.
METHODS
We analyzed 100 Computed Tomography shoulder scans of patients aged 59.1 ± 20.5 with no signs of gleno-humeral arthritis nor humeral dysplasia. The width of the intramedullary diaphyseal canal was determined at four transverse sections 65, 70, 100 and 105 mm below the head center. The inter-observer agreement was excellent for intramedullary canal width (ICC = 0.96), head diameter (ICC = 0.97) and global head offset (ICC = 0.85). Correlations were analysed using Pearson's coefficients and multivariable regressions were performed to determine associations between head offset and five independent variables (gender, age, intramedullary canal width, head diameter).
RESULTS
Global head offset was negatively correlated with head diameter (r = - 0.31, p = 0.002), but not correlated with intramedullary canal width (r = - 0.11, p = 0.282). Multivariable regression confirmed that global head offset was independently associated with head diameter (beta = - 0.15, p = 0.005), but not with intramedullary canal width (beta = 0.06, p = 0.431).
CONCLUSIONS
The present study revealed that humeral offset is not correlated with intramedullary canal width. Implant manufacturers and shoulder surgeons should be aware of the subtle morphologic features, to enhance humeral stem design and restore native anatomy. | 10.1186/s40634-018-0148-2 |
pubmed_65_945 | We have previously shown that substitution of the D-Tic-Oic dipeptide by a (3S)-[amino]-5-(carbonylmethyl)-2,3-dihydro-1, 5-benzothiazepin-4(5H)-one (D-BT) moiety in the bradykinin B(2) receptor antagonist HOE 140 resulted in a full potent and selective bradykinin B(2) receptor agonist (H-DArg-Arg-Pro-Hyp-Gly-Thi-Ser-D-BT-Arg-OH, JMV1116) exhibiting a high affinity for the human receptor (K(i) 0.7 nM). In the present study, we have investigated the effects of replacement of the D-Tic-Oic moiety by various constrained dipeptide mimetics. The resulting compounds were tested for their binding affinity toward the cloned human B(2) receptor and for their functional interaction with the bradykinin-induced contraction of isolated human umbilical vein. Subsequently, we have designed novel bradykinin B(2) receptor agonists which are likely to be resistant to enzymatic cleavage by endopeptidases and which might represent interesting new pharmacological tools. In an attempt to increase the potency of compound JMV1116, both its N-terminal part and the D-BT moiety were modified. Substitution of the D-arginine residue by a L-lysine residue led to a 10-fold more potent bradykinin B(2) ligand [compound 22 (JMV1465) (K(i) 0.07 nM)], retaining full agonist activity on human umbilical vein. Substitution of the D-BT moiety by a (3S)-[amino]-5-(carbonylmethyl)-2,3-dihydro-8-methyl-1, 5-benzothiazepin-4(5H)-one [D-BT(Me)] moiety led to compound 23 (JMV1609) which exhibited a higher agonist activity (pD(2) = 7.4) than JMV1116 (pD(2) = 6.8). | 10.1021/jm9901531 |
pubmed_1115_18423 | PURPOSE
The purpose of this study was to evaluate the relationship between insertion torque and the biomechanical characteristics of soft tissue tendon graft tibia fixation with a bioabsorbable interference screw.
TYPE OF STUDY
Biomechanical study.
METHODS
Doubled tibialis anterior allografts (n = 20, length = 100 mm, diameter = 9 mm) prepared for anterior cruciate ligament (ACL) reconstructions were divided into 3 groups. Maximum insertion torque was measured as grafts were fixed by the same surgeon with a 10-mm diameter, 35-mm long screw in a 7-mm diameter tunnel (dilated to 9 mm) created in either 0.16 or 0.32 g/cm3 dense synthetic bone or cadaveric tibiae (0.84 +/- 0.15 g/cm2). Tensile testing to construct failure was then performed.
RESULTS
All constructs failed by tunnel pullout. Higher density synthetic bone had greater load at failure than lower density synthetic bone (486.6 +/- 83.8 v 271.6 +/- 52.6 N, P <.0001) and a slightly greater proportion of variance could be explained in synthetic bone (R2 = 0.74, P <.0001) than in cadaveric tibiae (R2 = 0.64, P =.017). Higher density synthetic bone displayed greater stiffness than lower density synthetic bone (68.1 +/- 21.6 v 37.7 +/- 11.2 N/mm, P =.012) and a higher proportion of variance could be explained in cadaveric tibiae (R2 = 0.72, P =.008) than in synthetic bone (R2 = 0.48, P =.012). Greater insertion torque levels were seen in higher density synthetic bone (2.97 +/- 0.35 v 1.24 +/- 0.06 Nm, P <.0001) than in lower density synthetic bone, and a higher proportion of variance could be explained in synthetic bone (R2 = 0.94, P <.0001) than in cadaveric tibiae (R2 = 0.74, P =.006).
CONCLUSIONS
Strong relationships were evident between insertion torque, bone mineral density (BMD) and load to failure across constructs. Differences between the synthetic bone groups and cadaveric tibiae, however, suggest the influence of mixed cortical and cancellous bone, nonuniform structural patterning, and differing BMD levels and distributions in the cadaveric tibiae.
CLINICAL RELEVANCE
Soft tissue graft tibial tunnel fixation is directly related to insertion torque and BMD. Synthetic models with mixed bone characteristics are needed to more accurately depict human tibiae during fixation testing. | 10.1016/j.arthro.2004.01.026 |
pubmed_615_4348 | An improved method for the synthesis of 17β-hydroxy-16α-iodo-wortmannin along with the first synthesis of 17β-hydroxy-16α-iodoPX866 and [(131)I] radiolabeled 17β-hydroxy-16α-[(131)I]iodo-wortmannin, as potential PET tracers for PI3K was also described. The differences between wortmannin and its iodo analogue were compared by covalently docking each structure to L833 in PI3K. | pubmed_615_4348 |
pubmed_942_322 | Tissue homogenates, etioplasts, and developing chloroplasts were prepared from cucumber (Cumucis sativus L.) cotyledons in tris-sucrose. They were incubated aerobically in the dark or in the light at pH 7.7 in the presence or absence of a cofactor mixture containing coenzyme A, glutathione, potassium phosphate, methyl alcohol, magnesium, nicotinamide adenine dinucleotide, and adenosine triphosphate. These cofactors were previously shown to be essential for protochlorophyll and chlorophyll biosynthesis. Ultrastructural changes were monitored by electron microscopy. The following observations were made. (a) Crude homogenates contained agents which degraded etioplasts and developing chloroplasts. (b) Added cofactors were essential for the maintenance of the membrane structure; they were also implicated in the transformation of the prolamellar body in the absence and presence of light. (c) Light pretreatment of the cotyledons improved the maintenance of the developing chloroplast membranes during subsequent in vitro incubation. (d) In the presence of the cofactors, grana formation appeared to take place in the absence of nuclear-cytoplasmic control. | 10.1104/pp.51.4.651 |
pubmed_550_9471 | BACKGROUND
Renal replacement therapy (RRT) for acute renal failure (ARF) can be applied intermittently (IRRT) or continuously (CRRT). It has been suggested that CRRT has several advantages over IRRT including better haemodynamic stability, lower mortality and higher renal recovery rates.
OBJECTIVES
To compare CRRT with IRRT to establish if any of these techniques is superior to each other in patients with ARF.
SEARCH STRATEGY
We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL). Authors of included studies were contacted, reference lists of identified studies and relevant narrative reviews were screened. Search date: October 2006.
SELECTION CRITERIA
RCTs comparing CRRT with IRRT in adult patients with ARF and reporting prespecified outcomes of interest were included. Studies assessing CAPD were excluded.
DATA COLLECTION AND ANALYSIS
Two authors assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes or mean difference (WMD) for continuous data with 95% confidence intervals (CI).
MAIN RESULTS
We identified 15 studies (1550 patients). CRRT did not differ from IRRT with respect to in-hospital mortality (RR 1.01, 95% CI 0.92 to 1.12), ICU mortality (RR 1.06, 95% CI 0.90 to 1.26), number of surviving patients not requiring RRT (RR 0.99, 95% CI 0.92 to 1.07), haemodynamic instability (RR 0.48, 95% CI 0.10 to 2.28) or hypotension (RR 0.92, 95% CI 0.72 to 1.16) and need for escalation of pressor therapy (RR 0.53, 95% CI 0.26 to 1.08). Patients on CRRT were likely to have significantly higher mean arterial pressure (MAP) (WMD 5.35, 95% CI 1.41 to 9.29) and higher risk of clotting dialysis filters (RR, 95% CI 8.50 CI 1.14 to 63.33).
AUTHORS' CONCLUSIONS
In patients who are haemodynamically stable, the RRT modality does not appear to influence important patient outcomes, and therefore the preference for CRRT over IRRT in such patients does not appear justified in the light of available evidence. CRRT was shown to achieve better haemodynamic parameters such as MAP. Future research should focus on factors such as the dose of dialysis and evaluation of newer promising hybrid technologies such as SLED. Triallists should follow the recommendations regarding clinical endpoints assessment in RCTs in ARF made by the Working Group of the Acute Dialysis Quality Initiative Working Group. | 10.1002/14651858.CD003773.pub3 |
pubmed_467_7381 | This paper discusses the optimal control of pressure using the zero-gradient control (ZGC) approach. It is applied for the first time in the study to control the optimal pressure of hydrogen natural gas mixture in an inclined pipeline. The solution to the flow problem is first validated with existing results using the Taylor series approximation, regression analysis and the Runge-Kutta method combined. The optimal pressure is then determined using ZGC where the optimal set points are calculated without having to solve the non-linear system of equations associated with the standard optimization problem. It is shown that the mass ratio is the more effective parameter compared to the initial pressure in controlling the maximum variation of pressure in a gas pipeline. | 10.1371/journal.pone.0228955 |
pubmed_288_16198 | BACKGROUND AND OBJECTIVES
The authors have previously shown that urine neutrophil gelatinase-associated lipocalin (NGAL), measured by a research ELISA, is an early predictive biomarker of acute kidney injury (AKI) after cardiopulmonary bypass (CPB). In this study, whether an NGAL immunoassay developed for a standardized clinical platform (ARCHITECT analyzer, Abbott Diagnostics Division, Abbott Laboratories, Abbott Park, IL) can predict AKI after CPB was tested.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
In a pilot study with 136 urine samples (NGAL range, 0.3 to 815 ng/ml) and 6 calibration standards (NGAL range, 0 to 1000 ng/ml), NGAL measurements by research ELISA and by the ARCHITECT assay were highly correlated (r = 0.99). In a subsequent study, 196 children undergoing CPB were prospectively enrolled and serial urine NGAL measurements obtained by ARCHITECT assay. The primary outcome was AKI, defined as a > or = 50% increase in serum creatinine.
RESULTS
AKI developed in 99 patients (51%), but the diagnosis using serum creatinine was delayed by 2 to 3 d after CPB. In contrast, mean urine NGAL levels increased 15-fold within 2 h and by 25-fold at 4 and 6 h after CPB. For the 2-h urine NGAL measurement, the area under the curve was 0.95, sensitivity was 0.82, and the specificity was 0.90 for prediction of AKI using a cutoff value of 100 ng/ml. The 2-h urine NGAL levels correlated with severity and duration of AKI, length of stay, dialysis requirement, and death.
CONCLUSIONS
Accurate measurements of urine NGAL are obtained using the ARCHITECT platform. Urine NGAL is an early predictive biomarker of AKI severity after CPB. | 10.2215/CJN.04010907 |
pubmed_897_11822 | Melanoma has an important metastatic potential and its incidence is greatly increasing. Even after many years of negative follow-up, gynecologists should be aware that a gynecological tumor might be a secondary location for a woman with a medical history of melanoma. Because of a poor prognosis and a reduced life expectancy, it is necessary to make a disease staging in order to offer a prompt diagnosis and a personalized strategy of treatment. Considering the increasing incidence of melanoma, gynecologists will face more frequently with this situation. | 10.1016/j.jgyn.2010.09.006 |
pubmed_643_20766 | A novel pigmented bacterium, initially identified as 11E, was isolated from a site historically known to have various iron-related ores. Phylogenetic analysis of this bacterial strain showed that it belongs to Serratia marcescens. This pigmented S. marcescens 11E cultured individually with glucose, acetate, and glycerol as electron donors along with the soluble electron acceptor iron (Fe) (III) citrate offered a large reduction extent (45.3 %, 31.4 %, and 13.5 %, respectively). On the other hand, when iron oxide (Fe2O3) is used as electron acceptor, the pigmented strain produced a null reduction extent. Surprisingly, the absence of prodigiosin on the bacterial surface (non-pigmented strain) resulted in a large reduction extent of the non-soluble iron form (20-49%). All these extents were comparable and, in some cases, superior to those presented in the literature. Additionally, in the present study, it was found that anthraquinone sulfonate (AQS) stimulated Fe(III) reduction of soluble and non-soluble Fe species only with pigmented S. marcescens. In contrast, in the culture media with the non-pigmented strain, the presence of AQS did not stimulate the Fe(III) reduction. These results suggest that the pigmented phenotype of S. marcescens 11E may perform non-soluble Fe(III) reduction by electron shuttling. In contrast, for the non-pigmented phenotype of this bacterium, non-soluble Fe(III) reduction seems to proceed by direct contact. Our study demonstrates that this bacterium may be used in bioreduction process of heavy metals or as a biocatalyst in bioelectrochemical devices. | 10.1007/s10123-019-00088-y |
pubmed_521_6618 | Conserved regions of the gag, pol, and env genes of HIV-1 pBH10 DNA (gag nucleotides(nt)1520-1665, pol nt 2326-2663, env nt 7192-7333; Ratner et al., 1985) were amplified by the polymerase chain reaction (PCR) using oligonucleotides complementary to the termini of these regions as primers. Primer areas of the amplified DNA were then removed by digestion with restriction endonucleases, and the internal fragments purified and cloned in both orientations into the 'riboprobe' transcription vector pGEM-5Z. Riboprobes made from these plasmids did detect the specific sequences of pBH10 DNA and of HIV-1 DNA amplified by PCR from clinical material. The riboprobes will be useful to confirm the specificity of PCR-amplified fragments of lymphocyte DNA obtained from infants of HIV-infected mothers and from high risk, but seronegative contacts of HIV-1-infected individuals. | 10.1016/0166-0934(94)90116-3 |
pubmed_801_11239 | Direct detection of pseudouridine (ψ), an isomer of uridine, in RNA is challenging. The most popular method requires chemical derivatization using N-cyclohexyl-N'-β-(4-methylmorpholinum ethyl) carbodiimide p-tosylate (CMCT) followed by radiolabeled primer extension mediated by reverse transcriptase. More recently, mass spectrometry (MS)-based approaches for sequence placement of pseudouridine in RNA have been developed. Nearly all of these approaches, however, only yield qualitative information regarding the presence or absence of pseudouridine in a given RNA population. Here, we have extended a previously developed liquid chromatography tandem mass spectrometry (LC-MS/MS) method to enable both the qualitative and quantitative analysis of pseudouridine. Quantitative selected reaction monitoring (SRM) assays were developed using synthetic oligonucleotides, with or without pseudouridine, and the results yielded a linear relationship between the ion abundance of the pseudouridine-specific fragment ion and the amount of pseudouridine-containing oligonucleotide present in the original sample. Using this quantitative SRM assay, the extent of pseudouridine hypomodification in the conserved T-loop of tRNA isolated from two different Escherichia coli strains was established. | 10.1007/s13361-011-0137-5 |
pubmed_655_3748 | Immunization of susceptible strains of mice with type II collagen (CII) elicits an autoimmune arthritis known as collagen-induced arthritis (CIA). One analogue peptide of the immunodominant T cell determinant, A9 (CII245-270 (I260-->A, A261-->B, F263-->N)), was previously shown to induce a profound suppression of CIA when coadministered at the time of immunization with CII. In the present study, A9 peptide was administered i.p., orally, intranasally, or i.v. 2 to 4 wk following CII immunization. We found that arthritis was significantly suppressed even when A9 was administered after disease was induced. To determine the mechanism of action of A9, cytokine responses to A9 and wild-type peptide A2 by CII-sensitized spleen cells were compared. An increase in IL-4 and IL-10, but not in IFN-gamma, was found in A9 culture supernatants. Additionally, cells obtained from A9-immunized mice produced higher amounts of IL-4 and IL-10 when cultured with CII compared with cells obtained from mice immunized with A2, which produced predominantly IFN-gamma. Suppression of arthritis could be transferred to naive mice using A9-immune splenocytes. Lastly, phosphorylation of TCRzeta was not altered in the immunoprecipitates from the lysates of cells exposed to analogue peptides (A9 and A10) together with wild-type A2 in a T cell line and two I-Aq-restricted, CII-specific T hybridomas. We conclude that analogue peptide A9 is effective in suppressing established CIA by inducing T cells to produce a Th2 cytokine pattern in response to CII. | pubmed_655_3748 |
pubmed_43_22476 | Food systems are at the center of global environmental, social, and economic challenges such as resource scarcity, ecosystem degradation, and climate change [...]. | 10.3390/ijerph18158073 |
pubmed_433_18155 | White matter hyperintensities (WMHs), mainly caused by cerebrovascular injury, may lead to cognitive impairment. In order to identify whether the volume of WMHs is associated with cognitive decline over years, this longitudinal study involved 818 individuals from the ADNI-2 dataset from August 2010 to May 2017. Cross-sectional and longitudinal associations of WMHs with 8 cognitive domains were explored, using Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Clinical Dementia Rating Sum of Boxes (CDRSB), Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog13), Rey Auditory Verbal Learning Test (RAVLT), Functional Assessment Questionnaire (FAQ), executive function (ADNI-EF), and memory function (ADNI-Mem). The association analyses were performed using multiple linear regression models, linear mixed models, Spearman rank correlation, and Kaplan-Meier survival curves. The volumes of WMHs were greater in patients with Alzheimer's disease (AD) dementia compared with controls (p < 0.001) and mild cognitive impairment (p = 0.006) patients at baseline. The bigger volumes of WMHs correlated with worse performances on ADAS-Cog13 and ADNI-EF (p = 0.029; p = 0.003) at baseline and MMSE, MoCA, CDRSB, ADAS-Cog13, FAQ, and ADNI-Mem (overall p < 0.05) longitudinally, after adjusting for age, sex, educational level, apolipoprotein E ɛ4 genotype, hypertension, hyperlipidemia, diabetes, smoking, infarction, and diagnosis. Additionally, the correlations between the change rate of WMHs and change rates of MMSE, MoCA, CDRSB, FAQ, ADNI-EF, and ADNI-Mem were statistically significant. Furthermore, patients with high WMH volumes showed an increased likelihood of dementia. The results of the study suggest that WMH volume is associated with cognitive decline, and it contributes to the conversion to AD. | 10.3233/JAD-191005 |
pubmed_347_10797 | Perlecan is a heparan sulfate proteoglycan assembled into the vascular basement membranes (BMs) during vasculogenesis. In the present study we have investigated vessel formation in mice, teratomas and embryoid bodies (EBs) in the absence of perlecan. We found that perlecan was dispensable for blood vessel formation and maturation until embryonic day (E) 12.5. At later stages of development 40% of mutant embryos showed dilated microvessels in brain and skin, which ruptured and led to severe bleedings. Surprisingly, teratomas derived from perlecan-null ES cells showed efficient contribution of perlecan-deficient endothelial cells to an apparently normal tumor vasculature. However, in perlecan-deficient EBs the area occupied by an endothelial network and the number of vessel branches were significantly diminished. Addition of FGF-2 but not VEGF(165) rescued the in vitro deficiency of the mutant ES cells. Furthermore, in the absence of perlecan in the EB matrix lower levels of FGFs are bound, stored and available for cell surface presentation. Altogether these findings suggest that perlecan supports the maintenance of brain and skin subendothelial BMs and promotes vasculo- and angiogenesis by modulating FGF-2 function. | 10.1371/journal.pone.0053715 |
pubmed_919_1815 | OBJECTIVE
To analyze the main reason of failure in treatment and compliance to protocol in children with acute lymphoblastic leukemia (ALL) at a single institute which is located at the most developed city of China.
METHODS
All the ALL patients who were diagnosed at the hospital from October 1998 to June 2003 were analyzed. The data were extracted from the department's tumor registry database. Failure in protocol compliance and treatment was analyzed within different risk groups, patients' resident area, and time period. The patients who had not received any therapy after ALL diagnosis were accounted as early protocol compliance failure, those who received therapy for less than 15 days were regarded as interim failure in protocol compliance, and those who gave up therapy or were lost in follow-up after 15 days with stable disease or complete remission (CR) were accounted as late compliance failure.
RESULTS
Totally 224 patients were diagnosed to have ALL, of them 38 patients went home without receiving any therapy, i.e., the rate of early protocol compliance failure was 17.1%. Of the remaining 186 patients, 22 (10.5%) belonged to interim protocol compliance failure, and 6 cases discontinued the therapy after 15 days treatment, who were classified into late compliance failure. Six cases (10.5%) were regarded as protocol compliance failure among 57 Shanghainese, and so were 22 cases (17.1%) out of 129 non-Shanghainese. There was no significant difference between the two groups (chi(2) = 1.332, P > 0.05). Up to a median 40 months follow-up showed that in 52 patients (31.7%) the treatment failed, of which 37 cases (22.6%) died of incomplete response and relapse, and 15 cases (9.5%) died of therapy complication. Among different risk groups, 24 cases (47.1%) came from high risk group, 18 (34.0%) from medium risk group, and 5 (9.4%) from low risk group. Very significant difference was found among the different risk group (chi(2) = 21.463, P < 0.01). Treatment failure was 28.6% (32/112) in non-Shanghainese and 38.5% (20/52) in Shanghainese. Total failure in protocol compliance and treatment was 42.9% (32 + 22/129) in non-Shanghainese and 45.6% (20 + 6/57) in Shanghainese. The difference of treatment failure was not significant different between the two groups (chi(2) = 1.354, P > 0.05).
CONCLUSION
Protocol compliance failure is the reason as important as the treatment failure for childhood ALL management failure. Either failure should not be neglected. Death from complications was relatively high which needs more attention, especially during induction period. Unusually high death rate occurred in high and medium risk group patients. The grouping criteria may need modification. | pubmed_919_1815 |
pubmed_904_11765 | The effects of long-term soil fertilizations on nutrient and non-essential element concentrations in edible parts of three crops important in human diet were investigated repeating four treatments (biowaste compost, biowaste compost plus mineral nitrogen, mineral NPK, unfertilized control) for seven consecutive years (2007-2014). Fruits of Solanum lycopersicum cv San Marzano collected in 2011 and 2012, bulbs of Allium cepa cv Bianca di Pompei collected in 2012 and 2013, and bulbs of Foeniculum vulgare cv Orbit collected in 2014 were analyzed. Wide variations in element concentrations were observed along time and among species, with Ca, K, Mg, and Na higher in fennel bulbs and Cd, Cr, Mn, Ni, Pb, and Zn higher in tomato fruits, where Cd reached concentrations up to ninefold higher than the permitted values (EU Regulation n. 488/2014). Despite the enrichments in soil total Cu and available Cd, Fe, K, Mn, and Zn concentrations due to long-term fertilization with biowaste compost (alone or with mineral fertilizers), plants showed lower micronutrient and non-essential element concentrations in respect to those on unfertilized soils. Considering the potential toxicity for human beings of these mobile and persistent elements, the obtained findings reassure on the safe use of biowaste compost in agriculture. Overall, this study suggests the use of compost as the most advisable fertilization practice and highlights the need of multiple crops analysis in evaluating the effects of long-term soil fertilization on their chemical composition. | 10.1007/s11356-018-3353-8 |
pubmed_856_6104 | Surrogate Safety Measures (SSM) are important for safety performance evaluation, since crashes are rare events and historical crash data does not capture near crashes that are also critical for improving safety. This paper focuses on SSM and their applications, particularly in Connected and Automated Vehicles (CAV) safety modeling. It aims to provide a comprehensive and systematic review of significant SSM studies, identify limitations and opportunities for future SSM and CAV research, and assist researchers and practitioners with choosing the most appropriate SSM for safety studies. The behaviors of CAV can be very different from those of Human-Driven Vehicles (HDV). Even among CAV with different automation/connectivity levels, their behaviors are likely to differ. Also, the behaviors of HDV can change in response to the existence of CAV in mixed autonomy traffic. Simulation by far is the most viable solution to model CAV safety. However, it is questionable whether conventional SSM can be applied to modeling CAV safety based on simulation results due to the lack of sophisticated simulation tools that can accurately model CAV behaviors and SSM that can take CAV's powerful sensing and path prediction and planning capabilities into crash risk modeling, although some researchers suggested that proper simulation model calibration can be helpful to address these issues. A number of critical questions related to SSM for CAV safety research are also identified and discussed, including SSM for CAV trajectory optimization, SSM for individual vehicles and vehicle platoon, and CAV as a new data source for developing SSM. | 10.1016/j.aap.2021.106157 |
pubmed_812_12835 | In early 2004, Dr Don Brash, leader of the National Party (New Zealand's opposition political party), gave a speech to a community group regarding what he perceived to be the preferential treatment of Maori in health and education policies. This viewpoint article is written by a group of concerned medical students at Otago University. It argues that epidemiological data provide strong support for specifically addressing Maori health need, whilst the Treaty of Waitangi represents a contractual obligation on behalf of the New Zealand Government to ensure equity of outcome for Maori. Underpinning both the epidemiological and legal arguments, are ethical principles. The central tenets of medicine (ie, to reduce suffering, and to improve and prolong the quality and length of life) should provide a strong driving force to address these inequalities. | pubmed_812_12835 |
pubmed_803_10163 | Twenty-seven firemen were divided into three groups. Group a performed one hour of unsupervised exercise three to four times per week. Group C performed similar but supervised exercise, and group B had no exercise program. After 12 weeks group A showed an average increase of 19% in maximal oxygen uptake (VO2 max); group C, an average increase of 20%; and group B, an average decrease of 2%. One-minute postalarm heart rates showed a correlation with VO2 max (p = 15). A serious cardiac arrhythmia was found in the oldest fireman. Careful physical screening followed by an on-the-job exercise program increases aerobic reserve. We suggest that postalarm tachycardia is dampened. This may lessen the risk of heart disease occurring in the postalarm period. | pubmed_803_10163 |
pubmed_540_15134 | Fast and accurate computational approaches to predicting reactivity in sulfa-Michael additions are required for high-throughput screening in toxicology (e.g., predicting excess aquatic toxicity and skin sensitization), chemical synthesis, covalent drug design (e.g., targeting cysteine), and data set generation for machine learning. The kinetic glutathione chemoassay is a time-consuming in chemico method used to extract kinetic data in the form of log(k GSH) for organic electrophiles. In this work, we use density functional theory to compare the use of transition states (TSs) and enolate intermediate structures following C-S bond formation in the prediction of log(k GSH) for a diverse group of 1,4 Michael acceptors. Despite the widespread use of transition state calculations in the literature to predict sulfa-Michael reactivity, we observe that intermediate structures show much better performance for the prediction of log(k GSH), are faster to calculate, and easier to obtain than TSs. Furthermore, we show how linear combinations of atomic charges from the isolated Michael acceptors can further improve predictions, even when using inexpensive semiempirical quantum chemistry methods. Our models can be used widely in the chemical sciences (e.g., in the prediction of toxicity relevant to the environment and human health, synthesis planning, and the design of cysteine-targeting covalent inhibitors), and represent a low-cost, sustainable approach to reactivity assessment. | 10.1021/acsomega.2c03739 |
pubmed_983_20378 | INTRODUCTION
Glaucoma affects a large number of people, and therapies for its management are based on the use of adrenergic agonist/antagonists, carbonic anhydrase (CA) inhibitors and prostaglandin (PG) analogs. However, no new drugs have been launched on the market, although some new drug classes, such as 5-hydroxy-tryptamine (5HT(2)) agonists and rho kinase inhibitors entered into advanced clinical investigations.
AREAS COVERED
The main classes of clinically used antiglaucoma drugs, as well as potential new targets (e.g., 5HT(2) agonist, rho kinase inhibitor, RNA interference), are reviewed. A patent literature review covering the period 2007 - 2011 is presented.
EXPERT OPINION
Most of the patents deal with sulfonamide CA inhibitors incorporating nitric oxide donating moieties or with PG analogs based on the latanoprost scaffold. The PG analogs are the predominant patented compounds. Several new potential targets emerged (e.g., rho kinase inhibitors), but no such derivatives progressed to the clinic due to adverse effects. There is an urgent need of new antiglaucoma drugs/approaches to treat and diagnose this disease in the very near future. | 10.1517/13543776.2012.649006 |
pubmed_126_11683 | Mitf encodes a basic helix-loop-helix-leucine-zipper (bHLHzip) protein that is known to function in the development of melanocytes, pigmented epithelial cells (PECs), osteoclasts, and mast cells. In this paper, we report on the isolation, expression, and overexpression of the chicken Mitf and discuss the role of its protein product in the differentiation and transdifferentiation of PECs. Northern blotting showed that chicken Mitf is predominantly expressed in embryonic retinal pigmented epithelium (PE), but is expressed at low levels in other tissues. A 5' RACE analysis revealed differences in the 5' region Mitf nRNA in PE and other tissues. Immunological analysis revealed that Mitf, the protein encoded by Mitf, is first detected in the nuclei of the optic vesicle cells at embryonic stage 13 in a restricted region covered with mesenchymal cells. From stage 14 to 24, the specific staining is observable in the PE and precursor of the PE, the outer layer of the optic cup. In embryos at stages later than stage 29 the signals for Mitf in the future iris, ciliary body, and posterior retinal regions become faint. These results show that expression of Mitf starts at the optic vesicle stage at which no other marker genes for PECs such as mmp115 and tyrosinase are expressed. Dedifferentiation of cultured retinal PECs (rPECs) was induced by phenylthiourea and testicular hyaluronidase, bFGF, or TGF-beta. Mitf expression was inhibited by these factors and reactivated during redifferentiation of the dedifferentiated cells into rPECs, showing the correlation between Mitf expression and rPEC differentiation. Retrovirus-mediated overexpression of Mtif inhibited bFGF-induced dedifferentiation and transdifferentiation of rPECs to both lens and neural cells. These findings showed that downregulation of Mitf expression is essential for the transdifferentiation of rPEC. Mitf overexpression caused hyperpigmentation in cultured rPECs and suppressed the changes in gene expression induced by bFGF. Mitf overexpression promoted expression of mmp115 and tyrosinase in bFGF-treated rPECs suggesting a critical role for Mitf in rPEC differentiation. Mitf overexpression, however, did not promote expression of another rPEC-specific gene, pP344, in bFGF-treated rPECs. This result suggests the presence of other regulatory genes promoting rPEC differentiation. The expression patterns of pax6 and Mitf are complementary both in vivo in vitro. Overexpression of Mitf inhibited expression of pax6 in cultured rPECs. These observations suggest that Mitf regulates pax6 expression negatively. | 10.1006/dbio.1997.8800 |
pubmed_442_11639 | PURPOSE
MicroRNA-622 has been proven down-regulated in many human malignancies and correlated with tumor progression. However, its role in esophageal squamous cell carcinoma (ESCC) is still unclear. The aim of this study was to explore the expression and function of miR-622 in ESCC.
METHODS
Using quantitative RT-PCR, we detected miR-622 expression in ESCC cell lines and primary tumor tissues. The association of miR-622 expression with clinicopathological factors and prognosis was also analyzed. Then, the effects of miR-622 on the biological behavior of ESCC cells were investigated. At last, the potential regulatory function of miR-622 on E2F1 expression was confirmed.
RESULTS
miR-622 was found to be down-regulated in ESCC tissues and cell lines. Decreased miR-622 expression was closely correlated with aggressive clinicopathological features and poor overall survival. Multivariate regression analysis corroborated that low level of miR-622 expression was an independent unfavourable prognostic factor for patients with ESCC. Up-regulation of miR-622 could significantly reduce ESCC cell proliferation, enhance cell apoptosis, and impair cell invasion and migration in vitro, while down-regulation of miR-622 showed opposite effects. Further, E2F1 was confirmed as a direct target of miR-622 by using Luciferase Reporter Assay.
CONCLUSIONS
These findings indicate that miR-622 may act as a tumor suppressor in ESCC and would serve as a potential therapy target for this disease. | 10.1016/j.biopha.2016.07.036 |
pubmed_866_24041 | The interpretation of functional magnetic resonance imaging (fMRI) studies of brain activity is often hampered by the presence of brain-wide signal variations that may arise from a variety of neuronal and non-neuronal sources. Recent work suggests a contribution from the sympathetic vascular innervation, which may affect the fMRI signal through its putative and poorly understood role in cerebral blood flow (CBF) regulation. By analyzing fMRI and (electro-) physiological signals concurrently acquired during sleep, we found that widespread fMRI signal changes often co-occur with electroencephalography (EEG) K-complexes, signatures of sub-cortical arousal, and episodic drops in finger skin vascular tone; phenomena that have been associated with intermittent sympathetic activity. These findings support the notion that the extrinsic sympathetic innervation of the cerebral vasculature contributes to CBF regulation and the fMRI signal. Accounting for this mechanism could help separate systemic from local signal contributions and improve interpretation of fMRI studies. | 10.1038/s42003-019-0659-0 |
pubmed_955_6471 | A periodic acid-thiocarbohydrazide-silver protein-physical development (PA-TCH-SP-PD) procedure was applied to the rat circumventricular organs (CVOs), which are known to be specialized structures in the brain. In the rat CVOs, vivid PA-TCH-SP-PD reactions were obtained in the apical surface and cytoplasm of the ependymal cells of the subcommissural organ (SCO) and the epithelial cells in the choroid plexuses (CPs) examined, and similar positive reactions were detected in the vascular walls and perivascular connective tissues in all the CVOs tested. Further, varying intensities of PA-TCH-SP-PD reactions were noted in the neuronal and glial networks of the organum vasculosum laminae terminalis (OVLT), subfornical organ (SFO) and area postrema (AP). The results obtained in the present study indicate that in the rat CVOs the histologic structures mentioned contain varying amounts of neutral carbohydrates and possible histophysiological significances of these carbohydrates in these organs have been discussed with references to their functions. | 10.2535/ofaj1936.71.5_325 |
pubmed_46_242 | Vitrectomy and associated techniques make up the surgical treatment of diabetic retinopathy. Vitrectomy does not replace laser photocoagulations, but greatly enlarges the range of diabetic retinopathy cases which may benefit from a treatment. | pubmed_46_242 |
pubmed_597_25656 | The aim of this study was to determine abdominal obesity risk factors in two successive cohorts of children and adolescents aged 4-18 from Cracow, Poland, examined during the years of political transformation. The influence of biological, socio-demographic and lifestyle factors on abdominal obesity was analysed by calculating odds ratios and 95% confidence intervals using logistic regression analysis. It was found that for girls obesity in both parents (OR=4.31; 95% CI 1.73-20.70) and high birth weight (OR=1.78; 95% CI 1.12-2.82) were significant risk factors for abdominal obesity in the 1983 cohort. In the 2000 cohort obesity in both parents for boys and girls (boys: OR=5.85; 95% CI 1.36-25.10; girls: OR=4.82; 95% CI 1.17-19.77), low level of parental education in girls (OR=2.06; 95% CI 1.15-3.69), having only one son (OR=1.96; 95% CI 1.36-3.40), parents' smoking habits in girls (OR=2.94; 95% CI 1.46-5.91) and lack of undertaking physical activity in sport clubs in boys (OR=6.11; 95% CI 1.46-25.47) were significant abdominal obesity risk factors. Higher number of hours of leisure time physical activity (OR=0.89; 95% CI 0.81-0.97) significantly lowered the risk of abdominal obesity in boys in the 2000 cohort. The greater differentiation of abdominal obesity risk factors in the 2000 cohort in comparison to the 1983 cohort may have resulted from the social and economic changes taking place in Poland at the end of the 20th century. | 10.1017/S0021932013000606 |
pubmed_99_2885 | The changes in size and weight of the calcified portions of the crowns of deciduous anterior teeth (maxillary and mandibular central and lateral incisors and canines) in human fetuses aged 5-10 months were studied. Relating the weight and size of each tooth to fetal age provided quantitative information on the rate of crown development in each of these teeth. There is a good correlation between crown height and fetal age. At the corresponding ages the length of the maxillary central incisor is greater than that of the maxillary lateral incisor which is greater than that of the maxillary canine. A similar pattern is found in the mandibular teeth. Generally, with the exception of a few mandibular central incisors, no type of anterior tooth crown has reached its final length before birth. | pubmed_99_2885 |
pubmed_826_19202 | OBJECTIVE
The objective of this study was to evaluate how the administration of different adjuvant therapies influences the risk for developing recurrences in the para-aortic area in endometrial cancer (EC) with positive pelvic and unknown para-aortic nodes.
METHODS
We retrospectively evaluated the data of 58 patients with EC affected by stage IIIC1 who had undergone pelvic but not para-aortic lymphadenectomy from January 1, 1990 to December 31, 2011. Survival outcomes within the first 5 years after surgery were assessed using the Kaplan-Meier model.
RESULTS
Chemotherapy plus radiotherapy, chemotherapy only, and external radiotherapy only were administered in 12 (23%), 18 (34%), and 23 (43%) patients, respectively. Five (9%) patients, who were selected to forego adjuvant therapy due to poor performance status, were excluded from the analysis. Disease-free and overall survivals assessed at 5 years were 54%, and 61%, respectively. All para-aortic recurrences were observed among the patients with endometrioid EC, whereas no cases of para-aortic recurrences were found in patients with nonendometrioid histology (5/36 (14%) vs 0/17 (0%); P = 0.16); the latter were more likely to develop distant (hematogenous, peritoneal, and distant lymphatic) recurrences (P = 0.09). Type of adjuvant therapy was the only factor influencing para-aortic failure: chemotherapy (± radiotherapy) reduced the rate of para-aortic node recurrence in comparison with pelvic radiotherapy as a sole modality (P = 0.01). However, adjuvant therapy did not influence the 5-year survival outcomes (P > 0.05).
CONCLUSIONS
In the absence of local treatment (ie, para-aortic lymphadenectomy and radiotherapy), the administration of chemotherapy seems effective in reducing recurrences in the para-aortic area among patients with stage IIIC1 endometrioid EC. | 10.1097/IGC.0000000000000337 |
pubmed_1007_114 | OBJECTIVE
Renin-angiotensin system gene polymorphisms are associated with essential hypertension; angiotensinogen gene variants are considered potential genetic risk factors. The aim of this study was to investigate the contribution of the G-6A, T174M, M235T polymorphisms, genotypic interactions, and haplotypes toward essential hypertension.
METHODS
In a case-control design, 810 consecutive ethnically matched unrelated individuals comprising 450 hypertensive patients and 360 controls were recruited. Genotyping by polymerase chain reaction-restriction fragment length polymorphism, genotypes combinations, and haplotypes analyses were performed. Plasma renin activity and plasma aldosterone concentration were measured.
RESULTS
The G-6A and M235T polymorphisms differed significantly (P = 0.007, odds ratio = 1.9, 95% confidence interval = 1.2-2.9; P < 0.0001, odds ratio = 3.7, 95% confidence interval = 2.3-5.7, respectively), wherein the -6A and 235T mutant alleles were over-represented in hypertensive patients (P < 0.0001, each). Genotypes combinations of six wild-type alleles versus the remaining resulted in odds ratio of 2.4 (P < 0.0001), further mutant alleles based combinations linearly correlated with systolic, diastolic, and mean blood pressure. Over-representation of the haplotypes, namely, A/174T, 174T/235T, A/235T, and A/174T/235T in hypertensive patients and G/174T, 174T/235M, G/235M, and G/174T/235M in controls, was identified as risk and protective haplotypes (P < 0.0001, each), respectively. The patients had significantly higher plasma aldosterone concentration and lower plasma renin activity (P < 0.0001), the former correlated with -6A and 235T alleles (P < 0.0001).
CONCLUSION
The interaction among G-6A, M235T and T174M polymorphisms in combinations or haplotypes emerged significant. These findings, conjoint with significant high plasma aldosterone concentration and low plasma renin activity, suggest low-renin hypertension in our study population. | 10.1097/HJH.0b013e3282fad951 |
pubmed_974_13399 | BACKGROUND
Eculizumab is a humanized anti-C5 antibody approved for the treatment of atypical hemolytic uremic syndrome (aHUS). Its use is increasing in children following reports of its safety and efficacy.
METHODS
We reviewed biochemical and clinical data related to possible drug-induced liver injury in 11 children treated with eculizumab for aHUS in a single center.
RESULTS
Elevated aminotransferases were observed in 7 children aged 6 to 11 years following eculizumab treatment for aHUS. Internationally accepted liver enzyme thresholds for drug-induced liver injury were exceeded in 5 cases. In all cases, liver injury was classified as mixed hepatocellular and cholestatic. Infectious and other causes were excluded in each case. One patient with no pre-existing liver disease developed tender hepatomegaly and liver enzyme derangement exceeding 20 times the upper limit of normal following initiation of eculizumab. Recurrent liver injury following re-challenge with eculizumab necessitated its discontinuation and transition to plasma therapy.
CONCLUSIONS
Hepatotoxicity in association with eculizumab is a potentially important yet previously unreported adverse event. We recommend monitoring liver enzymes in all patients receiving eculizumab. Further research is required to clarify the impact of this adverse event, to characterize the mechanism of potential hepatotoxicity, and to identify which patients are most at risk. | 10.1007/s00467-014-2990-5 |
pubmed_953_13548 | The field of biomechanics combines the disciplines of biology and engineering, attempting to quantitatively describe the complicated properties of biological materials. These properties depend not only upon the inherent attributes of its constituents but also upon how the constituents are arranged relative to each other. Its importance in understanding spinal column and spinal cord pathology cannot be overemphasized. This chapter is a primer on the application of biomechanical principles to the normal and pathological spine. The basic concepts of biomechanics will first be reviewed followed by a review of the structural anatomy of the osteoligamentous spinal column and the biomechanics of injury. Relevant spinal cord anatomy will then be addressed as well as current biomechanical theories of spinal cord injury. | pubmed_953_13548 |
pubmed_817_6685 | PURPOSE
To evaluate the performance of fixed complete dental prostheses supported by axial and tilted implants after at least 3 years of follow-up.
MATERIALS AND METHODS
An electronic search plus a hand search up to April 2021 was undertaken. Clinical studies were selected using specific inclusion criteria, independent of the study design. The main outcomes were cumulative implant survival rate, marginal bone level changes, and complications, after ≥ 3 years of follow-up. The difference in outcomes between axial and tilted implants and between the maxilla and mandible was evaluated using meta-analysis and the Mantel-Cox test.
RESULTS
Out of 824 articles retrieved, 24 were included. In total, 2,637 patients were rehabilitated with 2,735 full prostheses (1,464 maxillary, 1,271 mandibular), supported by 5,594 and 5,611 tilted and axial implants, respectively. In a range between 3 and 18 years of follow-up, 274 implants failed. The cumulative implant survival rate was 93.91% and 99.31% for implants and prostheses, respectively. The mean marginal bone level change was moderate, exceeding 2 mm in only two studies. Marginal bone loss was significantly lower around axial compared with tilted implants (P < .0001), whereas it was not affected by arch (maxilla vs mandible; P = .17).
CONCLUSION
Fixed complete dental prostheses supported by tilted and axially placed implants represent a predictable option for the rehabilitation of edentulous arches. Further randomized trials are needed to determine the efficacy of this surgical approach and the remodeling pattern of marginal bone in the long term. | 10.11607/jomi.9710 |
pubmed_191_22181 | Parents are aware that young age is a risk factor and are more likely to take an infant to the emergency room than an older child with similar symptoms. It is essential that the physician rapidly responds to the concerns of such parents. It is not possible to exhaustively address in a few pages all of the potential emergency conditions that may arise with infants younger than three months. We therefore focus our discussion to the most frequently occurring emergency conditions. In particular, we emphasize the serious nature of such conditions as fever, apparent life threatening, hyperbilirubinemia, weight loss, and excessive crying. | pubmed_191_22181 |
pubmed_733_9763 | A total of 51 monkeys maintained in a colony at the Institute of Primate Research (Kenya) and housed in doors with natural lighting in a group cage were used in this study. Monkeys belonging to 3 species were selected at random and blood samples collected. The serum samples were screened for presence of neutralizing antibodies (VTN) to rhesus rotavirus (RRV) by virus neutralization assay. Virus neutralization was determined by 60% reduction in fluorescent focus units (ffu). 96% of the animals screened had naturally occurring antibodies to rhesus rotavirus. Another group of 11 lactating monkeys (5 baboons, 6 vervets) and their infants were screened further for presence of IgG and IgA antibodies in serum and breast milk (mothers). Overall, the mothers had higher titres of both IgG and IgA than the infants. Taken together, these results demonstrate rotavirus infection is endemic in this primate colony. This mimics the human situation, hence, captive non human primates (such as the baboons) could be a suitable model for testing rotavirus candidate vaccines and for investigating the possible application in humans of passive-active immunization strategy. | pubmed_733_9763 |
pubmed_1063_11542 | Gradient projection rotation (GPR) is an openly available and promising tool for factor and component rotation. We compare GPR toward the Varimax criterion in principal component analysis to the built-in Varimax procedure in SPSS. In a simulation study, we tested whether GPR-Varimax yielded multiple local solutions by creating population simple structure with a single optimum and with two optima, a global and a local one (double-optimum condition). The other conditions comprised the number of components (k = 3, 6, 9, and 12), the number of variables per component (m/k = 4, 6, and 8), the number of iterations per rotation (i = 25 and 250), and whether loadings were Kaiser normalized before rotation or not. GPR-Varimax was conducted with unrotated and multiple (q = 1, 10, 50, and 100) random start loadings. We found equal results for GPR-Varimax and SPSS-Varimax in most conditions. The few very small differences in favor of SPSS-Varimax were eliminated when Kaiser-normalized loadings and 250 iterations per rotation were used. Selecting the best solution out of multiple random starts in GPR-Varimax increased proximity to population components in the double-optimum condition with Kaiser normalized loadings, for which GPR-Varimax recovered population structure better than SPSS-Varimax. We also included an empirical example and found that GPR-Varimax and SPSS-Varimax yielded highly similar solutions for orthogonal simple structure in a real data set. We suggest that GPR-Varimax can be used as an alternative to Varimax rotation in SPSS. Users of GPR-Varimax should allow for at least 250 iterations, normalize loadings before rotation, and select the best solution from at least 10 random starts to ensure optimal results. | 10.3389/fpsyg.2019.00645 |
pubmed_643_6155 | Artificial intelligence (AI) has recently surpassed human performance in several domains, and there is great hope that in healthcare, AI may allow for better prevention, detection, diagnosis, and treatment of disease. While many fear that AI will disrupt jobs and the physician-patient relationship, we believe that AI can eliminate many repetitive tasks to clear the way for human-to-human bonding and the application of emotional intelligence and judgment. We review several recent studies of AI applications in healthcare that provide a view of a future where healthcare delivery is a more unified, human experience. | 10.1038/s41746-017-0012-2 |
pubmed_82_8848 | Idiopathic thrombocytopenic purpura (ITP), caused by autoantibodies directed against certain platelet antigens, is the most common entity of the immune thrombocytopenias. ITP is an acquired disorder and can affect both children and adults. However, the clinical syndromes of ITP are distinct between children and adults. Childhood (acute) ITP characteristically is acute in onset, occurs within 1-2 weeks of an infection, usually of viral origin, resolves spontaneously within 6 months. Adult (chronic) ITP has an insidious onset and rarely resolves spontaneously. Over the last decade considerable new information has accumulated as to the pathophysiological mechanisms of immune thrombocytopenias. In addition, most of the knowledge on this disorder has been obtained from studies of adult patients with chronic ITP. The present work gives an updated overview of the platelet autoantigens and the molecular immunological reactions in ITP. | 10.1111/j.1651-2227.1998.tb01230.x |
pubmed_268_457 | Physicians endorse prevention but provide only low levels of screening, health counseling, and immunization. Between 1981 and 1986, a randomized controlled trial was conducted at the Seattle (Wash) Veterans Affairs Medical Center to assess the effectiveness of the following three methods of delivery of preventive services: (1) a physician-oriented model that includes education and motivation, a chart flowsheet listing recommended activities, and periodic feedback about performance; (2) a patient education model in which patients were mailed an informative brochure advising them to ask physicians for preventive services as depicted in a patient-held pocket guide; and (3) a health promotion clinic that patients were invited to attend. A control group received their usual care. A total of 1224 male outpatients were enrolled in the trial. Baseline prevention rates for 12 age-specific prevention activities were below 25%. Neither the control group rates during the 5-year trial nor the rates for the two educational models, either singly or as a combined intervention, changed. Only the health promotion clinic model was effective, tripling prevention rates in its first year and sustaining these levels for all 5 years. It is difficult to change the clinic roles of experienced physicians and their long-term patients in a specialized multiclinic setting. Providing a separate health promotion clinic option is popular with patients, bypasses gatekeeper barriers, is reasonable in cost, and warrants wider application. | 10.1001/archinte.150.12.2533 |
pubmed_977_7870 | BACKGROUND
Around 1800 pediatric transplantations were performed in 2021, which is approximately 5% of the annual rate of solid organ transplantations carried out in the United States. Effective family self-management in the transition from hospital to home-based recovery promotes successful outcomes of transplantation. The use of mHealth to deliver self-management interventions is a strategy that can be used to support family self-management for transplantation recipients and their families.
OBJECTIVE
The study aims to evaluate the acceptability of an mHealth intervention (myFAMI) that combined use of a smartphone app with triggered nurse communication with family members of pediatric transplantation recipients.
METHODS
This is a secondary analysis of qualitative data from family members who received the myFAMI intervention within a larger randomized controlled trial. Eligible participants used the app in the 30-day time frame after discharge and participated in a 30-day postdischarge telephone interview. Content analysis was used to generate themes.
RESULTS
A total of 4 key themes were identified: (1) general acceptance, (2) positive interactions, (3) home management after hospital discharge, and (4) opportunities for improvement.
CONCLUSIONS
Acceptability of the intervention was high. Family members rated the smartphone application as easy to use. myFAMI allowed the opportunity for families to feel connected to and engage with the medical team while in their home environment. Family members valued and appreciated ongoing support and education specifically in this first 30 days after their child's hospital discharge and many felt it contributed positively to the management of their child's medical needs at home. Family members provided recommendations for future refinement of the app and some suggested that a longer follow-up period would be beneficial. The development and refinement of mHealth care delivery strategies hold potential for improving outcomes for solid organ transplantation patients and their families and as a model to consider in other chronic illness populations.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03533049; https://clinicaltrials.gov/ct2/show/NCT03533049. | 10.2196/39263 |
pubmed_896_22176 | The pathogenesis of rheumatoid arthritis (RA) is still not fully clarified, and the development of therapeutic drugs for RA is particularly urgent. Our group studies a possibility that circ_ 0015756/miR-942-5p may participate in the pathogenesis of RA through disordered Cullin 4B (CUL4B) and the traditional Chinese medicine compound Huangqin Qingre Chubi Capsule (HQC) may inhibit the pathogenesis of RA through the CUL4B/Wnt pathway. Data showed that the expression of circ_0015756 increased not only in fibroblast-like synoviocytes (FLS) of RA, but also in synovium and FLS of CIA mice, and the expression of miR-942-5p decreased. Abnormal circ_0015756 up-regulated the CUL4B expression and activated the canonical Wnt signaling pathway by inhibiting the expression of miR-942-5p. Circ_0015756 participated in the pathogenesis of RA and promoted the abnormal proliferation of FLS. Further, circ_0015756 activated the secretion of IL-1 and IL-8 and promoted the production of RA pathological gene MMP3 and fibronectin. Further analysis showed that HQC inhibited the pathogenesis of RA through the CUL4B/Wnt pathway, and the specific target was CUL4B. HQC interfered with the effects of circ_0015756 on the pathogenesis of RA by inhibiting the CUL4B, showing a good therapeutic effect on RA. | 10.3389/fphar.2021.750233 |
pubmed_414_2115 | BACKGROUND AND PURPOSE
On clinical MR images, the subthalamic nuclei (STN) are poorly delineated from adjacent structures, impeding safe direct targeting for placement of electrodes in the treatment of Parkinson disease. Susceptibility-weighted MR phase imaging offers improved contrast and spatial resolution at reduced imaging times relative to clinically used T2-weighted spin-echo imaging for STN visualization. Our purpose was to assess STN visibility by using phase imaging, comparing phase and magnitude images obtained concurrently by using susceptibility-weighted imaging (SWI). The goal was to identify an efficient scanning protocol for high-quality phase images of STN.
MATERIALS AND METHODS
Seventy-eight SWI scans were acquired at 3T by using different TEs and acceleration factors. STN visibility and delimitation from adjacent structures were scored from 0 (not interpretable) to 5 (excellent). Regression analyses assessed the relationship of STN visibility to scanning parameters
RESULTS
STN were identified at all studied TEs on phase images. Visibility and delimitation of STN were consistently superior on phase images compared with magnitude images. Good visualization (score of >or=4) of STN on phase imaging occurred at a mean TE of 20.0 ms and a sensitivity encoding (SENSE) of 1.40. Scores of STN visualization on phase images were dependent on SENSE (P < .002) and TE (P < .031). Good delimitation of the STN on phase imaging occurred at a mean TE of 21.6 ms and a SENSE of 1.36.
CONCLUSIONS
Visualization and delimitation of STN was superior on phase images and was achieved at 3T in <2.5 minutes. A TE of 20 ms and an acceleration factor of <or=1.5 are recommended to visualize STN by using this method. | 10.3174/ajnr.A1669 |
pubmed_239_5437 | The bacterial flagellum exemplifies a system where even small deviations from the highly regulated flagellar assembly process can abolish motility and cause negative physiological outcomes. Consequently, bacteria have evolved elegant and robust regulatory mechanisms to ensure that flagellar morphogenesis follows a defined path, with each component self-assembling to predetermined dimensions. The flagellar rod acts as a driveshaft to transmit torque from the cytoplasmic rotor to the external filament. The rod self-assembles to a defined length of ~25 nanometers. Here, we provide evidence that rod length is limited by the width of the periplasmic space between the inner and outer membranes. The length of Braun's lipoprotein determines periplasmic width by tethering the outer membrane to the peptidoglycan layer. | 10.1126/science.aam6512 |
pubmed_283_7429 | Long-range migrations and the resulting admixtures between populations have been important forces shaping human genetic diversity. Most existing methods for detecting and reconstructing historical admixture events are based on allele frequency divergences or patterns of ancestry segments in chromosomes of admixed individuals. An emerging new approach harnesses the exponential decay of admixture-induced linkage disequilibrium (LD) as a function of genetic distance. Here, we comprehensively develop LD-based inference into a versatile tool for investigating admixture. We present a new weighted LD statistic that can be used to infer mixture proportions as well as dates with fewer constraints on reference populations than previous methods. We define an LD-based three-population test for admixture and identify scenarios in which it can detect admixture events that previous formal tests cannot. We further show that we can uncover phylogenetic relationships among populations by comparing weighted LD curves obtained using a suite of references. Finally, we describe several improvements to the computation and fitting of weighted LD curves that greatly increase the robustness and speed of the calculations. We implement all of these advances in a software package, ALDER, which we validate in simulations and apply to test for admixture among all populations from the Human Genome Diversity Project (HGDP), highlighting insights into the admixture history of Central African Pygmies, Sardinians, and Japanese. | 10.1534/genetics.112.147330 |
pubmed_239_9678 | The mechanism of human β-defensin 3 (HBD-3) in methicillin-resistant Staphylococcus aureus (MRSA-induced infection of implant drug-resistant bacteria biofilm in the mouse tibial bone marrow was studied. Healthy adult male Sprague-Dawley rats with average weight of 230 g were selected to construct the infection model of MRSA-induced implant drug-resistant bacteria biofilm in the mouse left tibial bone marrow. The drugs were intraperitoneally injected after 24 h medullary cavity infection, and the experimental groups included the model group, HBD-3 group, and vancomycin group (20 rats in each group). The model group was injected with 10 ml saline, HBD-3 group was injected with 10 ml of 8 µg/ml (1 MIC) and vancomycin group was injected with 10 ml of 0.5 µg/ml (1 MIC), five animals in each group were sacrificed on the 1, 7, 14 and 21 days, respectively. Observation was carried out on whether there was swelling and purulent secretion on the local wound; 1 ml venous sinus blood of eye socket was collected for blood routine examination and blood culture, and the laser scanning confocal microscopy was used to observe the morphology of the biofilm on the implant surface and the number of viable bacteria. Immunohistochemical staining was adopted to test the expression of nuclear factor-κB (NF-κB) and toll-like receptor 4 (TLR-4), and ELISA method was used to test interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), IL-1α and interferon-γ (INF-γ)-inducible protein-10 (IP-10) expression levels. There was no death due to infection in the HBD-3 group or vancomycin group, 1 case with significant wound swelling was found, respectively, in each group, but there was no purulent secretion. The percentage of the total white blood cells and neutrophil granulocytes as well as the biofilm morphology and the number of viable bacteria in the model group was gradually increased with time, while those in the HBD-3 group and vancomycin group were decreased with time. The comparative difference among groups was statistically significant (P<0.05); those in the HBD-3 group and vancomycin group at each time-point was decreased significantly compared with the model group, and the difference among groups was statistically significant (P<0.05), but in terms of the comparison between the HBD-3 group and vancomycin group, the difference was not significantly different (P>0.05). The NF-κB and TLR-4 expressions in the model group and vancomycin group were not significantly changed at each time-point, those in the HBD-3 group began to increase on the 1st day, and reached the peak on the 7th day and began to decline on the 14th day, and the comparative difference at each time-point was statistically significant (P<0.05); those in the HBD-3 group were significantly higher than the model group and vancomycin group at each time-point and the difference was statistically significant (P<0.05). The IL-10, TNF-α, IL-1α, and IP-10 expressions in the model group at each time were significantly higher than the other two groups and the difference was statistically significant (P<0.05); in terms of the comparison between the HBD-3 group and vancomycin group, the difference was not statistically significant (P>0.05). In conclusion, β-defensin 3 can inhibit the bacterial growth by regulating inflammation and immune responses in the MRSA-induced implant drug-resistant bacteria biofilm infection in the mouse tibial bone marrow. | 10.3892/etm.2017.4112 |
pubmed_122_24186 | Large-eddy simulations of an observed single-layer Arctic mixed-phase cloud are analyzed to study the value of forward modeling of profiling millimeter-wave cloud radar Doppler spectral width for model evaluation. Individual broadening terms and their uncertainties are quantified for the observed spectral width and compared to modeled broadening terms. Modeled turbulent broadening is narrower than the observed values when the turbulent kinetic energy dissipation rate from the subgrid-scale model is used in the forward model. The total dissipation rates, estimated with the subgrid-scale dissipation rates and the numerical dissipation rates, agree much better with both the retrieved dissipation rates and those inferred from the power spectra of the simulated vertical air velocity. The comparison of the microphysical broadening provides another evaluative measure of the ice properties in the simulation. To accurately retrieve dissipation rates as well as each broadening term from the observations, we suggest a few modifications to previously presented techniques. First, we show that the inertial subrange spectra filtered with the radar sampling volume is a better underlying model than the unfiltered -5/3 law for the retrieval of the dissipation rate from the power spectra of the mean Doppler velocity. Second, we demonstrate that it is important to filter out turbulence and remove the layer-mean reflectivity-weighted mean fall speed from the observed mean Doppler velocity to avoid overestimation of shear broadening. Finally, we provide a method to quantify the uncertainty in the retrieved dissipation rates, which eventually propagates to the uncertainty in the microphysical broadening. | 10.1029/2017JD028104 |
pubmed_845_11638 | Spinal deformities are common in people with cerebral palsy (CP), and there is a concern of an increase during the adult ageing period. There is especially a worry about the increase of scoliosis, thoracic hyperkyphosis, lumbar hyperlordosis, spondylolysis and spondylolisthesis incidence, though supporting literature is lacking. Therefore, the aim of this narrative review is to provide a scientific overview of how spinal curvatures should be measured, what the norm values are and the incidence in people with CP, as well as a description of the risk factors and the treatment regimens for these spinal abnormalities. This review can be used as a guideline relevant for a range of clinicians, including orthopaedic and neurosurgeons, radiologists, physiotherapists, and biokineticists, as well as academics. | 10.7196/SAMJ.2020.v110i8.14472 |
pubmed_773_1751 | A man with severe bilateral bronchopneumonia and a right lobar consolidation caused by Mycoplasma pneumoniae, had a concurrent myocarditis. The possible aetiology of the patchy pulmonary opacities is discussed. A literature review of cases of myocarditis associated with M.pneumoniae is presented. | 10.1007/BF01638427 |
pubmed_660_15806 | BACKGROUND
Ultrasound guided fine needle aspiration cytology (US-guided FNAC) can identify microscopic involvement of lymph nodes as in breast cancer and avoid surgical sentinel node (SN). Its utility in melanoma patients is controversial and subject of this study.
METHODS
Between 2001 and 2010 over 1000 stage I/II consecutive melanoma patients prospectively underwent US-FNAC prior to SN biopsy. All patients underwent lymphoscintigraphy prior to US-FNAC. The Berlin US morphology criteria: Peripheral perfusion (PP), loss of central echoes (LCE) and balloon shaped (BS) were registered. FNAC was performed in case of presence of any of these factors. SN tumour burden was measured according to the Rotterdam criteria. All patients underwent SN or lymph node dissection (LND) in case of positive FNAC.
FINDINGS
Mean/median Breslow thickness was 2.58/1.57 mm. Mean/median follow-up was 56/53 months (1-132). SN positivity rate was 21%. US-FNAC Sensitivity was 71% (US only) and 51% (US-FNAC). Sensitivity of US-FNAC was highest for T4 (76%) and ulcerated melanomas (63%). PP, LCE and BS had sensitivity of 69%, 24% and 24% respectively. Sensitivity of US-FNAC increased with increasing SN tumour burden. PP was an early sign of metastasis (58% in <0.1mm metastases). Threshold size of a metastasis for FNAC was 0.3mm. Five-year survival correlated to US-FNAC status (95% in negative and 59% in positive).
INTERPRETATION
Ultrasound guided FNAC (US-FNAC) according to the Berlin morphology criteria could correctly identify at least half of all tumour positive sentinel nodes, prior to the surgical SN procedure. Peripheral perfusion is an early sign of metastasis, which is very sensitive, but with lower positive predictive value (PPV). It is responsible for the sensitivity of the procedure. Balloon shape is a sign of advanced metastases, with lower sensitivity, but high PPV. US-FNAC sensitivity correlated with increasing T-stage, ulceration of the primary and increasing SN tumour burden. US-FNAC status accurately predicts survival. | pubmed_660_15806 |
pubmed_0_4464 | BACKGROUND
Structures in intensive care medicine comprise human as well as material resources, organization, and management and may be related to processes thereby affecting patients' outcomes. Utilizing a unique data base we evaluated structures of German intensive care units (ICUs).
METHODS
The study was carried out by the German Competence Network Sepsis (SepNet). Data were prospectively collected on a cross-sectional basis in a representative random sample of German hospitals utilizing a questionnaire. Structures were related to ICU outcome of patients with severe sepsis or septic shock. The sample was subdivided in 5 strata according to hospital size.
RESULTS
A total of 454 ICUs cared for 3877 patients including 415 patients (11%) with severe sepsis or septic shock. The mean number of beds per ICU was 10.4, the ratio of ICU to hospital beds 1:27, both with significant differences depending on hospital size. 81% of the ICUs provided around the clock physician presence (range: 66-98% across hospital strata, p < 0.001). Shift-wise, one nurse was responsible for a mean number of 2.7 patients (morning 1:2.3, afternoon 1:2.6, night 1:3.3 patients) with significant variation according to hospital size (smaller hospitals 1:2.9, university hospitals 1:2.1, p < 0.001). More than half of all German ICUs are lead by anesthesiologists. Neither physician nor nurse staffing was associated with mortality in the subset of patients with sepsis.
CONCLUSIONS
In a representative, nationwide sample of German ICUs key elements of structures varied considerably with respect to hospital size. This has to be considered when proposing standards, reimbursement strategies, or quality assessment. | 10.1007/s00508-010-1452-8 |
pubmed_748_7619 | This paper focuses on the role of religion and ethnicity in providing social support for elderly Dutch Canadian Catholic and Calvinist parents and in establishing ethno-religious retirement and long-term care facilities. The data come from a 1995 survey of elderly Dutch Canadian immigrants (N = 79) and their adult children (N = 364) examining intraethnic differences in ethnic persistence and parent care. Continuity theory provides the theoretical framework for this study. In the last few decades, second generation Dutch Calvinist immigrants have been busy establishing retirement and long-term care facilities to look after the needs of the older Calvinist generation. Dutch Catholic immigrants have established very few retirement and nursing homes for their elderly members. Ethnic and religious differences influence the kind of support available to elderly Dutch Canadians. | 10.1353/cja.2004.0012 |
pubmed_710_13216 | BACKGROUND
Friedreich's ataxia (FRDA) is a cerebellar ataxia due to GAA repeat expansions in the FXN gene, and in affected patients, lower left ventricular ejection fraction (LVEF) leads to poorer prognosis. We aimed to identify patients likely to develop worsening LVEF at an early stage.
METHODS
We included 115 FRDA patients aged 30 ± 10 years with 620 ± 238 GAA repeats on the shorter allele and disease onset of 15 ± 7 years.
RESULTS
At baseline, left ventricular (LV) hypertrophy was present in 53%, with LVEF 65 ± 7%, LV end diastolic diameter (LVEDD) 43 ± 5 mm, septal wall thickness (SWT) 11.8 ± 2.7 mm, and posterior wall thickness 11.1 ± 2.5 mm. After a mean follow-up of 13 ± 6 years, LVEF ≤ 50% was observed in 12 patients. The main determinants of LVEF ≤ 50% were GAA repeat number on the shorter allele (odds ratio [OR] 1.007, 95% confidence interval [CI] 1.003-1.012, p = 0.002), LVEDD (OR 1.217, 95% CI 1.058-1.399, p = 0.006), and SWT (OR 1.352, 95% CI 1.016-1.799, p = 0.04). High-risk patients were predicted 5 years before LVEF ≤ 50% occurred: area under the curve of 0.91, 95% CI 0.85-0.97. Patients with GAA repeats > 800 were categorized as high risk, patients with 500 < GAA < 800 were high risk if LVEDD was ≥ 52.6 mm and SWT was ≥ 13.3 mm, and patients with GAA < 500 were low risk if LVEDD was < 52.6 mm and SWT was < 13.3 mm.
CONCLUSIONS
Echocardiographic follow-up combined with size assessment of GAA repeat expansions is a powerful tool to identify patients at high risk of developing LV systolic dysfunction up to 5 years before clinical symptoms. Further studies are mandatory to investigate if these patients would benefit from cardiac interventions. | 10.1007/s40256-019-00375-z |
pubmed_963_18018 | BACKGROUND
In a number of patients with treated primary non-small cell lung cancer (NSCLC) a second primary tumor will be diagnosed. Our experience with surgery in these patients was analyzed and possible prognostic parameters were defined.
METHODS
Patients with metachronous NSCLC (n = 127) who underwent resection from 1970 through 1997 were analyzed. All tumors were classified postsurgically. Median interval between the tumors was 3.7 years. Actuarial survival time was estimated and risk factors influencing survival were evaluated.
RESULTS
Overall 5-year survival after the first resection was 70% and after the second resection was 26%. Patients with stage IA of the second primary tumor did have a significantly better survival (p < 0.005) as compared with patients with higher staged second primaries. Stage of second primary tumor and age were significant predictors of survival, whereas stage of first tumor, interval between resections, histology, and type of resection were not.
CONCLUSIONS
Survival of patients with metachronous NSCLC and resection of both tumors is high, but poorer than after resection of the first tumor. Irrespective of the interval, patients with stage IA second primary tumor may benefit more from pulmonary resection. | 10.1016/s0003-4975(00)02423-1 |
pubmed_120_249 | Recent research has shown that learned fear emerges in a response-specific sequence. For example, an odor conditioned stimulus (CS) previously paired with shock elicits behavioral expressions of fear like avoidance at a younger age than it elicits other behavioral expressions of fear like potentiation of the startle response (Richardson, Paxinos, & Lee, 2000). In the present study, the question of whether learned fear is expressed in a manner appropriate to the animal's age at training or its age at testing was explored in three experiments, all using a within-subjects design. The results suggest that learned fear is expressed in a manner appropriate to the rat's age at training, not its age at testing. The Discussion section focuses on the implications of these findings for (1) the developmental analysis of memory and (2) the idea that an aversive CS elicits a central state of fear. | 10.3758/bf03195964 |
pubmed_452_2375 | AIM
To investigate the effects of kinesio tape (KT) application on pain, anxiety, and menstrual complaints in women with PD and compare this application with control and sham tape (ST).
METHODS
Fifty-one women with PD were randomized into three groups: KT, ST, and control groups. No tape application was performed in the control group. KT was applied on the sacral and suprapubic regions with the ligament technique in the KT group, while it was applied on the trochanter major with no technique in the ST group. Pain, anxiety level, and menstrual complaints were assessed before and after the applications.
RESULTS
The decreases in pain, anxiety levels, and some menstrual complaints after the application were higher in the KT group than those in the other two groups (p < 0.05).
CONCLUSION
KT application seems to be an effective method in decreasing pain, anxiety level, and some menstrual complaints in women with PD. | 10.1016/j.ctcp.2020.101148 |
pubmed_83_18859 | Apatite-based minerals have attracted much attention in the remediation of heavy metal-contaminated environment. However, exploring apatite with efficient adsorption performance for inorganic oxyanions such as Cr(VI) remains a challenge. Herein, a novel nanocrystalline chlorapatite (ClAP) was promptly prepared by a green method using eggshell wastes as calcium source with the purpose to enhance Cr(VI) adsorption capability. The generated ClAP was characterized by XRD, SEM-EPMA, TEM, FTIR, and BET analyses. Batch and column experiments were subsequently carried out to explore the influencing factors, adsorption capacity and removal mechanism. Results showed that ClAP exhibited excellent stability and adsorption performance for Cr(VI) (63.47 mg g-1), which was much greater than that of hydroxyapatite and most reported materials. The adsorption process was fitted well by the pseudo-second-order model and the Langmuir model. In fixed bed column experiments, a novel time-fractional derivative model exhibited much better suitability in interpreting the observed breakthrough curves of Cr(VI) than traditional models. Furthermore, the reusability of ClAP in column was evaluated. Results showed that the adsorption capacity maintained well after consecutively reused for five cycles. Studies of the effect of pH, as well as FTIR and XPS investigations indicated that Cr(VI) adsorption was mainly ascribed to electrostatic interactions and surface complexation, while the reduction of Cr(VI) to the low-toxicity Cr(III) also existed in the adsorption process. The ClAP adsorbent was also successfully used for Cr(VI) remediation from real wastewater. Hence, nanocrystalline ClAP can be a promising material for enhancing the elimination of oxyanion contaminants such as Cr(VI) from water. | 10.1016/j.chemosphere.2020.128421 |
pubmed_373_11101 | Prostaglandin H synthase (PGHS) catalyzes a key step in the biosynthesis of a variety of bioactive lipid mediators. The two known isoforms (PGHS-1 and -2) share about 60% amino acid identity, but exhibit distinct interactions with substrates, activators, and inhibitors. Ovine PGHS-1 has previously been shown to have a distinctive protease-sensitive site near Arg277; cleavage by trypsin, chymotrypsin, or proteinase K produces fragments of 33 and 38 kDa and loss of activity. The ovine PGHS-1 crystal structure shows Arg277 located in an exposed loop structure; homology modeling predicts similar loop structures for both human isoforms (hPGHS-1 and -2). We have used limited proteolytic digestion of recombinant hPGHS-1 and hPGHS-2 to probe their structures. Incubation of hPGHS-1 with either trypsin or proteinase K produced 33- and 38-kDa fragments and loss of activity. In contrast, incubation of hPGHS-2 with the same proteases led to cleavage of only a 2- to 3-kDa fragment, with no decrease in activity. Immunoblotting with site-specific antibodies demonstrated that the cleaved fragment originated from the hPGHS-2 C-terminus. Similar immunoblotting experiments indicated that trypsin did not attack the ovine PGHS-1 C-terminus. Mutagenesis was used to replace Pro263 of hPGHS-2 (corresponds to Arg277 of ovine PGHS-1) with arginine, inserting a potential trypsin site. Incubation of this P263R hPGHS-2 mutant with either trypsin or proteinase K resulted in cleavage near the C-terminus and retention of activity, just as with wild-type hPGHS-2. A peptide containing residues 259-268 of the P263R mutant was cleaved by trypsin at the same rate as a peptide corresponding to hPGHS-1 residues 272-281, demonstrating that the sequence differences were not responsible for the lack of tryptic cleavage at residue 263 in the hPGHS-2 mutant. Preincubation of hPGHS-2 with graded levels of guanidinium HCl before incubation with proteinase K did not produce large proteolytic fragments, indicating that the hPGHS-2 loop region was not selectively unfolding. The results point to two regions of significant structural difference between PGHS-1 and -2: the Arg277 loop, which is protease-sensitive in PGHS-1 but protease-resistant in PGHS-2, and the C-terminus, which is protease-sensitive in PGHS-2 but not in PGHS-1. | 10.1006/abbi.1997.0192 |
pubmed_641_9726 | Dynamic visual identification was investigated in 4 experiments. In Experiments 1 and 2, 2 perceptual objects (2 frames, each containing a letter or 1 containing a letter and the other a plus sign) were previewed in the periphery. A saccade brought these objects to central vision. During the saccade the display was changed so that 1 frame contained a letter and the other a plus sign, and the subject identified the letter by naming it aloud as rapidly as possible. In Experiment 3, the retinal events of Experiments 1 and 2 were simulated. In Experiment 4, both the preview and the target were presented centrally within a single fixation. In all experiments both object-specific and nonspecific preview benefits were observed. These results support a theory in which the preview benefits observed during visual identification arise from 2 processes, object file review and type priming. | 10.1037//0096-1523.20.4.826 |
pubmed_426_134 | The formation of mutagens in fried, minced meat emulsion was evaluated by the Ames Salmonella test system. Exogenous addition of creatine to the emulsion prior to frying greatly enhanced the mutagenicity of the emulsion. Addition of 5% creatine resulted in a 40-fold increase in the mutagenicity of the fried meat emulsion in the frameshift test strain, TA98, and in a 8-fold increase in the base substitution test strain, TA100. The present results suggest that creatine is an important factor in the mutagen formation in fried meat products. | 10.1016/0165-7992(86)90113-2 |
pubmed_329_18513 | Platform technologies for the changing need of diagnostics are one of the main challenges in medical device technology. From one point-of-view the demand for new and more versatile diagnostic is increasing due to a deeper knowledge of biomarkers and their combination with diseases. From another point-of-view a decentralization of diagnostics will occur since decisions can be made faster resulting in higher success of therapy. Hence, new types of technologies have to be established which enables a multiparameter analysis at the point-of-care. Within this review-like article a system called Fraunhofer ivD-platform is introduced. It consists of a credit-card sized cartridge with integrated reagents, sensors and pumps and a read-out/processing unit. Within the cartridge the assay runs fully automated within 15-20 minutes. Due to the open design of the platform different analyses such as antibody, serological or DNA-assays can be performed. Specific examples of these three different assay types are given to show the broad applicability of the system. | pubmed_329_18513 |
pubmed_644_12764 | Drosophila FMR1 mutants are models of human fragile X syndrome. They show a loss of locomotor activity rhythm and severe degradation of eclosion timing. We analyzed the circadian behavior of FMR1 mutants (dfmr1B55) in two genetic backgrounds, yellow white (yw) and Canton S (CS). The arrhythmic phenotype of circadian locomotor activity in constant darkness (DD) did not significantly change in either genetic background. Surprisingly, eclosion timing was completely restored by backcrossing dfmr1B55 with yw or CS flies. Morphological analysis of the small ventrally located lateral neurons of FMR1 mutants revealed that the dorsal-projection area was significantly larger in arrhythmic than rhythmic flies. In addition, dfmr1B55 mutants in both genetic backgrounds had a significantly lower evening peak in the light-dark (LD) cycle. These results indicate that lack of FMR1 does not affect eclosion timing, but alters locomotor activity patterns in both LD and DD conditions by affecting the arborization of small ventrally located lateral neurons. Thus, the FMR1 gene may regulate the circadian-related locomotor activity of Drosophila. | 10.2108/zsj.25.561 |
pubmed_155_284 | Intrathecal IgG synthesis has been investigated by determining the IgG index and by isoelectric focusing in 30 cases of definite multiple sclerosis, in 15 cases of probable multiple sclerosis and in 128 patients affected by other neurological diseases. The blood-brain barrier function was evaluated at the same time by serum albumin/CSF albumin quotient and isoelectric focusing. The IgG index was found elevated in 73.3% of definite multiple sclerosis patients, while oligoclonal IgG bands occurred in 90%. In the other neurological diseases the IgG index was abnormally increased in 35.1% but IgG bands were present only in cerebrospinal fluid (CSF) in 1.5% and both in the CSF and serum in 7% of patients. The high capacity of isoelectric focusing to detect IgG oligoclonal bands in the CSF is pointed out as an extremely useful diagnostic tool in multiple sclerosis. | 10.1007/BF00314641 |
pubmed_1112_16887 | Taking the high-yielding summer maize cultivars Denghai 661 (DH661) and Zhengdan 958 (ZD958) as test materials, a field experiment was conducted to study their grain yield, nitrogen use efficiency, key enzymes activities of nitrogen metabolism, and antioxidant enzymes activities under effects of different nitrogen application periods. One-dose nitrogen application at jointing stage was not beneficial to the increase of grain yield and the nitrogen accumulation in plant and grain, while split application in combination with application after anthesis increased the nitrogen accumulation in plant and grain significantly and increased the grain yield. When the nitrogen was applied at a ratio of 2:4:4 at jointing stage, 10-leaf stage, and 10 days after anthesis, the grain yield of DH661 was up to 14123.0 kg x hm(-2); when the nitrogen was applied at a ratio of 1:2:5:2 as the basal and at jointing stage, 10-leaf stage, and 10 days after anthesis, the grain yield of ZD958 was up to 14517.1 kg x hm(-2). These two nitrogen application modes increased the grain yield of DH661 and ZD958 by 14.5% and 17.5%, respectively, as compared with one-dose nitrogen application at jointing stage. Split nitrogen application before anthesis increased plant nitrate reductase activity significantly. In the 0-42 days after anthesis under split nitrogen application, the glutamine synthetase, glutamate synthase, and glutamate dehydrogenase activities of DH661 and ZD958 were averagely increased by 32.6%, 47.1% and 50.4%, and 14.5%, 61.8% and 25.6%, and the superoxide dismutase and catalase activities were increased by 22. 0% and 36.6%, and 13.4% and 62.0%, respectively, and the malondialdehyde content was decreased significantly, as compared with one-off nitrogen application. It was suggested that for the high-yielding of summer maize, split application of nitrogen and appropriately increasing the nitrogen application ratio after anthesis could enhance the plant key nitrogen metabolism enzymes activities, delay leaf senescence, promote plant nitrogen uptake and its utilization, and increase grain yield. | pubmed_1112_16887 |
pubmed_95_16756 | MK801 (MK), an N-methyl-D-aspartate (NMDA) receptor antagonist, attenuates tolerance to spinal opioids. Whether this applies to other G-protein-coupled receptor systems is unknown. This study examines the effects of continuous spinal MK on tolerance to the antinociceptive effect of continuous spinal infusion of the alpha-2 agonist ST91 (ST). Intrathecal (i.t.) infusion pumps were implanted in rats which delivered for 7 days: saline (1 microl/h); ST (40 nmol/microl/h); MK (10 nmol/microl/h) + ST (40 nmol/microl/h); or MK (10 nmol/microl/h). Antinociception was measured daily on the hot plate. On day 8, groups received i.t. boluses of ST to generate dose-response curves. A separate ST-infused group received MK (10 nmol i.t.) on day 7. Each group received ST (40 nmol i.t.) 7 days after discontinuation of infusion. Co-infusion of MK with ST resulted in attenuation of the right shift in dose response seen in ST-infused rats and a small preservation of effect on daily testing. However, MK-infused rats showed a significant left shift in ST dose response. Acutely administered, MK did not restore ST sensitivity. One week after cessation of infusion, ST and ST + MK groups showed shorter duration of effect after i.t. ST bolus than controls. In conclusion, chronic spinal MK partially attenuates loss of sensitivity to chronic spinal ST. This supports the hypothesis that opioid- and adrenoceptor-induced tolerances are similarly modulated by the NMDA receptor. However, the increased sensitivity induced by MK alone suggests that NMDA receptor antagonism may not prevent the development of tolerance itself but may alter the expression of tolerance by inducing sensitivity via other alterations in cellular function. | pubmed_95_16756 |
pubmed_574_14095 | The nucleotide sequence of the 3' end of the second internal transcribed spacer region (ITS2) was determined for four isolates of Fasciola hepatica, two isolates of Fasciola gigantica, one isolate of Fascioloides magna and one isolate of Fasciola sp. from Japan. Intraspecific sequence divergence was negligible. Sequence divergence between F. hepatica and F. gigantica was 2.8% and between Fasciola hepatica and Fascioloides magna was 13.2%. The sequence of Fasciola sp. from Japan matched closely that of F. gigantica. This study demonstrates variability in nucleotide sequence within the ITS2 region which allows discrimination between species of Fasciolidae. | 10.1016/0020-7519(93)90022-q |
pubmed_378_7756 | In longitudinal studies, measurements of the same individuals are taken repeatedly through time. Often, the primary goal is to characterize the change in response over time and the factors that influence change. Factors can affect not only the location but also more generally the shape of the distribution of the response over time. To make inference about the shape of a population distribution, the widely popular mixed-effects regression, for example, would be inadequate, if the distribution is not approximately Gaussian. We propose a novel linear model for quantile regression (QR) that includes random effects in order to account for the dependence between serial observations on the same subject. The notion of QR is synonymous with robust analysis of the conditional distribution of the response variable. We present a likelihood-based approach to the estimation of the regression quantiles that uses the asymmetric Laplace density. In a simulation study, the proposed method had an advantage in terms of mean squared error of the QR estimator, when compared with the approach that considers penalized fixed effects. Following our strategy, a nearly optimal degree of shrinkage of the individual effects is automatically selected by the data and their likelihood. Also, our model appears to be a robust alternative to the mean regression with random effects when the location parameter of the conditional distribution of the response is of interest. We apply our model to a real data set which consists of self-reported amount of labor pain measurements taken on women repeatedly over time, whose distribution is characterized by skewness, and the significance of the parameters is evaluated by the likelihood ratio statistic. | 10.1093/biostatistics/kxj039 |
pubmed_632_735 | Mycobacterium abscessus, a rapidly growing nontuberculous mycobacterium, are increasingly present in soft tissue infections and chronic lung diseases, including cystic fibrosis, and infections are characterized by growth in neutrophil-rich environments. M. abscessus is observed as two distinct smooth and rough morphotypes. The environmental smooth morphotype initiates infection and has a relatively limited ability to activate neutrophils. The rough morphotype has increased virulence and immunogenicity. However, the neutrophil response to the rough morphotype has not been explored. Killing of the smooth and rough strains, including cystic fibrosis clinical isolates, was equivalent. Neutrophil uptake of M. abscessus was similar between morphotypes. Mechanistically, both rough and smooth morphotypes enhanced neutrophil reactive oxygen species generation but inhibition of NADPH oxidase activity did not affect M. abscessus viability. However, inhibition of phagocytosis and extracellular traps reduced killing of the smooth morphotype with lesser effects against the rough morphotype. Neutrophils treated with M. abscessus released a heat-labile mycobactericidal activity against the rough morphotype, but the activity was heat-tolerant against the smooth morphotype. Overall, M. abscessus stimulates ineffective neutrophil reactive oxygen species generation, and key mechanisms differ in killing of the smooth (phagocytosis-dependent, extracellular traps, and heat-tolerant secreted factor) and rough (extracellular traps and a heat-labile secreted factor) morphotypes. These studies represent an essential advancement in understanding the host response to M. abscessus, and help explain the recalcitrance of infection. | 10.1371/journal.pone.0196120 |
pubmed_64_27019 | OBJECTIVE
The aim: To obtain the first estimates of the current prevalence of healthcare-associated deep pelvic tissue infection and other infections of the female reproductive tract (vagina, ovaries, uterus) including chorioamnionitis, and antimicrobial resistance of causing pathogens in Ukraine.
PATIENTS AND METHODS
Materials and methods: We performed a retrospective multicenter cohort study was based on surveillance data. The study population included 3,053 women's who underwent gynecological surgery or other procedures from 2017 to 2019 in 7 women hospitals in Ukraine. Definitions of healthcare-associated reproductive tract infection were used from the CDC/ NHSN.
RESULTS
Results: The prevalence of healthcare-associated deep pelvic tissue infection and other infections of the female reproductive tract was 26.3%. Incidence of infection was: 13.3% Pelvic abscess or cellulitis, 14.6% Adnexa utery, 9.5% Salpingitis, 7.1% Oophoritis, 12.2% Parametritis, 4.6% Chorioamnionitis, and 38.8% Bacterial Vaginitis. The predominant pathogens were: Escherichia coli (25.6%), Enterobacter spp. (11.4%), Klebsiella pneumoniae (10.6%), Staphylococcus aureus (8.5%), Enterococcus faecalis (7.2%) and Pseudomonas aeruginosa (7.1%). Methicillin-resistance was observed in 14.3% of S. aureus (MRSA). The overall proportion of extended spectrum beta-lactamases (ESBL) production among Enterobacteriaceae was 20.8%. The prevalence of ESBL production among E. coli isolates was 24.7% and among K. pneumoniae 11.9%. Resistance to thirdgeneration cephalosporins was observed in 12.8% E.coli and 9.2% K. pneumoniae isolates. Carbapenem resistance was identified in 8.5% of P.aeruginosa isolates.
CONCLUSION
Conclusions: Healthcare associated deep pelvic tissue infection and other infections of the female reproductive tract in Ukraine is a common occurrence and many cases are caused by pathogens that are resistant to antibiotics. | pubmed_64_27019 |
pubmed_383_18856 | BACKGROUND
Comorbidity of tuberculosis (TB) and depression is common. It is associated with the decrease in function, increasing rate of medical cost, nonadherence to long-term medication and self-care, and upward trend of mortality. This study aims to determine the prevalence and distribution of depression in pulmonary TB patients by age, sex, and marital status.
METHODS
This study is a descriptive research conducted at the Pulmonary Clinic of the State Hospital of Makassar (RSUD Kota Makassar). Ninety-two of 820 patients were selected using the Slovin sample size formula. The patients of the study were collected from the population of patients with TB using consecutive sampling through an interview. The depression rate was examined using the Beck Depression Inventory-II (BDI-II) questionnaire. Interpretation of the BDI-II was determined by a score of ≤16 indicating no depression and >16 for depression.
RESULTS
The study indicates that the percentage of patients with depression constituted 31.5%. The number of female patients with depression was higher than that in males with 38.2% and 27.6%, respectively. The biggest proportion of patients with depression was in senior patients (>45 years old) with 37.5%. The fraction of unmarried/divorced respondents was bigger than coupled respondents, with a percentage of 43.5 and 27.5, respectively.
CONCLUSION
The prevalence of depression in pulmonary TB patients who visited the Pulmonary Clinic of the State Hospital of Makassar reached over one-third of the total patients. Depression was more prevalent among female patients, patients within the age of >45 years, and unmarried/divorced patients, respectively. | 10.4103/ijcm.IJCM_50_20 |
pubmed_784_20387 | Peptidylglycine alpha-amidating monooxygenase (PAM) is a bifunctional enzyme responsible for the alpha-amidation of peptides in secretory granules of neuroendocrine cells. The single gene encoding PAM undergoes tissue-specific alternative splicing and endoproteolytic processing to generate bifunctional membrane proteins with a single transmembrane domain as well as soluble proteins that are mono- or bifunctional. In order to examine the endoproteolytic processing and subcellular localization of the various forms of PAM in cells lacking regulated secretory granules, we established stably transfected hEK-293 cell lines expressing naturally occurring and mutant forms of PAM. As expected, newly synthesized soluble PAM proteins were rapidly secreted into the medium. Integral membrane protein forms of PAM were largely localized in the perinuclear region with punctate staining visible throughout the cell and 2-5% of the enzyme activity detectable on the cell surface. Bifunctional PAM proteins were slowly released into the medium after expression of integral membrane protein forms of PAM. Deletion of 77 amino acids from the COOH-terminus of the integral membrane forms of PAM resulted in a membrane-bound protein which retained both enzymatic activities but accumulated on the cell surface. Rapid internalization of full-length PAM proteins was observed by incubating live cells with antiserum to PAM; deletion of the COOH-terminal domain eliminated the ability of cells to internalize PAM. Thus the cytoplasmic domain of integral membrane PAM contains a routing determinant recognized by cells lacking the regulated secretory pathway. | 10.1210/mend.6.12.1491698 |
pubmed_1122_12913 | Staphylococcus aureus is a frequent cause of orthopedic infections in humans. The bacterium expresses several adhesins that facilitate bacterial binding to the bone matrix and to bone implant biomaterials coated with host plasma constituents. The relevant S. aureus adhesins are termed microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) and specific MSCRAMMs are involved in bone and joint infections. | 10.1111/j.1574-6968.1999.tb13514.x |
pubmed_786_13234 | We developed an antisense peptide nucleic acid (PNA) targeted against a unique sequence in the terminus of the 5'-UTR of N-myc, designed for selective inhibition of NMYC in neuroblastoma cells. Fluorescent microscopy showed carrier-free delivery of the PNA to two human neuro-blastoma cell lines: GI-LI-N (N-myc-amplified) and GI-CA-N (N-myc-unamplified). Only in the former, PNA treatment determined 70% cell-viability reduction (at 48 h). In N-myc-amplified GI-LI-N cells, the PNA determined NMYC-translation inhibition (Western blotting), accumulation of cells in G1, induction of differentiation and apoptosis. Selectivity of the PNA was demonstrated by altering three point mutations. These findings should encourage development of a PNA-based tumor-specific agent for neuroblastoma (or other neoplasms) with N-myc overexpression. | pubmed_786_13234 |
pubmed_101_9238 | Neural networks involved in placebo analgesia and nocebo hyperalgesia processes have been widely investigated with neuroimaging methods. However, few studies have directly compared these two processes and it remains unclear whether common or distinct neural circuits are involved. To address this issue, we implemented a coordinate-based meta-analysis and compared neural representations of placebo analgesia (30 studies; 205 foci; 677 subjects) and nocebo hyperalgesia (22 studies; 301 foci; 401 subjects). Contrast analyses confirmed placebo-specific concordance in the right ventral striatum, and nocebo-specific concordance in the dorsal anterior cingulate cortex (dACC), left posterior insula and left parietal operculum during combined pain anticipation and administration stages. Importantly, no overlapping regions were found for these two processes in conjunction analyses, even when the threshold was low. Meta-analytic connectivity modeling (MACM) and resting-state functional connectivity (RSFC) analyses on key regions further confirmed the distinct brain networks underlying placebo analgesia and nocebo hyperalgesia. Together, these findings indicate that the placebo analgesia and nocebo hyperalgesia processes involve distinct neural circuits, which supports the view that the two phenomena may operate via different neuropsychological processes. | 10.1016/j.neuroimage.2021.117833 |
pubmed_626_7933 | In aerobic anoxygenic phototrophs, oxygen is required for both the formation of the photosynthetic apparatus and an efficient cyclic electron transfer. Mutants of Bradyrhizobium sp. ORS278 affected in photosystem synthesis were selected by a bacteriochlorophyll fluorescence-based screening. Out of the 9,600 mutants of a random Tn5 insertion library, 50 clones, corresponding to insertions in 28 different genes, present a difference in fluorescence intensity compared to the WT. Besides enzymes and regulators known to be involved in photosystem synthesis, 14 novel components of the photosynthesis control are identified. Among them, two genes, hsIU and hsIV, encode components of a protein degradation complex, probably linked to the renewal of photosystem, an important issue in Bradyrhizobia which have to deal with harmful reactive oxygen species. The presence of homologs in non-photosynthetic bacteria for most of the regulatory genes identified during study suggests that they could be global regulators, as the RegA-RegB system. | 10.1007/s11120-009-9433-3 |
pubmed_150_3989 | PURPOSE OF REVIEW
There is increasing recognition that a minority of bereaved persons experiences persistent and disabling grief symptoms, also termed complicated grief. We review currently proposed criteria for complicated grief in the Diagnostic and Statistical Manual of Mental Disorders (DSM 5) and the International Statistical Classification of Diseases and Related Health Problems (ICD-11), highlight controversies with regard to establishing complicated grief as a psychiatric disorder, summarize recent complicated grief treatment research within a cognitive behavioral treatment framework, and establish a novel and systematic research agenda for complicated grief treatment.
RECENT FINDINGS
Clinicians should be wary of overdiagnosis and misdiagnosis of complicated grief. Recent changes to definitions of complicated grief may threaten generalizability and clinical application of research findings. Universal treatment, treatment for at-risk groups and preventive complicated grief treatment appear ineffective. Although medication is often prescribed to bereaved persons, evidence for its effectiveness is equivocal. Face-to-face and internet-based cognitive behavioral therapy techniques appear most effective in targeting complicated grief. However, little is known about what, how, and for whom treatment works best.
SUMMARY
In light of these findings, we recommend systematic investigation of: what works best in complicated grief treatment, by conducting well designed, stepped effectiveness trials and treatment component dismantling studies; how it works, by conducting investigations on therapeutic theories and examining mediators of therapeutic change; and for whom it works, by examining potential moderators of treatment effects. | 10.1097/YCO.0000000000000263 |
pubmed_760_25087 | Conflicts over land use and ownership are common in South America and generate frequent confrontations among indigenous peoples, small-scale farmers, and large-scale agricultural producers. We argue in this paper that an accurate identification of these conflicts, together with a participatory evaluation of their importance, will increase the social legitimacy of land use planning processes, rendering decision-making more sustainable in the long term. We describe here a participatory, multi-criteria conflict assessment model developed to identify, locate, and categorize land tenure and use conflicts. The model was applied to the case of the "Chaco" region of the province of Salta, in northwestern Argentina. Basic geographic, cadastral, and social information needed to apply the model was made spatially explicit on a Geographic Information System. Results illustrate the contrasting perceptions of different stakeholders (government officials, social and environmental non-governmental organizations, large-scale agricultural producers, and scholars) on the intensity of land use conflicts in the study area. These results can help better understand and address land tenure conflicts in areas with different cultures and conflicting social and enviornmental interests. | 10.1007/s00267-016-0779-y |
pubmed_730_8008 | Ultrasound has been used in the identification of two different morphological patterns of polycystic ovaries, namely a peripheral cystic pattern and a general cystic pattern. The aim of this study was to evaluate whether patients with the peripheral form of polycystic ovaries showed different ovarian and uterine blood flow from those with the general form, and to investigate whether there was a correlation between the forms and different hormonal parameters. Eighteen patients with the general form and 16 patients with the peripheral form of polycystic ovary underwent clinical, biochemical, gray-scale and color Doppler ultrasonographic evaluation. The parameters analyzed confirmed polycystic ovarian syndrome (PCOS) in all patients. Individual levels of plasma luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, androstenedione and estradiol did not differ between the groups. However, there was a significantly higher LH/FSH ratio and a greater stromal echodensity in the peripheral cystic group than in the general cystic group. Doppler ultrasonography demonstrated significantly lower pulsatility index values in the intraovarian arteries of the peripheral cystic group and a higher rate of visualization of these arteries than in the general cystic group. These findings suggest that, apart from the LH/FSH ratio, the different morphological types of polycystic ovary do not reflect differences in endocrine profile. The differences in blood flow demonstrated by Doppler assessment in each case, however, showed that PCOS does not predetermine a single intraovarian blood flow pattern. | 10.1046/j.1469-0705.1998.11050332.x |
pubmed_922_5273 | BACKGROUND
Performance Validity Testing (PVT) decision-making rules may be indeterminate in patients with neurological disease in which PVT characteristics have not been adequately studied. We report a patient with multiple sclerosis (MS) who failed computerized PVT testing but had normal memory scores with a neuropsychological profile consistent with expected MS disease-related weaknesses.
METHOD
Neuropsychological testing was conducted on two occasions in a middle-aged woman with an established MS diagnosis to address concerns of possible memory decline. Testing was discontinued after PVT scores below recommended cut-points were obtained during the first evaluation. During the second assessment, subthreshold PVT scores on a different computerized PVT were obtained, but unlike the first assessment, the entire neuropsychological protocol was administered.
RESULTS
Despite subthreshold computerized PVT scores, normal learning and memory performance was obtained providing objective data to answer the referral question. Other neuropsychological findings included decreased processing speed, poor working memory, and poor executive function consistent with her MS diagnosis. Embedded PVT scores were normal.
CONCLUSIONS
We speculate that poor computerized PVT scores resulted from the disease-related features of MS, although we also discuss approaches to reconcile apparently contradictory PVT versus neuropsychological results if the contributions of disease-related variables on PVTs scores are discounted. This case demonstrates the value of completing the assessment protocol despite obtaining PVT scores below publisher recommended cutoffs in clinical evaluations. If subthreshold PVT scores are considered evidence of performance invalidity, it is still necessary to have an approach for interpreting seemingly credible neuropsychological test results rather than simply dismissing them as invalid. | 10.1093/arclin/acz028 |
pubmed_1135_8525 | OBJECTIVE
to analyze the production of knowledge resulting from the professional master's degree programs in Nursing and to reflect about their perspectives for the area.
METHOD
descriptive and analytical study. Data collected from the dissertations of three educational institutions that graduated students in programs of professional master's degree in Nursing between 2006 and 2012 were included.
RESULTS
most of the 127 course completion studies analyzed were developed within hospital contexts; there was a focus on the organizational and healthcare areas, in the research fields care process and management, and predominance of qualitative studies. There are various products resulting from the course completion studies: evaluation of services/healthcare programs and development of processes, care or educational protocols.
CONCLUSION
the programs of professional master's degree in Nursing, which are undergoing a consolidation stage, have recent production under development and there is a gap in the creation of hard technologies and innovation. They are essential for the development of innovative professional practices that articulate the healthcare and educational areas. | pubmed_1135_8525 |
pubmed_129_8189 | The purpose of this study was to comparatively study and elucidate the characteristics of masticatory function of the subjects with complete denture and those with normal natural dentition. The study were carried out on 20 subjects with normal natural dentition and 30 subjects with complete denture having clinically good prognosis. Masticatory movements were analyzed by electromyograph (EMG) and sirognathograph (SGG) when the subjects were chewing peanuts and kamaboko (boiled fish paste). The results were as follows: 1. The duration of chewing cycle, closing phase, occluding phase, and EMGs burst duration (especially after tooth contact) were significantly longer in the subjects with complete denture. 2. The maximum opening distance was significantly shorter, the maximum opening and closing velocity were significantly slower, in the subjects with complete denture. Further, the standard deviation of the coordinates of the sample points in the occluding phase was indisordered in the subjects with complete denture, and standard deviation of the coordinates of sample points in occluding phase were varied in complete denture wearers. 3. The frontal masticatory pattern tended to unstable and typical tear drop shape pattern was found in about 60% of the subjects with complete denture. 4. Different reactions to the test foods were observed in the subjects with normal natural dentition, while such was not noted in the cases of the subjects with normal natural dentition. These results was suggest that the masticatory function in the subjects with complete denture were obviously differ from those of normal natural dentition due to the difference in the sensory-motor-system. | 10.2186/jjps.34.318 |
pubmed_130_25514 | The Seven Countries Study showed that traditional Japanese and Mediterranean diets are protective against cardiovascular diseases (CVDs). The Japanese diet is considered the healthiest because it provides Japanese populations with the highest longevity and health. DASH and Mediterranean-style diets are also considered healthy diets, although the Indo-Mediterranean-style diet may provide better protective effects among patients with CVDs compared to other diets. The concept of the Indo-Mediterranean type of diet was developed after examining its role in the prevention of CVDs in India, the value of which was confirmed by a landmark study from France: the Lyon Heart Study. These workers found that consuming an alpha-linolenic acid-rich Mediterranean-style diet can cause a significant decline in CVDs and all-cause mortality. Later in 2018, the PREDIMED study from Spain also reported that a modified Mediterranean-style diet can cause a significant decline in CVDs, type 2 diabetes mellitus (T2DM), and cancer. The Indo-Mediterranean diet may be superior to DASH and Mediterranean diets because it contains millets, porridge, and beans, as well as spices such as turmeric, cumin, fenugreek, and coriander, which may have better anti-inflammatory and cardioprotective effects. These foods are rich sources of nutrients, flavonoids, calcium, and iron, as well as proteins, which are useful in the prevention of under- and overnutrition and related diseases. It is known that DASH and Mediterranean-style diets have a similar influence on CVDs. However, the Indo-Mediterranean-style diet may be as good as the Japanese diet due to improved food diversity and the high content of antioxidants. | 10.3390/nu14040898 |
pubmed_321_8936 | Immunohistochemistry (IHC) for O6-methylguanine-DNA-methyltransferase (MGMT) has shown heterogeneous results. Cell staining intensity has not been included as a quantifiable variable in IHC analyses. We performed MGMT IHC in 29 patients diagnosed as glioblastoma classifying cells into three categories based on nuclear staining intensity compared with adjacent endothelium. The median proportions of strong-moderate, weak and no staining cells were 10%, 16% and 71%, respectively. The proportion of positive cases for MGMT expression varies from 38% to 52% depending on the classification of weakly stained cells. This letter challenges previous studies that have not included intensity as a variable for IHC analysis. | 10.1016/j.pjnns.2017.10.014 |
pubmed_639_9879 | PURPOSE
The purpose of this short review is to give a personal appreciation of a woman who was my mentor and friend and who made enormous contributions in the field of translational radiation biology.
CONCLUSION
Julie Denekamp was a talented and charismatic scientist and teacher. She was a major contributor to our understanding of the effects of fractionation schedules on the response of tumors and normal tissues to radiotherapy and of factors that could be manipulated to alter these responses. She was also one of the first to recognize that the fragile state of tumor vasculature could be exploited in targeted radiotherapy. | 10.1080/09553002.2021.1913530 |
pubmed_262_17535 | PURPOSE OF REVIEW
To summarize recent papers in the literature with respect to minimally invasive thyroidectomy and discuss indications and limits of the endoscopic/video-assisted treatment of differentiated thyroid carcinoma.
RECENT FINDINGS
During the 1990s, with the general tendency to develop minimally invasive operations, an endoscopic approach was applied to neck surgery for both parathyroidectomy and thyroidectomy. The most wide spread minimally invasive technique for thyroidectomy is minimally invasive video-assisted thyroidectomy (MIVAT).
SUMMARY
Papillary carcinoma is the main indication for MIVAT, this cancer usually being found in normal glands of young women. In contrast, for locally invasive carcinomas, lymph node metastasis or both, the procedure must be immediately converted to the conventional technique. MIVAT also is not indicated for the treatment of medullary and anaplastic carcinomas. Recent prospective randomized studies clearly demonstrate that MIVAT allows the same clearance to be achieved at the thyroid bed level and the same outcome as with the conventional technique, when dealing with 'low-risk' papillary carcinoma. At the same time, patients can benefit from the main advantages of this minimally invasive technique: less postoperative pain, faster postoperative recovery and excellent cosmetic outcome. | 10.1097/MOO.0b013e3283378239 |
pubmed_459_5502 | Thoracic sarcoidosis is a common disease, and its usual radiographic manifestations have been well described and are readily recognized. However, most physicians are not familiar with the unusual and often confusing manifestations of thoracic sarcoid, which have been sporadically reported. Using information derived from a systematic review of the literature and clinical material from our own institutions, a classification has been developed of the unusual thoracic manifestations of sarcoidosis, and their relative incidence has been determined and tabulated. These include lesions of the osseous, pleural, mediastinal, hilar, bronchial, pulmonary parenchymal, vascular, and cardiac structures. The information presented in this review is intended to provide physicians with a single comprehensive source to assist them when atypical radiographic findings of thoracic sarcoidosis are a diagnostic consideration. | 10.2214/ajr.144.3.513 |
pubmed_11_17424 | Over half a century of converging clinical and animal research indicates that early life experiences induce enduring neuroplasticity of the HPA-axis and the developing brain. This experience-induced neuroplasticity is due to alterations in the frequency and intensity of stimulation of pups' sensory systems (i.e., olfactory, somatosensory, gustatory) embedded in mother-infant interactions. This stimulation provides "hidden regulators" of pups' behavioral, physiological, and neural responses that have both immediate and enduring consequences, including those involving the stress response. While variation in stimulation can produce individual differences and adaptive behaviors, pathological early life experiences can induce maladaptive behaviors, initiate a pathway to pathology, and increase risk for later-life psychopathologies, such as mood and affective disorders, suggesting that infant-attachment relationships program later-life neurobehavioral function. Recent evidence suggests that the effects of maternal presence or absence during this sensory stimulation provide a major modulatory role in neural and endocrine system responses, which have minimal impact on pups' immediate neurobehavior but a robust impact on neurobehavioral development. This concept is reviewed here using two complementary rodent models of infant trauma within attachment: infant paired-odor-shock conditioning (mimicking maternal odor attachment learning) and rearing with an abusive mother that converge in producing a similar behavioral phenotype in later-life including depressive-like behavior as well as disrupted HPA-axis and amygdala function. The importance of maternal social presence on pups' immediate and enduring brain and behavior suggests unique processing of sensory stimuli in early life that could provide insight into the development of novel strategies for prevention and therapeutic interventions for trauma experienced with the abusive caregiver. | 10.3389/fendo.2014.00033 |
pubmed_389_19305 | The calcitonin-gene-related-peptide (CGRP) release is coupled to the signaling of Angeli's salt in determining vasodilator effects. However, it is unknown whether CGRP is involved in Angeli's salt cardioprotective effects and which are the mechanisms of protection. We aimed to determine whether CGRP is involved in myocardial protection induced by Angeli's salt. We also analyzed the intracellular signaling pathway activated by CGRP. Isolated rat hearts were pre-treated with Angeli's salt or Angeli's salt plus CGRP8-37, a specific CGRP-receptor antagonist, and subjected to ischemia (30-min) and reperfusion (120-min). Moreover, we studied CGRP-induced protection during oxidative stress (H2O2) and hypoxia/reoxygenation protocols in H9c2 cardiomyocytes. Cell vitality and mitochondrial membrane potential (ΔYm, MMP) were measured using MTT and JC-1 dyes. Angeli's salt reduced infarct size and ameliorated post-ischemic cardiac function via a CGRP-receptor-dependent mechanism. Pre-treatment with CGRP increased H9c2 survival upon challenging with either H2O2 (redox stress) or hypoxia/reoxygenation (H/R stress). Under these stress conditions, reduction in MMP and cell death were partly prevented by CGRP. These CGRP beneficial effects were blocked by CGRP8-37. During H/R stress, pre-treatment with either CGRP-receptor, protein kinase C (PKC) or mitochondrial KATP channel antagonists, and pre-treatment with an antioxidant (2-mercaptopropionylglycine) blocked the protection mediated by CGRP. In conclusion, CGRP is involved in the cardioprotective effects of Angeli's salt. In H9c2 cardiomyocytes, CGRP elicits PKC-dependent and mitochondrial-KATP-redox-dependent mechanisms. Hence, CGRP is an important factor in the redox-sensible cardioprotective effects of Angeli's salt. | 10.1016/j.biopha.2017.03.043 |
pubmed_390_5493 | The alterations of local glucose utilization in 101 cerebral nuclei following the subcutaneous administration of the specific opioid antagonist naloxone were measured using the quantitative autoradiographic 14C-deoxy-D-glucose technique in conscious rats. Met5-enkephalin-like immunoreactivity (MELI) and ME receptor binding (MERB) levels in 82 cerebral nuclei were assayed quantitatively by microdensitometry of fluorescence micrographs and autoradiographs of the brain slices. Naloxone administration significantly reduced glucose utilization rate in 18 lower brainstem nuclei including the n. tractus solitarii, n. dorsalis nervi vagi, substantia grisea centralis, n. parabrachialis dorsalis and ventralis, and n. interpeduncularis. These nuclei contained ME perikarya with high levels of MELI and MERB. However, naloxone did not alter glucose utilization of other lower brainstem nuclei containing ME neurons and all thalamic, epithalamic, hypothalamic and limbic nuclei with ME perikarya. The distribution and magnitude of the neuronal response of cerebral nuclei to naloxone were apparently not related to the distributions of ME neurons. The present study offers direct evidence for the selective action of naloxone per se in some lower brainstem nuclei with ME perikarya. | 10.1254/jjp.36.339 |
pubmed_261_5471 | OBJECTIVES
Flapless implant surgery is fast gaining popularity because of several advantages, such as reduced surgical time, postoperative bleeding, and swelling. Studies have shown that flap elevation results in some amount of bone loss. The aim of the current study was to compare the amount of bone loss in procedures using the flapless technique and those where flap elevation was done. Papillary fill was also compared in both techniques, which is unique to this study.
STUDY DESIGN
Forty patients, selected according to certain inclusion and exclusion criteria, were randomly assigned to 1 of 2 groups: Flap (F), or Flapless (FL). The amount of crestal bone loss was measured from standardized radiographs at baseline, 6 months, 1 year, and 2 years after implant placement. Papillary fill was evaluated using the Papillary presence index, which was measured 6 months after loading.
RESULTS
The bone loss was greater for the F group during all time periods and the mean papillary fill was greater for the FL group.
CONCLUSIONS
In conclusion, the results of the current study show that flapless implant surgery results in less crestal bone loss both during the healing period and after loading. In addition, it can produce better papillary fill. The cases selected for this study were ideal cases in terms of bone volume and the operator was well experienced, however. Care should be taken during case selection for flapless implant surgery. | pubmed_261_5471 |
pubmed_756_16954 | Cancer control programs are needed worldwide to combat the increases in cancer incidence and mortality predicted for sub-Saharan Africa in the next decades. The effective design, implementation, and evaluation of such programs require population-based cancer registries. Ghana's second largest medical center, the Komfo Anokye Teaching Hospital (KATH) in Kumasi, has made initial progress at developing a cancer registry. This registry, however, is housed in the medical oncology/radiotherapy center at KATH and does not currently include data from other departments that also interact with cancer patients. The aim of this study was to improve KATH cancer registration by compiling cancer data from other major departments that see cancer patients. Using recent population estimates, we calculated crude cancer incidence rates of the "minimally-reported cases" for the Ashanti region. The most common cancers found in this study were breast (12.6 per 100,000), cervix (9.2 per 100,000), and prostate (8.8 per 100,000). These cancers occur at similar crude incidence rates in other West African countries. Females had overall higher incidence rates than males, which is consistent throughout the West African region. This study identified a number of methodological challenges facing cancer registries in Ghana that can be addressed to improve the quality of cancer registries in other resource-limited settings. Such registries should be tailored to the local health system context. A lack of coordination among the sources reporting cancer cases and a lack of understanding of local health-care systems and payment plans may interfere with the quality, completeness, and comparability of data from cancer registries in resource-limited settings. Steps, barriers, and solutions for improving cancer registration in Ghana and countries at similar levels are discussed. | pubmed_756_16954 |
pubmed_335_18156 | Bone tumors are relatively rare in the foot and ankle region. Many of them present as cystic lesions on plain films. Due to the relative rarity of these lesions and the complex anatomy of the foot and ankle region, identification of such lesions is often delayed or they get misdiagnosed and mismanaged. This review discusses the most common cystic tumors of the foot and ankle including their radiographic features and principles of management. | 10.1002/jso.25088 |
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