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pubmed_259_17619
OBJECTIVE To investigate the usefulness of the 3-hydroxylation of quinine as a biomarker reaction for the activity of CYP3A4 in man and to study the interindividual variation in the metabolic ratio (MR), i.e. quinine/3-hydroxyquinine. METHODS Data from a previous study (A) was used for determination of the MR of quinine in plasma and urine at different time points. In study B, 24 healthy Swedish subjects received 250 mg quinine hydrochloride first alone and later together with four other CYP probe drugs [losartan (CYP2C9), omeprazole (CYP2C19), debrisoquine (CYP2D6) and caffeine (CYP1A2)] administered on the same day. Plasma and urine samples were collected before quinine intake and 16 h thereafter and analysed for quinine and 3-hydroxyquinine using high-performance liquid chromatography. Plasma and/or urine were collected for the other probes at different time points. MRs of all the probes were determined and correlations to quinine MR were studied. RESULTS In study A, the MR in plasma was stable over 96 h. The ratio increased from 5.8 to 12.2 (P=0.006) during co-administration with ketoconazole, whereas no significant difference (P=0.76) was observed during co-administration with fluvoxamine (from 5.8 to 6.0). In study B, there was no significant difference (P=0.36) between the mean MRs when quinine was given alone (4.7) or together with the four other drugs (4.5). There was a significant correlation between the MR of quinine and omeprazole sulphone formation (r=0.52, P<0.01), but not to the MRs of the other probes. There was a fivefold interindividual variability in the MR. CONCLUSIONS The MR of quinine in plasma or urine may serve as a stable measure of the activity of CYP3A4 in man. These results together with in vitro data show that quinine is also a specific CYP3A4 probe.
10.1007/s00228-003-0575-5
pubmed_883_1057
OBJECTIVE Afterload is increased in hypertensive patients and increased afterload associated with both ventricular repolarization inhomogeneity and impaired elastic properties of aorta. Thus, we investigated whether QT dispersion (QTd), which is a reflection of ventricular repolarization inhomogeneity, is related to aortic elastic properties in patients with hypertension. METHODS Overall 113 patients with newly diagnosed hypertension and 25 normal control subjects were included in this cross-sectional case-controlled study. Aortic strain (AS) and aortic distensibility (AD) were calculated echocardiographically from the derived ascending aorta diameters. Electrocardiograms were recorded in all subjects, and QTd and corrected QTd (cQTd) were then calculated. RESULTS Patients as compared with control subjects had lower mean AS and AD (p<0.001, for both). The QT interval maximum and corrected QT interval maximum durations, QTd and cQTd were increased in patients compared with control subjects. Multiple linear regression analysis showed that corrected QTd was independently related to age, left ventricular mass index (LVMI), AS and AD (b=0.204, p=0.030, b=0.219, p=0.026, b=-0.238, p=0.021 and b=-0.208, p=0.032 respectively) in hypertensive patients. The QTd was independently related to AS (p=0.043) and AD (p=0.037), as well as age (p=0.003) and LVMI (p=0.008). CONCLUSION The QTd and cQTd were increased in hypertensives. Aortic elastic properties may play a role in increased dispersion of QT and cQT intervals.
pubmed_883_1057
pubmed_909_571
Molybdenum and tungsten enzymes require specific chaperones for folding and cofactor insertion. PaoD is the chaperone of the periplasmic aldehyde oxidoreductase PaoABC. It is the last gene in the paoABCD operon in Escherichia coli and its presence is crucial for obtaining mature enzyme. PaoD is an unstable, 35 kDa, protein. Our biochemical studies showed that it is a dimer in solution with a tendency to form large aggregates, especially after freezing/thawing cycles. In order to improve stability, PaoD was thawed in the presence of two ionic liquids [C4mim]Cl and [C2OHmim]PF6 and no protein precipitation was observed. This allowed protein concentration and crystallization using polyethylene glycol or ammonium sulfate as precipitating agents. Saturation transfer difference - nuclear magnetic resonance (STD-NMR) experiments have also been performed in order to investigate the effect of the ionic liquids in the stabilization process, showing a clear interaction between the acidic ring protons of the cation and, most likely, negatively charged residues at the protein surface. DLS assays also show a reduction of the overall size of the protein aggregates in presence of ionic liquids. Furthermore, cofactor binding studies on PaoD showed that the protein is able to discriminate between molybdenum and tungsten bound to the molybdenum cofactor, since only a Mo-MPT form of the cofactor remained bound to PaoD.
10.1371/journal.pone.0087295
pubmed_779_15658
OBJECTIVE The aim of this study was to determine out-of-pocket costs (OOPC) in patients undergoing thyroidectomy for benign and malignant conditions in a commercially insured US population. SUMMARY BACKGROUND DATA Little is known about OOPC for thyroid surgery in the United States. METHODS Retrospective cohort study using claims of patients undergoing thyroidectomy from the IBM Watson Marketscan database from 2008 to 2017. OOPCs accrued from 90 days before surgery to 360 days after thyroid surgery were quantified. Costs were divided into expenditures for inpatient care, outpatient care and outpatient drug costs and over three time periods: from 90 days preoperatively to 30 days post operatively, from 30 days post operatively to 90 days postoperatively, and from 90 days to 1 year after surgery. RESULTS A total of 45,971 commercially insured patients aged 18 to 95 years who underwent thyroidectomy were identified after excluding patients who changed coverage and patients on capitated plans. The median OOPC per patient in the study period of 90 days before surgery to 360 days after surgery was $2434 [interquartile range (IQR) $1273-$4226], the median insurance reimbursement was $15,520 (IQR $7653-$29,149). Patients undergoing thyroidectomy for malignant conditions had a median OOPC of $3019 (IQR $1596-$5021) compared to $2271 (IQR $1201-3954) for benign conditions ( P < 0.0001).Patients with preferred provider organization coverage had a median OOPC of $2624 (IQR $1458-$4358) compared to HMO patients with a median OOPC of $1529 (IQR $739 to 3058), and high deductible health plans with a median OOPC of $4265 (IQR $2788-$6210) ( P < 0.0001). CONCLUSION Despite commercial insurance coverage, patients face substantial OOPCs in the surgical management of thyroid disease in the United States.
10.1097/SLA.0000000000005078
pubmed_574_2729
Studies have been made of mucus glycoprotein biosynthesis in different regions of the lower gastrointestinal tract in normal patients and those with ulcerative colitis (UC), active or inactive, by means of 3H-glucosamine (3H-GlcNH2)--35S-sulphate double labelling of epithelial biopsy specimens under culture conditions. The time based rate of 3H-GlcNH2 labelling of mucus in rectal tissue was similar to that in active or inactive UC whereas the rate of 35SO4(2) labelling was significantly increased in active disease. The 3H specific activities measuring the amount of isotopic incorporation into surface and tissue mucus glycoproteins were increased in patients with active UC compared with normal or inactive subjects. The 35S specific activities did not differ significantly between patients with active UC and those in remission. In the rectum, glycosylation of mucus glycoproteins decreases with the increasing age of the patient. Regional differences in 3H-labelling of mucus components are reported for ascending colon, transverse colon, sigmoid colon, and rectum. Sulphation (35S-labelling) was higher in all parts of the colon in left sided UC. Results point to accelerated glycosylation of core proteins in the active phase of UC.
10.1136/gut.34.7.926
pubmed_448_12762
Zinc finger proteins (ZNF) are among the most abundant proteins in eukaryotic genomes. It contains several zinc finger domains that can selectively bind to certain DNA or RNA and associate with proteins, therefore, ZNF can regulate gene expression at the transcriptional and translational levels. In terms of neurological diseases, numerous studies have shown that many ZNF are associated with neurological diseases. The purpose of this review is to summarize the types and roles of ZNF in neuropsychiatric disorders. We will describe the structure and classification of ZNF, then focus on the pathophysiological role of ZNF in neuro-related diseases and summarize the mechanism of action of ZNF in neuro-related diseases.
10.3389/fnins.2021.760567
pubmed_167_6321
Superresolution, single-particle tracking reveals effects of the cationic antimicrobial peptide LL-37 on the Escherichia coli cytoplasm. Seconds after LL-37 penetrates the cytoplasmic membrane, the chromosomal DNA becomes rigidified on a length scale of ∼30 nm, evidenced by the loss of jiggling motion of specific DNA markers. The diffusive motion of a subset of ribosomes is also frozen. The mean diffusion coefficients of the DNA-binding protein HU and the nonendogenous protein Kaede decrease twofold. Roughly 108 LL-37 copies flood the cell (mean concentration ∼90 mM). Much of the LL-37 remains bound within the cell after extensive rinsing with fresh growth medium. Growth never recovers. The results suggest that the high concentration of adsorbed polycationic peptides forms a dense network of noncovalent, electrostatic linkages within the chromosomal DNA and among 70S-polysomes. The bacterial cytoplasm comprises a concentrated collection of biopolymers that are predominantly polyanionic (e.g., DNA, ribosomes, RNA, and most globular proteins). In normal cells, this provides a kind of electrostatic lubrication, enabling facile diffusion despite high biopolymer volume fraction. However, this same polyanionic nature renders the cytoplasm susceptible to massive adsorption of polycationic agents once penetration of the membranes occurs. If this phenomenon proves widespread across cationic agents and bacterial species, it will help explain why resistance to antimicrobial peptides develops only slowly. The results suggest two design criteria for polycationic peptides that efficiently kill gram-negative bacteria: facile penetration of the outer membrane and the ability to alter the cytoplasm by electrostatically linking double-stranded DNA and 70S-polysomes.
10.1073/pnas.1814924116
pubmed_259_19481
Noncompliance with cardiac rehabilitation programs is a major concern for female coronary heart disease patients. In this article I argue for the use of the common-sense model of illness in developing interventions to increase compliance with cardiac rehabilitation programs among women with heart disease. First, the common-sense model of illness is discussed. Second, a personal narrative technique that addresses the key components of the common-sense model of illness is presented. I recommend that a modified version of the personal narrative technique be used to increase women's compliance with cardiac rehabilitation programs because this technique is well suited for women's health issues.
10.1080/07399330390191715
pubmed_537_16136
A new method of scapulothoracic fusion is described for patients with facioscapulohumeral dystrophy. To improve upper limb function by abolishing scapula winging, bilateral procedures were performed in six patients with an average age of 30 years (range 17 to 44 years). The average follow-up was 49 months (range 1 to 7 years). A good functional and cosmetic result was obtained in all patients. An average postoperative increase in shoulder abduction of 28 degrees and flexion of 40 degrees was seen. Only a small diminution in respiratory function occurred (mean decrease in forced expiratory volume in 1 second of 14% and forced vital capacity of 21%).
10.1016/s1058-2746(05)80006-0
pubmed_54_19174
The human papillomavirus (HPV) is a sexually transmitted disease (STD) that is rampant among young adults and is linked with cervical and oropharyngeal cancers (OPC). As the preventive arm of oral health care, dental hygienists can take the lead in educating the young adult population about risk factors for HPV and OPC. Dental hygienists' active involvement in educational initiatives may help minimize the spread of HPV associated STDs, prevent transmission of HPV to the head and neck region, and decrease the development of OPC.
pubmed_54_19174
pubmed_417_19930
AIMS To develop a sensitive and specific polymerase chain reaction (PCR) based system for detecting genomic variation in JC virus. To apply this system to formalin fixed, paraffin wax embedded brain tissue from patients with and without progressive multifocal leucoencephalopathy (PML). METHODS A pair of primers (JC1 and JC2) were designed to be complementary to the early and late regions of JC and BK polyomaviruses, respectively. A third primer (JC3), internal to JC1 and JC2, was designed to be specific for JC virus. The specificity of JC3 was investigated by amplifying plasmids with BK or JC virus genomes. Sensitivity was estimated by titration of a plasmid containing JC virus genome. Seven brains from patients with PML (PMLB) and 30 from patients without PML (non-PMLB) were amplified using JC1 and JC2, followed by JC1 and JC3. Amplification of the beta globin gene was used as an amplification control. RESULTS Amplification with JC1 and JC2 was common for JC and BK viruses, but with JC1 and JC3 it was specific for JC virus. The sensitivity of the system was 25 copies of JC plasmid per 10 microliters of digested tissue. Five out of seven PMLB and 28 of the 30 non-PMLB amplified for beta globin, but only the PMLB gave a signal with polyoma primers. Hypervariation of the length of the regulatory region of the JC isolates in the PML tissues was consistent with the presence of multiple strains of JC. CONCLUSIONS Variation in the regulatory region of JC virus can be specifically and sensitively detected from routinely processed, paraffin wax embedded brain tissue. Variation in the regulatory region is common in PML derived JC strains, but JC virus was not detectable in non-PMLB tissue.
10.1136/jcp.46.7.646
pubmed_17_8043
The justification of a request of ERCP in a patient with hematobilia, was evaluated, based on the medical history and negative endoscopy findings for gastrocolic bleeding. The diagnostic examination was performed: it confirmed the release of blood from the papilla of Vater, however the definitive diagnosis could not be established; CT, as the examination of first choice was performed. It provided additional information and the diagnosis of aneurysm of the splenic vein apparently non communicating with the main pancreatic duct, was established. Angiography of the splenic artery was performed as the examination of second choice to definitely ascertain the source of bleeding. During the examination, the aneurysm embolization excluded the affected vessel from the circulation and allowed immediate benefit to the patient.
pubmed_17_8043
pubmed_142_2938
Older adults have increased risk for depression, and the use of selective serotonin reuptake inhibitors (SSRIs) is common. Serotonin syndrome is a potential adverse event associated with the use of SSRIs, the combination of SSRIs and trazodone, and the combination of SSRIs and linezolid. Pharmacists are ideal for assessing older adult drug regimens and recognizing potential drug interactions associated with proserotonergic drugs and alleviating adverse events for patients.
10.4140/TCP.n.2015.455
pubmed_1027_1422
The purpose of this study was to examine the relationship between self-care responses and variables concerning health status, disease and treatment, socioeconomic resources, demographic characteristics, and health beliefs in a heterogeneous sample of 227 cancer patients referred to home care. Data were collected prior to discharge from the hospital using the OARS Functional Assessment Questionnaire, the Karnofsky Performance Status, the Multidimensional Health Locus of Control Scale, and the Preference for Participation in Care Tool. The results indicated that the variables related to health status, disease and treatment were highly correlated with self-care behavior (SCB), and to a lower extent to self-care preference (SCP). Karnofsky performance status, cancer-related impairments, perceived physical health, and stage of disease were identified as significant predictors of SCB explaining 57% of the variance. Age, gender, education, live-in resources, and perceived mental health were dominant predictors of SCP explaining only 17% of the variance. Further research endeavors should investigate other models that might prove to be better predictors of SCP.
10.3109/02841869709109222
pubmed_697_8196
Over the past few years, there has been a growing interest in the interconnection between translation and metabolism. Important oncogenic pathways, like those elicited by c-Myc transcription factor and mTOR kinase, couple the activation of the translational machinery with glycolysis and fatty acid synthesis. Eukaryotic initiation factor 6 (eIF6) is a factor necessary for 60S ribosome maturation. eIF6 acts also as a cytoplasmic translation initiation factor, downstream of growth factor stimulation. eIF6 is up-regulated in several tumor types. Data on mice models have demonstrated that eIF6 cytoplasmic activity is rate-limiting for Myc-induced lymphomagenesis. In spite of this, eIF6 is neither transcriptionally regulated by Myc, nor post-transcriptionally regulated by mTOR. eIF6 stimulates a glycolytic and fatty acid synthesis program necessary for tumor growth. eIF6 increases the translation of transcription factors necessary for lipogenesis, such as CEBP/β, ATF4 and CEBP/δ. Insulin stimulation leads to an increase in translation and fat synthesis blunted by eIF6 deficiency. Paradoxycally, long-term inhibition of eIF6 activity increases insulin sensitivity, suggesting that the translational activation observed upon insulin and growth factors stimulation acts as a feed-forward mechanism regulating lipid synthesis. The data on the role that eIF6 plays in cancer and in insulin sensitivity make it a tempting pharmacological target for cancers and metabolic diseases. We speculate that eIF6 inhibition will be particularly effective especially when mTOR sensitivity to rapamycin is abrogated by RAS mutations.
10.1042/BST20160179
pubmed_581_15323
Pharmacists and other practitioners increasingly must focus on data collection, analysis, and communication to maximize quality and reduce adverse events that lead to readmissions. As a result, they are seeking systems and software that provide them with real-time access to the information they need and enable them to communicate with other stakeholders. To date, there have been barriers, including lack of system/software interoperability and electronic health records that make it difficult for practitioners to access and/or input data. The American Society of Consultant Pharmacists, and the National Association for the Support of Long Term Care convened pharmacists, software vendors, and other stakeholders to survey the health information technology/electronic health records (HIT/EHR) landscape to identify challenges, and discuss possible solutions.
10.4140/TCP.n.2017.502
pubmed_533_4817
Pigmented squamous cell carcinoma in situ (PSCCIS) is very rare, being clinically described as a pigmented lesion with histological characteristics of an in-situ carcinoma presenting pigmentation within neoplastic cells. A 50-year-old Afro-descendant man came for clinical evaluation of a painful black and red lesion located on the right aspect of the oropharyngeal isthmus. After incisional biopsy, the resulting sample was described as a pigmented squamous cell carcinoma in situ, a diagnosis further confirmed by immunohistochemical analysis. Treatment consisted in total excision of the lesion, and no recurrence was observed after a 30-month follow-up. Clinicians and pathologists should be aware of PSCCIS as a differential diagnosis of melanoma, a lesion which significantly increases the morbidity and mortality rates among these patients. Key words:Pigmented squamous cell carcinoma in situ; oropharyngeal mucosa; immunohistochemistry.
10.4317/jced.54053
pubmed_58_775
Multistrain microbial communities often exhibit complex spatial organization that emerges because of the interplay of various cooperative and competitive interaction mechanisms. One strong competitive mechanism is contact-dependent neighbor killing enabled by the type VI secretion system. It has been previously shown that contact-dependent killing can result in bistability of bacterial mixtures so that only one strain survives and displaces the other. However, it remains unclear whether stable coexistence is possible in such mixtures. Using a population dynamics model for two interacting bacterial strains, we found that coexistence can be made possible by the interplay of contact-dependent killing and long-range growth inhibition, leading to the formation of various cellular patterns. These patterns emerge in a much broader parameter range than that required for the linear Turing-like instability, suggesting this may be a robust mechanism for pattern formation.
10.1016/j.bpj.2018.02.012
pubmed_681_12367
A reactive ability of immunocompetent cells was assessed by the level of cytokines TNF alpha and IL-8 estimated by enzyme immunoassay ("Genzyme diagnostics" kit) in 18 patients with chronic obstructive bronchitis (mean age 58 +/- 4.2 years, mean duration of the disease 11.2 +/- 5.2 years) and 15 control patients matched for age, with normal external respiration function, free of chronic bronchopulmonary pathology and allergic diseases. The greatest differences in cytokine levels were registered between the control group and patients with moderate generalized irreversible obstruction. These patients had similar basal and E. coli LPS induced synthesis of the above cytokines showing the lack of cell reserves, adequate immune response to exogenic antigen.
pubmed_681_12367
pubmed_540_9797
Our study purpose was to evaluate the variation and accuracy of tailored parenting plans individually generated as a supplement to reproductive health education on the genetic inheritance of sickle cell disease or sickle cell trait. We present a secondary data analysis of experimental group data from a randomized controlled trial. Participants completed the valid and reliable Internet-based Sickle Cell Reproductive Health Knowledge Parenting Intent Questionnaire. We created a computerized algorithm that used participants' responses to generate tailored parenting plans based on their parenting preferences and partner's sickle cell status. Thirty-one different parenting plans were generated to meet the variety in the participants' preferences. The most frequently generated plan was for participants with sickle cell disease who had a partner with hemoglobin AA, who wanted to be a parent, was not likely to be pregnant, and wanted their child to be sickle cell disease free. More than half of the participants required alteration in their reproductive behavior to achieve their parenting goals. Findings provide insight into the variety and accuracy of computer algorithm-generated parenting plans, which could further guide refinement of the algorithm to produce patient-centered, tailored parenting plans supplemental to Internet-based genetic inheritance education.
10.1097/CIN.0000000000000933
pubmed_556_15244
Although sibling ties are typically among the longest lasting family relationships, relatively little is known about how adult siblings navigate family caregiving when a brother or sister has a serious mental illness. The present study examined the role of primary caregiver status, perceived sibling illness severity, sibling relationship quality, and self and sibling caregiving attitudes in understanding reports of personal loss and stress-related personal growth among siblings of adults with serious mental illness. Online surveys were completed by 226 adult siblings (141 women; 85 men; mean age = 34 years; SD = 9.05). Results suggest that well siblings' reports of self and sibling caregiving attitudes significantly differed as a function of primary caregiver status (i.e., sibling, parents, or others as primary caregiver or no caregiver). Sibling caregiving attitudes differentially predicted well siblings' experience of personal loss and stress-related growth, regardless of demographics and primary caregiver status, perceived sibling illness severity, and sibling relationship quality. Greater ambivalence about providing care to their sibling with mental illness was associated with adults' reports of greater personal loss while higher levels of sibling balanced care priorities were significantly related to higher levels of personal growth. Greater self-care attitudes were significantly related to lower levels of both personal loss and personal growth for well siblings. Understanding sibling caregiving attitudes has important implications for research and interventions with families coping with mental illness. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
10.1037/ort0000511
pubmed_371_18821
Epizootic haematopoietic necrosis virus (EHNV) was grown in Bluegill fry (BF-2) cells and purified using differential and gradient centrifugation. The lower band (B2) from 15-60% sucrose gradients contained infective EHNV but few contaminating cell components when assessed by electron microscopy, SDS-PAGE, and Western blotting using anti-BF-2 serum and anti-B2 serum. Both rabbit and sheep anti-B2 sera precipitated B2 in agarose gel immunodiffusion and detected EHNV in cell culture supernatant when used in an indirect antigen-capture ELISA. Rabbit anti-B2 serum was used as capture antibody while sheep anti-B2 serum was used to detect viral antigen. Pre-adsorption of diluted sheep anti-B2 serum using BF-2 cell lysate greatly improved the specificity and sensitivity of the technique.
10.1016/0166-0934(91)90019-v
pubmed_637_18143
Endoscopic cannulation of the biliary tree and the pancreatic duct (ERCP) was first described in 1968. Six years later the technique of endoscopic sphincterotomy (ES) opened the door to endoscopic treatment procedures of pancreatic and biliary diseases. Techniques have been developed to remove bile duct stones, to break large stones and to drain bile duct or pancreatic duct strictures.
pubmed_637_18143
pubmed_901_4193
The influence of the L-DOPA preparation on the bioelectrical activity of the brain was studied in 15 patients with Itsenko-Cushing's disease and in 12 patients with diencephalic obesity. L-DOPA administration caused an increase of the theta-rhythm index in the anterior leads in comparison with the initial recording, although the periods of detection of this elevation differed in various patients. No changes of the character of the EEG recording during the test with L-DOPA in comparison with the background recording was revealed in the patients with Itsenko-Cushings disease.
pubmed_901_4193
pubmed_471_25633
PURPOSE This study tested the hypothesis that autologous blood transfusion (ABT) of ~50% of the red blood cells (RBC) from a standard 450-mL phlebotomy would increase mean power in a cycling time trial. In addition, the study investigated whether further ABT of RBC obtained from another 450-mL phlebotomy would increase repeated cycling sprint ability. METHODS In a randomized, double-blind, placebo-controlled crossover design (3-month wash-out), nine highly trained male subjects donated two 450-mL blood bags each (BT trial) or were sham phlebotomized (PLA trial). Four weeks later, a 650-kcal time trial (n = 7) was performed 3 d before and 2 h after receiving either ~50% (135 mL) of the RBC or a sham transfusion. On the following day, transfusion of RBC (235 mL) from the second donation or sham transfusion was completed. A 4 × 30-s all-out cycling sprint interspersed by 4 min of recovery was performed 6 d before and 3 d after the second ABT (n = 9). RESULTS The mean power was increased in time trials from before to after transfusion (P < 0.05) in BT (213 ± 35 vs 223 ± 38 W; mean ± SD) but not in PLA (223 ± 42 vs 224 ± 46 W). In contrast, the mean power output across the four 30-s sprint bouts remained similar in BT (639 ± 35 vs 644 ± 26 W) and PLA (638 ± 43 vs 639 ± 25 W). CONCLUSIONS ABT of only ~135 mL of RBC is sufficient to increase mean power in a 650-kcal cycling time trial by ~5% in highly trained men. In contrast, a combined high-volume transfusion of ~135 and ~235 mL of RBC does not alter 4 × 30-s all-out cycling performance interspersed with 4 min of recovery.
10.1249/MSS.0000000000001837
pubmed_929_10544
People segment the stream of experience into events, or temporal segments that have a beginning and an ending. But how are such event boundaries defined? Linguistic theories of event encoding draw a distinction between bounded events that include an inherent endpoint ("eat a pretzel") and unbounded events that lack such an endpoint ("eat cheerios"). Even though the literature on event cognition has not focused on such abstract aspects of event structure, we hypothesize that sensitivity to boundedness could shape the way events are processed. In the present study, we show that viewers are sensitive to event boundedness in a category identification task and distinguish it from event completion; furthermore, viewers identify bounded events more easily than unbounded events. Sensitivity to boundedness emerges even when viewers are prevented from encoding the events linguistically and thus does not depend on the online use of linguistic distinctions. We conclude that event cognition relies on highly abstract properties of events and their boundaries, and sketch implications of these findings for the way events are described, processed, and used to interact with the world.
10.1016/j.cognition.2020.104197
pubmed_292_23037
INTRODUCTION Low-flow vascular malformation, which usually develops during the first stage of infancy, is a rare cause of recurrent effusion of the knee. History, laboratory and X-rays are usually non-specific. OBJECTIVE To describe a rare disease in pediatrics, emphasizing the correct classification and suspicion. CASE REPORT A case is presented of a two-year-old patient with a history of effusion of the right knee who required multiple hospitalizations and antibiotic treatments. Laboratory work-up was normal. Plain X-rays of the knee revealed no bone changes. MR imaging reported low-flow vascular malformation. Surgical resection was performed, evidencing vascular lesion among the muscle fibers of the vastus lateralis of quadriceps until the capsule of the knee, as well as dissection of the fibers until the vastus lateralis of the right leg. Histology was consistent with low-flow vascular malformation. Due to the benign outcome and favorable evolution, an outpatient management was possible. CONCLUSIONS Although low-flow synovial vascular malformation is a rare disease among the pediatric population, it should be considered in the differential diagnosis of patients with repeated hemarthrosis and no history of either coagulopathy or hemophilia.
pubmed_292_23037
pubmed_1026_10085
BACKGROUND Previous meta-analyses have shown that statins may cause incident diabetes. This article reviews randomized controlled trials using proprotein convertase subtilisin/kexin 9 inhibitors (PCSK9i) or ezetimibe on the risk of new-onset diabetes. METHODS Eight trials involving PCSK9i and 3 trials of ezetimibe were selected for review. PubMed, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov were thoroughly searched for relevant trials. Inclusion criteria included at least 100 patients per treatment arm, follow-up of at least 52 weeks, and at least double-blinded study design. Exclusion criteria included patients with previously diagnosed diabetes, nonrandomized, placebo-controlled, open-label, and crossover trials. The primary outcome was the number of incident diabetes cases. A random effects model was used. Heterogeneity in effect sizes was measured with I2 parameter and the Q statistic was used to test for excessive between-study heterogeneity. RESULTS A total of 52 214 participants for the PCSK9i and a total of 20 084 for the ezetimibe meta-analyses were included. Participants randomized to PCSK9i did not differ from the control patients in diabetes incidence (risk ratio [RR] = 0.99, P = .87, 95% CI = 0.92-1.07). Participants randomized to ezetimibe did not differ from the control patients in diabetes incidence (RR = 1.05, P = .37, 95% CI = 0.95-1.15). DISCUSSION The use of PCSK9i and ezetimibe does not appear to impact the risk of incident diabetes mellitus when added to guideline-directed medical therapy.
10.1177/1074248420924983
pubmed_330_8758
Three methods are described for measurement of glare from automotive chromium surfaces. The first is a performance measure: a glare illumination technique that measures at the driver's eye location the amount of light reflected to that location. The other two methods measure a surface property rather than performance. One is the standard glossmeter method of measuring gloss on flat surfaces. The other is a substitute gloss image method that measures gloss on both flat and curved surfaces. Results when using the glare illumination technique on flat and curved surfaces, with both bright and satin chromium finishes, indicated that glare decreased as surface curvature was increased. The effect of the satin finish was a reduction in glare from flat surfaces but not from curved surfaces.
10.1364/AO.8.001791
pubmed_74_8457
Cardiac amyloidosis (CA) is considered a rare disease with poor prognosis and limited therapeutic options. However, non-biopsy diagnostic modalities as well as emerging therapies are challenging this long-held belief. Radionuclide bone scintigraphy is increasingly being used in the diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CA). As such, it is expected that the number of patients diagnosed with ATTR-CA will continue to rise. Emerging therapies decrease the progressive morbidity and mortality associated with ATTR-CA. The importance of early recognition of ATTR-CA is imperative as prompt initiation of these novel agents is essential to maximize their therapeutic potential. Herein, we outline the current approach to diagnosis of ATTR-CA and review the therapeutic management of the disease.
10.1016/j.tcm.2019.12.003
pubmed_69_15219
The Supplemental Nutrition Assistance Program (SNAP), the largest federal food assistance program, currently serves 44.7 million Americans with a budget of $75 billion in 2011. This study engaged leading experts for in-depth, semi-structured interviews to explore their opinions concerning the existing challenges and barriers to eating nutritiously in SNAP. Experts also proposed strategies for improving nutritional status among SNAP recipients. Twenty-seven individuals were interviewed from advocacy, government, industry, and research organizations. Interviews were recorded, transcribed, coded, and analyzed for thematic content. The high cost of nutrient-rich foods, inadequate SNAP benefits, limited access to purchasing healthy foods, and environmental factors associated with poverty were identified as barriers that influence nutrition among low-income households in the United States. Six themes emerged among respondents from diverse sectors about how to address these challenges, including providing SNAP participants with incentives to purchase nutrient-rich food consistent with the 2010 Dietary Guidelines for Americans, restricting the purchase of nutrient-poor foods and beverages with program benefits, modifying the frequency of SNAP benefit distribution, enhancing nutrition education, improving the SNAP retailer environment, and increasing state and federal level coordination and consistency of program implementation. Given the recent dramatic increase in SNAP enrollment, policymakers must address existing barriers as well as consider new strategies to improve nutrition policies in SNAP so that the program can continue to address food insecurity needs as well as provide a healthful diet for SNAP beneficiaries.
pubmed_69_15219
pubmed_162_17814
BACKGROUND Few data are available on the management of elderly rectal cancer patients, and especially on the ability to provide optimal oncological treatment. The aim of this study was to determine the feasibility and results of multimodality treatment for rectal cancer in patients 75years and older after simplified comprehensive geriatric assessment (CGA) according to Balducci score. METHODS We reviewed the charts of elderly patients who underwent surgery for localized middle or low rectal cancer. Patients were classified into three CGA groups depending on their functional reserve, comorbidities, geriatric syndromes, and life expectancy. RESULTS Neoadjuvant therapy was discussed for 27 patients (47%), but only 56% of them were treated, including 8, 7, and 1 patient from CGA groups 1, 2, and 3, respectively. Fifty-three patients (93%) underwent sphincter-preserving surgical resection and four patients underwent abdominoperineal resection (7%). Postoperative complications were observed in 21 patients (37%). The postoperative complication rate was correlated non-significantly with age (<85years: 40.6%; ≥85years: 57.1%; P=0.3), and with the CGA (P=0.64). In total, 10 patients (18%) had definitive colostomy, including five anastomotic leakages (9%), and one incontinence (2%). The total rate of sphincter preservation was 82% (n=47). The risk of secondary definitive colonic stoma formation was not correlated with CGA (group 1: 14%; group 2/3: 16%; P=0.8). Estimated OS at five years was 52%. CONCLUSIONS After routine geriatric assessment, elderly rectal cancer patients have good rates of sphincter conservation and acceptable morbidity/mortality.
10.1016/j.jviscsurg.2017.06.005
pubmed_623_20419
Surface modified ZnO nanomaterial is widely used in the field of bioimaging worldwide due to its optical properties, electronic characteristics and biocompatibility. Fluorescent enhanced, Polyquaternium-7(PQ7) capped, ZnO hexagonal nano disks (ZnO-PQ7) were synthesised by simple wet chemical method. The structural and optical properties of ZnO-PQ7 hexagonal nano disks were characterized using XRD, UV-Visible, Fluorescence, HRTEM, EDAX and FTIR studies. The size of synthesised ZnO-PQ7 were around 30-45 nm as confirmed by HRTEM studies. Fluorescence emission intensity increased with increase in PQ7 concentration. ZnO-PQ7 was further conjugated with folic acid (FA) to target human breast cancer cell line (MCF-7) via EDC/NHS coupling chemistry. Conjugation of folic acid with ZnO-PQ7 was confirmed by FTIR studies. The cell viability study using Methyl thiazolyltetrazolium(MTT) assay has demonstrated that the ZnO-PQ7 conjugated FA composites (ZnO-PQ7-FA) exhibit low toxicity towards MCF-7 up to a concentration of 125 μg/mL. Confocal laser scanning microscopic images confirmed the uptake of ZnO-PQ7-FA nanoparticles by MCF-7 cells. This study reveals ZnO-PQ7-FA nano disks as a potential imaging agent for detection of cancer cells. The synthesis route reported in this article is simple and easy to follow for the synthesis of ZnO-PQ7-FA in bulk quantities with high purity.
10.1007/s10895-016-1932-y
pubmed_540_10621
Lateralization is a fundamental characteristic of many behaviors and the organization of the brain, and atypical lateralization has been suggested to be linked to various brain-related disorders such as autism and schizophrenia. Right-handedness is one of the most prominent markers of human behavioural lateralization, yet its neurobiological basis remains to be determined. Here, we present a large-scale analysis of handedness, as measured by self-reported direction of hand preference, and its variability related to brain structural and functional organization in the UK Biobank (N = 36,024). A multivariate machine learning approach with multi-modalities of brain imaging data was adopted, to reveal how well brain imaging features could predict individual's handedness (i.e., right-handedness vs. non-right-handedness) and further identify the top brain signatures that contributed to the prediction. Overall, the results showed a good prediction performance, with an area under the receiver operating characteristic curve (AUROC) score of up to 0.72, driven largely by resting-state functional measures. Virtual lesion analysis and large-scale decoding analysis suggested that the brain networks with the highest importance in the prediction showed functional relevance to hand movement and several higher-level cognitive functions including language, arithmetic, and social interaction. Genetic analyses of contributions of common DNA polymorphisms to the imaging-derived handedness prediction score showed a significant heritability (h2=7.55%, p <0.001) that was similar to and slightly higher than that for the behavioural measure itself (h2=6.74%, p <0.001). The genetic correlation between the two was high (rg=0.71), suggesting that the imaging-derived score could be used as a surrogate in genetic studies where the behavioural measure is not available. This large-scale study using multimodal brain imaging and multivariate machine learning has shed new light on the neural correlates of human handedness.
10.1016/j.neuroimage.2022.119534
pubmed_669_889
Fasciola hepatica is a parasite that is widespread in Europe, having been reported in ruminants of several European countries and causing an important economic impact. This study ascertained the occurrence and distribution of fasciolosis in Portuguese ovine livestock by assessing F. hepatica IgG antibodies in a cohort of confined sheep from a high-altitude region of central Portugal in a 2-year period. Positive animals were found in most locations and in both years, with 18 of the 92 animals (19.6% [95% confidence interval CI: 12.03-19.15]) and 17 of the same 92 animals (18.5% [95% CI: 11.15-27.93]) showing to be seropositive in the first year and second year, respectively (p = 0.85). Pasture contamination by F. hepatica eggs could be reduced by thorough anthelmintic treatments.
10.3390/ani11123344
pubmed_83_15714
Natalizumab is being used in recurrent multiple sclerosis despite its history of market withdrawal due to lethal cases. We have carried out a bibliometric analysis of this drug from 1999 to February 2020 in order to assess the real impact of the use natalizumab with the goal to identify the key articles that sustain the current knowledge on the therapeutic possibilities of this compound. We have extracted from the Web of Science the top 100 most cited records (T100) and tabulated data on the journal, authors, publication year, number of citations, countries and institutions of publication, T100-records, citation density and citations per record of the works. The 100 most cited articles were selected from a total of 32,507 citations out of 2817 publications with an h-number of 74, 11.54 citations/publication, and a density of 1544.79 citations/year. Citations ranged from 63 of the paper placed in the 100th position (T100) to 1940 of the paper in the first position (T1). T2 was cited 888 times, and the difference in the number of citations between T1 and T2 was higher than that between T2 and T10. T1, T2 and T3 are clinical trials. When articles are arranged by institution and nationality having more than 10 T100 articles, biotechnology company Biogen and the USA, respectively, lead the ranking, but we also find that 8 out of 10 are academic European institutions. A co-authorship analysis reveals an intense collaborative activity between countries and institutions. We conclude that the clinical and academic communities have shown a sustained interest in natalizumab for the therapy of recurrent multiple sclerosis over the last 20 years.
10.1016/j.jneuroim.2020.577379
pubmed_973_4085
OBJECTIVE To develop a consensus-based guideline as well as an atlas defining pelvic nodal clinical target volumes in external beam radiotherapy for uterine cervical cancer. METHODS A working subgroup to establish the consensus-based guideline on clinical target volumes for uterine cervical cancer was formulated by the Radiation Therapy Study Group of the Japan Clinical Oncology Group in July 2008. The working subgroup consisted of seven radiation oncologists. The process resulting in the consensus included a comparison of contouring on CT images among the members, reviewing of published textbooks and the relevant literature and a distribution analysis of metastatic nodes on computed tomography/magnetic resonance imaging of actual patients. RESULTS The working subgroup defined the pelvic nodal clinical target volumes for cervical cancer and developed an associated atlas. As a basic criterion, the lymph node clinical target volume was defined as the area encompassed by a 7 mm margin around the applicable pelvic vessels. Modifications were made in each nodal area to cover adjacent adipose tissues at risk of microscopic nodal metastases. Although the bones and muscles were excluded, the bowel was not routinely excluded in the definition. Each of the following pelvic node regions was defined: common iliac, external iliac, internal iliac, obturator and presacral. Anatomical structures bordering each lymph node region were defined for six directions; anterior, posterior, lateral, medial, cranial and caudal. Drafts of the definition and the atlas were reviewed by members of the JCOG Gynecologic Cancer Study Group (GCSG). CONCLUSIONS We developed a consensus-based guideline defining the pelvic node clinical target volumes that included an atlas. The guideline will be continuously updated to reflect the ongoing changes in the field.
10.1093/jjco/hyp191
pubmed_839_18014
BACKGROUND Difficulty falling asleep (prolonged sleep latency) is a frequently reported problem in school-aged children. AIMS This study aimed to describe the distribution of sleep latency and factors that influence its duration. METHODS 871 children of European mothers were recruited at birth. 591 (67.9%) children took part in the follow-up at 7 years of age. Sleep and daytime activity were measured objectively by an actigraph worn for 24 h. RESULTS Complete sleep data were available for 519 children (87.8%) with a mean age of 7.3 years (SD 0.2). Median sleep latency was 26 minutes (interquartile range 13-42). Higher mean daytime activity counts were associated with a decrease in sleep latency (-1.2 minutes per 102 movement count per minute, p = 0.05). Time spent in sedentary activity was associated with an increase in sleep latency (3.1 minutes per hour of sedentary activity, p = 0.01). CONCLUSIONS These findings emphasise the importance of physical activity for children, not only for fitness, cardiovascular health and weight control, but also for promoting good sleep.
10.1136/adc.2009.157453
pubmed_225_13640
A case of craniopagus twins is presented. Large contralateral flaps were used to cover the bony defect and exposed brain. Details of the planning and problems are discussed.
10.1016/0007-1226(91)90178-m
pubmed_908_1341
A unique cohort of chemo-naive gastrointestinal stromal tumors (GISTs) with double-primary tyrosine kinase mutations was characterized particularly to determine whether coexistent mutations represent a single mutational event. Up to 2013, 4 UK centers reported 9 GISTs with 2 primary tyrosine kinase mutations. In each of 8 cases validated by next generation sequencing, both mutations were present in the same allele of the same exon (KIT exon 11 or 17, or PDGFRA exon 18). One case showed the second mutation only on some of the mutant alleles. Seven cases showed both mutations in all the reads, but in 2 cases, additional variants were found only in some reads. Clinicopathologic features of the 8 cases were similar to GISTs with single-primary mutations. When GIST genotyping rarely uncovers multiple tyrosine kinase variants in an exon, they occur in the same allele but are likely to represent separate mutational events and lack clinical significance.
10.1097/PAI.0000000000000660
pubmed_807_363
Idealized gene therapy of autoimmune diseases would mean getting the right drug to the right place at the right time to affect the right mechanism of action. In other words, a specific gene therapy strategy needs to have functional, spatial and temporal specificity. Functional specificity implies targeting the cellular, molecular and/or genetic mechanisms relevant to the disease, without affecting nondiseased organs or tissues through mechanisms that cause adverse effects. Spatial specificity means the delivery of the therapeutic agent exclusively to sites and cells that are relevant to the disease. Temporal specificity is, in principle, synonymous with controlled on-demand expression of the therapeutic gene and thus represents a major safety feature. This article reviews recent advances in strategies to use gene therapy in the treatment of autoimmune diseases.
10.1586/1744666X.1.3.385
pubmed_302_13490
INTRODUCTION Genital skin loss in men may be caused by avulsion injuries of the penis and scrotum or by gangrene of the male genitalia. Reconstruction of the scrotum after complete loss of the overlying skin is a challenging problem. We report our experience on the management of this problem. MATERIAL AND METHOD Medical records of all male patients with massive scrotal skin loss and exposed testes treated at Ramathibodi Hospital and Noparat Rajthanee Hospital from 1990 to 1999 were reviewed. The etiologies of scrotal skin loss, technique of treatment, post-operative consequence as well as complications were noted. RESULTS Twelve patients were described in this study. Nine patients had avulsion injuries of the penile and scrotal skin secondary to agricultural machinery accidents. Three patients were after extensive debridement of Fournierrís gangrene. The exposed testes had been placed in thigh pouches and scrotal reconstruction using thigh pedicle flaps was done 4-6 weeks later. No immediate and delayed complications were detected in all of the patients. They recovered without any sequelae and had a satisfactory cosmetic result. CONCLUSION Extensive scrotal skin loss should be immediately treated surgically. Implantation of the exposed testes in the upper thigh pouch and delayed reconstruction of the scrotum using thigh pedicle flaps can provide excellent results
pubmed_302_13490
pubmed_949_2973
This paper reports two experiments, each designed to clarify different aspects of bilabial stop consonant production. The first one examined events during the labial closure using kinematic recordings in combination with records of oral air pressure and force of labial contact. The results of this experiment suggested that the lips were moving at a high velocity when the oral closure occurred. They also indicated mechanical interactions between the lips during the closure, including tissue compression and the lower lip moving the upper lip upward. The second experiment studied patterns of upper and lower lip interactions, movement variability within and across speakers, and the effects on lip and jaw kinematics of stop consonant voicing and vowel context. Again, the results showed that the lips were moving at a high velocity at the onset of the oral closure. No consistent influences of stop consonant voicing were observed on lip and jaw kinematics in five subjects, nor on a derived measure of lip aperture. The overall results are compatible with the hypothesis that one target for the lips in bilabial stop production is a region of negative lip aperture. A negative lip aperture implies that to reach their virtual target, the lips would have to move beyond each other. Such a control strategy would ensure that the lips will form an air light seal irrespective of any contextual variability in the onset positions of their closing movements.
10.1044/jslhr.4004.877
pubmed_30_10716
High-altitude headache and taste dysfunction are usually cured within a few months by descent to sea level. We studied a patient who had persistent bitemporal throbbing headache with the associated findings of high-altitude headache syndrome 15 years after a compression chamber accident. He also had loss of taste without loss of smell since the incident.
10.1001/archneur.1989.00520390106027
pubmed_188_14626
Cytoplasmic male sterility is crucial for the utilization of hybrid heterosis and it possibly occurs in parallel with tapetal programmed cell death (PCD) and oxidative metabolism responses. However, little is known about the mechanisms that underlie pollen abortion in wheat. Therefore, we obtained two isonuclear alloplasmic male sterile lines (IAMSLs) with Aegilops kotschyi and Ae. juvenalis cytoplasm. Compared with the maintainer line, cytochemical analyses of the anthers demonstrated that the IAMSLs exhibited anomalous tapetal PCD and organelles, with premature PCD in K87B1-706A and delayed PCD in Ju87B1-706A. We also found that the dynamic trends in reactive oxygen species (ROS) were consistent in these two IAMSLs during anther development and they were potentially associated with the initiation of tapetal PCD. In addition, the activities of ROS-scavenging enzymes increased rapidly, whereas non-enzymatic antioxidants were downregulated together with excess ROS production in IAMSLs. Real-time PCR analysis showed that the expression levels of superoxide dismutase, catalase, and ascorbate peroxidase genes, which encode important antioxidant enzymes, were significantly upregulated during early pollen development. Thus, we inferred that excessive ROS and the abnormal transcript levels of antioxidant enzyme genes disrupted the balance of the antioxidant system and the presence of excess ROS may have been related to aberrant tapetal PCD progression, thereby affecting the development of microspores and ultimately causing male sterility. These relationships between the mechanism of PCD and ROS metabolism provide new insights into the mechanisms responsible for abortive pollen in wheat.
10.3389/fpls.2018.00595
pubmed_828_22767
Graded-refractive-index-rod lenses (GRIN-rod lenses) have a number of features that make them particularly suitable for use in optical devices for manipulating and processing the optical signals in fiber communication systems. Such lenses can be cemented directly to the other elements of a device, thus giving a structure that is compact, solid, stable, and rugged. They also have significantly smaller aberrations than equivalent simple homogeneous lenses, and this results in lower insertion losses. Designs for various GRIN-rod lens devices, including connectors, attenuators, directional couplers, switches, isolators and wavelength-division multiplexers are reviewed. A consistent set of loss estimates is provided for all the device designs considered.
10.1364/AO.19.001127
pubmed_1009_11164
During the National Cooperative Gallstone Study, chenodiol (chenodeoxycholate), 750 or 375 mg/day, resulted in complete gallstone dissolution in only 13.5% and 5.2% of patients, respectively. The purpose of this study was to analyze the composition and morphology of gallstones from patients who underwent cholecystectomy during the National Cooperative Gallstone Study to determine if calcium salts on the gallstone surface could have been responsible for failure of dissolution. Total gallstone calcium content was not different between the treated and placebo groups; however, surface calcium levels were different, being greater than 1.0% in 47.6% of stones from chenodiol-treated patients (n = 63) but in only 16.7% of those from placebo-treated patients (n = 18), p less than 0.02. Pigmented outer rims were found in 52.4% of the stones from the chenodiol-treated group compared with only 16.7% of stones from the placebo group, p less than 0.01. The rim calcium content of 36 stones with pigmented outer rims was 3.7% +/- 1.0%, whereas that of 45 stones with nonpigmented outer rims was only 1.0% +/- 0.3%, p less than 0.01. We conclude that the presence of rings of increased concentrations of calcium salts on the gallstone surface may impair dissolution by chenodiol.
10.1016/0016-5085(86)90643-8
pubmed_929_18805
Despite its importance as the prime method for non-invasive assessment of human brain function, functional MRI (fMRI) was repeatedly challenged with regards to the validity of the fMRI-derived brain activation maps. Amygdala fMRI was particularly targeted, as the amygdala's anatomical position in the ventral brain combined with strong magnetic field inhomogeneities and proximity to large vessels pose considerable obstacles for robust activation mapping. In this high-resolution study performed at ultra-high field (7T) fMRI, we aimed at (1) investigating systematic replicability of amygdala group-level activation in response to an established emotion processing task by varying task instruction and acquisition parameters and (2) testing for intra- and intersession reliability. At group-level, our results show statistically significant activation in bilateral amygdala and fusiform gyrus for each of the runs acquired. In addition, while fusiform gyrus activations are consistent across runs and sessions, amygdala activation levels show habituation effects across runs. This amygdala habituation effect is replicated in a session repeated two weeks later. Varying task instruction between matching emotions and matching persons does not change amygdala activation strength. Also, comparing two acquisition protocols with repetition times of either 700 ​ms or 1400 ​ms did not result in statistically significant differences of activation levels. Regarding within-subject reliability of amygdala activation, despite considerable variance in individual habituation patterns, we report fair to good inter-session reliability for the first run and excellent reliability for averages over runs. We conclude that high-resolution fMRI at 7T allows for robust mapping of amygdala activation in a broad range of variations. Our results of amygdala 7T fMRI are suitable to inform methodology and may encourage future studies to continue using emotion discrimination paradigms in clinical and non-clinical applications.
10.1016/j.neuroimage.2020.116585
pubmed_866_22089
Rumen temperature boluses are becoming increasingly used as a means of monitoring core body temperature for the detection of ill health. However, the effect of behavior on rumen temperature is largely unknown. This research investigates the impact of behaviour and diet on the rumen temperature of Holstein bulls, both at grass, and in a housed environment. Rumen temperature was recorded at five-minute intervals using a bolus. Direct observations were conducted on young bulls in two studies (i) at grass (n = 30) and (ii) while housed (n = 32). In addition, activity monitors were attached to bulls at grass (n = 24). Within each study, diet differed by the level of concentrate supplementation. There was no effect of diet on rumen temperature. Significant differences in rumen temperature were observed between behaviour groups for bulls at grass (p < 0.001) and housed (p < 0.001). Furthermore, drinking resulted in the lowest rumen temperature (grass 35.97 °C; housed 36.70 °C). Therefore, rumen temperature is affected by behavior; however, the temperatures recorded were not outside the normal temperature range for healthy cattle.
10.3390/ani9111000
pubmed_1098_14150
Isolated tricuspid regurgitation (TR) has gained increasing recognition in recent years both in the surgical and in the cardiological community. Left untreated, isolated TR significantly worsens survival. Despite being a strong predictor of negative prognosis, interventions to correct TR are rarely performed due to increased surgical risk and late patient presentation. Recently, the ultimate focus has been on patient selection, surgical or transcatheter indication, and correct timing. Furthermore, of paramount importance is the identification of predictors of outcome following treatment, in order to discriminate between favorable and unfavorable responders and guide the decision-making process of the most adequate treatment for every patient.
10.3389/fcvm.2022.980639
pubmed_403_12402
OBJECTIVE The Clinician and Group Consumer Assessment of Healthcare Providers and Systems (CG-CAHPS) survey was developed by the Centers for Medicare and Medicaid Services as a result of their value-based purchasing initiative. It allows patients to rate their experience with their provider in the outpatient setting. This presents a unique situation in healthcare in which the patient experience drives the marketplace, and since its creation, providers have sought to improve patient satisfaction. Within the spine surgery setting, however, the question remains whether improved patient satisfaction correlates with improved outcomes. METHODS All patients who had undergone lumbar spine surgery between 2009 and 2017 and who completed a CG-CAHPS survey after their procedure were studied. Demographic and surgical characteristics were then obtained. The primary outcomes of this study include patient-reported health outcomes measures such as the Patient-Reported Outcomes Measurement Information System Global Health (PROMIS-GH) surveys for both mental health (PROMIS-GH-MH) and physical health (PROMIS-GH-PH), and the visual analog scale for back pain (VAS-BP). A multivariable linear regression analysis was used to assess whether patient satisfaction with their provider was associated with changes in each health status measure after adjusting for potential confounders. RESULTS The study population included 647 patients who had undergone lumbar spine surgery. Of these, 564 (87%) indicated that they were satisfied with the care they received. Demographic and surgical characteristics were largely similar between the two groups. Multivariable linear regression demonstrated that patient satisfaction with their provider was not a significant predictor of change in two of the three patient-reported outcomes (PROMIS-GH-MH and PROMIS-GH-PH) assessed at 1 year. However, top-box patient satisfaction with their provider was a significant predictor of improvement in VAS-BP scores at 1 year. CONCLUSIONS The authors found that after adjusting for patient-level covariates such as age, diagnosis of disc displacement, self-reported mental health, self-reported overall health, and preoperative patient-reported outcome measure status, a significant association was observed between top-box overall provider rating and 1-year improvement in VAS-BP, but no such association was observed for PROMIS-GH-PH and PROMIS-GH-MH. This suggests that pain-related outcome measures may serve as better predictors of patients' satisfaction with their spine surgeons. Furthermore, this suggests that the current method by which patient satisfaction is being assessed and publicly reported may not necessarily correlate with validated measures that are used within the spine surgery setting to assess surgical efficacy.
pubmed_403_12402
pubmed_762_18859
We set out to complete the audit cycle of caesarean deliveries in order to determine if improvements could be achieved. This was a prospective review of clinical notes in a Central London Teaching Hospital. The study involved 152 women delivering between 18 May and 23 August 1998, and 226 women over the same time period in 1999. For each case, a proforma was completed within 72 hours of delivery. We recorded the total and emergency section rate; indications; decision-to-delivery times; reasons for delay; prescription of ranitidine and heparin; fetal blood samples and cord pH values. The total caesarean section rate decreased from 20.9% to 19.2%. The emergency section rate was unchanged at 14.8% in 1998 (70.9% of total) and 13.6% in 1999 (70.8% of total). Main reasons for emergency sections were failure to progress (59% in 1998, 47% in 1999) and fetal distress (27% in 1998, 34% in 1999). For failure to progress 76% of cases were performed within 1 hour in 1998 vs. 64% of cases in 1999. For fetal distress 39% of cases were delivered within 30 minutes in both years. Fetal blood samples were taken in 41% of fetal distress cases in 1998 and 34% in 1999. Cord pH was documented in 60% of emergency cases in 1998 (96% in 1999). Prescription of ranitidine rose from 53% to 81%. Heparin was well prescribed in both years (88% vs. 87%). Following the initial audit, the total caesarean section rate was significantly lower but there was no difference in the emergency section rate. The implementations had no effect on decision-to-delivery times or use of fetal blood sampling. Improvements were seen in obtaining cord pH values and ranitidine prescription.
10.1080/01443610220130553
pubmed_656_15863
The choroid plexus (ChP) regulates brain development by secreting instructive cues and providing a protective brain barrier. Here, we show that polyI:C-mediated maternal immune activation leads to an inflammatory response in the developing embryonic mouse brain that manifests as pro-inflammatory cerebrospinal fluid (CSF) and accumulation of ChP macrophages. Elevation of CSF-CCL2 was sufficient to drive ChP immune cell recruitment, activation, and proliferation. In addition, ChP macrophages abandoned their regular tiling pattern and relocated to the ChP-free margin where they breached the weakened epithelial barrier. We further found that these immune cells entered from the ChP into the brain via anatomically specialized "hotspots" at the distal tips of ChP villi. In vivo two-photon imaging demonstrated that surveillance behaviors in ChP macrophages had already emerged at this early stage of embryogenesis. Thus, the embryonic ChP forms a functional brain barrier that can mount an inflammatory response to external insults.
10.1016/j.devcel.2020.09.020
pubmed_1108_13390
Carbon-carbon sigma-bond activation is a contemporary challenge for organometallic chemistry and catalysis. Herein, we disclose a new alkene carboacylation reaction initiated by quinoline-directed, rhodium-catalyzed C-C sigma bond activation. The alkene carboacylation allows for the construction of all-carbon quaternary centers, with a broad substrate scope, providing access to carbocyclic and heterocyclic ring systems in good to excellent yields.
10.1021/ja8066308
pubmed_598_23130
Invasive ductal carcinoma (IDC) is the most common type of breast cancer and the leading cause of breast cancer related mortality. In the present study, metabolomic profiles of 72 tissue samples and 146 serum samples were analysed using targeted liquid chromatography multiple reaction monitoring mass spectrometry (LC-MRM/MS) and untargeted gas chromatography mass spectrometry (GC-MS) approaches. Combination of univariate and multivariate statistical treatment identified significant alterations of 42 and 32 metabolites in tissue and serum samples of IDC, respectively when compared to control. Some of the metabolite changes from tissue were also reflected in serum, indicating a bi-directional interaction of metabolites in IDC. Additionally, 8 tissue metabolites and 9 serum metabolites showed progressive change from control to benign to IDC suggesting their possible role in malignant transformation. We have identified a panel of three metabolites viz. tryptophan, tyrosine, and creatine in tissue and serum, which could be useful in screening of IDC subjects from both control and benign. The metabolomic alterations in IDC showed perturbations in purine and pyrimidine metabolism, amino sugar metabolism, amino acid metabolism, fatty acid biosynthesis etc. Comprehensively, this study provides valuable insights into metabolic adaptations of IDC, which can help to identify diagnostic markers as well as potential therapeutic targets.
10.18632/oncotarget.23626
pubmed_743_21438
The incidental or malicious release of toxic gases in the atmosphere is one of the most critical scenarios for cities. The impact of these releases varies with the ventilation potential of the urban environment. To disentangle this crucial aspect, vulnerability to airborne releases is here traced back to essential properties of the urban fabric. To this aim, pollutant dispersion is disassembled in its fundamental bricks and the main drivers of the process are captured. The analysis is based on four cities with emblematic architectures: Paris, Firenze, Lyon and New York. Results show that vulnerability is driven by the topology of the city and by its interaction with the approaching wind. In this sense, fragility to toxic releases is written in the layout of the urban fabric and results from its historical evolution. This study paves the way to the assessment of air pollution-related issues from a morphological point of view.
10.1038/s41598-021-02403-y
pubmed_851_3031
BACKGROUND A novel bare metal stent with an SiO2coating was developed to prevent excessive neointimal hyperplasia by inertization of the metallic stent surface. The efficacy of the device was demonstrated in a preclinical model. The aim of this first-in-man trial was to assess the safety and feasibility of the new device.Methods and Results:This prospective non-randomized single-arm trial was designed to enroll 35 patients with a de novo coronary lesion. Quantitative coronary angiography and optical coherence tomography (OCT) were performed at the baseline procedure and at the 6-month follow-up. Stent implantation was performed with OCT guidance according to optimal stent implantation criteria. The trial was terminated upon the advice of the data safety monitoring board after enrolling 14 patients due to the high incidence of re-intervention. Optimal OCT implantation criteria were achieved in only 8.3% of lesions. At 6 months, angiographic in-stent late lumen loss as the primary endpoint was 0.77±0.44 mm, and binary restenosis occurred in 33.3% of lesions. At the 6-month OCT, neointimal volume obstruction was 32.8±15.6% with a neointimal thickness of 237±117 µm. At 12 months, the device-oriented composite endpoint (defined as cardiac death, target vessel myocardial infarction, and clinically indicated target lesion revascularization rate) was 33.3%. CONCLUSIONS In contrast with the preclinical study, the Axetis stent did not efficiently suppress neointimal hyperplasia in humans in this trial.
10.1253/circj.CJ-17-0337
pubmed_625_9598
OBJECTIVES Use systematic review and meta-analytic methodology to estimate the pooled incidence, prevalence, and proportion of delirium cases for each delirium subtype (hypoactive, hyperactive, and mixed) in an adult ICU population. DATA SOURCES We conducted a search of the MEDLINE, EMBASE, CINAHL, SCOPUS, Web of Science, and PsycINFO databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards from database inception until October 22, 2017, with no restrictions. STUDY SELECTION We included original research conducted in adults admitted to any medical, surgical, or speciality ICU that reported incidence or prevalence estimates of delirium according to delirium subtype. DATA EXTRACTION Data were extracted on sample size, population demographics, condition information, and reported delirium estimates. DATA SYNTHESIS Forty-eight studies (27,342 patients; 4,550 with delirium) with an overall pooled prevalence of 31% (95% CI, 24-41; I = 99%) met inclusion criteria. The pooled incidence (n = 18 studies) of delirium subtypes were hyperactive (4% [95% CI, 2-6]; I = 92%]), hypoactive (11% [95% CI, 8-17; I = 97%]), and mixed (7% [95% CI, 4-11; I = 97%]). The pooled prevalence (n = 31 studies) of delirium subtypes were hyperactive (4% [95% CI, 3-6; I = 94%]), hypoactive (17% [95% CI, 13-22; I = 97%]), and mixed (10% [95% CI, 6-16; I = 99%]). The pooled prevalence of hypoactive delirium in study populations with a similarly high severity of illness or mechanically ventilated was higher (severity of illness: 29% [95% CI, 18-46%; I = 95%], 100% mechanically ventilated: 35% [95% CI, 23-55%; I = 93%]) compared with the pooled prevalence of hypoactive delirium. CONCLUSIONS Despite significant heterogeneity between studies, these data show the majority of delirious ICU patients to have hypoactive delirium, a finding with potential monitoring, management, and prognostic implications. The prevalence of hypoactive delirium varies between-study populations and is higher in patients with greater severity of illness.
10.1097/CCM.0000000000003402
pubmed_117_9114
This study examined the association between naturalistically-observed in-person contact with one's ex-partner and separation-related psychological distress (SRPD). 122 recently-separated adults were assessed using the Electronically Activated Recorder (Mehl, 2017) on three occasions across five months. The association between in-person contact with one's ex-partner, as a between-person variable, and concurrent SRPD was not reliably different from zero, nor was the time-varying effect of in-person contact. However, more frequent in-person contact with one's ex-partner predicted higher SRPD two months later, above and beyond the variance accounted for by concurrent in-person contact, demographic, relationship, and attachment factors. Follow-up analyses yielded that this effect was only present for people without children; a one standard deviation increase in in-person contact offset and slowed the predicted decline in SRPD over two months by 112%. Our discussion emphasizes new ways to think about the role of in-person contact in shaping adults' psychological adjustment to separation over time.
10.1177/2167702620916454
pubmed_880_18066
One of the most studied in vitro alternative testing methods for identification of developmental toxicity is the embryonic stem cell test (EST). Although the EST has been formally validated, the applicability domain as well as the predictability of the model needs further study to allow successful implementation of the EST as an alternative testing method in regulatory toxicity testing. Genomics technologies have already provided a proof of principle of their value in identification of toxicants such as carcinogenic compounds. Also within the EST, gene expression profiling has shown its value in the identification of developmental toxicity and in the evaluation of factors critical for risk assessment, such as dose and time responses. It is expected that the implementation of genomics into the EST will provide a more detailed end point evaluation as compared to the classical morphological scoring of differentiation cultures. Therefore, genomics may contribute to improvement of the EST, both in terms of definition of its applicability domain as well as its predictive capacity. In the present review, we present the progress that has been made with regard to the prediction of developmental toxicity using the EST combined with transcriptomics. Furthermore, we discuss the developments of additional aspects required for further optimization of the EST, including kinetics, the use of human embryonic stem cells (ESC) and computational toxicology. Finally, the current and future use of the EST model for prediction of developmental toxicity in testing strategies and in regulatory toxicity evaluations is discussed.
10.1016/j.reprotox.2011.04.008
pubmed_278_10553
Smoking is the main cause of avoidable death and a major public health problem worldwide, with primary healthcare being a strategic setting for treating this problem. Aims: to evaluate the effectiveness of motivational interviewing associated with the cognitive behavioral therapy (CBT) in smoking groups in primary healthcare. A community-based cluster randomized clinical trial was conducted in Brazil, starting in July 2016. Professionals in the test group were trained in motivational interviewing for eight hours to associate it with the CBT. The usual treatment for smoking cessation in groups consists of four structured weekly sessions of 90 minutes each using a CBT. Taylor's linearization was used to correct the p-values; the chi-square test with Pearson correlation was used for categorical variables, and analysis of variance as well as the Student t-test were used for continuous variables. In total, 44 smoking groups were conducted, totaling 329 patients (178 in the motivational interviewing group and 151 in the control group). The smoking cessation rate with motivational interviewing was 61.8%, with RR = 1.25 (95%CI: 1.01-1.54, p = 0.043), and 47.7% in the control group, in the fourth weekly group treatment session. Mean session attendance was 3.1 (95%CI: 2.9-3.3) in the motivational interviewing group and 2.9 (95%CI: 2.5-3.4) in the control group. The completion rate for the motivational interviewing group was 65.2% and for the control group, 57.6%. Motivational interviewing associated with the CBT was shown to be effective and superior to only CBT to smoking cessation in groups in the fourth weekly session and for the population profile of the study (women with an average age of 50.6 years).
10.1590/0102-311X00038820
pubmed_722_8448
Renal ammonia excretion is the predominant component of renal net acid excretion. The majority of ammonia excretion is produced in the kidney and then undergoes regulated transport in a number of renal epithelial segments. Recent findings have substantially altered our understanding of renal ammonia transport. In particular, the classic model of passive, diffusive NH3 movement coupled with NH4+ "trapping" is being replaced by a model in which specific proteins mediate regulated transport of NH3 and NH4+ across plasma membranes. In the proximal tubule, the apical Na+/H+ exchanger, NHE-3, is a major mechanism of preferential NH4+ secretion. In the thick ascending limb of Henle's loop, the apical Na+-K+-2Cl- cotransporter, NKCC2, is a major contributor to ammonia reabsorption and the basolateral Na+/H+ exchanger, NHE-4, appears to be important for basolateral NH4+ exit. The collecting duct is a major site for renal ammonia secretion, involving parallel H+ secretion and NH3 secretion. The Rhesus glycoproteins, Rh B Glycoprotein (Rhbg) and Rh C Glycoprotein (Rhcg), are recently recognized ammonia transporters in the distal tubule and collecting duct. Rhcg is present in both the apical and basolateral plasma membrane, is expressed in parallel with renal ammonia excretion, and mediates a critical role in renal ammonia excretion and collecting duct ammonia transport. Rhbg is expressed specifically in the basolateral plasma membrane, and its role in renal acid-base homeostasis is controversial. In the inner medullary collecting duct (IMCD), basolateral Na+-K+-ATPase enables active basolateral NH4+ uptake. In addition to these proteins, several other proteins also contribute to renal NH3/NH4+ transport. The role and mechanisms of these proteins are discussed in depth in this review.
10.1152/ajprenal.00554.2010
pubmed_750_20630
Combining with a CRISPR/Cas9 system, Agrobacterium-mediated transformation can lead to precise targeted T-DNA integration in the rice genome. Agrobacterium-mediated T-DNA integration into the plant genomes is random, which often causes variable transgene expression and insertional mutagenesis. Because T-DNA preferentially integrates into double-strand DNA breaks, we adapted a CRISPR/Cas9 system to demonstrate that targeted T-DNA integration can be achieved in the rice genome. Using a standard Agrobacterium binary vector, we constructed a T-DNA that contains a CRISPR/Cas9 system using SpCas9 and a gRNA targeting the exon of the rice AP2 domain-containing protein gene Os01g04020. The T-DNA also carried a red fluorescent protein and a hygromycin resistance (hptII) gene. One version of the vector had hptII expression driven by an OsAct2 promoter. In an effort to detect targeted T-DNA insertion events, we built another T-DNA with a promoterless hptII gene adjacent to the T-DNA right border such that integration of T-DNA into the targeted exon sequence in-frame with the hptII gene would allow hptII expression. Our results showed that these constructs could produce targeted T-DNA insertions with frequencies ranging between 4 and 5.3% of transgenic callus events, in addition to generating a high frequency (50-80%) of targeted indel mutations. Sequencing analyses showed that four out of five sequenced T-DNA/gDNA junctions carry a single copy of full-length T-DNA at the target site. Our results indicate that Agrobacterium-mediated transformation combined with a CRISPR/Cas9 system can efficiently generate targeted T-DNA insertions.
10.1007/s11103-018-00819-1
pubmed_988_11715
Exposure of weanling rats to a diet containing elemental tellurium results in a peripheral neuropathy characterized by segmental demyelination and minimal axonal degeneration. One of the earliest ultrastructural abnormalities in tellurium neuropathy is an increased number of cytoplasmic lipid droplets in myelinating Schwann cells. The pathogenesis of these lipid droplets was investigated using light and electron microscopic autoradiography. Nerve lipids were either "prelabeled" with [3H]acetate via in vivo intraneural injection 3 days before a 2-day exposure to tellurium, or "postlabeled" via in vivo intraneural injection or in vitro incubation with [3H]acetate following a 2-day exposure to tellurium. In the prelabeled nerves, myelin became heavily labeled, but the tellurium-induced cytoplasmic lipid droplets were rarely labeled. In the postlabeled nerves, the tellurium-induced cytoplasmic lipid droplets were the most heavily labeled structures within the nerve. These data indicate that the tellurium-induced lipid droplets in Schwann cells are derived from newly synthesized lipid rather than from the early breakdown and internalization of myelin lipids. The earliest biochemical abnormality observed in tellurium neuropathy is an inhibition of cholesterol synthesis at the squalene epoxidase step. This leads to an accumulation of squalene within the nerve. We conclude that the cytoplasmic lipid droplets in Schwann cells contain this accumulated lipid.
10.1111/j.1471-4159.1990.tb05778.x
pubmed_165_22808
Two forces are generally hypothesised as being responsible for conditioning the origin of the organization of the genetic code: the physicochemical properties of amino acids and their biosynthetic relationships (relationships between precursor and product amino acids). If we assume that the biosynthetic relationships between amino acids were fundamental in defining the genetic code, then it is reasonable to expect that the distribution of physicochemical properties among the amino acids in precursor-product relationships cannot be random but must, rather, be affected by some selective constraints imposed by the structure of primitive proteins. Analysis shows that measurements representing the 'size' of amino acids, e.g. bulkiness, are specifically associated to the pairs of amino acids in precurso-product relationships. However, the size of amino acids cannot have been selected per se but, rather, because it reflects the beta-sheets of proteins which are, therefore, identified as the main adaptive theme promoting the origin of genetic code organization. Whereas there are no traces of the alpha-helix in the genetic code table. The above considerations make it necessary to re-examine the relationship linking the hydrophilicity of the dinucleoside monophosphates of anticodons and the polarity and bulkiness of amino acids. It can be concluded that this relationship seems to be meaningful only between the hydrophilicity of anticodons and the polarity of amino acids. The latter relationship is supposed to have been operative on hairpin structures, ancestors of the tRNA molecule. Moreover, it is on these very structures that the biosynthetic links between precursor and product amino acids might have been achieved, and the interaction between the hydrophilicity of anticodons and the polarity of amino acids might have had a role in the concession of codons (anticodons) from precursors to products.
10.1007/BF01808222
pubmed_944_20904
INTRODUCTION Noise can affect well-being and performance of individuals and might be associated with an increased risk of cardiovascular events. To date most epidemiological studies considered exposure from a single source of noise. The EU Environmental Noise Directive (2002/49/EC) requires a summative measurement of ambient noise. This study aimed to capture the participants' exposure to environmental noise by means of personal noise dosimetry. METHODS Children (n=628, participation=61%, age 8-12 years), adolescents (n=632, participation=58%, age 13-17 years) and adults (n=482, participation=40%, age 18-65 years) were selected randomly from the population registry of 4 Bavarian towns and were invited to participate in a 24-h measurement using noise dosimetry. Noise exposures during day and night were analyzed separately. In addition, predictors of noise exposure were assessed. RESULTS For daytime noise exposure mean±standard deviation were in children 80.0±5.8 dB(A), in adolescents 76.0±6.2 dB(A), in adults 72.1±6.1 dB(A) (p(ANOVA)<0.001). During the day personal noise exposure was statistically significantly higher for participants from smaller towns than for those living in Munich, while nighttime noise exposure was highest for participants from Munich [44.1±7.2 dB(A)]. CONCLUSION The summative noise exposure in urban Bavaria is high, in particular among children at daytime. Increased exposure levels in children might be caused by themselves while, e.g., playing. Whether the higher daytime exposure in towns is due to high noise levels commuting between home and work has to be assessed in future studies.
10.1055/s-0031-1285864
pubmed_63_3414
Genetic and biochemical studies have shown that PARP-1 and poly(ADP-ribosyl)ation play an important role in DNA repair, genomic stability, cell death, inflammation, telomere maintenance, and suppressing tumorigenesis, suggesting that the homeostasis of poly(ADP-ribosyl)ation and PARP-1 may also play an important role in aging. Here we show that PARP-1(-/-) mice exhibit a reduction of life span and a significant increase of population aging rate. Analysis of noninvasive parameters, including body weight gain, body temperature, estrous function, behavior, and a number of biochemical indices suggests the acceleration of biological aging in PARP-1(-/-) mice. The incidence of spontaneous tumors in both PARP-1(-/-) and PARP-1(+/+) groups is similar; however, malignant tumors including uterine tumors, lung adenocarcinomas and hepatocellular carcinomas, develop at a significantly higher frequency in PARP-1(-/-) mice than PARP-1(+/+) mice (72% and 49%, resp.; P < .05). In addition, spontaneous tumors appear earlier in PARP-1(-/-) mice compared to the wild type group. Histopathological studies revealed a wide spectrum of tumors in uterus, ovaries, liver, lungs, mammary gland, soft tissues, and lymphoid organs in both groups of the mice. These results demonstrate that inactivation of DNA repair gene PARP-1 in mice leads to acceleration of aging, shortened life span, and increased spontaneous carcinogenesis.
10.1155/2008/754190
pubmed_595_11332
OBJECTIVE The purpose of this study was to compare autologous versus cadaveric grafts in pubovaginal slings. STUDY DESIGN Women who had pubovaginal slings from 1994 to 2003 completed history, questionnaires, prolapse staging, and cough stress testing. Failure was defined by recurrent urinary incontinence symptoms and reoperation for stress incontinence. Group differences were evaluated using Student t test or chi-square test. The log-rank test was used to evaluate time to failure between the groups. RESULTS Of 303 women enrolled, 153 had autologous and 150 had cadaveric grafts. Regular urine leakage (39.6% vs 28.3%, P = .04) and reoperation for stress incontinence (12.7% vs 3.3%, P = .003) occurred more in the cadaveric versus autologous group, respectively. Adjusting for differing follow-up times, the cadaveric versus autologous group experienced higher rates of urinary incontinence (16 vs 5 per 100 women-years, P < .0001) and higher rates of reoperation (4 vs 1 per 100 women-years, P < .0003). CONCLUSION Autologous grafts used in pubovaginal slings have superior continence outcomes compared with cadaveric fascia.
10.1016/j.ajog.2006.01.058
pubmed_337_15105
Proliferating cancer cells are exposed to nutrient deprivation. Numerous previous studies have demonstrated how nutrient deprivation affects cancer cells; however, immune cells exposed to the identical conditions have not been completely examined. Furthermore, T-helper 2 lymphocyte predominance in certain neoplastic diseases has been reported; however, the mechanism remains unclear. The present study aimed to confirm whether nutrient deprivation affected proliferation and cytokine secretion of peripheral blood lymphocytes (PBLs). The proliferation of PBLs from healthy donors, cultured in a medium containing various glucose levels, was assessed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. The expression levels of interleukin (IL)-4 and interferon (IFN)-γ among CD4(+) T cells, cultured with or without glucose and activated with phorbol 12-myristate 13-acetate and ionomycin, were examined using an intracellular cytokine staining method. The proliferation of PBLs cultured in a medium containing <100 mg/dl glucose of the standard blood sugar (BS) level was significantly reduced compared with the proliferation observed in a medium containing a standard BS level or higher. PBLs cultured in a glucose-free medium contained a significantly higher percentage of IL-4-positive and a lower percentage of IFN-γ-positive CD4(+) T cells compared with those cultured in a high-glucose medium. Nutrient deprivation suppressed the proliferation of PBLs, fostered the secretion of IL-4 and reduced secretion of IFN-γ. It is therefore possible that glucose-deficient microenvironments in local cancer tissues cause a partial immunodeficiency, which is advantageous to cancer growth.
10.3892/mco.2016.763
pubmed_292_18193
Intradural extramedullary tuberculoma of the spinal cord (IETSC) is an uncommon disease which can occurs secondary to tuberculous meningitis. A 31-year-old woman was diagnosed as tuberculous meningitis after mental disorientation. Her mentality was recovered after antituberculous therapy. After 7 months of antituberculous therapy, paraplegia has developed. Magnetic resonance imaging (MRI) revealed a mass lesion between the T1 and T12 spinal levels with arachnoid thickening which results in the development of tuberculoma. She received surgical resection of IETSC followed by antituberculous therapy and neurological function has been improved. The two years after surgical treatment, spinal MRI showed syringomyelia between T1 to L1. But, her neurological outcome was not aggravated.
10.14245/kjs.2015.12.2.107
pubmed_1019_3520
PURPOSE OF REVIEW To provide a clinically relevant synopsis of research findings regarding childhood and adolescent vaccines. RECENT FINDINGS Much research confirms the safety, immunogenicity, and efficacy of specific vaccines as well as the positive impact on overall morbidity and mortality. Prevention and control strategies involve the expansion of vaccine recommendations to include more individuals and/or more vaccine doses. In addition, the role of universal infant vaccination, the advantages of even partial immunization, and the documented benefits of recently introduced vaccines are explored. The material in this review includes important areas of clinical practice improvement, such as awareness of interim recommendations or monitoring of vaccine failures. Literature on hepatitis B, rotavirus, Haemophilus influenzae type b conjugate, and pneumococcal vaccines is included in this first of two articles. SUMMARY New research on childhood and adolescent vaccines is anticipated to shape the practice of pediatric providers. Research will continue to provide the science to optimize protection and to promote the health and well being of all children and adolescents.
10.1097/MOP.0b013e32834877f1
pubmed_365_5499
Iron-chelating low-molecular-weight compounds or catecholate siderophores have been suggested to be involved in wood biodegradation. To help in understanding the mechanism involved in the enzyme-like activity of catecholate siderophores, the oxidative properties of 2,3-dihydroxybenzoic acid (DHBA) and 3, 4-dihydroxyphenylacetic acid (DHPAA) chelated with iron were studied. The pH and catechol/Fe(III) ratios were optimized for o-dianisidine oxidation, obtaining a maximum at pH 7.0, in the absence of buffer, and a catechol/Fe(III) ratio of 1:2 to DHBA and 1:1 to DHPAA was found. Under these conditions, the catechols were able to reduce Fe(III) to Fe(II) acting like siderophore models. The Fe(III) complex of DHBA and of DHPAA degraded dioxane-lignin in 60% after 2 h and 85% after 24 h, respectively. DHBA/Fe(III) oxidized the bleaching effluent (E1) in 80% in 5 min under the studied conditions.
10.1006/bbrc.1998.9315
pubmed_579_1356
OBJECTIVES Predictors of acute hematologic toxicities during definitive chemoradiation for non-small cell lung cancer (NSCLC) are incompletely defined. MATERIALS AND METHODS We retrospectively analyzed 604 patients treated with definitive platinum-based doublet chemoradiation therapy for stage III NSCLC. The outcome of interest was grade ≥3 acute hematologic toxicities, specifically white blood cell, hemoglobin, platelet, neutrophil, and lymphocyte decrease during chemoradiation therapy. We assessed the association between any grade ≥3 acute hematologic toxicity with patient demographic, disease, radiation factors (specifically modality and dose), and chemotherapy agents via stepwise multivariate logistic regression. Survival was compared via log-rank and univariate Cox regression analyses. RESULTS There was no significant association between radiation modality and any hematologic toxicity on multivariate analysis. However, use of etoposide was found to be significantly associated with white blood cell, platelet, and neutrophil decrease compared with paclitaxel and docetaxel (all P<0.05). No differences were found between platinum agents. Overall survival (OS) and event-free survival (EFS) were significantly worse in patients who experienced grade ≥3 hemoglobin (OS: hazard ratio [HR]=1.5; 95% confidence interval [CI], 1.05-2.26; P=0.03, EFS: HR=1.7; 95% CI, 1.2-2.4; P=0.0032) and lymphocyte (OS: HR=1.5; 95% CI, 1.1-2.1; P=0.01, EFS: HR=1.4; 95% CI, 1.1-1.9; P=0.02) decreases. CONCLUSIONS Chemotherapy identity, specifically the nonplatinum agent, was significantly associated with grade ≥3 hematologic toxicities, whereas radiation modality was not.
10.1097/COC.0000000000000206
pubmed_271_23510
Neural circuits associated with response conflict are active during deception. Here we use transcranial magnetic stimulation to examine for the first time whether competing responses in primary motor cortex can be used to detect lies. Participants used their little finger or thumb to respond either truthfully or deceitfully regarding facial familiarity. Motor-evoked-potentials (MEPs) from muscles associated with both digits tracked the development of each motor plan. When preparing to deceive, the MEP of the non-responding digit (i.e. the plan corresponding to the truth) exceeds the MEP of the responding digit (i.e. the lie), whereas a mirror-reversed pattern occurs when telling the truth. This give away response conflict interacts with the time of stimulation during a speeded reaction period. Lies can even activate digit-specific cortical representations when only verbal responses are made. Our findings support neurobiological models which blend cognitive decision-making with motor programming, and suggest a novel index for discriminating between honest and intentionally false facial recognition.
10.1016/j.biopsycho.2011.12.019
pubmed_449_1723
Leucinostatin, a peptide antibiotic, was separated by silica gel and alumina column chromatography into two related components designated as leucinostatin A hydrochloride (C61H111-N11O13.HCl) and leucinostatin B hydrochloride (C61H109N11O13.HCl). Physico-chemical as well as biological properties of the two separated components were analyzed. These properties pointed to closely resembling chemical structures.
10.7164/antibiotics.36.1606
pubmed_268_2129
In order to investigate the relationship between coronary perfusion pressure and blood flow distribution in the left ventricle (LV), we measured myocardial blood flow in small regions using radioactive microspheres in six anesthetized, open-chest dogs. Mean coronary perfusion pressure (CPP) was controlled with a femoral artery to left main coronary artery shunt which included a pressurized, servo-controlled blood reservoir. In each dog, we measured flow in 192 regions of the LV free wall (mean weight per region = 206 +/- 38 mg) at different perfusion pressures. At CPP = 80 mm Hg, blood flow to individual regions varied fourfold (0.30 to 1.18 ml/min/g; relative dispersion (RD) = 21.8 +/- 2.3%). At CPP = 50 mm Hg, flow varied over sevenfold (0.08 to 0.60 ml/min/g; RD = 42.8 +/- 10%; P less than 0.01 vs 80 mm Hg). This relationship between flow variability and CPP was present within individual LV layers as well between layers and is much higher than the error associated with the microsphere technique. We conclude that blood flow to small regions of the LV is markedly nonuniform. This heterogeneity becomes more profound at lower CPP. These findings suggest that (1) global measurements of coronary flow must be interpreted with caution, and (2) even in hearts with normal coronary arteries some regions of the LV are more susceptible to ischemia than others. In addition, these findings may help explain the patchy nature of myocardial damage that occurs following periods of low coronary pressure or inadequate myocardial protection during cardiopulmonary bypass.
10.1016/0022-4804(90)90183-3
pubmed_827_19496
This was a hospital based prospective study to determine the cut-off respiratory rates which can identify children (age < or =14.5 yr) with sever pneumonia with chest indrawing and to evaluate the validity of the cutoff respiratory rate so obtained in identifying sever pneumonia requiring hospitalization. All children diagnosed with pneumonia (radiologically proven) between September 1997 and October 1999 were enrolled. Of 1,665 cases, 54.7% were males; the median age was 1.8 yr (range 8 days-14.5 yr, mean 2.8 +/- 2.7 yr). Frequency of hospitalization, tachypnea and chest indrawing were 29.9%, 58.9% and 42.7%. In hospitalized children, cutoff respiratory rate > or =57, > or =48, and > or =36 were found to identify sever pneumonia requiring hospitalization in the age groups 2-11 mo, 12-59 mo and > or =5 yr, respectively.
pubmed_827_19496
pubmed_572_15593
Alpha7 nicotinic acetylcholine receptors (α7 nAChRs) are important drug targets in neurological disorders and inflammation, making their detection and localization by validated antibodies highly desirable. However, tests in knockout animals raised questions about specificity of antibodies to mouse α7 nAChRs. To date, methods for validating antibodies for rat or human α7 nAChR have not been reported. We developed a gel-shift assay for western blots using GH4C1 cells expressing either native rat receptors or α7 nAChR-green fluorescent protein (GFP) chimeras to evaluate seven commercially available α7 nAChR antibodies. Blots with anti-GFP antibody detected GFP or α7 nAChR-GFP expressed in GH4C1 cells, and 125I-α-bungarotoxin binding and RNA analysis demonstrated α7 nAChR expression. Validated samples were used to evaluate α7 nAChR antibodies by western blot and immunofluorescence studies. These methods confirmed that two of seven α7 nAChR antibodies identify gel-shifts for α7 nAChR/nAChR-GFP but only one antibody demonstrated low background and significant immunofluorescence differences between wild-type and α7 nAChR expressing GH4C1 cells. However, that polyclonal antibody displayed lot-to-lot variability. Our findings suggest that careful validation methods are required for all α7 nAChR receptor species and antibody lots and that the gel-shift assay may allow for relatively rapid antibody screening.
10.1369/0022155417725304
pubmed_568_15162
AIM The aim of this study is to elucidate the demographics, symptoms and outcome of sick persons visiting coronavirus (COVID) screening OPD of a tertiary institute in North India. STUDY DESIGN The present descriptive, prospective study was done on 1030 patients and information about presenting symptoms, demographics (age, sex, nationality, residence), contact and travel history, comorbidities etc., were recorded. On the basis of criteria given by Indian Council of Medical Research, patients were divided into suspected (SARS-CoV-2) and non-suspected group. Of the suspected patients, with RT-PCR test positive were classified as confirmed COVID-19 case and negative RT-PCR symptomatic individual were defined as negative COVID-19 case. RESULTS Out of the total patients, 65.6% were male and 34.4% were females. The mean age was 37.04 years. Fever 49.3%, cough 57.1% and sore throat 43.5% were the main symptoms. Comorbidities were seen in 8.5% patients with hypertension (3.5%) and diabetes mellitus (3.4%). Forty patients were positive. Highly significant correlation (P < 0.01) was found between COVID-19 positive status and in patients without any symptoms, between COVID-19 and cough and sore throat, between COVID-19 and comorbidity (diabetes mellitus), between COVID-19 and high-risk exposures (resident of hot spot and history of contact with confirmed case). Our study also found COVID-19 positive status, shortness of breath and tachycardia as independent predictors of mortality (P < 0.05). CONCLUSIONS Most of the patients were young adults and males were mainly affected. Main presentation was cough followed by fever. Infectivity was higher in patients who had underlying comorbid diseases, especially diabetes and chronic kidney disease. Critical patients with decreased oxygen saturation, tachypnoea and tachycardia had strong predictability for COVID-19 positivity. COVID-19 positive status, shortness of breath and tachycardia are important predictors of mortality.
10.4103/jfmpc.jfmpc_1827_20
pubmed_757_7773
Life expectancy has increased by three decades since the mid-twentieth century. Parallel healthspan expansion has however not followed, largely impeded by the pandemic of chronic diseases afflicting a growing older population. The lag in quality of life is a recognized challenge that calls for prioritization of disease-free longevity. Contemporary communal, clinical and research trends aspiring to extend the health horizon are here outlined in the context of an evolving epidemiology. A shared action integrating public and societal endeavors with emerging interventions that target age-related multimorbidity and frailty is needed. A multidimensional buildout of a curative perspective, boosted by modern anti-senescent and regenerative technology with augmented decision making, would require dedicated resources and cost-effective validation to responsibly bridge the healthspan-lifespan gap for a future of equitable global wellbeing.
10.1038/s41536-021-00169-5
pubmed_532_1845
BACKGROUND Surges in heart rate (HR) and blood pressure (BP) at apnea termination contribute to the hypertension seen in obstructive sleep apnea (OSA). Because childhood OSA prevalence peaks in the preschool years, we aimed to characterize the cardiovascular response to obstructive events in preschool-aged children. METHODS Clinically referred children aged 3-5 years were grouped by obstructive apnea-hypopnea index (OAHI) into the following: primary snoring (PS) (OAHI≤1 event/h [n=21]), mild OSA (OAHI>1-≤5 [n=32]), and moderate to severe (MS) OSA (OAHI>5 [n=28]). Beat-to-beat pulse transit time (PTT), an inverse continuous indicator of BP changes, and HR were averaged during the two halves (early and late) and during the peak after (post) each obstructive event and were expressed as percentage change from late- to post-event. RESULTS We analyzed 422 events consisting of 55 apneas and 367 hypopneas. A significant post-event increase in HR and fall in PTT occurred in all severity groups (P<.05 for all). A greater response was associated with OSA, nonrapid eye movement sleep (NREM), cortical arousal, hypopneas, and oxygen desaturation (P<.05 for all). CONCLUSIONS Obstructive events elicit acute cardiovascular changes in preschool children. Such circulatory perturbations have been implicated in the development of hypertension, and our findings complement previous studies to suggest a cumulative impact of snoring on the cardiovascular system from childhood into adulthood.
pubmed_532_1845
pubmed_235_19451
Numerous mass spectrometry-based strategies ranging from hydrogen-deuterium exchange to ion mobility to native mass spectrometry have been developed to advance biophysical and structural characterization of protein conformations and determination of protein-ligand interactions. In this study, we focus on the use of ultraviolet photodissociation (UVPD) to examine the structure of human carbonic anhydrase II (hCAII) and its interactions with arylsulfonamide inhibitors. Carbonic anhydrase, which catalyzes the conversion of carbon dioxide to bicarbonate, has been the target of countless thermodynamic and kinetic studies owing to its well-characterized active site, binding cavity, and mechanism of inhibition by hundreds of ligands. Here, we showcase the application of UVPD for evaluating structural changes of hCAII upon ligand binding on the basis of variations in fragmentation of hCAII versus hCAII-arylsulfonamide complexes, particularly focusing on the hydrophobic pocket. To extend the coverage in the midregion of the protein sequence, a supercharging agent was added to the solutions to increase the charge states of the complexes. The three arylsulfonamides examined in this study largely shift the fragmentation patterns in similar ways, despite their differences in binding affinities.
10.1021/jasms.1c00004
pubmed_150_10137
OBJECTIVES To describe lung transplant recipients (LTRs') acceptance and use of mobile technology for health self-monitoring during the first year post-transplantation, and explore correlates of the use of technology in the 0 to 2, >2 to ≤6, >6 to ≤12, and 0 to 12 months. METHODS Secondary analysis of data from 96 LTR assigned to use Pocket PATH(®), a smartphone application, for daily health self-monitoring in a randomized controlled trial. Use of Pocket PATH was categorized as low, moderate, and high use. Proportional odds models for ordinal logistic regression were employed to explore correlates of use of technology. RESULTS LTR reported high acceptance of Pocket PATH at baseline. However, acceptance was not associated with actual use over the 12 months (p=0.45~0.96). Actual use decreased across time intervals (p<0.001). Increased self-care agency was associated with the increased odds of higher use in women (p=0.03) and those less satisfied with technology training (p=0.02) in the first 2 months. Higher use from >2 to ≤6 months was associated with greater satisfaction with technology training (OR=3.37, p=0.01) and shorter length of hospital stay (OR=0.98, p=0.02). Higher use from >6 to ≤12 months was associated with older age (OR=1.05, p=0.02), lower psychological distress (OR=0.43, p=0.02), and better physical functioning (OR=1.09, p=0.01). Higher use over 12 months was also associated with older age (OR=1.05, p=0.007), better physical functioning (OR=1.13, p=0.001), and greater satisfaction with technology training (OR=3.05, p=0.02). CONCLUSIONS Correlates were different for short- and long-term use of mobile technology for health self-monitoring in the first year post-transplantation. It is important to follow up with LTR with longer hospital stay, poor physical functioning, and psychological distress, providing ongoing education to improve their long-term use of technology for health self-monitoring.
10.4338/ACI-2015-12-RA-0170
pubmed_456_6498
Tissue-nonspecific alkaline phosphatase (TNAP) is a key enzyme in the biomineralization process as it produces phosphate from a number of phospho-substrates stimulating mineralization while it also inactivates inorganic pyrophosphate, a potent mineralization inhibitor. We have previously reported on the reconstitution of TNAP on Langmuir monolayers as well as proteoliposomes. In the present study, thin films composed of dimyristoylphosphatidic acid (DMPA) were deposited on titanium supports by the Langmuir-Blodgett (LB) technique, and we determined preservation of TNAP's phosphohydrolytic activity after incorporation into the LB films. Increased mineralization was observed after exposing the supports containing the DMPA:TNAP LB films to solutions of phospho-substrates, thus evidencing the role of TNAP on the growth of calcium phosphates after immobilization. These coatings deposited on metallic supports can be potentially applied as osteoconductive materials, aiming at the optimization of bone-substitutes integration in vivo.
10.1016/j.abb.2019.01.014
pubmed_864_11998
Annexin II receptor (AXIIR) is also known as chromosome 5 open reading frame 39 (C5orf39), it was originally identified as a cell surface receptor for Annexin II. AXIIR gene is peculiar to human. So far, the only known function about AXIIR is mediating Annexin II signal. In this study, we find that over-expression of AXIIR induces apoptosis, and this phenomenon is found in multiple human cell types. AXIIR is located in cytoplasm, binds to and activates pro-Caspase-8, which subsequently activates Caspase-3/7. AXIIR also down-regulates BCL2, BCL-XL, and activates Caspase-9, which finally activates Caspase-3/7 as well. Over-expression of BCL-XL does not affect AXIIR-induced apoptosis, whereas inhibition of Caspase-8 partially abolished AXIIR-induced apoptosis. AXIIR induces apoptosis independent of Annexin II and FADD. AXIIR is neither required for TRAIL-induced Caspase-8 activation. Although the transcriptional level of AXIIR in multiple cell types is considerably high, the translational level of AXIIR can hardly be detected. And inhibition of protein degradation pathways does not elevate AXIIR expression. Taken together, our observations reveal that besides being a cell surface receptor of Annexin II, AXIIR can also be located in cytoplasm and act as a novel inducer of apoptosis in human cells, partially through activating Caspase-8 in a manner that is different from conventional apoptotic pathways. The translation of AXIIR is generally tightly inhibited in cells. The physiological significance of such inhibition might be to prevent cells from apoptosis.
10.1007/s10495-013-0846-2
pubmed_692_19891
OBJECTIVE To retrospectively evaluate the clinical feasibility of high-pitch excretory phase images during dual-source CT urography with Stellar photon detector. METHODS Totally 100 patients received dual-source CT high-pitch urinary excretory phase scanning with Stellar photon detector [80 kV, ref.92 mAs, CARE Dose 4D and CARE kV, pitch of 3.0, filter back projection reconstruction algorithm (FBP)] (group A). Another 100 patients received dual-source CT high-pitch urinary excretory phase scanning with common detector(100 kV, ref.140 mAs, CARE Dose 4D, pitch of 3.0, FBP) (group B). Quantitative measurement of CT value of urinary segments (Hounsfield units), image noise (Hounsfield units), and effective radiation dose (millisievert) were compared using independent-samples t test between two groups. Urinary system subjective opacification scores were compared using Mann-Whitney U test between two groups. RESULTS There was no significant difference in subjective opacification score of intrarenal collecting system and ureters between two groups (all P>0.05). The group A images yielded significantly higher CT values of all urinary segments (all P<0.01). There was no significant difference in image noise (P>0.05). The effective radiation dose of group A (1.1 mSv) was significantly lower than that of group B (3.79 mSv) (P<0.01). CONCLUSION High-pitch low-tube-voltage during excretory phase dual-source CT urography with Stellar photon detector is feasible, with acceptable image noise and lower radiation dose.
10.3881/j.issn.1000-503X.2014.05.011
pubmed_708_3216
We have isolated a chimpanzee processed pseudogene for subunit IV of cytochrome c oxidase (COX; EC 1.9.3.1) by screening a chimpanzee genomic library in lambda Charon 32 with a bovine liver cDNA encoding COX subunit IV (COX IV), and localized it to a 1.9-kb HindIII fragment. Southern-blot analysis of genomic DNA from five primates showed that DNAs from human, gorilla, and chimpanzee each contained the 1.9-kb pseudogene fragment, whereas orangutan and pigtail macaque monkey DNA did not. This result clearly indicates that the pseudogene arose before the divergence of the chimpanzee and gorilla from the primate lineage. By screening Chinese hamster x human hybrid panels with the human COX4 cDNA, we have mapped COX4 genes to two human chromosomes, 14 and 16. The 1.9-kb HindIII fragment containing the pseudogene, COX4P1, can be assigned to chromosome 14, and by means of rearranged chromosomes in somatic cell hybrids, to 14q21-qter. Similarly, the functional gene, COX4, has been mapped to 16q22-qter.
10.1016/0378-1119(90)90281-u
pubmed_60_23190
The aim of this study was to investigate the histochemical parameters of muscle fibers, and to estimate the correlation of muscle fiber characteristic to postmortem metabolic rate and meat quality traits in pigs. A total of 231 crossbred pigs were evaluated. Samples of the longissimus dorsi muscle were taken to evaluate the histochemical characteristics, postmortem metabolic rate and meat quality. Fiber type composition was mainly related to postmortem metabolic rate and meat quality traits among various muscle fiber characteristics. The percentage of type IIb fiber was negatively related to pH(45min) (r=-0.33) and positively to R-value (r=0.32). Drip loss was negatively related to fiber area percentages of type I and IIa (r=-0.25 and -0.26, respectively) and positively related to type IIb percentage (r=0.39). A similar tendency was found between lightness and fiber area percentage. In conclusion, increasing the percentage of type IIb fiber is related to increasing the postmortem metabolic rate, and is related to the deterioration of meat quality.
10.1016/j.meatsci.2005.04.015
pubmed_333_694
Rejection of a xenograft by BALB/c mice results in a highly potent immune peritoneal population. When these immune cells are analysed by using two in vitro assays in parallel, at least two active cytotoxic mechanisms can be demonstrated. Target cells can be labelled with [125I]iododeoxyuridine (IUdR) before the effector cells are added and the detachment of the DNA from plastic can be used to detect cell-mediated immunity. This is referred to as the direct cytotoxicity test. This assay is largely dependent on T-cell function and evidence is presented here that it can be inhibited by anti-immunoglobulin (anti-Ig) antisera. The second test, which reflects the inhibition of incorporation of IUdR by previously mixed effector and target cells, is called the cytostatic assay. This test, although presumably affected by cytotoxic T cells, also reflects a T-independent mechanism which is not inhibited by anti-Ig sera.
pubmed_333_694
pubmed_789_16982
Understanding the numerous functions that RNAs play in living cells depends critically on knowledge of their three-dimensional structure. Due to the difficulties in experimentally assessing structures of large RNAs, there is currently great demand for new high-resolution structure prediction methods. We present the novel method for the fully automated prediction of RNA 3D structures from a user-defined secondary structure. The concept is founded on the machine translation system. The translation engine operates on the RNA FRABASE database tailored to the dictionary relating the RNA secondary structure and tertiary structure elements. The translation algorithm is very fast. Initial 3D structure is composed in a range of seconds on a single processor. The method assures the prediction of large RNA 3D structures of high quality. Our approach needs neither structural templates nor RNA sequence alignment, required for comparative methods. This enables the building of unresolved yet native and artificial RNA structures. The method is implemented in a publicly available, user-friendly server RNAComposer. It works in an interactive mode and a batch mode. The batch mode is designed for large-scale modelling and accepts atomic distance restraints. Presently, the server is set to build RNA structures of up to 500 residues.
10.1093/nar/gks339
pubmed_639_23438
PURPOSE To describe the clinical and molecular spectrum of Stargardt disease (STGD) in a cohort of Argentinean patients. METHODS This retrospective study included 132 subjects comprising 95 probands clinically diagnosed with STGD and relatives from 16 of them. Targeted next-generation sequencing of the coding and splicing regions of ABCA4 and other phenocopying genes (ELOVL4, PROM1, and CNGB3) was performed in 97 STGD patients. RESULTS We found two or more disease-causing variants in the ABCA4 gene in 69/95 (73%) probands, a single ABCA4 variant in 9/95 (9.5%) probands, and no ABCA4 variants in 17/95 (18%) probands. The final analysis identified 173 variants in ABCA4. Seventy-nine ABCA4 variants were unique, of which nine were novel. No significant findings were seen in the other evaluated genes. CONCLUSION This study describes the phenotypic and genetic features of STGD1 in an Argentinean cohort. The mutations p.(Gly1961Glu) and p.(Arg1129Leu) were the most frequent, representing almost 20% of the mutated alleles. We also expanded the ABCA4 mutational spectrum with nine novel disease-causing variants, of which eight might be associated with South American natives.
10.3389/fgene.2021.646058
pubmed_698_12873
BACKGROUND Published literature that describes the use of the Internet by nurses is scant, but it does reveal that there has been a delay in the acceptance of the Internet as a workplace tool by the medical community and, in particular by nurses. AIMS The purpose of this article is to report on a study of how often and from what location nurses accessed the Internet, as well as the types of information they were seeking. In addition, our goal was to compare nurses' Internet use with that of physicians and the public at large, and to highlight structural and institutional challenges to nurses' use. METHODS Surveys (1996 and 1998) of Alberta Registered Nurses were used to examine their use of technology at work and at home. Additional data sources were used to compare nurses to physicians and to the general public. RESULTS While nurses' Internet and e-mail use at home increased over the 2-year period and was comparable with other groups, Internet use at work was low compared with other groups despite adequate workplace access. CONCLUSIONS Nurses are more likely to value interpersonal contact, and prefer to use personal experience and communication with colleagues and patients rather than on-line and traditional sources of practice knowledge. In order for an information source to be seen as valuable in the clinical setting, contextually relevant information needs to be accessed quickly and efficiently. Energies should be focused on constructing information systems that address the particular needs of nurses.
10.1046/j.1365-2648.2003.02581.x
pubmed_916_11931
The high prevalence of obesity and associated chronic conditions in persons with severe and persistent mental illness has contributed to a mortality rate that is nearly two times higher than the overall population. In 2008, the Central O'ahu Community Mental Health Center of the Hawai'i State Department of Health, Adult Mental Health Division began an unfunded, health counseling intervention pilot project to address such concerns for the health of persons with severe and persistent mental illness. This article reviews the results of this intervention. Forty-seven persons with schizophrenia or related disorders were included in the intervention which involved health counseling and monitoring of weight as a risk factor for chronic disease. After five years of counseling and monitoring, medical chart reviews were conducted for each person for data on weight change. Analysis showed weight loss and improvements in body mass index. The results of this project show potential for long-term counseling and monitoring as an intervention for obesity in persons with severe and persistent mental illness.
pubmed_916_11931
pubmed_419_17687
Polybenzimidazoles (PBI) doped with phosphoric acid (PA) are promising electrolytes for medium temperature fuel cells. Their significant disadvantage is a partial or complete loss of mechanical properties and an increase in hydrogen permeability at elevated temperatures. Covalent silanol crosslinking is one possible way to stabilize PBI membranes in the presence of PA. Three organo-substituted silanes, namely (3-Bromopropyl)trimethoxysilane (SiBr), trimethoxy [2-(7-oxabicyclo [4.1.0]hept-3-yl)ethyl]silane (Si-biC) and (3-Glycidyloxypropyl)trimethoxysilane (KH 560), were used as covalent crosslinkers of PBI-O-PhT in order to determine the effect of the silane structure and crosslinking degree on membrane properties. The crosslinking degree was 1-50%. All crosslinked membranes were characterized by impedance and IR-spectroscopy. The mechanical properties, morphology, stability and hydrogen permeability of the membranes were determined. In the case of silanes with linear substituents (SiBr, KH 560), a denser structure is formed, which is characterized by greater oxidative stability and lower hydrogen permeability in comparison to the silane with a bulk group. All the crosslinked membranes have a higher mechanical strength compared with the initial PBI-O-PhT membrane both before and after doping with PA. Despite the hardening of the polymer matrix of the membranes, their proton conductivity changes insignificantly. It was shown that cross-linked membranes can be used in fuel cells.
10.3390/membranes12111078
pubmed_1058_12497
The largest voluntary loads on bones come from muscles. To adapt bone strength and mass to them, special strain threshold ranges determine where modeling adds and strengthens bone, and where remodeling conserves or removes it, just as different thermostat settings control the heating and cooling systems in a house. If estrogen lowers the remodeling threshold, two things should occur. First, at puberty in girls, bone mass should begin to increase more than in boys with similar muscle strengths, owing to reduced remodeling-dependent bone losses, while gains from longitudinal bone growth and bone modeling continue normally. That increase in bone mass in girls should plateau when their muscle strength stops increasing, since their stronger bones could then reduce bone strains enough to turn modeling off, but could let remodeling keep conserving existing bone. Second, decreased estrogen secretion [or a related factor(s)], as during menopause, should raise the remodeling threshold and make remodeling begin removing that extra bone. That removal should also tend to plateau after the remaining and weaker bone lets bone strains rise to the higher threshold. Postmenopausal bone loss shows the second effects. Previously unremarked relationships in the data of a 1995 Argentine study showed the first effects. This supports the idea that estrogen can affect human bone strength and mass by lowering the remodeling threshold, and loss of estrogen would raise the threshold and help cause postmenopausal bone loss even if other factors help to do it. The Argentine study also suggested ways to study those things and the roles of muscle strength and other factors in controlling bone strength and mass in children and adult humans. Those factors included, in part, hormones, vitamins, calcium, diet, sex, race, age, medications, cytokines, genetic errors, gene expression patterns, and disease.
10.1016/s8756-3282(97)00223-8
pubmed_476_13688
Construction and assembly pistols are widely used but single observations are described in the forensic medical literature and, as a rule, concerning shots to the head. An unusual case of suicide by a shot in the neck from a TOUA 307 construction and assembly pistol is presented: a blind shell wound was found to the left half of the neck and with damage to the cervical spine and spinal cord. The above observation complements the existing ideas about the possibility of causing self-harm from an atypical weapon - a construction and assembly pistol.
10.17116/sudmed20226501146
pubmed_441_7335
This paper, based on a recent visit to Denmark, outlines some aspects of the Danish system of delivering services to the mentally handicapped that contrast sharply wtih the United Kingdom system. It attempts to review some of the implications of putting into practice a philosophy of normalization, viewed from both the administrative and client standpoints.
10.1111/j.1365-2214.1981.tb00818.x
pubmed_517_17974
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT SLCO1B3 is an influx transporter located at the hepatocyte basolateral membrane and it is involved in the uptake of a broad range of drug substrates including docetaxel. The pharmacogenetics of SLCO1B3 is not well characterized and previous in vivo and in vitro studies reported conflicting results with regards to the functional effects of the limited number of SLCO1B3 polymorphisms that were studied. Docetaxel displays a wide interindividual variability in its pharmacokinetics and pharmacodynamics and an understanding of SLCO1B3 pharmacogenetics might provide clinical benefits in guiding docetaxel dosing. WHAT THIS STUDY ADDS The SLCO1B3 gene was comprehensively screened in the local healthy Asian populations (n= 168). A strong linkage disequilibrium pattern was detected across a total of 88 polymorphisms and 15 haplotype-tag SNPs (htSNPs) were identified. These htSNPs were profiled in a cohort of Chinese nasopharyngeal cancer (NPC) patients (n= 50). Genotypic-phenotypic analysis showed that a haplotypic construct comprising of four variants [IVS4+76G>A, 699G>A(Met233Ile), IVS12-5676A>G, and *347_*348insA] was the critical determinant of docetaxel disposition. This study suggests that the comprehensive screening and haplotypic linkage analysis of SLCO1B3 can better elucidate its pharmacogenetic effects on interpatient variability of docetaxel and other putative drug substrates. Further studies are warranted in cancer patients belonging to other ethnic groups. AIMS To completely screen the SLCO1B3 gene in three distinct healthy Asian populations (Chinese, Malay and Indian, n= 168) and investigate the influence of haplotype-tag SNPs (htSNPs) on docetaxel disposition in 50 nasopharyngeal carcinoma patients. METHODS Genomic DNA of individuals was screened for SLCO1B3 polymorphisms by direct sequencing. htSNPs were derived based on the sequence clustering algorithm and profiled in the patients. Population based genetic association analysis was performed using Haplostats package implemented in R and PLINK. RESULTS A strong linkage disequilibrium pattern was detected across a total of 88 polymorphisms and 15-htSNPs were identified. The SLCO1B3 haplotypic region comprising seven htSNPs was found to be significantly associated with docetaxel clearance (P= 0.003). Conditional haplotype analyses revealed that the haplotypic constructs comprising the IVS4+76G>A, 699G>A(Met233Ile), IVS12-5676A>G, and *347_*348insA polymorphisms were critical determinants of variability in docetaxel disposition [clearance and area under the plasma concentration-time curve (AUC(0,∞)): r(2) = 29% and 22%, respectively]. Patients harbouring the GAG*347insA haplotype were significantly associated with a 30% decrease in clearance and a 40% increase in AUC(0,∞) of docetaxel compared with patients harbouring the reference haplotype, GGA*347wt (P= 0.025 and 0.018, respectively). In contrast, a 50% higher clearance was observed in patients carrying the GAG*347wt haplotype compared with those with the reference haplotype (P= 0.002). The functional SLCO1B3 haplotypic constructs included the widely studied Met233Ile variant and *347_*348insA located in the putative miR-890 binding site in the 3'-untranslated region which may influence the transport characteristics of SLCO1B3. CONCLUSIONS This study highlights the importance of SLCO1B3 polymorphic variations in influencing docetaxel disposition in nasopharyngeal carcinoma patients.
10.1111/j.1365-2125.2011.04123.x
pubmed_437_17900
Lysosomal soluble proteins are targeted to endosomes and lysosomes by specific receptors resident in the endoplasmic reticulum and/or the Golgi apparatus. The enteric protozoan parasite Entamoeba histolytica has a novel class of lysosomal targeting receptors, named the cysteine protease binding protein family (CPBF). Among 11 CPBFs (CPBF1-11), ligands for three members, CPBF1, CPBF6 and CPBF8, were previously shown to be cysteine proteases, α- and γ- amylases, and β-hexosaminidase and lysozymes, respectively. To further understand the heterogeneity of the ligands of CPBFs, we attempted to isolate and identify the ligands for other members of CPBFs, namely CPBF2, 3, 4, 5, 7, 9, 10 and 11, by immunoprecipitation and mass spectrometric analysis. We found that CPBF2 and CPBF10 bound to α-amylases while CPBF7 bound to β-hexosaminidases. It is intriguing that cysteine protease are exclusively recognised by CPBF1, whereas three α-amylases and β-hexosaminidases are redundantly recognised by three and two CPBFs, respectively. It was shown by bioinformatics analysis and phylogenetic reconstruction that each CPBF contains six prepeptidase carboxyl-terminal domains, and the domain configuration is evolutionarily conserved among CPBFs. Taken together, CPBFs with unique and conserved domain organisation have a remarkable ligand heterogeneity toward cysteine protease and carbohydrate degradation enzymes. Further structural studies are needed to elucidate the structural basis of the ligand specificity.
pubmed_437_17900
pubmed_708_316
O2-evolving photosystem II (PSII) membranes from spinach have been cryogenically stabilized in the S3 state of the oxygen-evolving complex. The cryogenic trapping of the S3 state was achieved using a double-turnover illumination of dark-adapted PSII preparations maintained at 240 K. A double turnover of PSII was accomplished using the high-potential acceptor, Q400, which is the high-spin iron of the iron-quinone acceptor complex. EPR spectroscopy was the principal tool establishing the S-state composition and defining the electron-transfer events associated with a double turnover of PSII. The inflection point energy of the Mn X-ray absorption K-edge of PSII preparations poised in the S3 state is the same as for those poised in the S2 state. This is surprising in light of the loss of the multiline EPR signal upon advancing to the S3 state. This indicates that the oxidative equivalent stored within the oxygen-evolving complex (OEC) during this transition resides on another intermediate donor which must be very close to the manganese complex. An analysis of the Mn extended X-ray absorption fine structure (EXAFS) of PSII preparations poised in the S2 and S3 states indicates that a small structural rearrangement occurs during this photoinduced transition. A detailed comparison of the Mn EXAFS of these two S states with the EXAFS of four multinuclear mu-oxo-bridged manganese compounds indicates that the photosynthetic manganese site most probably consists of a pair of binuclear di-mu-oxo-bridged manganese structures. However, we cannot rule out, on the basis of the EXAFS analysis alone, a complex containing a mononuclear center and a linear trinuclear complex. The subtle differences observed between the S states are best explained by an increase in the spread of Mn-Mn distances occurring during the S2----S3 state transition. This increased disorder in the manganese distances suggests the presence of two inequivalent di-mu-oxo-bridged binuclear structures in the S3 state.
10.1021/bi00454a023