Miracle-dz/UniFAR-FTUs huggingface dataset:
Repeat instability during DNA repair: Insights from model systems

Abstract The expansion of repeated sequences is the cause of over 30 inherited genetic diseases, including Huntington disease, myotonic dystrophy (types 1 and 2), fragile X syndrome, many spinocerebellar ataxias, and some cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Repeat expansions are dynamic, and disease inheritance and progression are influenced by the size and the rate of expansion. Thus, an understanding of the various cellular mechanisms that cooperate to control or promote repeat expansions is of interest to human health. In addition, the study of repeat expansion and contraction mechanisms has provided insight into how repair pathways operate in the context of structure-forming DNA, as well as insights into non-canonical roles for repair proteins. Here we review the mechanisms of repeat instability, with a special emphasis on the knowledge gained from the various model systems that have been developed to study this topic. We cover the repair pathways and proteins that operate to maintain genome stability, or in some cases cause instability, and the cross-talk and interactions between them.
Changes in Hip Bone Mineral Density and Objectively Measured Physical Activity in Middle-Aged Women: A 6-Year Prospective Study

Purpose. This study was conducted to determine if physical activity volume (PAv) and intensity (PAi) at baseline influence the likelihood of gaining hip bone mineral density (BMD) over 6 years. Design and Sample. In a prospective study, the sample was limited to 244 female nonsmokers, ages 35 to 45 years, and was approximately 90% white. Setting and Measures. PAv and PAi were measured in daily living conditions using accelerometers at baseline. BMD, measured by dual energy x-ray absorptiometry, and several confounding factors were measured in the lab. Analysis. On the basis of BMD change scores, participants were divided into three categories: BMD loss, minimal change, and BMD gain. Risk ratios were used to show the likelihood of BMD gains over time across different levels of PAv and PAi at baseline. Results. Women with higher PAv were more likely to show improvements in hip BMD from baseline to follow-up than their counterparts, as indicated by the Mantel-Haenszel chi-square (χ2mh = 6.1, p = .01). Women with high PAv were 2.50 times (95% CI, 1.19–5.24) more likely to experience hip BMD gains than women with low PAv, and women with moderate PAv were 2.20 times (95% CI, 1.08–4.45) more likely. PAi was not predictive of gains in hip BMD. Adjusting for potential confounders had little influence on the results. Conclusions. Middle-aged women with moderate or high levels of PAv are more likely to experience BMD gains at the hip over time compared with those who have low levels of PAv. However, PAi does not appear to influence the likelihood of gaining BMD at the hip over 6 years.
The female football player, disordered eating, menstrual function and bone health

Most female football players are healthy. However, recent findings from our studies on Norwegian female elite athletes also show that football players are dieting and experiencing eating disorders, menstrual dysfunction and stress fractures. Dieting behaviour and lack of knowledge of the energy needs of the athlete often leads to energy deficit, menstrual dysfunction and increased risk of bone mass loss. Although dieting, eating disorders and menstrual dysfunction are less common than in many other sports, it is important to be aware of the problem as eating disorders in female athletes can easily be missed. Therefore, individuals, including the players themselves, coaches, administrators and family members, who are involved in competitive football, should be educated about the three interrelated components of the female athlete triad (disordered eating, menstrual dysfunction and low bone mass), and strategies should be developed to prevent, recognise and treat the triad components.
Clinical and molecular epidemiology of chromosome-mediated resistance to third-generation cephalosporins in Enterobacter isolates in eastern France.

OBJECTIVE To determine both the prevalence of group I beta-lactamase-related resistance and the clinical setting in which resistance to expanded-spectrum cephalosporins occurs. METHODS Isolates of Enterobacter spp. were sensitivity tested to a range of antibiotics, and selected isolates were DNA fingerprinted by pulsed-field gel electrophoresis. The medical records of all patients with positive cultures for Enterobacter spp. were reviewed to determine the effect of previous antibiotic treatment on the susceptibility profile of these organisms. RESULTS The crude incidence of colonization/infection (n = 315) was 0.51 per 100 patients and 0.73 per 1000 days of hospitalization. The 4-day and 7-day Kaplan-Meier rates of colonization/infection with Enterobacter were estimated to be 7.57% (standard deviation (SD = 3.26%) and 4.16% (SD = 2.88%)), respectively. The time lag to colonization/infection with isolates producing large amounts of Bush group 1 beta-lactamase (HLBL) (27.35 +/- 27.30 days) was significantly different from that to colonization/infection with wild-type isolates (13.59 +/- 17.93 days) (P = 0.036). Ninety-six isolates (30.5%) demonstrated acquired resistance to expanded-spectrum cephalosporins: 34 isolates (10.8%) produced extended-spectrum beta-lactamase, and 62 isolates (19.7%) produced HLBL. The 89 Enterobacter isolates susceptible to third-generation cephalosporins yielded 84 major DNA patterns, and the 45 HLBL isolates yielded 38 major DNA patterns. The risk of colonization/infection with HLBL-producing Enterobacter was higher in cases of antimicrobial treatment with third-generation cephalosporins or a fluoroquinolone, and in cases of urinary tract colonization/infection. CONCLUSIONS The judicious use in hospitals of both expanded-spectrum cephalosporins and other antibiotics such as fluoroquinolones is necessary to curtail the emergence of resistance in Enterobacter spp.
Risk of hypertension and renal dysfunction with an angiogenesis inhibitor sunitinib: Systematic review and meta-analysis

Background. Sunitinib is a multitargeted tyrosine kinase inhibitor used in the treatment of metastatic renal cell carcinoma (RCC) and gastrointestinal stromal tumor (GIST), and undergoing evaluation for other malignancy. Hypertension is one of its major side effects with a substantial variation in the reported incidences among clinical studies. We here performed a systematic review and meta-analysis of published clinical trials to determine its overall risk. Methods. Relevant studies were searched and identified in MEDLINE (OVID 1966 to July, 2007), Web of Science, and abstracts presented at the American Society of Clinical Oncology annual meetings from 2004 through 2007. Eligible studies were prospective clinical trials that had described events of hypertension for patients who received single agent sunitinib. The incidence of hypertension and relative risk (RR) were calculated using the random-effects or the fixed-effects model. Results. A total of 4, 999 patients with RCC and other malignancies from 13 clinical trials were included for analysis. Among patients receiving sunitinib, the incidence of all-grade and high-grade hypertensions were 21.6% (95% CI: 18.7–24.8%) and 6.8% (95% CI: 5.3–8.8%) respectively. The risk may vary with tumor type and the dosing schedule of sunitinib. Sunitinib was associated with a significantly increased risk of high-grade hypertension (RR=22.72, 95% CI: 4.48 to 115.29, p<0.001) and renal dysfunction (RR: 1.36, 95% CI: 1.20 to 1.54, p<0.001) in comparison with controls. Conclusions. There is a significant risk of developing hypertension and renal dysfunction among patients receiving sunitinib. Adequate monitoring and treatment of hypertension is recommended.
Tc17 CD8+ T Cells Potentiate Th1-Mediated Autoimmune Diabetes in a Mouse Model

An increase in IL-17–producing CD8+ T (Tc17) cells has been reported in the peripheral blood of children with recent onset type 1 diabetes (T1D), but their contribution to disease pathogenesis is still unknown. To directly study the pathogenic potential of β cell-specific Tc17 cells, we used an experimental model of T1D based on the expression of the neo-self Ag hemagglutinin (HA) in the β cells of the pancreas. When transferred alone, the IL-17–producing HA-specific CD8+ T cells homed to the pancreatic lymph nodes without causing any pancreatic infiltration or tissue destruction. When transferred together with small numbers of diabetogenic HA-specific CD4+ T cells, a strikingly different phenotype developed. Under these conditions, Tc17 cells sustained disease progression, driving the destruction of β-islet cells, causing hyperglycemia and ultimately death. Disease progression did not correlate with functional or numerical alterations among the HA-specific CD4+ T cells. Rather, the transferred CD8+ T cells accumulated in the pancreatic islets and a considerable fraction converted, under the control of IL-12, to an IFN-γ–producing phenotype. Our data indicate that Tc17 cells are not diabetogenic but can potentiate a Th1-mediated disease. Plasticity of the Tc17 lineage is associated with transition to overt disease in this experimental model of T1D.
Health status of individuals entering a cardiac rehabilitation program as measured by the medical outcomes study 36-item short-form survey (SF-36).

BACKGROUND AND PURPOSE The goal of health care for individuals with chronic disease is the improvement of function and well-being. Although the individual's perception of his or her quality of life may be the best indicator of achievement of this goal, measurement of self-perceived quality of life, or health status, is not a routine component of evaluation. The purposes of this article are to describe the health status of individuals upon entry into a cardiac rehabilitation program and to demonstrate the use of a comprehensive, generic health status measure in this group. SUBJECTS The subjects of this study were 789 men and women enrolled in one of 13 cardiac rehabilitation programs in the state of Massachusetts. METHODS As part of a large database, subjects completed a 36-item generic questionnaire, Short Form 36 (SF-36), that examines eight health concepts. Scores range from 0% to 100%; a higher score is consistent with better health status. Results. Mean uncontrolled scores ranged from 26.6 to 70.8. Mean scores adjusted for sex, age, and education ranged from 27.1 to 70.9. In light of previously published data using a similar 20-item scale, our results show that cardiac disease is associated with reductions in health-related quality of life. CONCLUSION AND DISCUSSION Health status measurement provides information that can supplement the usual measures of impairment in patients with cardiovascular disease. The findings of this study contribute to the understanding of health status of individuals who enroll in cardiac rehabilitation programs. The health status instrument used in this study has potential as a useful, practical measurement tool for use in the clinical setting.
Course of Depressive Symptoms in Patients Undergoing Heart Surgery: Confirmatory Analysis of the Factor Pattern and Latent Mean Structure of the Center for Epidemiologic Studies Depression Scale

Objective: The purpose of this study was to examine the dimensionality, stability, and course of depressive symptoms over the 12-month period beginning approximately 1 week before heart surgery. Methods: The Center for Epidemiological Studies Depression Scale (CES-D) was administered to 570 patients before heart surgery and 1, 3.5, 6.5, and 12.5 months later. Results: Confirmatory factor analysis rejected a four-factor model as a result of small variances for two interpersonal items. With their elimination, a three-factor solution (negative affect, low positive affect, somatic/vegetative symptoms) showed good psychometric properties. Except for the somatic/vegetative factor at the 1-month follow up, there was a high degree of stability in the factor pattern over a 12-month period beginning approximately 1 week before heart surgery. Latent mean structure analysis indicated that, apart from elevations in several somatic/vegetative symptoms during the month after surgery, means for all three depressive symptoms declined over time. The recovery of positive affect showed a steeper trajectory toward the end of the follow-up period by comparison with the rates of decline for depressed affect and somatic/vegetative symptoms. Conclusions: These findings support using 18 CES-D items to measure three depressive symptom dimensions in heart patients and may reflect a normative pattern of adjustment to heart surgery. CES-D = Center for Epidemiological Studies Depression Scale; CABG = coronary artery bypass graft surgery; CHD = coronary heart disease; MI = myocardial infarction; CFA = confirmatory factor analysis; RWJUH = Robert Wood Johnson University Hospital; UMDNJ = University of Medicine and Dentistry of New Jersey; EM = expectation maximization; MAR = missing at random; DA = depressed affect; PA = positive affect; S/V = somatic/vegetative; RMSEA = root mean square error of approximation; CI = confidence interval; CFI = comparative fit index.
Lice, nits, and school policy.

BACKGROUND The epidemiology of head lice infestation is poorly understood. Many schools treat all children with nits as though they are contagious. Children with nits but no lice are often removed from school until they are treated and all visible nits are removed. OBJECTIVE To investigate the probability that children with nits alone will become infested with lice. DESIGNS Prospective cohort study. SETTING Two metropolitan Atlanta elementary schools. PARTICIPANTS A total of 1729 children were screened for head lice. Twenty-eight children (1.6%) had lice, whereas 63 (3.6%) had nits without lice. Fifty of the 63 children (79%) with nits alone completed follow-up. OUTCOME MEASURE Conversion (ie, becoming infested with lice) within 14 days after initial screening. RESULTS Nine of 50 children (18.0%) followed for nits alone converted. Although children who converted did not have significantly more nits than did nonconverters, having nits near the scalp was a risk factor for conversion. Seven of 22 children (31.8%) with >/=5 nits within one fourth inch of the scalp converted, compared with 2 of 28 children (7.1%) with fewer (relative risk: 4.45; 95% confidence interval: 1.03-19.35). This risk remained statistically significant after separately stratifying for sex, recent treatment, and total number of nits. CONCLUSIONS Although having >/=5 nits within one fourth inch of the scalp was a risk factor for conversion, most children with nits alone did not become infested. Policies requiring exclusion from school and treatment for all children with nits alone are likely excessive. Instead, these children may benefit from repeated examination to exclude the presence of crawling lice.lice, pediculus, lice infestations, pediatrics, school.
Fabrication of scaffold‐free contractile skeletal muscle tissue using magnetite‐incorporated myogenic C2C12 cells

We have fabricated a functional skeletal muscle tissue using magnetite‐incorporated myogenic cell line C2C12 and a magnetic field. Magnetite‐incorporated C2C12 cells were patterned linearly on a monolayer of fibroblast NIH3T3 cells, using a magnetic field concentrator. After induction of differentiation, the C2C12 cells fused and formed multi‐nucleated myotubes. The 3T3 layer became detached in a sheet‐like manner after cultivation in differentiation medium for 5–8 days. When two separate collagen films were placed on a culture dish as tendon structures, a cylindrical construct was formed. Histological observation of the fabricated cylindrical tissue revealed the presence of multinucleate cells within it. Immunofluorescence staining of the construct showed the presence of sarcomere structures within the construct. Western blot analysis showed that muscle proteins were expressed in the construct. When the construct was stimulated with electric pulses, it exhibited active tension of approximately 1 µN. These results demonstrate that functional skeletal muscle tissue was formed through magnetic force‐based tissue engineering. This is the first report of fabrication of skeletal muscle tissue with active tension‐generating capability using magnetic force‐based tissue engineering. The scaffold‐free skeletal muscle tissue engineering technique presented in this study will be useful for regenerative medicine, drug screening or use as a bio‐actuator. Copyright © 2010 John Wiley & Sons, Ltd.
Analysis of quantitative trait loci in mice suggests a role of Enoph1 in stress reactivity

Significant progress in elucidating the genetic etiology of anxiety and depression has been made during the last decade through a combination of human and animal studies. In this study, we aimed to discover genetic loci linked with anxiety as well as depression in order to reveal new candidate genes. Therefore, we initially tested the behavioral sensitivity of 543 F2 animals derived from an intercross of C57BL/6J and C3H/HeJ mice in paradigms for anxiety and depression. Next, all animals were genotyped with 269 microsatellite markers with a mean distance of 5.56 cM. Finally, a Quantitative Trait Loci (QTL) analysis was carried out, followed by selection of candidate genes. The QTL analysis revealed several new QTL on chromosome 5 with a common core interval of 19 Mb. We further narrowed this interval by comparative genomics to a region of 15 Mb. A database search and gene prioritization revealed Enoph1 as the most significant candidate gene on the prioritization list for anxiety and also for depression fulfilling our selection criteria. The Enoph1 gene, which is involved in polyamine biosynthesis, is differently expressed in parental strains, which have different brain spermidine levels and show distinct anxiety and depression‐related phenotype. Our result suggests a significant role in polyamines in anxiety and depression‐related behaviors.
Levels of Organochlorine Pesticide Residues in Marine-, Surface-, Ground- and Drinking Waters from the Eastern Cape Province of South Africa

Abstract Persistent organochlorine pesticides (OCPs) such as DDT and its metabolites (DDDs and DDEs), chlordane, hexachlorobenzene (HCB), heptachlor and endosulfan were determined in drinking-, ground-, surface- and marine waters from the Eastern Cape Province of South Africa. Percentage recoveries of the OCPs from spiked river water ranged from 71.03 ± 8.15% (dieldrin) to 101.25 ± 2.17% (α-BHC). The levels of OCPs ranged from 5.5 ng/L (2,4-DDD) to 160 ng/L (HCB) in the water samples. Some endocrine disrupting OCPs such as DDT, DDE, heptachlor, endosulfan and chlordane were detected.
Pre-steady-state DNA unwinding by bacteriophage T4 Dda helicase reveals a monomeric molecular motor

Helicases are molecular motor enzymes that unwind and translocate nucleic acids. One of the central questions regarding helicase activity is whether the process of coupling ATP hydrolysis to DNA unwinding requires an oligomeric form of the enzyme. We have applied a pre-steady-state kinetics approach to address this question with the bacteriophage T4 Dda helicase. If a helicase can function as a monomer, then the burst amplitude in the pre-steady state might be similar to the concentration of enzyme, whereas if the helicase required oligomerization, then the amplitude would be significantly less than the enzyme concentration. DNA unwinding of an oligonucleotide substrate was conducted by using a Kintek rapid quench-flow instrument. The substrate consisted of 12 bp adjacent to 12 nucleotides of single-stranded DNA. Dda (4 nM) was incubated with substrate (16 nM) in buffer, and the unwinding reaction was initiated by the addition of ATP (5 mM) and Mg2+ (10 mM). The reaction was stopped by the addition of 400 mM EDTA. Product formation exhibited biphasic kinetics, and the data were fit to the equation for a single exponential followed by a steady state. The amplitude of the first phase was 3.5 ± 0.2 nM, consistent with a monomeric helicase. The burst amplitude of product formation was measured over a range of enzyme and substrate concentrations and remained consistent with a functional monomer. Thus, Dda can rapidly unwind oligonucleotide substrates as a monomer, indicating that the functional molecular motor component of a helicase can reside within a single polypeptide.
Comparison of spatial filters and features for the detection and classification of movement-related cortical potentials in healthy individuals and stroke patients

Objective. The possibility of detecting movement-related cortical potentials (MRCPs) at the single trial level has been explored for closing the motor control loop with brain–computer interfaces (BCIs) for neurorehabilitation. A distinct feature of MRCPs is that the movement kinetic information is encoded in the brain potential prior to the onset of the movement, which makes it possible to timely drive external devices to provide sensory feedback according to the efferent activity from the brain. The aim of this study was to compare methods for the detection (different spatial filters) and classification (features extracted from various domains) of MRCPs from continuous electroencephalography recordings from executed and imagined movements from healthy subjects (n = 24) and attempted movements from stroke patients (n = 6) to optimize the performance of MRCP-based BCIs for neurorehabilitation. Approach. The MRCPs from four cue-based tasks were detected with a template matching approach and a set of spatial filters, and classified with a linear support vector machine using the combination of temporal, spectral, time-scale, or entropy-based features. Main results. The best spatial filter (large Laplacian spatial filter (LLSF)) resulted in a true positive rate of 82 ± 9%, 78 ± 12% and 72 ± 9% (with detections occurring ∼200 ms before the onset of the movement) for executed, imagined and attempted movements (stroke patients). The best feature combination (temporal and spectral) led to pairwise classification of 73 ± 9%, 64 ± 10% and 80 ± 12%. When the detection was combined with classification, 60 ± 10%, 49 ± 10% and 58 ± 10% of the movements were both correctly detected and classified for executed, imagined and attempted movements. A similar performance for detection and classification was obtained with optimized spatial filtering. Significance. A simple setup with an LLSF is useful for detecting cued movements while the combination of features from the time and frequency domain can optimize the decoding of kinetic information from MRCPs; this may be used in neuromodulatory BCIs.
SHOCK AND HEMORRHAGE: AN OVERVIEW OF ANIMAL MODELS

Shock resulting from life-threatening blood loss (hemorrhage) remains a common complication of traumatic injury. Intensive experimental efforts are needed if we are to understand the pathological effect(s) of hemorrhagic shock, alone or in association with traumatic tissue injury, and to reverse this deleterious process in trauma patients. Here, we overview selected studies that are representative of the different hemorrhagic shock models, considering their advantages and disadvantages from a scientific and clinical perspective. Fixed-pressure versus fixed-volume versus uncontrolled hemorrhage models, with or without tissue injury, will be discussed, as well as small versus large animal models. Most of these models are nonlethal in nature, and allow the researcher to understand the changes that contribute to increased susceptibility to subsequent infection or the development of multiple organ failure. We also consider some of the confounders in these models, including anesthesia, the nature of resuscitation, and the use of anticoagulants. The selection of model must take into consideration not only the need for experimental control but must also adequately reflect the clinical pathobiology of shock if we are to develop better pharmacological interventions.