title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
|---|---|---|
[Quality of life specific questionnaire for constipated patients: development and validation of CVE-20]. | Although constipation affects quality of life, questionnaires hardly exist for its evaluation. We aimed to develop and validate a questionnaire able to measure the quality of life in patients with constipation. A Spanish multicenter study was performed in 2 stages: a) questionnaire development (open interview to patients with constipation, pilot questionnaire, quantitative and factorial analysis, Rasch analysis, and specific questionnaire design), and b) questionnaire validation in 136 patients. These patients were divided in 2 groups: a) reliability group (n = 55; no need to begin or change treatment; re-tested after 15 days), and b) sensibility to change group (n = 81; need to begin or change treatment; re-tested after 3 months). We collected clinical and socio-demographic data and we evaluated the quality of life through the general questionnaire EuroQoL-5D (EQ-5D) and the specific one, design in the previous stage (25 items). After that, we analysed feasibility, reliability and validity (of content, convergent and longitudinal). The trial questionnaire was obtained during the development stage and the results were 51 items that were later reduced to 25 in the validation stage. A total of 126 patients (93% women; mean age [standard deviation]: 43.4 [1] years) completed the study properly. The answer average time was 12 min. The content validity process reduced the questionnaire to 20 items (CVE-20) within 4 domains: emotional, general physical, rectal physical and social. The reliability was good in relation to the general punctuation (Cronbach alpha coefficient = 0.87), being in the different domains of 0.79, 0.73, 0.75 and 0.60, respectively. The construct validity showed a good correlation between the CVE-20 results and constipation severity. The CVE-20 score positively correlated with EQ -5D changes. The test and re-test reliability were good: interclass correlation coefficient = 0.89 (ranging from 0.80 to 0.88 in the different domains). The clinically relevant and minimal difference was 17 points (95% confidence interval, 11-23). The content validity showed a strong correlation between CVE-20 and constipation severity. The CVE-20 is the first specific questionnaire in Spanish language for constipated patients; it is valid, reliable, sensitive to changes and it meets the psychometric requirements to be applied in daily practice and clinical trials. | 18,842,210 |
[Posterior reversible leukoencephalopathy in a patient with postpartum eclampsia]. | We report the clinical-radiological case of a 25 year-old female patient who developed reversible posterior leukoencephalopathy syndrome (RPLS) in the postpartum period, without evidence of preeclampsia-eclampsia or chronic arterial hypertension. RPLS is associated with diverse clinical entities including eclampsia. Ten days after giving birth, the patient presented with clinical symptoms of headache, elevated blood pressure and seizures. Reversible vasogenic oedema affecting the white matter in the posterior regions was the characteristic finding in magnetic resonance imaging (MRI) of the brain. Although the prognosis is favourable, treatment needs to be early and aggressive, with rapid control of the convulsions and arterial hypertension, with the aim of preventing ischemia and cerebral infarct from developing. There is a need to be highly alert and to consider the diagnosis of RPLS in women presenting with convulsions and other neurological symptoms in postpartum. | 18,842,228 |
[Characterization and molecular epidemiology of ESBL in Escherichia coli and Klebsiella pneumoniae in 11 Spanish hospitals (2004)]. | The epidemiological distribution of extended-spectrum beta-lactamase (ESBL) types in Escherichia coli and Klebsiella pneumoniae was evaluated in various hospitals in Spain and compared with previous studies. A total of 11 Spanish hospitals participated in this study. Each center collected the first 15 isolates of E. coli and the first 5 of K. pneumoniae suspected of being ESBL-producers and isolated during the first quarter of 2004. Clonal study was done by PFGE after total DNA digestion with XbaI and by ERIC-PCR (Enterobacterial Repetitive Intergenic Consensus Sequences-Polymerase Chain Reaction), typing. ESBL-producers were characterized by isoelectric focusing (IEF), PCR and sequencing. A total of 124 strains were collected. PFGE restriction patterns showed considerable diversity among E. coli strains; 4 clusters of 2 strains each were detected. ESBL characterization of 92 E. coli strains showed a predominance of CTX-M-14 (45.7%), CTX-M-9 (20.6%) and SHV-12 (21.7%). Clonal diversity among the 32 K. pneumoniae strains was less pronounced than in E. coli; 3 clusters included 53.1% of strains. The ESBL detected in these strains included a CTX-M type in 20 cases (62.5%) (CTX-M-1, CTX-M-9, CTX-M-14 and CTX-M-15); a SHV type in 11 (34.4%) (SHV-12 and SHV-5) and TEM-4 (3.1%) in 1 case. The E. coli and K. pneumoniae strains analyzed in this period displayed a greater diversity of ESBL than has been observed in previous epidemiological studies. Analysis of clonal relationships revealed a greater diversity in E. coli than in K. pneumoniae. | 18,842,234 |
Fragrance material review on 1-methyl-2-(1-methylpropyl) cyclohexyl acetate. | A toxicologic and dermatologic review of 1-Methyl-2-(1-methylpropyl)cyclohexyl acetate when used as a fragrance ingredient is presented. | 18,842,249 |
The size, extent and nature of the learning disability nursing research base: a systematic scoping review. | A research base should be of sufficient quality and quantity to inform nursing practice. It must allow nurses to access information about clients' needs and to identify effective strategies for meeting those needs. This paper presents the findings of a scoping review of 'learning disability nursing research'. The review aimed to determine whether there is a research base sufficient to support learning disability nursing practice. We undertook searches of the Cochrane Library and electronic databases (Medline, Psychinfo, Embase, CINAHL and British Nursing Index) for the years 1996-2006. Full references and abstracts were downloaded for papers returned. Papers considered relevant to the topic of the review were organised into three categories according to whether the main focus of the research was people with learning disabilities, carers or family members, or nurses. For each paper, information about the locality of the research, the topic of the research, design/method and sample size was extracted. We identified 180 relevant research studies, most of which made use of convenience samples of less than one hundred people. Very few studies evaluated the clinical impact of nursing interventions or the delivery of care by learning disability nurses. A small number of studies examined the impact or patient experiences of nurse-led interventions. These tend to small-scale evaluations of new service initiatives, such as the management of behavioural problems. Overall there was an absence of strong evidence about the effectiveness of specific nursing interventions. The extent of learning disability nursing research is limited in quantity and it is difficult to draw comparisons across research studies. Much of the available evidence is drawn from small-scale evaluations; which may provide useful guidance and inspiration for service development but do not, in themselves, constitute a sufficient body of research evidence to support learning disability nursing practice. | 18,842,263 |
Sperm structure and ultrastructure of the Melittobia hawaiiensis, Perkins and M. australica, Girault (chalcidoidea: eulophidae). | Spermatozoa morphology has, for some years, been used to help answer some phylogenetic questions for Hymenoptera. This is the second study describing spermatozoa morphology of an Eulophidae species in which important characteristics were observed. Melittobia spermatozoa are spiralled and measure approximately 270microm in length. The head contains a small acrosome, apparently formed only by an acrosomal vesicle, which, together with the initial nuclear region, is surrounded by an extracellular sheath, from which innumerable filaments irradiate. The nucleus is helicoidal and completely filled with compact chromatin. A centriolar adjunct is observed at the nucleus-flagellum transition; it associates laterally with the nucleus and exhibits two small expansions, which reach around the centriole. In the flagellum there are two mitochondrial derivatives, which in cross-sections are asymmetric. In the derivative with the larger diameter, two distinct regions are observed, a small one, near the axoneme, with a clear "fissure" inside, and a larger region where the cristae occur. Both derivatives initiate at the nuclear base, but the larger diameter derivative finishes first, before the flagellum extremity. At the end of the axoneme, the accessory microtubules are the first to finish. | 18,842,277 |
Outcomes for older adults in an inpatient rehabilitation facility following hip fracture (HF) surgery. | The purpose of the study was to evaluate patient and system outcomes regarding older community-residing adults who participated in a rehabilitation program following HF surgery. The health care professionals on the rehabilitation unit in this feasibility study had never cared for such patients who were so frail, with multiple co-morbidities including cognitive impairment (CI). After an innovative model of care was developed and the staff trained in the novel approach to care, the unit opened for all patients living within the community who had fractured their hip, regardless of their CI. Of the 31 elderly patients consecutively admitted post-HF in this retrospective study, 18 were found to have CI postoperatively as determined by a Mini-Mental State Examination (MMSE) score < or = 23. There were no differences in length of stay (LOS), rehabilitation efficiency, and motor FIM gain scores between the two groups of patients. This feasibility retrospective study suggests that staff can learn how to care for patients with CI in rehabilitation settings, and that such clients can achieve outcomes comparable to those without CI in a setting dedicated to caring for patients with a HF. | 18,842,307 |
Metric issues in the study of eye movements in psychiatry. | This review provides a description of the measurement methods, task definitions and measurement parameters in the study of smooth eye pursuit and saccade-antisaccade tasks in psychiatry. The large heterogeneity in task definitions and definitions of parameters and its potential impact on the large variability of the parameter measures is presented. Finally issues relating to data aggregation, practice effects and reliability of these smooth eye pursuit and saccade-antisaccade task performance measures are also discussed. The main conclusion of this review is that oculomotor function testing is still lacking standardization of methods, tasks and parameters affecting its usefulness in certain areas of psychiatric research. A future research program could derive a set of tentative recommendations for test standardization. | 18,842,328 |
[Polyomavirus newly discovered]. | Three new polyoma viruses have been recently identified; two of them, the KI et WU viruses are present in nasopharyngeal aspirates during the course of acute respiratory infections. The incidence of these viruses is low compared to other respiratory viruses and the disease has not shown a high severity of clinical signs. The physiopathology of the diseases and the mode of cultivation of these viruses remain unknown. The third virus was discovered from cutaneous biopsies of Merkel tumours with a higher incidence than in tissue from healthy patients. Its mode of transmission and its role in the cancerogenesis need more studies. However, as the virus can integrate into the cellular DNA, it signifies that the virus may have a role in various human tumors. | 18,842,352 |
CNS mastitis: nothing to worry about? | In this paper, we analyzed a very large field data set on intramammary infections (IMI) and the associated somatic cell count (SCC) in dairy cows. The objective of the study was to analyze the impact of coagulase-negative staphylococci (CNS) IMI on cow SCC, both mean and variability, and on the potential of these infections to have a major impact on the bulk milk SCC (BMSCC). Data and milk samples for bacterial culture were collected by Quality Milk Production Services (QMPS) between 1992 and March of 2007. The QMPS program services dairy farms in New York State and other states in the Northeastern USA and operates in conjunction with Cornell University. Only records from cows where SCC and milk production data were available, and where only one organism was isolated from bacterial cultures of milk samples (or where culture was negative) were used for this analysis. A total of 352,614 records from 4200 whole herd mastitis screening sampling qualified for this study. Within herds an average of 15% (S.D. 12%) of cows sampled were infected with CNS, ranging between 0 and 100%. Average within herd prevalence of cows with a CNS IMI and an SCC over 200,000 cells/ml was 2% (S.D. 4%) with a minimum of 0% and a maximum of 50%. Results of linear mixed models showed three distinct populations of IMI statuses: negative cultures with the lowest SCC; CNS and Corynebacterium bovis with a moderate increase in SCC, and Streptococcus agalactiae, Streptococcus spp. and Staphylococcus aureus showing an important increase in SCC. Surprisingly, milk production was slightly but significantly higher in CNS infected cows compared to culture-negative cows, whereas it was strongly reduced in cows with a major pathogen IMI. The percentage contribution of CNS infections to the BMSCC was 17.9% in herds with a BMSCC less than 200,000 cells/ml. This value decreased to 11.9 and 7.9% in herds with bulk milk SCC between 200,000 and 400,000 and over 400,000 cells/ml, respectively. We concluded that very few herds with milk quality problems would have an important increase in BMSCC that could be mostly attributed to CNS infections. On the other hand, in herds with low BMSCC, CNS infections may be an important contributor to the total number of somatic cells in the bulk milk. | 18,842,362 |
Magnetoencephalography using total intravenous anesthesia in pediatric patients with intractable epilepsy: lesional vs nonlesional epilepsy. | Magnetoencephalography (MEG) provides source localization of interictal spikes. We use total intravenous anesthesia (TIVA) with propofol to immobilize uncooperative children. We evaluate the effect of TIVA on interictal spikes in children who have intractable epilepsy with or without MRI lesions. We studied 28 children (3-14 years; mean, 6.6). We intravenously administered propofol (30-60 microg/kg/min) to record MEG with simultaneous EEG. We evaluated MEG spike sources (MEGSSs). We compared spikes on simultaneous EEG under TIVA with those on scalp video-EEG without TIVA. There was a significant decrease in frequent spikes (10 patients, 36%) on simultaneous EEG under TIVA compared to those (22 patients, 79%) on scalp video-EEG without TIVA (P<0.01). MEGSSs were present in 21 (75%) of 28 patients. Clustered MEGSSs occurred in 15 (83%) of 18 lesional patients but in 3 (30%) of 10 nonlesional patients (P<0.05). MEGSSs were more frequently absent in nonlesional (6 patients, 60%) than lesional (one patient, 5%) patients (P<0.01). Thirteen patients with MRI and/or histopathologically confirmed neuronal migration disorder most frequently showed clustered MEGSSs (11 patients, 85%) compared to those of other lesional and nonlesional patients. Propofol-based TIVA reduced interictal spikes on simultaneous EEG. TIVA for MEG still had utility in identifying spike sources in a subset of pediatric patients with intractable epilepsy who were uncooperative and surgical candidates. In lesional patients, MEG under TIVA frequently localized the clustered MEGSSs. Neuronal migration disorders were intrinsically epileptogenic and produced clustered MEGSSs under TIVA. Nonlesional patients often had no MEGSS under TIVA. | 18,842,368 |
Lack of effects of isoflavones on the lipid profile of Brazilian postmenopausal women. | To evaluate the effects of soy isoflavone supplementation on profile lipid and endogenous hormone levels. In this double-blind, placebo-controlled study, 47 postmenopausal women 47-66 y of age received 40 mg of isoflavone (n = 25) or 40 mg of casein placebo (n = 22). Cardiovascular risk factors were assessed by evaluating lipid profile at baseline and after 6 mo of treatment. To examine the effects of this regime on endogenous hormone levels, follicle-stimulating hormone and beta-estradiol were measured. Urinary isoflavone concentrations (genistein and daidzein) were measured as markers of both compliance and absorption using high performance liquid chromatography. Baseline characteristics were compared by the unpaired Student's t-test. Within-group changes were determined by paired Student's t-test and comparison between the isoflavone and casein placebo groups were determined by analysis of variance. Lipid levels (low-density lipoprotein and total cholesterol) similarly decreased in both groups. High-density lipoprotein increased significantly in both groups and cannot thus be attributable to treatment; the reason for such variation is unknown and can be attributed to chance or to bias (even that of a real placebo effect in both groups or perhaps in spontaneous changes in exercise and dietary habits of patients after their inclusion). Furthermore, in both groups very low-density lipoprotein and triacylglycerol levels increased in a non-significant manner. The results of the present study do not support any biologically significant estrogenic effects of isoflavone on the parameters assessed. Further research will be necessary to definitively assess the safety and efficacy of isoflavone. | 18,842,392 |
[Vascular anomalies of the children's hand]. | Vascular anomalies are common on the hand of children. There are two types of vascular anomalies: the vascular tumours and the vascular malformations. The most frequent vascular tumour is infantile haemangioma. The vascular malformations could be predominantly venous, lymphatic, capillary or arteriovenous. Combined vascular malformations, often syndromic, must be searched for. Diagnosis is sometimes difficult. It is based on clinical history, aspect, evolution and radiological examinations (color-Doppler ultrasound and MRI). Treatment is often a combination of medical and surgical approaches performed by a multidisciplinary team. | 18,842,438 |
[Symbrachydactyly]. | Symbrachydactyly is literally defined as a combination of short fingers with syndactyly. Blauth and Gekeler described four types of symbrachydactyly, ranging from simple shortness of middle phalanges to complete absence of digital rays. In type I (short finger) function is quite normal and syndactyly release is usually the only procedure needed. In type II (cleft hand), presence of a thumb and at least one ulnar finger allows pinch function. Surgical treatment, when needed, consists in separation of webbed fingers, resection of nonfunctional digital stumps, or finger translocation. In type III (monodactyly) all long fingers are absent. Pinch function can be created between the thumb and a toe transfer in ulnar location. Bone lengthening is an alternative procedure to create a pincer. Surgery is not always indicated in type IV (peromely) as function can only be restored if active motion is already present at wrist or carpometacarpal levels. | 18,842,444 |
Masseteric-facial nerve coaptation--an alternative technique for facial nerve reinnervation. | Reinnervation of the facial musculature when there is loss of the proximal facial nerve poses a difficult clinical problem. Restoration of spontaneous mimetic motion is the aim and, to this end, the use of cross-facial nerve grafts has long been considered the reconstruction of choice. The nerve to masseter has been used very successfully for reinnervation of microvascular functioning muscle transfers for facial reanimation in established facial palsy but its use as a direct nerve transfer to the facial nerve to reinnervate 'viable' facial musculature has been scarce. Electron micrographic studies of axonal counts in the nerve to masseter and nerve to gracilis in a clinical series of seven patients undergoing surgery for facial nerve palsy were made. Based on these results, and previous success with the use of the nerve to masseter for reinnervation of free gracilis transfers, we report our experience with the transfer of the nerve to masseter for direct coaptation with the ipsilateral facial nerve to restore facial motion. Our axonal counts of the nerve to masseter have, on average, 1542+/-291.70 (SD) axons. Historical data have shown that the buccal branch of the facial nerve has 834+/-285 (SD) where the distal end of a cross-facial nerve graft has 100 to 200 axons. Our clinical use of the nerve to masseter as a direct nerve transfer in three patients based on these data has resulted in significant improvement in facial symmetry in repose (at a minimum of 1 year follow up), restoration of facial motion with occasional spontaneous activity and minimal synkinesis without any donor morbidity. The advantages of this technique include the ease of dissection, constant and reliable anatomy, powerful reinnervation of the facial muscles without donor site morbidity and the potential for return of spontaneous facial movement. | 18,842,469 |
Generalized linear discriminant analysis: a unified framework and efficient model selection. | High-dimensional data are common in many domains, and dimensionality reduction is the key to cope with the curse-of-dimensionality. Linear discriminant analysis (LDA) is a well-known method for supervised dimensionality reduction. When dealing with high-dimensional and low sample size data, classical LDA suffers from the singularity problem. Over the years, many algorithms have been developed to overcome this problem, and they have been applied successfully in various applications. However, there is a lack of a systematic study of the commonalities and differences of these algorithms, as well as their intrinsic relationships. In this paper, a unified framework for generalized LDA is proposed, which elucidates the properties of various algorithms and their relationships. Based on the proposed framework, we show that the matrix computations involved in LDA-based algorithms can be simplified so that the cross-validation procedure for model selection can be performed efficiently. We conduct extensive experiments using a collection of high-dimensional data sets, including text documents, face images, gene expression data, and gene expression pattern images, to evaluate the proposed theories and algorithms. | 18,842,480 |
New delay-dependent stability results for neural networks with time-varying delay. | This paper studies the problem of stability analysis for neural networks (NNs) with a time-varying delay. Unlike the previous works, the activation functions are assumed to be neither monotonic, nor differentiable, nor bounded. By defining a more general type of Lyapunov functionals, some new less conservative delay-dependent stability criteria are established in terms of linear matrix inequalities (LMIs). Meanwhile, the computational complexity of the newly obtained stability conditions is reduced because less variables are involved. Numerical examples are given to illustrate the effectiveness and the benefits of the proposed method. | 18,842,481 |
Idiopathic cystic artery aneurysm complicated with hemobilia and acute pancreatitis. | Aneurysm of the cystic artery is not common, and it is a rare cause of hemobilia. Most of reported cases are pseudoaneurysms resulting from either an inflammatory process in the abdomen or abdominal trauma. We report a healthy individual who developed hemobilia and acute pancreatitis associated with cystic artery aneurysm. The patient was managed with angio-embolization with an uneventful post-embolization course. Visceral artery aneurysms are rare and can rupture with potentially grave outcome due to excessive bleeding. Angiographic embolization as a common method of treatment for visceral artery aneurysms was used in our patient with good outcome. | 18,842,506 |
Cyclooxygenase-2-derived prostaglandin E2 stimulates Id-1 transcription. | Cyclooxygenase-2 (COX-2) and Id-1 are overexpressed in a variety of human malignancies. Recently, each of these genes was found to play a role in mediating breast cancer metastasis to the lungs, but their potential interdependence was not evaluated. Hence, the main objective of the current study was to determine whether COX-2-derived prostaglandin (PGE(2)) activated Id-1 transcription, leading in turn to increased invasiveness of mammary epithelial cells. In MDA-MB-231 cells, treatment with PGE(2) induced Id-1, an effect that was mimicked by an EP(4) agonist. PGE(2) via EP(4) activated the epidermal growth factor receptor (EGFR) --> ERK1/2 pathway, which led to increased expression of Egr-1. PGE(2) stimulated EGFR signaling by inducing the release of amphiregulin, an EGFR ligand. The ability of PGE(2) to activate Id-1 transcription was mediated by enhanced binding of Egr-1 to the Id-1 promoter. Silencing of COX-2 or pharmacological inhibition of COX-2 led to reduced PGE(2) production, decreased Id-1 expression, and reduced migration of cells through extracellular matrix. A similar decrease in cell migration was found when Id-1 was silenced. The interrelationship between COX-2, PGE(2), Id-1, and cell invasiveness was also compared in nontumorigenic SCp2 and tumorigenic SCg6 mammary epithelial cells. Consistent with the findings in MDA-MB-231 cells, COX-2-derived PGE(2) induced Id-1, leading in turn to increased cell invasiveness. Taken together, these results suggest that PGE(2) via EP(4) activated the EGFR --> ERK1/2 --> Egr-1 pathway, leading to increased Id-1 transcription and cell invasion. These findings provide new insights into the relationship between COX-2 and Id-1 and their potential role in metastasis. | 18,842,581 |
Inferring population history with DIY ABC: a user-friendly approach to approximate Bayesian computation. | Genetic data obtained on population samples convey information about their evolutionary history. Inference methods can extract part of this information but they require sophisticated statistical techniques that have been made available to the biologist community (through computer programs) only for simple and standard situations typically involving a small number of samples. We propose here a computer program (DIY ABC) for inference based on approximate Bayesian computation (ABC), in which scenarios can be customized by the user to fit many complex situations involving any number of populations and samples. Such scenarios involve any combination of population divergences, admixtures and population size changes. DIY ABC can be used to compare competing scenarios, estimate parameters for one or more scenarios and compute bias and precision measures for a given scenario and known values of parameters (the current version applies to unlinked microsatellite data). This article describes key methods used in the program and provides its main features. The analysis of one simulated and one real dataset, both with complex evolutionary scenarios, illustrates the main possibilities of DIY ABC. The software DIY ABC is freely available at http://www.montpellier.inra.fr/CBGP/diyabc. | 18,842,597 |
Diagnostic difficulty and error in primary care--a systematic review. | Diagnostic error in primary care can have serious implications for the patient, the clinician and the health-care system, possibly more so than other types of error. To identify common characteristics of diseases that GPs may misdiagnose. Systematic search of the MEDLINE and EMBASE databases for primary research on diagnostic error/delay in primary care. Papers on system errors, patient delay, case reports, reviews, opinion pieces, studies not based on actual cases and studies not using a systematic sample were excluded from the review. Twenty-one papers were included. All papers were assessed for quality using the GRADE system. Common features were identified across diseases and presentations that made diagnosis difficult and led to error/delay. Most studies were retrospective cohorts of patients recruited in hospital and collected data from patient interviews and/or hospital records, resulting in incomplete and potentially biased information. It was usually not possible to determine preventability of the delay. Some conditions were extremely rare, suggesting a specialist research interest rather than an increased rate of misdiagnosis. Conditions investigated were malignancies, myocardial infarction, meningitis, dementia, iron deficiency anaemia, asthma, tremor in the elderly and HIV. Common features of difficulty were atypical presentations, non-specific presentations, very low prevalence, the presence of co-morbidity and perceptual features and could be missed. Misdiagnosis in primary care covers a wide range of conditions that may be related in the manner in which they present. The challenge is to identify ways of supporting the diagnostic process in potentially difficult presentations. | 18,842,618 |
Semaphorin 5B is a novel inhibitory cue for corticofugal axons. | Neuronal connectivity is generated by the precise guidance of neuronal growth cones in response to the spatiotemporal distribution of molecular guidance cues in the developing embryo. Here we show that the class 5 semaphorin, Semaphorin 5B, is expressed in regions of the cortex and subcortex flanking the projection of and avoided by descending cortical axons, suggesting a role as a repulsive guidance cue in the formation of the internal capsule. Axons from cortical explants cultured in vitro with Semaphorin 5B-expressing cells exhibited characteristic avoidance behaviors. In organotypic slices, ectopic Semaphorin 5B expression along the presumptive internal capsule was sufficient to cause cortical axons to avoid their normal trajectory, resulting in either stalling at the boundary of Semaphorin 5B or turning into inappropriate areas of the cortex. In contrast, thalamocortical axons were not inhibited either in vitro or in slice culture by ectopic Semaphorin 5B. To further examine the function of Semaphorin 5B in situ, we knocked down its expression in the ventricular zone (VZ) at the corticostriatal angle. We found that labeled cortical fibers aberrantly navigated into the VZ where Semaphorin 5B expression was reduced. We propose that Semaphorin 5B functions to prevent corticofugal axons from abnormally projecting into germinal regions as they project to their subcortical targets. | 18,842,660 |
Decoding the cortical transformations for visually guided reaching in 3D space. | To explore the possible cortical mechanisms underlying the 3-dimensional (3D) visuomotor transformation for reaching, we trained a 4-layer feed-forward artificial neural network to compute a reach vector (output) from the visual positions of both the hand and target viewed from different eye and head orientations (inputs). The emergent properties of the intermediate layers reflected several known neurophysiological findings, for example, gain field-like modulations and position-dependent shifting of receptive fields (RFs). We performed a reference frame analysis for each individual network unit, simulating standard electrophysiological experiments, that is, RF mapping (unit input), motor field mapping, and microstimulation effects (unit outputs). At the level of individual units (in both intermediate layers), the 3 different electrophysiological approaches identified different reference frames, demonstrating that these techniques reveal different neuronal properties and suggesting that a comparison across these techniques is required to understand the neural code of physiological networks. This analysis showed fixed input-output relationships within each layer and, more importantly, within each unit. These local reference frame transformation modules provide the basic elements for the global transformation; their parallel contributions are combined in a gain field-like fashion at the population level to implement both the linear and nonlinear elements of the 3D visuomotor transformation. | 18,842,662 |
Functional dissociations of risk and reward processing in the medial prefrontal cortex. | Making a risky decision is a complex process that involves evaluation of both the value of the options and the associated risk level. Yet the neural processes underlying these processes have not so far been clearly identified. Using functional magnetic resonance imaging and a task that simulates risky decisions, we found that the dorsal region of the medial prefrontal cortex (MPFC) was activated whenever a risky decision was made, but the degree of this activity across subjects was negatively correlated with their risk preference. In contrast, the ventral MPFC was parametrically modulated by the received gain/loss, and the activation in this region was positively correlated with an individual's risk preference. These results extend existing neurological evidence by showing that the dorsal and ventral MPFC convey different decision signals (i.e., aversion to uncertainty vs. approach to rewarding outcomes), where the relative strengths of these signals determine behavioral decisions involving risk and uncertainty. | 18,842,669 |
Timing of genome duplications relative to the origin of the vertebrates: did cyclostomes diverge before or after? | Two rounds of whole-genome duplications are thought to have played an important role in the establishment of gene repertoires in vertebrates. These events occurred during chordate evolution after the split of the urochordate and cephalochordate lineages but before the radiation of extant gnathostomes (jawed vertebrates). During this interval, diverse agnathans (jawless fishes), including cyclostomes (hagfishes and lampreys), diverged. However, there is no solid evidence for the timing of these genome duplications in relation to the divergence of cyclostomes from the gnathostome lineage. We conducted cDNA sequencing in diverse early vertebrates for members of homeobox-containing (Dlx and ParaHox) and other gene families that would serve as landmarks for genome duplications. Including these new sequences, we performed a molecular phylogenetic census using the maximum likelihood method for 55 gene families. In most of these gene families, we detected many more gene duplications before the cyclostome-gnathostome split, than after. Many of these gene families (e.g., visual opsins, RAR, Notch) have multiple paralogs in conserved, syntenic genomic regions that must have been generated by large-scale duplication events. Taken together, this indicates that the genome duplications occurred before the cyclostome-gnathostome split. We propose that the redundancy in gene repertoires possessed by all vertebrates, including hagfishes and lampreys, was introduced primarily by genome duplications. Apart from subsequent lineage-specific modifications, these ancient genome duplication events might serve generally to distinguish vertebrates from invertebrates at the genomic level. | 18,842,688 |
Functional pseudotyping of human immunodeficiency virus type 1 vectors by Western equine encephalitis virus envelope glycoprotein. | We investigated the ability of western equine encephalitis virus envelope glycoproteins (WEEV GP) to pseudotype lentiviral vectors. The titers of WEEV GP-pseudotyped human immunodeficiency virus type 1 (HIV) ranged as high as 8.0 x 10(4) IU/ml on permissive cells. Sera from WEEV-infected mice specifically neutralized these pseudotypes; cell transduction was also sensitive to changes in pH. The host range of the pseudotyped particles in vitro was somewhat limited, which is atypical for most alphaviruses. HIV vectors pseudotyped by WEEV GP may be a useful tool for characterizing WEEV cell binding and entry and screening for small-molecule inhibitors. | 18,842,711 |
RAG2-/- gamma(c)-/- mice transplanted with CD34+ cells from human cord blood show low levels of intestinal engraftment and are resistant to rectal transmission of human immunodeficiency virus. | Rectal transmission is one of the main routes of infection by human immunodeficiency virus type 1 (HIV-1). To efficiently study transmission mechanisms and prevention strategies, a small animal model permissive for rectal transmission of HIV is mandatory. We tested the susceptibility of RAG2(-/-)gamma(c)(-/-) mice transplanted with human cord blood hematopoietic stem cells to rectal infection with HIV. We rectally exposed these humanized mice to cell-free and cell-associated HIV. All mice remained HIV negative as assessed by plasma viral load. The same mice infected intraperitoneally showed high levels of HIV replication. In the gut-associated lymphatic tissue, we found disproportionately smaller numbers of human cells than in other lymphoid organs. This finding may explain the observed resistance to rectal transmission of HIV. To increase the numbers of local HIV target cells and the likelihood of HIV transmission, we treated mice with different proinflammatory stimuli: local application of interleukin-1beta, addition of seminal plasma to the inoculum, or induction of colitis with dextran sodium sulfate. These procedures attracted some human leukocytes, but the transmission rate was still very low. The humanized mice showed low levels of human engraftment in the intestinal tract and seem to be resistant to rectal transmission of HIV, and thus they are an unsuitable model for this application. | 18,842,716 |
Initial B-cell responses to transmitted human immunodeficiency virus type 1: virion-binding immunoglobulin M (IgM) and IgG antibodies followed by plasma anti-gp41 antibodies with ineffective control of initial viremia. | A window of opportunity for immune responses to extinguish human immunodeficiency virus type 1 (HIV-1) exists from the moment of transmission through establishment of the latent pool of HIV-1-infected cells. A critical time to study the initial immune responses to the transmitted/founder virus is the eclipse phase of HIV-1 infection (time from transmission to the first appearance of plasma virus), but, to date, this period has been logistically difficult to analyze. To probe B-cell responses immediately following HIV-1 transmission, we have determined envelope-specific antibody responses to autologous and consensus Envs in plasma donors from the United States for whom frequent plasma samples were available at time points immediately before, during, and after HIV-1 plasma viral load (VL) ramp-up in acute infection, and we have modeled the antibody effect on the kinetics of plasma viremia. The first detectable B-cell response was in the form of immune complexes 8 days after plasma virus detection, whereas the first free plasma anti-HIV-1 antibody was to gp41 and appeared 13 days after the appearance of plasma virus. In contrast, envelope gp120-specific antibodies were delayed an additional 14 days. Mathematical modeling of the earliest viral dynamics was performed to determine the impact of antibody on HIV replication in vivo as assessed by plasma VL. Including the initial anti-gp41 immunoglobulin G (IgG), IgM, or both responses in the model did not significantly impact the early dynamics of plasma VL. These results demonstrate that the first IgM and IgG antibodies induced by transmitted HIV-1 are capable of binding virions but have little impact on acute-phase viremia at the timing and magnitude that they occur in natural infection. | 18,842,730 |
Illness beliefs about heart disease and adherence to secondary prevention regimens. | We investigated illness beliefs of recently hospitalized patients with coronary artery disease (CAD) and the prospective association between these beliefs and adherence to secondary prevention behaviors. Causal attributions of CAD and their concordance with actual patient risk profiles were also examined. A prospective study of 193 patients was conducted. Data were collected by self-report and from medical records at 3, 6, and 9 months after discharge. Baseline depression was assessed by structured clinical interview. The association between illness beliefs and adherence was tested with hierarchical linear regression controlling for clinical and demographic confounders. Most participants perceived high personal and treatment control and believed CAD to be chronic in duration with severe consequences. A relatively low number of symptoms were endorsed as being part of CAD. Heredity was considered the single most important and most commonly perceived cause of CAD. Smoking, alcohol, emotional state, and heredity were significantly more likely to be endorsed as causal factors by respondents with these risk profiles. In multivariate analysis, illness beliefs contributed an additional 6% of the total variance explained by the model (p = .02). Perceptions of more serious consequences predicted better adherence (p = .03). Social desirability was the best single predictor of adherence. Patient perceptions of risk factors were largely consistent with actual risk factors. Despite modest effect sizes, illness beliefs do contribute to our understanding of adherence to secondary prevention behavior. Interventions aimed at modifying these beliefs, particularly those related to the consequences of CAD, may improve patient outcomes. | 18,842,739 |
MR imaging of orbital inflammatory syndrome, orbital cellulitis, and orbital lymphoid lesions: the role of diffusion-weighted imaging. | Orbital inflammatory syndrome (OIS) has clinical features that overlap with orbital lymphoid lesions and orbital cellulitis. Prompt diagnosis is needed in all 3 conditions because the management of each one differs greatly. CT and MR imaging, though useful, do not always distinguish among these conditions. The aim of this study was to identify the role of diffusion-weighted imaging (DWI) in differentiating these 3 diagnoses. A retrospective analysis of orbital MR imaging was conducted. T1- and T2-weighted and postcontrast images were analyzed. Region-of-interest analysis was performed by using measurements in areas of abnormality seen on conventional MR imaging sequences and measurements of the ipsilateral thalamus for each patient. The DWI signal intensity of the lesion was expressed as a percentage of average thalamic intensity in each patient. Similarly, lesion apparent diffusion coefficients (ADCs) and lesion-thalamus ADC ratios were calculated. Statistical significance was determined by the Kruskal-Wallis test, and post hoc pairwise comparisons, by the Mann-Whitney U test for DWI-intensity ratio, ADC, and ADC ratio. A significant difference was noted in DWI intensities, ADC, and ADC ratio between OIS, orbital lymphoid lesions, and orbital cellulitis (P < .05). Lymphoid lesions were significantly brighter than OIS, and OIS lesions were significantly brighter than cellulitis. Lymphoid lesions showed lower ADC than OIS and cellulitis. A trend was seen toward lower ADC in OIS than in cellulitis (P = .17). DWI may help differentiate OIS from lymphoid lesions and cellulitis and may allow more rapid management. | 18,842,758 |
Intracranial internal carotid artery calcifications: association with vascular risk factors and ischemic cerebrovascular disease. | Atherosclerotic calcifications are present not only in the extracranial carotid bifurcation but also in the intracranial part of the internal carotid artery. We assessed the association between intracranial internal carotid artery calcifications and cardiovascular risk factors in patients with ischemic cerebrovascular disease and the association between calcifications and the presence of this disease. Patients undergoing multidetector CT (MDCT) angiography of the carotid arteries for assessment of stenosis degree were included in the study. A semiautomatic custom-made system to quantify calcifications was developed. The associations between the volume of calcifications and cardiovascular risk factors and the type of ischemic cerebrovascular symptoms were assessed with logistic regression. MDCT angiography was performed in 406 patients (age, 62 +/- 14 years; 242 men). Men had a significantly higher calcification volume (66 mm(3)) than women (33 mm(3)). Calcification volume was positively associated with age in both men and women. Smoking, hypercholesterolemia, and a history of cardiac disease were independently related to the presence of calcifications. A history of cardiac disease and ischemic cerebrovascular disease were independently related to the volume of calcifications. No association was found between calcifications and the presence or type of ischemic cerebrovascular disease in the vascular territory of the intracranial internal carotid artery. Calcifications were associated with higher age and male gender. The presence and volume of calcifications were independently associated with cardiovascular risk factors. Calcifications were not related to the presence or type of ischemic cerebrovascular disease. | 18,842,764 |
Home use of vegetable oils, markers of systemic inflammation, and endothelial dysfunction among women. | Most knowledge about adverse health effects of trans fats was mainly derived from studies done in Western populations of European or American origins; few data are available in the understudied region of the Middle East. We assessed the association between consumption of partially hydrogenated vegetable oils (PHVOs) and non-HVOs and circulating concentrations of inflammatory markers among Tehrani women aged 40-60 y. Usual dietary intakes were assessed with a food-frequency questionnaire among 486 apparently healthy women. PHVOs (commonly used for cooking in Iran) were considered as PHVOs category. Sunflower oil, corn oil, canola oil, soybean oil, and olive oil were defined as non-HVOs. Anthropometric measurements were done, and fasting blood samples were taken to measure inflammatory markers. The energy-adjusted daily intakes (mean +/- SD) of PHVOs and non-HVOs were 23 +/- 11 and 22 +/- 10 g/d, respectively. After control for potential confounders, women in the highest quintile of PHVO intake had higher plasma concentrations of C-reactive protein (CRP; percentage difference from lowest quintile: 45%; P for trend: <0.01), tumor necrosis factor-alpha (TNF-alpha; 66%; P for trend: <0.01), interleukin-6 (72%; P for trend: <0.05), and soluble intercellular adhesion molecule-1 (sICAM-1; 22%; P for trend: <0.01) than did women in the lowest quintile. In contrast, higher consumption of non-HVOs was associated with lower circulating concentrations of CRP (percentage difference between top and bottom quintiles: -23%; P for trend: 0.05), TNF-alpha (-29%; P for trend: <0.01), serum amyloid A (-24%; P for trend: <0.01), and sICAM-1 (-19%; P for trend:<0.05). Adjustment for body mass index, fasting plasma glucose, and lipid profiles slightly attenuated the associations in some cases. Higher intakes of PHVOs are associated with elevated concentrations of inflammatory biomarkers, whereas higher intakes of non-HVOs are associated with lower plasma concentrations of these biomarkers. | 18,842,776 |
Manipulation of lipid bioaccessibility of almond seeds influences postprandial lipemia in healthy human subjects. | Plant cell walls are known to influence the rate and extent of lipid release from plant food tissues during digestion; however, the effect of cell wall structure on postprandial lipemia is unknown. The objective was to investigate the effects of lipid release (bioaccessibility) on postprandial lipemia by comparing lipid encapsulated by cell walls with lipid present as free oil. A randomized crossover trial (n = 20 men) compared the effects of 3 meals containing 54 g fat provided as whole almond seed macroparticles (WA), almond oil and defatted almond flour (AO), or a sunflower oil blend as control (CO) on postprandial changes in oxidative stress (8-isoprostane F(2)alpha concentrations), vascular tone (peripheral augmentation index), and plasma triacylglycerol, glucose, and insulin concentrations. The postprandial increase in plasma triacylglycerol was lower [74% and 58% lower incremental area under curve (iAUC)] after the WA meal than after the AO and CO meals (P < 0.001). Increases in plasma glucose concentrations (0-180 min) were significantly higher after the WA meal (iAUC: 114; 95% CI: 76, 153) than after the AO meal (iAUC: 74; 95% CI: 48, 99) (P < 0.05), but no significant differences from the CO meal were observed (iAUC: 88; 95% CI: 66, 109). The peak reductions in peripheral augmentation index after the WA, AO, and CO meals (-9.5%, -10.1%, and -12.6%, respectively, at 2 h) were not significantly different between meals. Plasma 8-isoprostane F(2)alpha and insulin concentrations did not differ significantly between meals. The bioaccessibility of lipid in almond seeds, which is regulated by the structure and properties of cell walls, plays a primary role in determining postprandial lipemia. | 18,842,777 |
FADS genotypes and desaturase activity estimated by the ratio of arachidonic acid to linoleic acid are associated with inflammation and coronary artery disease. | The delta-5 and delta-6 desaturases, encoded by FADS1 and FADS2 genes, are key enzymes in polyunsaturated fatty acid (PUFA) metabolism that catalyze the conversion of linoleic acid (LA) into arachidonic acid (AA) and that of alpha-linolenic acid (ALA) into eicosapentaenoic acid (EPA). Single-nucleotide polymorphisms (SNPs) in FADS1 and FADS2 have been associated with different concentrations of AA and LA, and those associations have possible functional consequences for desaturase activity. We aimed to evaluate the possible association among FADS genotypes, desaturase activity, inflammation, and coronary artery disease (CAD). Thirteen FADS SNPs and the ratio of AA to LA (AA/LA) on red blood cell (RBC) membranes, a marker of desaturase activity, were evaluated in 876 subjects with (n = 610) or without (n = 266) angiographically documented CAD. Both AA/LA and the ratio of EPA to ALA (EPA/ALA) were higher in patients with CAD than in those without CAD, but, in a multiple logistic regression model, only a higher AA/LA resulted an independent risk factor for CAD (odds ratio: 2.55; 95% CI: 1.61, 4.05 for higher compared with lower ratio tertile; P for trend < 0.001). Furthermore, concentrations of high-sensitivity C-reactive protein increased progressively across tertiles of AA/LA. Graded increases in high-sensitivity C-reactive protein concentrations and CAD risk were related to the carriership of FADS haplotypes, including the alleles associated with a higher ratio. In populations following a Western diet, subjects carrying FADS haplotypes that are associated with higher desaturase activity may be prone to a proinflammatory response favoring atherosclerotic vascular damage. | 18,842,780 |
Portal infusion of amino acids is more efficient than peripheral infusion in stimulating liver protein synthesis at the same hepatic amino acid load in dogs. | Hepatic glucose uptake is enhanced by the portal delivery of glucose, which creates a negative arterioportal substrate gradient. Hepatic amino acid (AA) utilization may be regulated by the same phenomenon, but this has not been proven. We aimed to assess hepatic AA balance and protein synthesis with or without a negative arterioportal AA gradient. Somatostatin was infused intravenously, and insulin and glucagon were replaced intraportally at 4- and 3-fold basal rates, respectively, in 3 groups (n = 9 each) of conscious dogs with catheters for hepatic balance measurement. Arterial glucose concentrations were clamped at 9 mmol/L. An AA mixture was infused intravenously to maintain basal concentrations (EuAA), intraportally to mimic the postmeal AA increase (PoAA), or intravenously (PeAA) to match the hepatic AA load in PoAA. Protein synthesis was assessed with a primed, continuous [(14)C]leucine infusion. Net hepatic glucose uptake in the PoAA condition was < or =50% of that in the EuAA and PeAA conditions (P < 0.05). In the PoAA and PeAA conditions, hepatic intracellular leucine concentrations were 2- to 2.5-fold those in the EuAA condition (P < 0.05); net hepatic leucine uptake and [(14)C]leucine utilization were approximately 2-fold greater (P < 0.05) and albumin synthesis was 30% greater (P < 0.05) in the PoAA condition than in the EuAA and PeAA conditions. Phosphorylation of ribosomal protein S6 [downstream of the mammalian target of Rapamycin complex 1 (mTORC1)] was significantly higher in the PoAA, but not PeAA, condition than in the EuAA condition. Portal, but not peripheral, AA delivery significantly enhanced hepatic protein synthesis under conditions in which AAs, glucose, insulin, and glucagon did not differ at the liver, an effect apparently mediated by mTORC1 signaling. | 18,842,785 |
No evidence of mass dependency of specific organ metabolic rate in healthy humans. | In humans, resting energy expenditure (REE) can be calculated from organ and tissue masses using constant specific organ metabolic rates. However, interspecies data suggest allometric relations between body mass and organ metabolic rate with higher specific metabolic rates in mammals with a smaller body mass. The objective was to compare the accuracy of REE prediction with the use of either constant or body mass-dependent specific organ metabolic rates. Healthy subjects (79 women, 75 men) within the normal range of fat mass (FM) expected for a healthy body mass index and aged 18-78 y were stratified into tertiles of body mass. Fifty subjects were grouped as tertile 1 (<66.3 kg), 52 as tertile 2 (> or =66.3 to < or =77.2 kg), and 52 as tertile 3 (>77.2 kg). Magnetic resonance imaging was used to assess the volume of 4 internal organs (brain, heart, liver, and kidneys). REE was measured by indirect calorimetry (REE(m)) and compared with REE calculated from previously published constant (REE(c1)) and body mass-dependent organ metabolic rates (REE(c2)). REE(m) increased significantly with weight tertile (tertile 1: 5536 +/- 529 kJ/d; tertile 2: 6389 +/- 672 kJ/d; tertile 3: 7467 +/- 745 kJ/d; P < 0.01). The deviation REE(m)-REE(c1) did not differ between weight tertiles (tertile 1: 66 +/- 382 kJ/d; tertile 2: 167 +/- 507 kJ/d; tertile 3: 86 +/- 480 kJ/d; NS) and showed no relation with body mass (r = -0.05, NS). By contrast, REE(m)-REE(c2) increased with increasing weight tertile (tertile 1: -45 +/- 369 kJ/d; tertile 2: 150 +/- 503 kJ/d; tertile 3: 193 +/- 482 kJ/d; P < 0.05) and correlated significantly with body mass (r = 0.16, P < 0.05). Our data do not support a lower specific organ metabolic rate in humans with a larger body mass than in those with a smaller body mass. | 18,842,787 |
Meta-analysis of the quantity of calcium excretion associated with the net acid excretion of the modern diet under the acid-ash diet hypothesis. | The acid-ash diet hypothesis of osteoporosis suggests that acid from the modern diet causes a demineralization of the skeleton, and mobilized bone calcium is excreted. A systematic approach has not been used to summarize the findings of the numerous studies about the hypothesis. The purpose of this meta-analysis was to estimate the quantity of net acid excretion and calciuria associated with the modern diet, to assess the association between acid excretion and calcium excretion, and to assess the influence of urine preservatives on calcium measurement. We systematically searched for trials of the acid-ash hypothesis and conducted a meta-analysis. Twenty-five of 105 studies met the inclusion criteria. The estimated quantity of net acid excretion from the weighted average of the control diets from 11 studies was 47 mEq/d. The increase in urinary calcium with a change in renal net acid excretion depended on whether the urine was acidic or alkaline (P < 0.001). A significant linear relation was observed between net acid excretion and calcium excretion for both acidic and alkaline urine (P < 0.001). The estimated change in urine calcium associated with a change of 47 mEq of net acid excretion in acidic urine was 1.6 mmol/d (66 mg/d) of calcium. Evidence suggests a linear association between changes in calcium excretion in response to experimental changes in net acid excretion. However, this finding is not evidence that the source of the excreted calcium is bone or that this calciuria contributes to the development of osteoporosis. | 18,842,807 |
The Wnt signaling regulator R-spondin 3 promotes angioblast and vascular development. | The vertebrate embryonic vasculature develops from angioblasts, which are specified from mesodermal precursors and develop in close association with blood cells. The signals that regulate embryonic vasculogenesis and angiogenesis are incompletely understood. Here, we show that R-spondin 3 (Rspo3), a member of a novel family of secreted proteins in vertebrates that activate Wnt/beta-catenin signaling, plays a key role in these processes. In Xenopus embryos, morpholino antisense knockdown of Rspo3 induces vascular defects because Rspo3 is essential for regulating the balance between angioblast and blood cell specification. In mice, targeted disruption of Rspo3 leads to embryonic lethality caused by vascular defects. Specifically in the placenta, remodeling of the vascular plexus is impaired. In human endothelial cells, R-spondin signaling promotes proliferation and sprouting angiogenesis in vitro, indicating that Rspo3 can regulate endothelial cells directly. We show that vascular endothelial growth factor is an immediate early response gene and a mediator of R-spondin signaling. The results identify Rspo3 as a novel, evolutionarily conserved angiogenic factor in embryogenesis. | 18,842,812 |
Mobilisation of Ca2+ stores and flagellar regulation in human sperm by S-nitrosylation: a role for NO synthesised in the female reproductive tract. | Generation of NO by nitric oxide synthase (NOS) is implicated in gamete interaction and fertilisation. Exposure of human spermatozoa to NO donors caused mobilisation of stored Ca(2+) by a mechanism that did not require activation of guanylate cyclase but was mimicked by S-nitroso-glutathione (GSNO; an S-nitrosylating agent). Application of dithiothreitol, to reduce protein -SNO groups, rapidly reversed the actions of NO and GSNO on [Ca(2+)](i). The effects of NO, GSNO and dithiothreitol on sperm protein S-nitrosylation, assessed using the biotin switch method, closely paralleled their actions on [Ca(2+)](i). Immunofluorescent staining revealed constitutive and inducible NOS in human oviduct and cumulus (the cellular layer investing the oocyte). 4,5-diaminofluorescein (DAF) staining demonstrated production of NO by these tissues. Incubation of human sperm with oviduct explants induced sperm protein S-nitrosylation resembling that induced by NO donors and GSNO. Progesterone (a product of cumulus cells) also mobilises stored Ca(2+) in human sperm. Pre-treatment of sperm with NO greatly enhanced the effect of progesterone on [Ca(2+)](i), resulting in a prolonged increase in flagellar excursion. We conclude that NO regulates mobilisation of stored Ca(2+) in human sperm by protein S-nitrosylation, that this action is synergistic with that of progesterone and that this synergism is potentially highly significant in gamete interactions leading to fertilisation. | 18,842,814 |
Site selectivity of competitive antagonists for the mouse adult muscle nicotinic acetylcholine receptor. | The muscle-type nicotinic acetylcholine receptor has two nonidentical binding sites for ligands. The selectivity of acetylcholine and the competitive antagonists (+)-tubocurarine and metocurine for adult mouse receptors is known. Here, we examine the site selectivity for four other competitive antagonists: cisatracurium, pancuronium, vecuronium, and rocuronium. We rapidly applied acetylcholine to outside-out patches from transfected BOSC23 cells and measured macroscopic currents. We have reported the IC(50) of the antagonists individually in prior publications. Here, we determined inhibition by pairs of competitive antagonists. At least one antagonist was present at a concentration producing > or =67% receptor inhibition. Metocurine shifted the apparent IC(50) of (+)-tubocurarine in quantitative agreement with complete competitive antagonism. The same was observed for pancuronium competing with vecuronium. However, pancuronium and vecuronium each shifted the apparent IC(50) of (+)-tubocurarine less than expected for complete competition but more than expected for independent binding. The situation was similar for cisatracurium and (+)-tubocurarine or metocurine. Cisatracurium did not shift the apparent IC(50) of pancuronium or vecuronium, indicating independent binding of these two pairs. The data were fit to a two-site, two-antagonist model to determine the antagonist binding constants for each site, L(alphaepsilon) and L(alphadelta). We found L(alphaepsilon)/L(alphadelta) = 0.22 (range, 0.14-0.34), 20 (9-29), 21 (4-36), and 1.5 (0.3-2.9) for cisatracurium, pancuronium, vecuronium, and rocuronium, respectively. The wide range of L(alphaepsilon)/L(alphadelta) for some antagonists may reflect experimental uncertainties in the low affinity site, relatively poor selectivity (rocuronium), or possibly that the binding of an antagonist at one site affects the affinity of the second site. | 18,842,832 |
Leptospira wolffii sp. nov., isolated from a human with suspected leptospirosis in Thailand. | A single Leptospira strain (designated Khorat-H2(T)) was isolated from the urine of an adult male patient with suspected leptospirosis from the province of Nakornrachasima, Thailand. The isolate showed typical Leptospira motility and morphology under dark-field microscopy. Cells were 10-13 mum long and 0.2 mum in diameter, with a wavelength of 0.5 mum and an amplitude of approximately 0.3 mum. Phenotypically, strain Khorat-H2(T) did not grow at 13 degrees C but grew at 30 and 37 degrees C and in the presence of 8-azaguanine. Serological identification using the microscopic agglutination test revealed that strain Khorat-H2(T) had no cross-reaction with any recognized Leptospira serogroups. Phylogenetic analysis of the 16S rRNA gene sequence placed the novel strain within the radiation of the genus Leptospira, with sequence similarities of 88.1-97.7 % to recognized Leptospira species. DNA-DNA hybridization against the type strains of the three most closely related Leptospira species was used to confirm the results of the 16S rRNA sequence analysis. The G+C content of strain Khorat-H2(T) was 41.8 mol%. On the basis of phenotypic, serological and phylogenetic data, strain Khorat-H2(T) represents a novel species of the genus Leptospira, for which the name Leptospira wolffii sp. nov. is proposed. The type strain is Khorat-H2(T) (=WHO LT1686(T) =KIT Khorat-H2(T)). | 18,842,846 |
Curtobacterium ginsengisoli sp. nov., isolated from soil of a ginseng field. | A Gram-positive, non-motile, pale-yellow, short rod-shaped bacterium, strain DCY26(T), was isolated from soil of a ginseng field in South Korea and was investigated to determine its taxonomic position. The organism grew optimally at 30-37 degrees C. The G+C content of its DNA was 65.8 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain DCY26(T) was related most closely to species of the genus Curtobacterium, in the family Microbacteriaceae. Strain DCY26(T) showed highest 16S rRNA gene sequence similarity to Curtobacterium pusillum DSM 20527(T) (96.3 %), Curtobacterium luteum DSM 20542(T) (96.2 %), Curtobacterium flaccumfaciens LMG 3645(T) (96.2 %), Curtobacterium citreum DSM 20528(T) (96.1 %), Curtobacterium albidum DSM 20512(T) (96.1 %) and Curtobacterium herbarum DSM 14013(T) (95.3 %). The predominant menaquinone of strain DCY26(T) was MK-9. Other chemotaxonomic data also supported the affiliation of strain DCY26(T) to the genus Curtobacterium. On the basis of its phenotypic properties and phylogenetic distinctiveness, strain DCY26(T) is considered to represent a novel species of the genus Curtobacterium, for which the name Curtobacterium ginsengisoli sp. nov. is proposed. The type strain is DCY26(T) (=KCTC 13163(T) =JCM 14773(T)). | 18,842,862 |
Phycicoccus bigeumensis sp. nov., a mesophilic actinobacterium isolated from Bigeum Island, Korea. | An actinomycete strain, designated MSL-03(T), was isolated from a soil sample collected from Bigeum Island in the Republic of Korea. The coccoid cells of the organism were Gram-positive and non-motile and did not form endospores. The colonies were yellow, small, circular with entire margins and contained meso-diaminopimelic acid as the diagnostic diamino acid in the peptidoglycan. The major menaquinone was MK-8(H4). The polar lipids detected were diphosphatidylglycerol and phosphatidylglycerol. The major fatty acids were iso-C(15 : 0), iso-C(16 : 0), C(17 : 0), anteiso-C(15 : 0), 10-methyl C(17 : 0), iso-C(14 : 0) and C(17 : 1)omega8c. The DNA G+C content was 73.4 mol%. Phylogenetic analyses based on the 16S rRNA gene sequence positioned strain MSL-03(T) in a clade comprising Phycicoccus jejuensis KSW2-15(T) and Phycicoccus dokdonensis DS-8(T). The organism showed the highest level of sequence similarity with respect to P. dokdonensis DS-8(T) (99.58 % over 1424 nt), with differences in 64 positions out of 1488. The levels of DNA-DNA relatedness with its closest neighbours (<70 %) showed that the isolate represents a distinct genomic species. On the basis of the phenotypic and genotypic results, strain MSL-03(T) represents a novel species of the genus Phycicoccus, for which the name Phycicoccus bigeumensis sp. nov. is proposed. The type strain is strain MSL-03(T) (=KCTC 19266(T) =DSM 19264(T)). | 18,842,868 |
Proposed revision of Rule 33c to perpetuate the citation of revived names. | All names published prior to 1980 that were not included in the Approved Lists are available for reuse without reference to their past application. However, the International Code of Nomenclature of Bacteria endorses the revival of disused names in the sense in which they were previously used and provides Rules (28a, 33c and 33d) as guidance. Nevertheless, the Code is obscure as to how citations are to be reported for this use to be perpetuated in subsequent nomenclatural revisions. A revision of Rule 33c is proposed. | 18,842,877 |
Transformation of a virtual action plan into a motor plan in the premotor cortex. | Before preparing to initiate a forthcoming motion, we often acquire information about the future action without specifying actual motor parameters. The information for planning an action at this conceptual level can be provided with verbal commands or nonverbal signals even before the associated motor targets are visible. Under these conditions, the information signifying a virtual action plan must be transformed to information that can be used for constructing a motor plan to initiate specific movements. To determine whether the premotor cortex is involved in this process, we examined neuronal activity in the dorsal premotor cortex (PMd) of monkeys performing a behavioral task designed to isolate the behavioral stages of the acquisition of information for a future action and the construction of a motor plan. We trained the animals to receive a symbolic instruction (color and shape of an instruction cue) to determine whether to select the right or left of targets to reach, despite the physical absence of targets. Subsequently, two targets appeared on a screen at different locations. The animals then determined the correct target (left or right) based on the previous instruction and prepared to initiate a reaching movement to an actual target. The experimental design dissociated the selection of the right/left at an abstract level (action plan) from the physical motor plan. Here, we show that activity of individual PMd neurons initially reflects a virtual action plan transcending motor specifics, before these neurons contribute to a transformation process that leads to activity encoding a motor plan. | 18,842,888 |
Central contributions to acoustic variation in birdsong. | Birdsong is a learned behavior remarkable for its high degree of stereotypy. Nevertheless, adult birds display substantial rendition-by-rendition variation in the structure of individual song elements or "syllables." Previous work suggests that some of this variation is actively generated by the avian basal ganglia circuitry for purposes of motor exploration. However, it is unknown whether and how natural variations in premotor activity drive variations in syllable structure. Here, we recorded from the premotor nucleus robust nucleus of the arcopallium (RA) in Bengalese finches and measured whether neural activity covaried with syllable structure across multiple renditions of individual syllables. We found that variations in premotor activity were significantly correlated with variations in the acoustic features (pitch, amplitude, and spectral entropy) of syllables in approximately a quarter of all cases. In these cases, individual neural recordings predicted 8.5 +/- 0.3% (mean +/- SE) of the behavioral variation, and in some cases accounted for 25% or more of trial-by-trial variations in acoustic output. The prevalence and strength of neuron-behavior correlations indicate that each acoustic feature is controlled by a large ensemble of neurons that vary their activity in a coordinated manner. Additionally, we found that correlations with pitch (but not other features) were predominantly positive in sign, supporting a model of pitch production based on the anatomy and physiology of the vocal motor apparatus. Collectively, our results indicate that trial-by-trial variations in spectral structure are indeed under central neural control at the level of RA, consistent with the idea that such variation reflects motor exploration. | 18,842,896 |
GABAergic afferents activate both GABAA and GABAB receptors in mouse substantia nigra dopaminergic neurons in vivo. | Most in vivo electrophysiological studies of substantia nigra have used rats. With the recent proliferation of the use of mice for in vitro neurophysiological studies because of the availability of various genetically modified strains to identify the roles of various channels and proteins in neuronal function, it is crucial to obtain data on in vivo responses in mice to verify that the in vitro results reflect functioning of systems comparable with those that have been well studied in rat. Inhibitory responses of rat nigral dopaminergic neurons by stimulation of afferents from striatum, globus pallidus, or pars reticulata have been shown to be mediated predominantly or exclusively by GABA(A) receptors. This is puzzling given the substantial expression of GABA(B) receptors and the ubiquitous appearance of GABA(B) synaptic responses in rat dopaminergic neurons in vitro. In the present study, we studied electrically evoked GABAergic inhibition in nigral dopaminergic neurons in C57BL/6J mice. Stimulation of the three major GABAergic inputs elicited stronger and longer-lasting inhibitory responses than those seen in rats. The early inhibition was GABA(A) mediated, whereas the later component, absent in rats, was GABA(B) mediated and selectively enhanced by GABA uptake inhibition. Striatal-evoked inhibition exhibited a slower onset and a weaker initial component compared with inhibition from globus pallidus or substantia nigra pars reticulata. These results are discussed with respect to differences in the size and neuronal density of the rat and mouse brain and the different sites of synaptic contact of the synapses from the three GABAergic afferents. | 18,842,898 |
Novel selective allosteric activator of the M1 muscarinic acetylcholine receptor regulates amyloid processing and produces antipsychotic-like activity in rats. | Recent studies suggest that subtype-selective activators of M(1)/M(4) muscarinic acetylcholine receptors (mAChRs) may offer a novel approach for the treatment of psychotic symptoms associated with schizophrenia and Alzheimer's disease. Previously developed muscarinic agonists have provided clinical data in support of this hypothesis, but failed in clinical development because of a lack of true subtype specificity and adverse effects associated with activation of other mAChR subtypes. We now report characterization of a novel highly selective agonist for the M(1) receptor with no agonist activity at any of the other mAChR subtypes, termed TBPB [1-(1'-2-methylbenzyl)-1,4'-bipiperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one]. Mutagenesis and molecular pharmacology studies revealed that TBPB activates M(1) through an allosteric site rather than the orthosteric acetylcholine binding site, which is likely critical for its unprecedented selectivity. Whole-cell patch-clamp recordings demonstrated that activation of M(1) by TBPB potentiates NMDA receptor currents in hippocampal pyramidal cells but does not alter excitatory or inhibitory synaptic transmission, responses thought to be mediated by M(2) and M(4). TBPB was efficacious in models predictive of antipsychotic-like activity in rats at doses that did not produce catalepsy or peripheral adverse effects of other mAChR agonists. Finally, TBPB had effects on the processing of the amyloid precursor protein toward the non-amyloidogenic pathway and decreased Abeta production in vitro. Together, these data suggest that selective activation of M(1) may provide a novel approach for the treatment of symptoms associated with schizophrenia and Alzheimer's disease. | 18,842,902 |
Targeting of RGS7/Gbeta5 to the dendritic tips of ON-bipolar cells is independent of its association with membrane anchor R7BP. | Complexes of regulator of G-protein signaling (RGS) proteins with G-protein beta5 (Gbeta5) subunits are essential components of signaling pathways that regulate the temporal characteristics of light-evoked responses in vertebrate retinal photoreceptors and ON-bipolar cells. Recent studies have found that RGS/Gbeta5 complexes bind to a new family of adapter proteins, R9AP (RGS9 anchor protein) and R7 family binding protein (R7BP), that in case of the RGS9/Gbeta5 complex were shown to determine its precise subcellular targeting to either the outer segment of photoreceptors or postsynaptic structures of striatal neurons, respectively. In this study, we establish that another trimeric complex consisting of RGS7, Gbeta5, and R7BP subunits is specifically targeted to the dendritic tips of retinal bipolar cells. However, examination of the mechanisms of complex targeting in vivo surprisingly revealed that the delivery of RGS7/Gbeta5 to the dendrites of ON-bipolar cells occurs independently of its association with R7BP. These findings provide a new mechanism for adapter-independent targeting of RGS/Gbeta5 complexes. | 18,842,904 |
Etanercept-induced lupus erythematosus presenting as a unilateral pleural effusion. | A 72-year-old man receiving etanercept for the treatment of psoriatic arthritis had an exudative pleural effusion with nonspecific fluid analysis and pleural biopsy findings. He was ultimately found to have drug-induced lupus erythematosus due to the etanercept. The spectrum of autoimmune disease due to the use of tumor necrosis factor inhibitors is reviewed. | 18,842,918 |
Anxiety and depression in COPD: current understanding, unanswered questions, and research needs. | Approximately 60 million people in the United States live with one of four chronic conditions: heart disease, diabetes, chronic respiratory disease, and major depression. Anxiety and depression are very common comorbidities in COPD and have significant impact on patients, their families, society, and the course of the disease. We report the proceedings of a multidisciplinary workshop on anxiety and depression in COPD that aimed to shed light on the current understanding of these comorbidities, and outline unanswered questions and areas of future research needs. Estimates of prevalence of anxiety and depression in COPD vary widely but are generally higher than those reported in some other advanced chronic diseases. Untreated and undetected anxiety and depressive symptoms may increase physical disability, morbidity, and health-care utilization. Several patient, physician, and system barriers contribute to the underdiagnosis of these disorders in patients with COPD. While few published studies demonstrate that these disorders associated with COPD respond well to appropriate pharmacologic and nonpharmacologic therapy, only a small proportion of COPD patients with these disorders receive effective treatment. Future research is needed to address the impact, early detection, and management of anxiety and depression in COPD. | 18,842,932 |
Uropathogens and host characteristics. | Uropathogens other than Escherichia coli occur with greater frequency in patients with risk factors for urinary tract infection (UTI). However, little is known about associations between uropathogen species and host characteristics. Three hundred nineteen urine specimens containing a balanced distribution of uropathogen species were selected from inpatients and outpatients at a university hospital clinical microbiology laboratory. Information on host characteristics was retrospectively collected by chart review. Differences in the frequencies of host characteristics in UTI groups, as defined by the causative uropathogen, were compared by chi-square/Fisher analysis. Multivariate classification and regression tree analysis were used to identify host characteristic subsets that distinguish among uropathogen groups. In this exploratory study, several uropathogen species were found to be strongly linked to host characteristics relevant to UTI. Patients with Pseudomonas aeruginosa UTIs were more likely to have undergone urinary tract procedures (43% versus 15% overall), to have a neurogenic bladder (29% versus 12% overall), to have received recent antibiotic therapy (52% versus 24% overall), and to be male (76% versus 28% overall). Patients with Proteus mirabilis UTIs were more likely to have a foreign body in the lower urinary tract (48% versus 30% overall). The classification tree identified males over the age of 27 years who had undergone a prior urinary tract procedure as belonging to a host characteristic profile associated with P. aeruginosa UTI: 38% of patients with P. aeruginosa UTIs fit this profile. These data may be useful for planning future targeted prophylaxis studies. | 18,842,936 |
Early stages of melody processing: stimulus-sequence and task-dependent neuronal activity in monkey auditory cortical fields A1 and R. | To explore the effects of acoustic and behavioral context on neuronal responses in the core of auditory cortex (fields A1 and R), two monkeys were trained on a go/no-go discrimination task in which they learned to respond selectively to a four-note target (S+) melody and withhold response to a variety of other nontarget (S-) sounds. We analyzed evoked activity from 683 units in A1/R of the trained monkeys during task performance and from 125 units in A1/R of two naive monkeys. We characterized two broad classes of neural activity that were modulated by task performance. Class I consisted of tone-sequence-sensitive enhancement and suppression responses. Enhanced or suppressed responses to specific tonal components of the S+ melody were frequently observed in trained monkeys, but enhanced responses were rarely seen in naive monkeys. Both facilitatory and suppressive responses in the trained monkeys showed a temporal pattern different from that observed in naive monkeys. Class II consisted of nonacoustic activity, characterized by a task-related component that correlated with bar release, the behavioral response leading to reward. We observed a significantly higher percentage of both Class I and Class II neurons in field R than in A1. Class I responses may help encode a long-term representation of the behaviorally salient target melody. Class II activity may reflect a variety of nonacoustic influences, such as attention, reward expectancy, somatosensory inputs, and/or motor set and may help link auditory perception and behavioral response. Both types of neuronal activity are likely to contribute to the performance of the auditory task. | 18,842,950 |
Differential effects of divalent cations on spontaneous and evoked glycine release from spinal interneurons. | The effects of Ca2+, Sr2+, and Ba2+ on spontaneous and evoked glycinergic inhibitory postsynaptic currents (mIPSCs and eIPSCs) were studied using the "synaptic bouton" preparation of rat spinal neurons and conventional whole cell recording under voltage-clamp conditions. In response to application of Ca2+-free solution, the frequency of mIPSC initially rapidly decreased to 40 approximately 50% of control followed by a gradual further decline in mIPSC frequency to approximately 30% of control. Once mIPSC frequency had significantly decreased in Ca2+-free solution, application of Ca2+, Sr2+, or Ba2+ increased mIPSC frequency. The rank order of effect in restoring mIPSCs was Ba2+>>Ca2+>Sr2+. Moreover, the application of excess external [K+]o solution (30 mM) containing Sr2+ or Ba2+ after 2 h in Ca2+-free solution also increased mIPSC frequency in the order Sr2+>or==Ba2+>Ca2+. The mean mIPSC amplitude was not affected at all. In contrast, eIPSCs produced by focal stimulation of single boutons were completely abolished in Ca2+-free solution or when Ca2+ was replaced by Sr2+ or Ba2+ (2 mM each). However, eIPSCs were restored in increased concentrations of Sr2+ or Ba2+ (5 mM each). The results show that these divalent cations affect mIPSC and eIPSCs differently and indicate that the mechanisms underlying transmitter release that generates eIPSCs and mIPSC in presynaptic nerve terminals are different. The different mechanisms might be explained by the different sensitivity of synaptotagmin isoforms to Ca2+, Sr2+, and Ba2+. | 18,842,954 |
Balance of increases and decreases in firing rate of the spontaneous activity of basal ganglia high-frequency discharge neurons. | Most neurons in the external and internal segments of the globus pallidus and the substantia nigra pars reticulata (GPe, GPi, and SNr) are characterized by a high-frequency discharge (HFD) rate (50-80 Hz) that, in most GPe neurons, is also interrupted by pauses. Almost all (approximately 90%) of the synaptic inputs to these HFD neurons are GABAergic and inhibitory. Nevertheless, their responses to behavioral events are usually dominated by increases in discharge rate. Additionally, there are no reports of prolonged bursts in the spontaneous activity of these cells that could reflect their disinhibition by GPe pauses. We recorded the spontaneous activity of 385 GPe, GPi, and SNr HFD neurons during a quiet-wakeful state from two monkeys. We developed three complementary methods to quantify the balance of increases and decreases in the spontaneous discharge of HFD neurons and validated them by simulations. Unlike the behavioral evoked responses, the spontaneous activity of pallidal and SNr neurons is not dominated by increases. Moreover, the activity of basal ganglia neurons does not include bursts that could reflect disinhibition by the spontaneous pauses of GPe neurons. These findings suggest that the discharge increase/decrease balance during a quiet-wakeful state better reflects the inhibitory input of the HFD basal ganglia neurons than during responses to behavioral events; however, the GPe pauses are not echoed by comparable bursts either in the GPe or in the output nuclei. Changes in the excitatory drive of these structures (e.g., during behavioral activity) thus may lead to a remarkable change in this balance. | 18,842,958 |
Prescribing quality indicators of type 2 diabetes mellitus ambulatory care. | Existing performance indicators for assessing quality of care in type 2 diabetes mellitus (T2DM) focus mostly on registration of measurements and clinical outcomes, and not on quality of prescribing. To develop a set of valid prescribing quality indicators (PQI) for internal use in T2DM, and assess the operational validity of the PQI using electronic medical records. Potential PQI for hypertension, hyperglycaemia, dyslipidaemia and antiplatelet treatment in T2DM were based on clinical guidelines, and assessed on face and content validity in an expert panel followed by a panel of GPs and diabetologists. Analysis of ratings was performed using the RAND/UCLA Appropriateness Method. The operational validity of selected indicators was assessed in a dataset of 3214 T2DM patients registered with 70 GPs. Out of 31 potential prescribing indicators, the expert panel considered 18 indicators as sufficiently valid, of which 14 indicators remained valid after assessment by the panel of GPs and diabetologists. Of these 14 indicators, one could not be calculated because of an absence of eligible patients. For the remaining indicators, outcomes varied from 10% for timely prescribing of insulin to 96% for prescribing of any antihyperglycemic medication in patients with elevated HbA1c levels. This study provides a set of face- and content-valid PQI for pharmacological management of patients with T2DM. While outcomes of some PQI were limited to patients with registration of clinical values, the selected PQI had good operational validity to be used in practice for assessment of prescribing quality. | 18,842,968 |
Genetic polymorphisms, messenger RNA expression of p53, p21, and CCND1, and possible links with chromosomal aberrations in Chinese vinyl chloride-exposed workers. | This study explores the relationship between genetic polymorphisms of p53, p21, and CCND1, and the susceptibility of chromosomal damage induced by vinyl chloride monomer (CH(2)=CHCl, VCM). Besides gene polymorphisms, we detected the mRNA expression of p53, p21, and CCND1 in VCM-exposed workers and in a control group. One hundred and eighty-three workers occupationally exposed to VCM were investigated. Chromosome damage in peripheral lymphocyte was measured by cytokinesis-block micronucleus assay. The PCR-restriction fragment length polymorphism technique was applied to detect polymorphisms of p53, p21 (exon 2 and exon 3), and CCND1 genes (exon 4). The quantity of gene mRNA expression was detected by real-time PCR (SYBR Green I). Taking into account the effects of genetic polymorphisms, as well as demographic and habitual factors, Poisson regression analysis showed that the risk of chromosomal damage induced by VCM for individuals carrying the p53 intron 6 heterozygous and mutant homozygous genotype was 1.23 times larger (90% confidence interval, 1.01-1.51 P=0.0814), compared with those carrying wild-type homozygous genotypes. The p53 exon 4, intron 3, and intron 6 haplotype pairs of MMM/WWW (M, mutation allele; W, wild allele), and MWM/WWW were associated with increased frequencies of micronuclei. The p53 mRNA expression of VCM-exposed workers was significantly lower than that of nonexposed workers, but p21 mRNA expression in VCM-exposed workers was significantly higher than that of nonexposed workers. Our findings suggest that the p53 intron 6 polymorphism is one of the factors that potentially influence the frequency of micronuclei induced by VCM. | 18,842,998 |
Single-dose pharmacokinetics and tolerability of absorption-enhanced 3,3'-diindolylmethane in healthy subjects. | We have completed a single ascending dose clinical study of the proposed chemopreventive agent 3,3'-diindolylmethane (DIM). The study agent was nutritional-grade, absorption-enhanced BioResponse 3,3'-diindolylmethane (BR-DIM). We determined the safety, tolerability, and pharmacokinetics of single doses of BR-DIM in drug-free, non-smoking, healthy men and women. Groups of four subjects were enrolled for each dose level. After randomization, one subject in each group received placebo whereas three received active BR-DIM. The doses administered were 50, 100, 150, 200, and 300 mg, with the 300-mg dose repeated in an additional group. No BR-DIM-related adverse effects were reported at doses up to 200 mg. At the 300-mg dose, one of six subjects reported mild nausea and headache and one also reported vomiting. Only the latter effect was judged as probably related to the study agent. Analysis of serial plasma samples showed that only one subject at the 50-mg dose had detectable concentrations of DIM. The single 100-mg dose of BR-DIM resulted in a mean maximum plasma concentration (C(max)) of 32 ng/mL and a mean area under the curve (AUC) of 128 h ng/mL, and a single 200-mg dose produced a mean C(max) of 104 ng/mL and a mean AUC of 553 h ng/mL. The single 300-mg dose of BR-DIM resulted in a mean C(max) of 108 ng/mL and a mean AUC of 532 h ng/mL. We conclude that BR-DIM is well tolerated at single doses of up to 200 mg, and that increasing the dose to 300 mg did not result in an increase in C(max). | 18,843,002 |
Comparing the reliability of responses to telephone-administered versus self-administered Web-based surveys in a case-control study of adult malignant brain cancer. | To determine whether a Web-based survey was an acceptable method of data collection for a clinic-based case-control study of adult brain cancer, the authors compared the reliability of paired responses to a main and resurvey for participants completing surveys by telephone (n=74) or self-administered on the Web (n=465) between 2003 and 2006. Recruitment of cases was done at the Evanston Northwestern Healthcare Kellogg Cancer Care Center and the Duke University Medical Center Cancer Control division, and controls were friends and siblings of cases. Twenty-five variables were examined, including smoking, oral contraceptive and residential histories, water sources, meat preparation, fruit and vegetable consumption, and pesticide use. Weighted and simple kappa's were estimated for categorical and binary variables, respectively. The number of concordant paired responses was summed for use in linear regression. Respondents were 97% White and 85% had postsecondary education. Kappa's for individual questions ranged from 0.31 (duration of residence in a single family house) to 0.96 (ever smoked), with a median of 0.57 (95% confidence interval, 0.47-0.64). The median number of concordant responses was 16.2 (range, 5-22). Reliability was greater for controls than cases, Web-based versus telephone responders, females, and higher-income responders. Frequency of e-mail and Internet use was not associated with reliability. A self-administered, Web-based survey was a feasible and appropriate mode of interview in this study. The comparable reliability of Web compared with telephone responses suggest that Web-based self-interviews could be a cost-effective alternative to traditional modes of interview. | 18,843,005 |
Differential suture loading in an experimental rotator cuff repair. | Repairs of large rotator cuff tears often fail to heal. A possible factor in these failures is excessive tension in the repair sutures, causing them to pull through the tendon. Arm positions encountered during early rehabilitation after cuff repair can dramatically increase the relative tension in the different sutures of the cuff repair. Controlled laboratory study. In a cadaver model, a 4-suture supraspinatus repair was carried out with transosseous sutures. After the repair, the arm was placed in 12 different positions. The tension in each suture was monitored using individual load cells. When the arm was externally rotated relative to the plane of the scapula, the tension in the anterior suture was over 10 times that in the posterior suture (P < .001). When the arm was internally rotated, the tension in the posterior suture was over 10 times that in the anterior suture (P < .0005). When the arm was in neutral rotation, there was no significant difference in the suture tension. This study is the first report of direct suture tension measurement after a model rotator cuff repair. In this model, 30 degrees of either internal or external rotation of the arm in relation to the plane of the scapula created substantial imbalances in the tension between the most anterior and most posterior sutures of a supraspinatus repair, regardless of the position of abduction. Avoiding external rotation stretching during the healing of supraspinatus repairs may prevent tension overload in the critical anterior suture. | 18,843,038 |
Posttranslational regulation of the scaffold for Fe-S cluster biogenesis, Isu. | Isu, the scaffold protein on which Fe-S clusters are built in the mitochondrial matrix, plays a central role in the biogenesis of Fe-S cluster proteins. We report that the reduction in the activity of several components of the cluster biogenesis system, including the specialized Hsp70 Ssq1, causes a 15-20-fold up-regulation of Isu. This up-regulation results from changes at both the transcriptional and posttranslational level: an increase in ISU mRNA levels and in stability of ISU protein. Its biological importance is demonstrated by the fact that cells lacking Ssq1 grow poorly when Isu levels are prevented from rising above those found in wild-type cells. Of the biogenesis factors tested, Nfs1, the sulfur donor, was unique. Little increase in Isu levels occurred when Nfs1 was depleted. However, its presence was required for the up-regulation caused by reduction in activity of other components. Our results are consistent with the existence of a mechanism to increase the stability of Isu, and thus its level, that is dependent on the presence of the cysteine desulfurase Nfs1. | 18,843,040 |
CCAAT/enhancer-binding protein beta promotes osteoblast differentiation by enhancing Runx2 activity with ATF4. | Although CCAAT/enhancer-binding protein beta (C/EBPbeta) is involved in osteocalcin gene expression in osteoblast in vitro, the physiological importance of and molecular mechanisms governing C/EBPbeta in bone formation remain to be elucidated. In particular, it remains unclear whether C/EBPbeta acts as a homodimer or a heterodimer with other proteins during osteoblast differentiation. Here, deletion of the C/EBPbeta gene from mice resulted in delayed bone formation with concurrent suppression of chondrocyte maturation and osteoblast differentiation. The expression of type X collagen as well as chondrocyte hypertrophy were suppressed in mutant bone, providing new insight into the possible roles of C/EBPbeta in chondrocyte maturation. In osteoblasts, luciferase reporter, gel shift, DNAP, and ChIP assays demonstrated that C/EBPbeta heterodimerized with activating transcription factor 4 (ATF4), another basic leucine zipper transcription factor crucial for osteoblast maturation. This complex interacted and transactivated osteocalcin-specific element 1 (OSE1) of the osteocalcin promoter. C/EBPbeta also enhanced the synergistic effect of ATF4 and Runx2 on osteocalcin promoter transactivation by enhancing their interaction. Thus, our results provide evidence that C/EBPbeta is a crucial cofactor in the promotion of osteoblast maturation by Runx2 and ATF4. | 18,843,047 |
Neonatal Fc receptor mediates internalization of Fc in transfected human endothelial cells. | The neonatal Fc receptor, FcRn mediates an endocytic salvage pathway that prevents degradation of IgG, thus contributing to the homeostasis of circulating IgG. Based on the low affinity of IgG for FcRn at neutral pH, internalization of IgG by endothelial cells is generally believed to occur via fluid-phase endocytosis. To investigate the role of FcRn in IgG internalization, we used quantitative confocal microscopy to characterize internalization of fluorescent Fc molecules by HULEC-5A lung microvascular endothelia transfected with GFP fusion proteins of human or mouse FcRn. In these studies, cells transfected with FcRn accumulated significantly more intracellular Fc than untransfected cells. Internalization of FcRn-binding forms of Fc was proportional to FcRn expression level, was enriched relative to dextran internalization in proportion to FcRn expression level, and was blocked by incubation with excess unlabeled Fc. Because we were unable to detect either surface expression of FcRn or surface binding of Fc, these results suggest that FcRn-dependent internalization of Fc may occur through sequestration of Fc by FcRn in early endosomes. These studies indicate that FcRn-dependent internalization of IgG may be important not only in cells taking up IgG from an extracellular acidic space, but also in endothelial cells participating in homeostatic regulation of circulating IgG levels. | 18,843,053 |
Recombinant activated factor VII use in the emergency department. | Recombinant activated factor VII (rFVIIa) has recently gained wide attention as a potent prohaemostatic agent for patients with excessive or life-threatening blood loss. Originally licensed for the treatment of patients with bleeding haemophilia with antibodies to factor VIII or IX, rFVIIa is now being used on an off-label basis to thwart blood loss in a variety of other clinical situations. Despite concerns over the drug's cost, risk profile and the lack of large-scale clinical trials validating its use, more and more patients are being treated with rFVIIa in the emergency department. With few clinical trials available to guide its administration, emergency physicians must weigh the existing evidence when considering whether to use rFVIIa for their patients with bleeding. This paper reviews the current literature regarding rFVIIa as it pertains to the practice of emergency medicine. | 18,843,055 |
Paediatric allergic reactions in the emergency department: a review. | Allergic diseases are increasing in incidence worldwide and large numbers of children are now affected by allergy. Few studies have examined allergic reactions in children, particularly in the emergency department (ED) setting. Primary--to describe the epidemiology of acute paediatric allergic reactions. Secondary--to describe the treatment and outcome of allergic reactions presenting to a paediatric ED. The ED of a paediatric tertiary referral hospital with approximately 29,000 ED attendances annually. A retrospective review of allergic reactions presenting to a paediatric ED over a 2-year period. 237 patients (61% male, median age 46 months) had reactions. 137/100,000 children attend the ED annually. The main identified causative agents were nuts (23%), dairy products (16.5%) and medication (10%). Oral contact was associated with 58.6% of reactions and dermatological symptoms were the most frequent presentation. Only 11(5%) received adrenaline (epinephrine). 46 (19%) were admitted. 55% of all patients received no formal follow-up. Acute allergic reactions affect boys more than girls and frequently occur at a young age. Food allergies, in particular to nuts, are a major cause of reactions. Allergy represents a frequent presentation to the paediatric ED. There remains a concern about the adequacy of follow-up. | 18,843,063 |
Hepatitis B vaccine and the risk of CNS inflammatory demyelination in childhood. | The risk of CNS inflammatory demyelination associated with hepatitis B (HB) vaccine is debated, with studies reporting conflicting findings. We conducted a population-based case-control study where the cases were children with a first episode of acute CNS inflammatory demyelination in France (1994-2003). Each case was matched on age, sex, and geographic location to up to 12 controls, randomly selected from the general population. Information on vaccinations was confirmed by a copy of the vaccination certificate. The odds ratios (ORs) of CNS inflammatory demyelination associated with HB vaccination were estimated using conditional logistic regression. The rates of HB vaccination in the 3 years before the index date were 24.4% for the 349 cases and 27.3% for their 2,941 matched controls. HB vaccination within this period was not associated with an increase in the rate of CNS inflammatory demyelination (adjusted OR, 0.74; 0.54-1.02), neither >3 years nor as a function of the number of injections or brand type. When the analysis was restricted to subjects compliant with vaccination, HB vaccine exposure >3 years before index date was associated with an increased trend (1.50; 0.93-2.43), essentially from the Engerix B vaccine (1.74; 1.03-2.95). The OR was particularly elevated for this brand in patients with confirmed multiple sclerosis (2.77; 1.23-6.24). Hepatitis B vaccination does not generally increase the risk of CNS inflammatory demyelination in childhood. However, the Engerix B vaccine appears to increase this risk, particularly for confirmed multiple sclerosis, in the longer term. Our results require confirmation in future studies. | 18,843,097 |
Novel congenital myopathy locus identified in Native American Indians at 12q13.13-14.1. | Native American myopathy (NAM) is an autosomal recessive congenital myopathy first reported in the Lumbee Indian people. Features of NAM include congenital weakness, cleft palate, ptosis, short stature, and susceptibility to malignant hyperthermia provoked by anesthesia. We identified five individuals with NAM from the Lumbee population, and hypothesized that these affected individuals have disease alleles shared identical-by-descent inherited from common ancestry. To identify a NAM disease locus, homozygosity mapping methods were employed on a genomewide 10K single-nucleotide polymorphism (SNP) screen. To confirm regions of homozygosity identified in the SNP screen, microsatellite repeat markers were genotyped within those homozygous segments. The SNP data demonstrated five regions of shared homozygosity in individuals with NAM. The additional genotyping data narrowed the region to one common segment of homozygosity spanning D12S398 to rs3842936 mapping to 12q13.13-14.1. Notably, loss of heterozygosity estimates from the SNP data also detected this same 12q region in the affected individuals. This study reports the first gene mapping of Native American myopathy (NAM) using single-nucleotide polymorphism-based homozygosity mapping in only a few affected individuals from simplex families and identified a novel NAM locus. Identifying the genetic basis of NAM may suggest new genetic etiologies for other more common conditions such as congenital myopathy and malignant hyperthermia. | 18,843,099 |
Rab11a-dependent exocytosis of discoidal/fusiform vesicles in bladder umbrella cells. | The discoidal/fusiform vesicles (DFV) of bladder umbrella cells undergo regulated exocytosis in response to stretch, but little is known about their biogenesis or the molecular machinery that modulates this process. We observed that Rab11a was expressed in umbrella cells (but not Rab11b or Rab25) and was associated with DFV. Using adenovirus-mediated delivery we transduced umbrella cells in situ with either dominant active (DA) or dominant negative (DN) mutants of Rab11a. DA-Rab11a stimulated an increase in apical surface area in the absence of stretch, whereas DN-Rab11a inhibited stretch-induced changes. Endocytosed fluid and membrane markers had little access to Rab11a-positive DFV, but virally expressed human growth hormone (hGH), a secretory protein, was packaged into DFV. Whereas expression of DA-Rab11a stimulated release of hGH into the bladder lumen, expression of DN-Rab11a had the opposite effect. Our results indicate that DFV may be biosynthetic in nature and that their exocytosis depends on the activity of the Rab11a GTPase. | 18,843,107 |
Reconstruction of the human gastrocnemius force-length curve in vivo: part 1-model-based validation of method. | The muscle fiber force-length relationship has been explained in terms of the cross-bridge theory at the sarcomere level. In vivo, for a physiologically realistic range of joint motion, and therefore range of muscle fiber lengths, only part of the force-length curve may be used; that is, the section of the force-length curve expressed can vary. The purpose of this study was to assess the accuracy of a method for determining the expressed section of the force-length curve for biarticular muscles. A muscle model was used to simulate the triceps surae muscle group. Three model formulations were used so that the gastrocnemius operated over different portions of the force-length curve: the ascending limb, the plateau region, and the descending limb. Joint moment data were generated for a range of joint configurations and from this simulated data the region of the force- length relationship that the gastrocnemius muscle operated over was successfully reconstructed using the algorithm of Herzog and ter Keurs (1988a). Further simulations showed that the correct region of the force-length curve was accurately reconstructed even in the presence of random and systematic noise generated to reflect the effects of sampling errors, and incomplete muscle activation. | 18,843,149 |
Continuous relative phase variability during an exhaustive run in runners with a history of iliotibial band syndrome. | Previous research has proposed that a lack of variability in lower extremity coupling during running is associated with pathology. The purpose of the study was to evaluate lower extremity coupling variability in runners with and without a history of iliotibial band syndrome (ITBS) during an exhaustive run. Sixteen runners ran to voluntary exhaustion on a motorized treadmill while a motion capture system recorded reflective marker locations. Eight runners had a history of ITBS. At the start and end of the run, continuous relative phase (CRP) angles and CRP variability between strides were calculated for key lower extremity kinematic couplings. The ITBS runners demonstrated less CRP variability than controls in several couplings between segments that have been associated with knee pain and ITBS symptoms, including tibia rotation-rearfoot motion and rearfoot motion-thigh ad/abduction, but more variability in knee flexion/extension-foot ad/abduction. The ITBS runners also demonstrated low variability at heel strike in coupling between rearfoot motion-tibia rotation. The results suggest that runners prone to ITBS use abnormal segmental coordination patterns, particular in couplings involving thigh ad/abduction and tibia internal/external rotation. Implications for variability in injury etiology are suggested. | 18,843,156 |
Determining carotid artery pressure from scaled diameter waveforms: comparison and validation of calibration techniques in 2026 subjects. | Calibrated diameter distension waveforms could provide an alternative for local arterial pressure assessment more widely applicable than applanation tonometry. We compared linearly and exponentially calibrated carotid diameter waveforms to tonometry readings. Local carotid pressures measured by tonometry and diameter waveforms measured by ultrasound were obtained in 2026 subjects participating in the Asklepios study protocol. Diameter waveforms were calibrated using a linear and an exponential calibration scheme and compared to measured tonometry waveforms by examining the mean root-mean-squared error (RMSE), carotid systolic blood pressure (SBPcar) and augmentation index (AIx) of calibrated and measured pressures. Mean RMSE was 5.2(3.3) mmHg (mean(stdev)) for linear and 4.6(3.6) mmHg for exponential calibration. Linear calibration yielded an underestimation of SBPcar by 6.4(4.1) mmHg which was strongly correlated to values of brachial pulse pressure (PPbra) (R = 0.4, P < 0.05). Exponential calibration underestimated true SBPcar by 1.9(3.9) mmHg, independent of PPbra. AIx was overestimated by linear calibration by 1.9(10.1)%, the difference significantly increasing with increasing AIx (R = 0.25, P < 0.001) and by exponential calibration by 5.4(10.6)%, independently of the value of AIx. Properly calibrated diameter waveforms offer a viable alternative for local pressure estimation at the carotid artery. Compared to linear calibration, exponential calibration significantly improves the pressure estimation. | 18,843,161 |
ECG scaling properties of cardiac arrhythmias using detrended fluctuation analysis. | We applied detrended fluctuation analysis to characterize at very short time scales during episodes of cardiac arrhythmias the raw electrocardiogram (ECG) waveform, aiming to get a global insight into its dynamical behaviour in patients who experienced sudden death. We found that in 15 recordings involving different types of arrhythmias (taken from PhysioNet's Sudden Cardiac Death Holter Database), the ECG waveform, besides showing a less-random dynamics, becomes more regular during bigeminy, ventricular tachycardia or even atrial fibrillation and ventricular fibrillation. The ECG waveform scaling properties thus suggest that reduced complexity dominates the underlying mechanisms of arrhythmias. Among other explanations, this may result from shorted or restricted (i.e. less diverse) pathways of conduction of the electrical activity within ventricles. | 18,843,162 |
Dynamic measures of regional lung air volume using phase contrast x-ray imaging. | Phase contrast x-ray imaging can provide detailed images of lung morphology with sufficient spatial resolution to observe the terminal airways (alveoli). We demonstrate that quantitative functional and anatomical imaging of lung ventilation can be achieved in vivo using two-dimensional phase contrast x-ray images with high contrast and spatial resolution (<100 microm) in near real time. Changes in lung air volume as small as 25 microL were calculated from the images of term and preterm rabbit pup lungs (n = 28) using a single-image phase retrieval algorithm. Comparisons with plethysmography and computed tomography showed that the technique provided an accurate and robust method of measuring total lung air volumes. Furthermore, regional ventilation was measured by partitioning the phase contrast images, which revealed differences in aeration for different ventilation strategies. | 18,843,172 |
Efficacy of ER-alpha polymorphisms and the intrafollicular IGF system for predicting pregnancy in IVF-ET patients. | To evaluate the efficacies of the estrogen receptor-alpha (ER-alpha) gene polymorphisms and of the intrafollicular insulin-like growth factor (IGF) system for predicting pregnancy in in vitro fertilization and embryo transfer (IVF-ET) patients. A total of 96 patients undergoing IVF-ET were included in this study. Genotyping for the ER-alpha gene PvuII and XbaI polymorphisms was performed using polymerase-chain reaction and single base extension method. Follicular fluid (FF) IGF-I, IGF-II, and IGFBP-3 concentrations were measured by RIA, and IGFBP-4 by ELISA. We compared, between pregnant (n = 28) and non-pregnant groups (n = 68), the allele frequency, genotype distribution and haplotype distribution of PvuII and XbaI polymorphisms, and then FF IGF-I, IGF-II, IGFBP-3, IGFBP-4 concentrations and their ratios. No significant differences were found between the two groups in terms of allele, genotype or haplotype distributions of the ER-alpha gene PvuII and XbaI polymorphisms between the two groups. The mean FF IGF-I/IGFBP-3 ratio was significantly higher in the pregnant group (5.9 +/- 1.5 vs. 4.8 +/- 1.5 x 10(-2)). The intrafollicular IGF-I/IGFBP-3 ratio of the FF of the dominant follicle during oocyte retrieval appears to be related to the establishment of pregnancy in IVF-ET patients, whereas the ER-alpha gene PvuII and XbaI polymorphisms do not. | 18,843,190 |
14-3-3 Gamma is required to enforce both the incomplete S phase and G2 DNA damage checkpoints. | Checkpoint pathways inhibit mitotic progression by inducing the phosphorylation of serine 216 in cdc25C resulting in the generation of a 14-3-3 binding site on cdc25C. Two 14-3-3 isoforms, 14-3-3epsilon and 14-3-3gamma form a complex with cdc25C and inhibit cdc25C function. To examine the contribution of 14-3-3gamma to checkpoint regulation, the expression of 14-3-3gamma was inhibited in HCT116 cells using vector based RNA interference. A transient reduction in the expression of 14-3-3gamma in HCT116 cells resulted in an override of both the incomplete S phase and the G(2) DNA damage checkpoint. A 14-3-3gamma knockdown clone also showed an override of both checkpoint pathways. These phenotypes were reversed upon expression of a shRNA resistant 14-3-3gamma cDNA. Override of the G(2) DNA damage checkpoint pathway was accompanied by a decrease in the levels of inhibitory phosphorylation on cdc25C and cdk1. However, there was no difference in the gamma-H2AX foci formation and levels of phospho-chk1 and phospho-chk2, suggesting that activation of the DNA damage checkpoint response and subsequent activation of the checkpoint kinases Chk1 and Chk2 was not perturbed. These results suggest that the override of checkpoint observed in 14-3-3gamma knockdown cells is due to failure to inhibit cdc25C function. | 18,843,201 |
IRES-mediated translational control of AMAP1 expression during differentiation of monocyte U937 cells. | Global control of mRNA translation plays key roles in cell regulation, including growth, differentiation and apoptosis. Human monocyte-like U937 cells differentiate into macrophage-like cells upon 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment, a process which is known to be accompanied with a large decrease in general protein synthesis. Here, we found that protein levels of AMAP1 (also called ASAP1 or DDEF1), a GTPase-activating protein for Arf GTPases, increase several fold during U937 cell differentiation. This increase was not accompanied with a notable increase in the AMAP1 gene transcript, nor seemed to be due to 5'-Cap-dependent mRNA translational activities in differentiated U937 cells. We identified the 5'-untranslated region (5'-UTR) of AMAP1 mRNA, and found that this 5'-UTR exhibits significant internal ribosome entry site (IRES)-dependent translational activity in differentiated U937 cells, but not in undifferentiated cells. Our results indicate that monocyte differentiation involves enhancement of IRES activity, by which protein levels of AMAP1 are primarily upregulated. | 18,843,202 |
Treatment of a critically ill child with disseminated Candida glabrata with a recombinant human antibody specific for fungal heat shock protein 90 and liposomal amphotericin B, caspofungin, and voriconazole. | To report a case of fungal sepsis treated prospectively with liposomal amphotericin, caspofungin, and a novel monoclonal antibody specific for candidal heat shock protein 90 (Mycograb, Neutec Pharma, Manchester, UK). Case report. Pediatric intensive care unit in a tertiary care children's hospital. A 7-yr-old male with a history of global developmental delay, epilepsy, and gastroesophageal reflux, who presented to the emergency department with a transdiaphragmatic herniation of bowel and subsequent Candida glabrata infection. Efungumab 1 mg/kg twice daily for 5 days. C-reactive protein fell from 225 mg/L to 99 mg/L, and physiological monitoring parameters improved when Mycograb was used in conjunction with high-dose antifungals. Mycograb therapy was well tolerated, but further experience with this therapy in children is needed. | 18,843,247 |
Vitamin D levels and patient outcome in chronic kidney disease. | Vitamin D deficiency has been linked to cardiovascular disease and early mortality in patients on hemodialysis; however, it is not known if the same association exists at earlier stages of chronic kidney disease. To determine this we enrolled 168 consecutive new referrals to a chronic kidney disease clinic over a 2 year period and followed them for up to 6 years. All patients were clinically stable and had an estimated glomerular filtration rate (eGFR) at stage 2 or less and were without an imminent need for dialysis. Baseline 25-hydroxyvitamin D levels directly and significantly correlated with eGFR. After an average follow-up of 48 months, 48 patients started dialysis and 78 had died. In crude analyses, 25-hydroxyvitamin D predicted both time to death and end-stage renal disease. A dual-event Cox's model confirmed 25-hydroxyvitamin D as an independent predictor of study outcomes when adjusted for age, heart failure, smoking, C-reactive protein, albumin, phosphate, use of converting enzyme inhibitors or angiotensin receptor blockers, and eGFR. Our study shows that plasma 25-hydroxyvitamin D is an independent inverse predictor of disease progression and death in patients with stage 2-5 chronic kidney disease. | 18,843,258 |
Asian promise: the state and future of collaborations in neuroscience. | As investment in science and technology continues to grow in Asia, countries such as China, Japan and Singapore are witnessing great improvements in their neuroscience research environments; this is reflected in the opening of new research institutions and in the influx of neuroscientists trained abroad. Collaborative projects between researchers in these countries and laboratories in the United States and Europe are not only helping to shape these institutions, they are also leading to a surge in high-quality publications in both basic and translational neuroscience, resulting in increasing international recognition. Nature Reviews Neuroscience asks four neuroscientists about their collaborative experiences and the impact that such collaborations are having on neuroscience research. | 18,843,270 |
A lupus-susceptibility C57BL/6 locus on chromosome 3 (Sle18) contributes to autoantibody production in 129 mice. | Epistatic interactions between the non-autoimmune strains 129 and C57BL/6 (B6), used for generating gene-targeted animals, can induce a lupus-like disease. Genome-wide scan analyses of testcross progeny between these two strains have identified several lupus susceptibility loci, with the strongest linkage to the production of autoantibodies (auto-Abs) displayed by an interval on chromosome 1 of 129 origin (Sle16). However, the contribution of B6 loci to the lupus phenotype remained unknown. We used a congenic approach to deduce the contribution to the autoimmune traits of the B6 genomic interval on chromosome 3 (Sle18), previously shown to be linked to antinuclear Ab production. This interval, when transferred on a 129 background (a strain termed 129.B6-Sle18), promoted auto-Ab production targeting a broad spectrum of autoantigens, expansion of activated CD4(+)T and B cells and mild glomerulonephritis. Surprisingly, these immunological and serological defects were accompanied by a significant increase in the percentage of regulatory T cells (Tregs; CD4(+) Foxp3(+)). However, these cells, that expressed lower levels of Foxp3, had no impaired regulatory function when tested in vitro. These findings illustrate further the efficacy of congenic dissection for functional characterisation of individual lupus susceptibility loci and highlight the contribution of loci derived from non-autoimmune strains to the disease pathogenesis. | 18,843,275 |
The Sp1 transcription factor binds to the G-allele of the -1087 IL-10 gene polymorphism and enhances transcriptional activation. | The objectives of this study were to evaluate the influence of the -1087 single nucleotide polymorphism (SNP) on the gene expression of interleukin (IL)-10 and to identify transcription factors binding to this site in B cells. Using electrophoretic mobility-shift assays and nuclear extract from the DG75 B-cell line, we demonstrated that the Sp1 transcription factor bound to the -1087 G-allele of the IL-10 promoter and that the transcription factors PU.1 and Spi-B bound to both the G- and A-alleles. Transient transfections showed that lipopolysaccharide stimulation resulted in a 15-fold increase in promoter activity for the G-allele as compared to a 6-fold increase for the A-allele. Co-transfection with Sp1 expression vector in Sp1-deficient SL2 cells leading to Sp1 binding to the G-allele of the -1087 SNP resulted in increased IL-10 promoter activity. The results suggest a role for Sp1 transcription factor in the activation of IL-10 through the G-allele of the -1087 SNP in response to inflammatory signals. | 18,843,277 |
HMGA2 protein expression correlates with lymph node metastasis and increased tumor grade in pancreatic ductal adenocarcinoma. | Pancreatic ductal adenocarcinoma is a highly aggressive, lethal human malignancy that continues to elude successful treatment. Although most patients present with metastatic disease, the molecular pathways that underlie tumor progression and metastases are poorly understood. The high mobility group A2 (HMGA2) protein is an architectural transcription factor that has recently been implicated in the development and progression of malignant tumors. Here, we examined HMGA2 gene expression in pancreatic ductal adenocarcinoma to determine if it could be a marker for more advanced disease. By real time quantitative RT-PCR, we showed a marked increase in HMGA2 mRNA in two of three cultured pancreatic ductal adenocarcinoma cell lines compared to normal pancreatic tissue. Using tissue microarrays generated from 124 pancreatic ductal adenocarcinoma cases, we also assessed HMGA2 protein levels by immunohistochemical analysis. We found that HMGA2 nuclear immunoreactivity correlates positively with lymph node metastases and high tumor grade. Our results support a role for HMGA2 in the progression of pancreatic ductal adenocarcinoma and suggest that it could be a useful biomarker and rational therapeutic target in more advanced disease. | 18,843,278 |
Cytokine-induced CEACAM1 expression on keratinocytes is characteristic for psoriatic skin and contributes to a prolonged lifespan of neutrophils. | Carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1) is a cell-surface glycoprotein, belonging to the carcinoembryonic antigen family, expressed by human neutrophils, epithelial cells, activated T and NK cells. CEACAM1 is expressed as a cell-surface molecule with different isoforms or can be secreted as a soluble protein. Here, we show that keratinocytes in the outer epidermal layer of psoriatic skin express CEACAM1, unlike those in healthy skin or in cutaneous lesions of patients with atopic or nummular dermatitis. Stimulation of primary human keratinocytes or in vitro reconstituted epidermis with culture supernatants of activated psoriatic lesion-infiltrating T cells, IFN-gamma or oncostatin M, but not IL-17, induced the expression of transcripts for the CEACAM1-long and -short isoforms and cell-surface CEACAM1, whereas soluble CEACAM1 was not produced. The uppermost layers of the epidermis in psoriatic lesions also contain neutrophils, a cell type with inflammatory and antimicrobial properties. Coculture of CEACAM1-expressing keratinocytes or CHO transfectants with neutrophils delayed spontaneous apoptosis of the latter cells. These results show that cytokine-induced cell-surface expression of CEACAM1 by keratinocytes in the context of a psoriatic environment might contribute to the persistence of neutrophils and thus to ongoing inflammation and the decreased propensity for skin infection, typical for patients with psoriasis. | 18,843,289 |
Mitotic Origins of Chromosomal Instability in Colorectal Cancer. | Mitosis is a crucial part of the cell cycle. A successful mitosis requires the proper execution of many complex cellular behaviors. Thus, there are many points at which mitosis may be disrupted. In cancer cells, chronic disruption of mitosis can lead to unequal segregation of chromosomes, a phenomenon known as chromosomal instability. A majority of colorectal tumors suffer from this instability, and recent studies have begun to reveal the specific ways in which mitotic defects promote chromosomal instability in colorectal cancer. | 18,843,382 |
Use of headspace SPME-GC-MS for the analysis of the volatiles produced by indoor molds grown on different substrates. | An automated headspace solid phase microextraction method followed by GC-MS analysis was used to evaluate and compare the in vitro production of microbial volatile organic compounds (MVOCs) on malt extract agar, plasterboard and wallpaper. Five fungal strains were isolated from the walls of water-damaged houses and identified. In addition, four other common molds were studied. In general, MVOC production was the highest on malt extract agar. On this synthetic medium, molds typically produced 2-methylpropanol, 2-methylbutanol and 3-methylbutanol. On wallpaper, mainly 2-ethylhexanol, methyl 2-ethylhexanoate and compounds of the C8-complex such as 1-octene-3-ol, 3-octanone, 3-octanol and 1,3-octadiene were detected. The detection of 2-ethylhexanol and methyl 2-ethylhexanoate indicates an enhanced degradation of the substrate by most fungi. For growth on plasterboard, no typical metabolites were detected. Despite these metabolite differences on malt extract agar, wallpaper and plasterboard, some molds also produced specific compounds independently of the used substrate, such as trichodiene from Fusarium sporotrichioides and aristolochene from Penicillium roqueforti. Therefore, these metabolites can be used as markers for the identification and maybe also mycotoxin production of these molds. All five investigated Penicillium spp. in this study were able to produce two specific diterpenes, which were not produced by the other species studied. These two compounds, which remain unidentified until now, therefore seem specific for Penicillium spp. and are potentially interesting for the monitoring of this fungal genus. Further experiments will be performed with other Penicillium spp. to study the possibility that these two compounds are specific for this group of molds. | 18,843,388 |
Highly efficient formation of halodiazoacetates and their use in stereoselective synthesis of halocyclopropanes. | Halogenated analogues of ethyl diazoacetate are synthesised by a novel and highly efficient procedure and give halocyclopropanes in good to excellent yields when exposed to a Rh(ii) catalyst in the presence of alkenes. | 18,843,396 |
High yielding selective access to spirocyclopropanated 5-oxopiperazine-2-carboxylates and 1,4-diazepane-2,5-diones from methyl 2-chloro-2-cyclopropylideneacetate. | The 2-spirocyclopropanated methyl 5-oxopiperazine-2-carboxylate and the 3-spirocyclopropanated 6-chloro-1,4-diazepane-2,5-dione could both be prepared at choice in 93 and 88% yield, respectively, from methyl 2-chloro-2-cyclopropylideneacetate () in a sequence of Michael addition of 3-benzyloxypropylamine, peptide coupling with N-Boc-glycine, Boc-group removal and cyclization. Transformation of the benzyloxypropyl side chain, peptide coupling with N-Boc-(S)-asparagine, deprotection and repeated cyclization led to the octahydro[2H]pyrazino[1,2-a]pyrazinetrione scaffold containing a rigidified mimic of a tripeptide with a DGR motif. The overall yield of after deprotection of (a total of 13 steps in 8 distinct operations) was 30%. | 18,843,412 |
Stannyl ceramides as efficient acceptors for synthesising beta-galactosyl ceramides. | beta-Galactosyl ceramides have been obtained in excellent yields and stereoselectivities by reacting disarmed glycosyl donors with stannyl ethers. The broad compatibility of stannyl ethers with various leaving group-promoter pairs is demonstrated. | 18,843,414 |
Electronically varied quinazolinaps for asymmetric catalysis. | The synthesis and resolution of electronically varied axially chiral Quinazolinaps is reported. These ligands bear different aryl groups on the donor phosphorus atom and were synthesised as part of our investigations into electronic effects within this ligand class. A diastereomerically pure palladacycle of one ligand was characterised by X-ray crystallography. The application of these Quinazolinaps to the rhodium-catalysed hydroboration of vinylarenes resulted in enantioselectivities of up to 92%. Their application to the palladium-catalysed allylic alkylation of 1,3-diphenylprop-2-enyl acetate resulted in conversions of up to 99% and enantioselectivities of up to 94%. | 18,843,417 |
Driving behaviour after brain injury: a follow-up of accident rate and driving patterns 6-9 years post-injury. | A follow-up of accident rate and driving patterns of patients 6-9 years after brain injury. Postal questionnaire sent to patients with brain injury who were assessed consecutively in the period 1997-2000 and who were re-issued. A total of 93 persons, 69 men and 24 women, mean age 57 years, average 9 years post-injury, 65 persons with brain injury after cerebrovascular accidents and 28 with traumatic brain injury. The questionnaire covered self-reported driving accidents pre- and post-injury, yearly distance driven, behaviour in traffic and self-reported care taken in driving. The cerebrovascular accident group had reduced their driving significantly post-injury and had also changed their driving patterns. No significant changes were found in distance driven and driving patterns for the group with traumatic brain injury. Compared with normative data, reported accidents post-injury in the cerebrovascular accident group showed no increased accident rate, while the accident rate in the traumatic brain injury-group was more than 2 times higher. Patients with traumatic brain injury represent a risk group for accidents post-injury, while those with brain injury after cerebrovascular accidents do not. Possible causes for this difference are discussed. | 18,843,425 |
An orthosis and physiotherapy programme for camptocormia: a prospective case study. | Camptocormia, or bent spine syndrome, is an acquired postural disease leading to lumbar kyphosis observed when the patient stands up. Classic orthoses and physiotherapy programmes provide little correction and are often poorly tolerated. The aim of this study was to evaluate the effectiveness and tolerance of a new orthosis combined with physiotherapy for treating camptocormia. Fifteen patients (5 men and 10 women, 71.4 (standard deviation (SD) 7.3) years old) consulting for camptocormia were consecutively included in the study. Patients who had pain when they straightened up were excluded. Patients equipped with the orthosis were hospitalized for 5 days in order to learn a self-rehabilitation programme. They were evaluated before and after hospitalization, then at 30 and 90 days. In comparison with day 0 (without orthosis), the mean increase in lumbar lordosis with the orthosis was 10.1 degrees (SD 9.9) at day 30 (p < 0.05) and 12.5 degrees (SD 9.7) at day 90 (p < 0.001). Average pain values showed a reduction of 69% (SD 36) and 70% (SD 35) in the initial pain at days 30 and 90, respectively. The average increase in quality of life was 87% and 92% at days 30 and 90, respectively. This new orthosis, relying on the principle of thoraco-pelvic anterior distraction, gives excellent results in the treatment of camptocormia. | 18,843,430 |
Effects of resistance training in combination with coenzyme Q10 supplementation in patients with post-polio: a pilot study. | Coenzyme Q10 supplementation leads to increased muscle metabolism in patients with post-polio syndrome. The aim of this study was to investigate the effect of resistance training in combination with oral supplementation with coenzyme Q10 in patients with post-polio syndrome regarding muscle strength and endurance as well as functional capacity and health-related quality of life. Parallel randomized, controlled, double-blind pilot study. A total of 14 patients (8 women and 6 men) with post-polio syndrome participated in a 12-week muscular resistance training, 3 days/week. The patients were randomized for oral supplementation with coenzyme Q10, 200 mg/day, or placebo. Measurements used were: sit-stand-sit test, timed up & go test, 6-minute walk test, muscle strength measurement by means of dynamic dynamometer and short-form (SF)-36 questionnaire. Muscle strength, muscle endurance and quality of life regarding mental health increased statistically significantly in all 14 patients. There was no significant difference between the coenzyme Q10 and placebo groups regarding muscle strength, muscle endurance and quality of life. There was no effect of coenzyme Q10 supplementation during resistance training on post-polio syndrome symptoms. Thus, supplementation with coenzyme Q10 has no beneficial effect on muscle function in patients with post-polio syndrome. | 18,843,432 |
Laparoscopic-assisted combined colon and liver resection for primary colorectal cancer with synchronous liver metastases: initial experience. | Laparoscopic approaches have become increasingly used in selected patients with either colorectal or liver cancer. However, the feasibility of laparoscopic-assisted combined colon and liver resection in primary colorectal cancer with synchronous liver metastases remains unknown. The aim of the present study was to determine the feasibility of laparoscopic-assisted combined colon and liver resection for primary colorectal cancer with synchronous liver metastases. Laparoscopic surgery involving intestinal anastomosis was performed for primary colorectal cancer. The liver was then mobilized with the assistance of a hand inserted through the upper midline incision. For minor resections, the parenchymal transection was performed laparoscopically. For major resection involving a hilar dissection, transection was performed according to the standard open techniques under direct vision through the incision. Resected specimens were retrieved directly through the midline incision. Ten patients with primary colorectal cancer and synchronous liver metastases underwent the above procedure between September 2006 and April 2007. Surgical procedures for colorectal cancer included 5 low anterior resections, 3 anterior resections, 1 right hemicolectomy, and 1 subtotal colectomy. Combined hepatic surgery included 6 major hepatectomies, 3 segmentectomies, and 1 tumorectomy. All procedures were successful, with no conversions to open surgery required. The median operation time was 439 min (range: 210-690 min), and the median estimated blood loss was 350 ml (range: 300-1,200 ml). There was no surgical mortality or major morbidity, except in one patient in whom postoperative bleeding at the site of para-aortic node dissection was promptly controlled. Laparoscopic-assisted combined colon and liver resection is a feasible and safe procedure for the treatment of primary colorectal cancer with synchronous liver metastases. | 18,843,442 |
Modified technique of pancreaticojejunal anastomosis with invagination following pancreaticoduodenectomy: a cohort study. | Leakage from pancreatic anastomoses remains the single most important morbidity after pancreaticoduodenectomy and contributes to prolonged hospitalization and mortality. This observational cohort study reported the surgical outcome of a modified invagination technique of pancreaticojejunostomy after pancreaticoduodenectomy. Between December 2001 and December 2007, a total of 52 consecutive patients underwent elective pancreaticoduodenectomy for benign or malignant pathologies of the pancreas or the periampullary region in a tertiary referral center. All patients underwent our modified invagination technique of pancreaticojejunostomy regardless of the characteristics of the pancreatic stump. Data were collected prospectively. The mean hospital stay was 12.6 +/- 3.2 days. The incidence of overall surgical complications was 9.6%. No patient developed pancreatic fistula. One patient (1.9%) died of respiratory failure on postoperative day 7. We reported our pancreaticojejunostomy anastomosis technique with a pancreatic fistula rate of 0% and low intra-abdominal complication rate. The favorable results of this technique warrant further investigation in large prospective cohort studies and prospective randomized controlled studies. | 18,843,443 |
Advances in amino acid analysis. | Amino acids are important targets for metabolic profiling. For decades, amino acid analysis has been accomplished by either cation-exchange or reversed-phase liquid chromatography coupled to UV absorbance or fluorescence detection of pre-column or post-column-derivatized amino acids. Recent years have seen great progress in the development of direct-infusion or hyphenated mass spectrometry in the analysis of free amino acids in physiological fluids, because mass spectrometry not only matches optical detection in sensitivity, but also offers superior selectivity. The advent of cryo-probes has also brought NMR spectroscopy within the detection limits required for the analysis of free amino acids. But there is still room for further improvement, including expansion of the analyte spectrum, reduction of sample preparation and analysis time, automation, and synthesis of affordable isotope standards. | 18,843,484 |
Determination of biogenic amines in food samples using derivatization followed by liquid chromatography/mass spectrometry. | A liquid chromatography (LC)/mass spectrometry method was developed for the determination of selected biogenic amines in various fish and other food samples. It is based on a precolumn derivatization of the amines with succinimidylferrocenyl propionate under formation of the respective amides and their reversed-phase liquid-chromatographic separation with subsequent electrospray ionization mass-spectrometric detection. Deuterated putescine, cadaverine, and histamine are added prior to the derivatization as internal standards that are coeluted, thus allowing excellent reproducibility of the analysis to be achieved. Depending on the analyte, the limits of detection were between 1.2 and 19.0 mg/kg, covering between 2 and 3 decades of linearity. The limit of detection and the linear range for histamine are suitable for the surveillance of the only defined European threshold for biogenic amines in fish samples. Compared with the established ortho-phthalaldehyde (OPA)/LC/fluorescence method, the newly developed method allows an unambiguous identification of the biogenic amines by their mass spectra in addition to only retention times, a fivefold acceleration of the separation, and independency from the sample matrix owing to the isotope-labeled internal standards. Various fish, calamari, and salami samples were successfully analyzed with the new method and validated with an independent OPA/LC/fluorescence method. | 18,843,485 |
A systematic review on the effect of bevacizumab in exudative age-related macular degeneration. | To provide evidence for the effect of bevacizumab on visual acuity (VA) and central retinal thickness (CRT) in exudative age-related macular degeneration A systematic review of all articles of bevacizumab for exudative AMD was conducted. Articles published up to March 2008 were identified in Medline, Embase, the Cochrane Controlled Trials Register and references from included articles. Search terms were "Bevacizumab or Avastin" and "Macula* or ARMD or AMD or intra(-)vitreal or intra(-)vitreous". Three observers participated in the data retrieval and assignment of the quality scores. A total of 561 articles were retrieved. Three randomised controlled trials (RCT) and 23 before-and-after studies of patients (n = 1,435) who had received bevacizumab were published. Inclusion criteria varied. Lack of masking was the main methodological shortcoming. These RCTs showed that bevacizumab is more effective than PDT. Bevacizumab was given intravenously or as intravitreal injection. The latter was given once, or repeatedly every 4 weeks, and with or without additional injection when a recurrence occurred, mostly based on visual acuity and/or findings from optical coherence tomography. After intravenous administration, the weighted mean change in VA was +12.8 ETDRS letters (range +11 to +14) and the weighted mean change for CRT was -129 microm (range -100 to -202). For the 23 studies with intravitreal injections, the change in VA was +8.6 letters (range +2 to +26) and the change in CRT was -90 microm (range -46 to -190). The incidence of adverse events was low. The change in VA was 2.7 letters higher for studies with a higher quality vs lower quality. Visual acuity improves and central retinal thickness decreases in patients with exudative AMD after bevacizumab. There is no reasonable doubt that this is caused by bevacizumab. It is likely that a randomised controlled trial will show that bevacizumab is equivalent in effect to ranibizumab, which showed a change in ETDRS of +5.9 letters for occult or minimally classic CNV and +9.8 letters for classic CNV after three monthly injections in two large RCTs. | 18,843,500 |
Mechanical-statistical modeling in ecology: from outbreak detections to pest dynamics. | Knowledge about large-scale and long-term dynamics of (natural) populations is required to assess the efficiency of control strategies, the potential for long-term persistence, and the adaptability to global changes such as habitat fragmentation and global warming. For most natural populations, such as pest populations, large-scale and long-term surveys cannot be carried out at a high resolution. For instance, for population dynamics characterized by irregular abundance explosions, i.e., outbreaks, it is common to report detected outbreaks rather than measuring the population density at every location and time event. Here, we propose a mechanical-statistical model for analyzing such outbreak occurrence data and making inference about population dynamics. This spatio-temporal model contains the main mechanisms of the dynamics and describes the observation process. This construction enables us to account for the discrepancy between the phenomenon scale and the sampling scale. We propose the Bayesian method to estimate model parameters, pest densities and hidden factors, i.e., variables involved in the dynamics but not observed. The model was specified and used to learn about the dynamics of the European pine sawfly (Neodiprion sertifer Geoffr., an insect causing major defoliation of pines in northern Europe) based on Finnish sawfly data covering the years 1961-1990. In this application, a dynamical Beverton-Holt model including a hidden regime variable was incorporated into the model to deal with large variations in the population densities. Our results gave support to the idea that pine sawfly dynamics should be studied as metapopulations with alternative equilibria. The results confirmed the importance of extreme minimum winter temperatures for the occurrence of European pine sawfly outbreaks. The strong positive connection between the ratio of lake area over total area and outbreaks was quantified for the first time. | 18,843,520 |
HIV/AIDS/STD/HCV, coinfection, seroprevalence and education in severe mental illness: health education pilot. | HIV/AIDS among the severely mentally ill (SMI) population exceeds the held belief that man to man contact is the leading type of, rate of transmission and infection placing an emphasis on high risk behavior management, education and testing as key in reducing the epidemic in psychiatric facility inpatient/outpatient populations (Rothbard, Psychiatric Services 54(9):1240-1246, 2003). The Information-Motivation-Behavioral Skills Model (IMB) is an integrative framework to explain HIV risk reduction most often used and tested with the SMI population (Carey et al. Journal of Consulting and Clinical Psychology 72(2), 2004; Donenberg AIDS Education and Prevention 17(3):200-216, 2005; Meade and Sikkema Clinical Psychology Review 25(4):433-457, 2005; Rosenberg et al. Comprehensive Psychiatry 42(4):263-271, 2001). This education pilot program was developed for the Department of Texas State Health Services (DSHS) Austin State Hospital (ASH) Education and Rehabilitation Adult Psychiatric Services (APS) acute and forensic inpatient units. | 18,843,534 |
Tissue-specific regulation and expression of heat shock proteins in type 2 diabetic monkeys. | The chaperone protein heat shock protein (HSP) 70 has been shown to protect against obesity-associated insulin resistance. Induction of HSPs is thus considered an exciting therapeutic strategy for diabetes (DM). The aims of this study were to (1) determine HSP levels in plasma, hepatic, and pancreatic tissues of type 2 DM primates and (2) assess the relationship between chaperone proteins of the HSP family and cellular protection. We collected plasma from 24 type 2 DM and 25 normoglycemic control (CTL) cynomolgus macaques. A subset of DM monkeys had liver and pancreas samples available which were compared to a second group of CTL monkeys. We found that DM monkeys had 32% lower HSP70 in circulation which remained significant even after adjustment for the greater age and bodyweight of these monkeys (p < 0.001). The liver demonstrated a similar reductions in both HSP70 and 90 that was related to 50% lower levels of the transcription factor, heat shock factor 1 (HSF1; p = 0.03). Pancreatic tissue had the opposite expression pattern with significantly higher HSF1 (p = 0.004) and accordingly higher HSP70 and 90. Pancreas from DM monkeys had less nitrosative oxidation (p = 0.03) which was unaccounted for by superoxide dismutases and was negatively associated with HSP levels (r = -0.57, p = 0.009). HSF1/HSP deficiency exists in DM liver which may contribute to hepatic insulin resistance and this deficiency was reflected in lower circulating concentrations. Pancreas maintains HSP levels despite hyperglycemia, likely in an attempt to protect vulnerable beta cells from exocrine pancreatic damage and from stress associated with insulin hypersecretion. | 18,843,550 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.