Miracle-dz/UniFAR-FTUs huggingface dataset:
Lower Melatonin Secretion in Older Females: Gender Differences Independent of Light Exposure Profiles

Background Melatonin is associated with a variety of diseases in advanced age, including insomnia, depression, and dementia, and its secretion is influenced by light exposure. Although studies in young and middle-aged subjects have shown that females tend to have higher melatonin levels than males, gender differences in melatonin levels among older people remain unclear. Methods To determine the gender differences in melatonin levels among older people in home settings, we conducted a cross-sectional study in 528 older people. We measured overnight urinary 6-sulfatoxymelatonin excretion (UME; an index of melatonin secretion), and ambulatory light intensity. Results The mean age of females was 1.8 years younger, and average intensity of daytime light exposure was half that in males (P < 0.01). In a univariate comparison, UME was significantly lower in females than in males (P < 0.01). A multivariate model using analysis of covariance showed that log-transformed UME remained significantly lower in females after adjustment for potential confounding factors, including age and daytime and nighttime light exposure profiles (males vs. females: 1.90 vs. 1.73 log µg; adjusted mean difference 0.17 log µg [95% confidence interval [CI] 0.02–0.32]; P = 0.02). This result indicates that older females have 18.4% (95% CI, 2.2–37.4%) lower UME than older males. Conclusions Older females have significantly lower UME than older males, an association which is independent of light exposure profiles in home settings. Our findings may be useful as basic data for further research to investigate gender differences in several diseases associated with melatonin in the elderly.
Epidemiology of mutations in superoxide dismutase in amyotrophic lateal sclerosis

We registered 366 families in a study of dominantly inherited amyotrophic lateral sclerosis. Two hundred ninety families were screened for mutations in the gene encoding copper‐zinc cytosolic superoxide dismutase (SOD1). Mutations were detected in 68 families. The most common SOD1 mutation is an alanine for valine substitution in codon 4 (50%). We present clinical and genetic data concerning 112 families with 395 affected individuals. The clinical characteristics of patients with familial amyotrophic lateral sclerosis arising from SOD1 mutation are similar to those lacking SOD1 defects. Mean age at onset was earlier (Wilcoxon test, p = 0.004) in the SOD1 group (46.9 years [standard deviation, 12.5] vs 50.5 years [11.5] in the non‐SOD1 group). Bulbar onset was associated with a later onset age. The presence of either of two mutations, G37R and L38V, predicted an earlier age at onset. Kaplan‐Meier plots demonstrated shorter survival in the SOD1 group compared with the non‐SOD1 group at early survival times (Wilcoxon test, p = 0.0007). The presence of one mutation, A4V, correlated with shorter survival. G37R, G41D, and G93C mutations predicted longer survival. This information suggests it will be productive to investigate other genetic determinants in amyotrophic lateral sclerosis and to use epidemiological characteristics of the disease to help discern molecular mechanisms of motor neuron cell death.
Risk factors for attempted suicide during adolescence.

It is unknown whether adolescents can provide the information necessary to identify their risk for attempted suicide. The present study was designed to determine whether data collected directly from adolescents can be used to develop a simple model for differentiating suicidal from nonsuicidal adolescents. Patients aged 13 to 19 years hospitalized for medical complications of serious suicide attempts (n = 56) or for acute illnesses unrelated to injuries or ingestions (n = 248) completed self-administered questionnaires pertaining to psychosocial function, recent stress, alcohol and drug use, and health care use. Compared with ill adolescents, suicidal adolescents had poorer mental health, impulse control, family relationships, and school performance; higher 3-month stress scores and alcohol-use scores; and more use of 7 of 12 drugs (P less than .05). Compared with ill adolescents, suicidal adolescents were more likely to report previous suicide attempts (39% vs 10%, P less than .001) and previous mental health care (27% vs 8%, P less than .001) but were less likely to identify a primary care site (61% vs 87%, P less than .001). In a logistic regression model based on previous suicide attempts, previous mental health care, poor school performance, marijuana use, and dependence on the emergency room for primary care, 84% of the suicidal and 55% of the ill adolescents were correctly identified. If validated prospectively, these five self-administered questions may constitute a helpful screen for the rapid identification of suicidal adolescents.
[Genetic isolates and inbreeding customs in three rural municipalities from Honduras].

BACKGROUND The isonymic method has been amply used to assess the approximate genetic structure of human communities. The objective of the study was to evaluate the magnitude of genetic isolation and inbreeding customs in 57 communities from three rural municipalities of Honduras using isonymy techniques. METHODS The list of 408 different surnames from 20712 voters registered in the national electoral organism, residing in the 57 Honduran communities, was used for this study. For each community, random (IR), non-random (IN), and total (IT) isonymy values were calculated in order to assess inbreeding coefficients FST, FIS and FIT. RESULTS High consanguinity due to isolation and to endogamous customs was unveiled in many communities. Significant deviation from the exogamous behavior typical of many human populations was observed in the three studied municipalities, when compared to other Honduran populations. CONCLUSIONS The studied communities present high consanguinity due to isolation, ethnic segregation and/or endogamous customs.
The Extended Overlap Alternate Arm Converter: A Voltage-Source Converter With DC Fault Ride-Through Capability and a Compact Design

The alternate arm converter (AAC) was one of the first modular converter topologies to feature dc-side fault ride-through capability with only a small penalty in power efficiency. However, the simple alternation of its arm conduction periods (with an additional short overlap period) resulted in 1) substantial six-pulse ripples in the dc current waveform, 2) large dc-side filter requirements, and 3) limited operating area close to an energy sweet spot. This paper presents a new mode of operation called extended overlap (EO) based on the extension of the overlap period to $60^{\circ }$, which facilitates a fundamental redefinition of the working principles of the AAC. The EO-AAC has its dc current path decoupled from the ac current paths, a fact allowing 1) smooth dc current waveforms, 2) elimination of dc filters, and 3) restriction lifting on the feasible operating point. Analysis of this new mode and EO-AAC design criteria are presented and subsequently verified with tests on an experimental prototype. Finally, a comparison with other modular converters demonstrates that the EO-AAC is at least as power efficient as a hybrid modular multilevel converter (MMC) (i.e., a dc fault ride-through-capable MMC), while offering a smaller converter footprint because of a reduced requirement for energy storage in the submodules and a reduced inductor volume.
Oxidative Stress Mediates Angiotensin II–Dependent Stimulation of Sympathetic Nerve Activity

Evidence indicates that angiotensin II (Ang II) enhances sympathetic nervous system (SNS) activity centrally and peripherally, but the exact mechanisms of this activation are not well established. We have previously shown that infusion of Ang II in the lateral cerebral ventricle raises blood pressure (BP), renal sympathetic nervous system activity (RSNA), and norepinephrine (NE) secretion from the posterior hypothalamic nuclei (PH), and reduces the abundance of interleukin-1β (IL-1β) and neuronal NO synthase (nNOS) mRNA in the PH. Pretreatment with an Ang II type 1 (AT1) receptor antagonist abolished these effects of Ang II. The data support the hypothesis that Ang II stimulates SNS through activation of AT1 receptors and downregulation of nNOS. In the current studies, we tested the hypothesis that the effects of Ang II on central SNS are mediated by reactive oxygen species. To this end, we evaluated the effects of Ang II alone or in combination with 2 superoxide dismutase (SOD) mimetics, tempol (4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl) and polyethylene glycol–SOD (PEG-SOD) on BP, NE secretion from the PH, RSNA, and abundance of IL-1β and nNOS mRNA in the PH Ang II raised BP, NE secretion from the PH, and RSNA and reduced the abundance of IL-1β and nNOS mRNA in the PH. Tempol and PEG-SOD completely abolished these actions of Ang II. In conclusion, these studies support the hypothesis that the effects of centrally administered Ang II on the SNS are mediated by increased oxidative stress in brain regions involved in the noradrenergic control of BP.
Smart autonomous wireless acoustic sensors for aeronautical SHM applications

Ultrasound technologies are of great interest for aeronautical structure inspection. Mainly deployed through Phased Array (PA) ultrasonic transducer, ultrasound inspection is currently used as a complementary tool for the local examination of the structure to determine geometry, damage or composition of invisible flaws like cracks, delamination and corrosion. This approach cannot be easily automated since the access to the area of interest often requires to pass through the complex aeronautical structure. Moreover this approach relies on a high degree of human interaction, as the user often decides the spatial inspection sampling according to his intuition and experience of the structure composition and vulnerability. Structure Health Monitoring, namely SHM, overcomes these limitations by enabling rapid, automated, remote, and real-time monitoring of the structure to reduce operational costs and increase lifetime of structures. This inspection strategy gains its strength from the use of a large amount of individual embedded sensors with embedded intelligence (sensing, signal processing, communicating and storing relevant data in non-volatile memories) organized in dense network, a Neural Network. We present in this paper the developments of a novel autonomous wireless acoustic sensor node, including: a flat flexural acoustic sensor capable of working in transmit and receive, a custom vibrational piezoelectric energy harvesting device (PEH) charging a 0.5 Farad buffer supercapacitance through a commercial rectifying IC, an ARM based cortex M3 microprocessor driving digitization, signal processing, data storage and two ways RF communication. The main objective was to create a versatile hardware platform that can be embedded within the structure to monitor, and capable of hosting different acoustic inspection strategies.
Position of chromatographic techniques in screening for detection of drugs or poisons in clinical and forensic toxicology and/or doping control

Abstract This paper reviews chromatographic screening procedures for simultaneous detection of several drug classes relevant to clinical and forensic toxicology or doping control in urine or blood using gas chromatography-mass spectrometry (GC-MS), liquid chromatography coupled with a diode-array detector (LC-DAD) or a mass spectrometer (LC-MS). The pros and cons of the different techniques and procedures are discussed leading to the following conclusions and perspectives. GC-MS, especially in the electron ionization full-scan mode, is still the method of choice for comprehensive screening providing best separation power, specificity and universality, although requiring derivatization. LC-DAD is also often used for screening, but its separation power and its specificity are still inferior to those of GC-MS. Finally, LC-MS has shown to be an ideal supplement, especially for the detection of more polar, thermolabile and/or low-dose drugs, especially in blood plasma. It may become the gold standard in clinical and forensic toxicology and doping control if, at a later date, the costs of the apparatus will be markedly reduced, the current disadvantages like irreproducibility of fragmentation, reduction of ionization by matrix, etc. will be overcome, and finally if one of the increasing number of quite different techniques will become the apparatus standard.
The Estimated Lifetime Probability of Acquiring Human Papillomavirus in the United States

Background Estimates of the lifetime probability of acquiring human papillomavirus (HPV) can help to quantify HPV incidence, illustrate how common HPV infection is, and highlight the importance of HPV vaccination. Methods We developed a simple model, based primarily on the distribution of lifetime numbers of sex partners across the population and the per-partnership probability of acquiring HPV, to estimate the lifetime probability of acquiring HPV in the United States in the time frame before HPV vaccine availability. Results We estimated the average lifetime probability of acquiring HPV among those with at least 1 opposite sex partner to be 84.6% (range, 53.6%–95.0%) for women and 91.3% (range, 69.5%–97.7%) for men. Under base case assumptions, more than 80% of women and men acquire HPV by age 45 years. Conclusions Our results are consistent with estimates in the existing literature suggesting a high lifetime probability of HPV acquisition and are supported by cohort studies showing high cumulative HPV incidence over a relatively short period, such as 3 to 5 years.
Intersection of the RNA Interference and X-Inactivation Pathways

In mammals, dosage compensation is achieved by X-chromosome inactivation (XCI) in the female. The noncoding Xist gene initiates silencing of the X chromosome, whereas its antisense partner Tsix blocks silencing. The complementarity of Xist and Tsix RNAs has long suggested a role for RNA interference (RNAi). Here, we report that murine Xist and Tsix form duplexes in vivo. During XCI, the duplexes are processed to small RNAs (sRNAs), most likely on the active X (Xa) in a Dicer-dependent manner. Deleting Dicer compromises sRNA production and derepresses Xist. Furthermore, without Dicer, Xist RNA cannot accumulate and histone 3 lysine 27 trimethylation is blocked on the inactive X (Xi). The defects are partially rescued by truncating Tsix. Thus, XCI and RNAi intersect, down-regulating Xist on Xa and spreading silencing on Xi.
Decreased Expression of Decorin and p57(KIP2) Correlates with Poor Survival and Lymphatic Metastasis in Lung Cancer Patients

Purpose Decorin, p57(KIP2), and TGF-beta 1 have been investigated as prognostic factors because they appear to be associated with tumorigenesis; however, the effect of decorin and p57(KIP2) in lung cancer remains poorly understood. The purpose of this study was to examine the expression of decorin, p57(KIP2), and TGF-beta 1 in 64 lung cancer specimens and 36 normal lung specimens, and to analyze the relationships with respect to clinicopathological features and patient survival in lung cancer. Methods The expression levels of decorin, p57(KIP2), and TGF-beta 1 were examined by in situ hybridization and immunohistochemistry. Results Normal tissues exhibited a higher expression level of decorin than tumor tissues (P<0.05) and tumor tissues exhibited a higher expression level of TGF-beta 1 than normal tissues (P<0.05). The expression levels of p57(KIP2) and TGF-beta 1 were significantly associated with histological types of lung cancer (P<0.05), and the expression levels of decorin and p57(KIP2) were significantly associated with lymphatic invasion (P<0.05). Moreover, increased expression of decorin and p57(KIP2) correlated with increased survival (decorin, p=0.018; p57(KIP2), p=0.012). Conclusion Decreased expression levels of decorin and p57(KIP2) were associated with poor postsurgical survival time and lymphatic metastasis in lung cancer patients; moreover, low expression was an adverse prognostic factor.
Workforce capacity to respond to children whose parents have a mental illness.

OBJECTIVE The first of the three objectives of this study was to identify the core barriers that impede adult mental health and other clinicians from working with patients about parenting and child-related issues. The second and third objectives were to rate the importance of these barriers and to compare barriers for adult mental health workers with other workers. METHOD There were two data collection phases; the first, qualitative phase involved collecting verbatim responses from 60 mental health and welfare workers, regarding barriers about working with mentally ill patients about their parenting role as well as with their children. The second involved 32 participants, including 20 adult mental health workers and 12 other workers, responding to the scaled questionnaire items based on the qualitative barriers identified at phase one. RESULTS The most important barriers highlighted by workers were patients not identifying their illness as a problem for their children and patients denying that they had a mental health problem. All workers reported that it was part of their role to get involved with issues regarding their patient's children. In comparison to other workers, adult mental health workers reported time and resource limitations, as well as skill and knowledge deficits regarding parenting and working with children. CONCLUSIONS The findings are discussed in relation to adult mental health policy and ongoing professional development, particularly for adult mental health workers.
Evidence for the contribution of muscle stem cells to nonhypertrophic skeletal muscle remodeling in humans

The purpose of this study was to explore the possible role of muscle stem cells, also referred to as satellite cells (SCs), in adaptation and remodeling following a nonhypertrophic stimulus in humans. Muscle biopsies were obtained from the vastus lateralis of previously untrained women (n=15; age: 27±8 yr, BMI: 29±6 kg/m2) before and after 6 wk of aerobic interval training. The fiber type‐specific SC response to training was analyzed using immunofluorescent microscopy of muscle cross sections. Following training, the number of SCs associated with fibers expressing myosin heavy‐chain type I and II isoforms (hybrid fibers) increased (pre: 0.062±0.035 SC/hybrid fiber; post: 0.38±0.063 SC/hybrid fiber; P<0.01). In addition, there was a greater number of MyoD+/Pax7– SCs, indicative of differentiating SCs, associated with hybrid fibers (0.18±0.096 MyoD+/Pax7– SC/hybrid fiber) compared to type I (0.015±0.00615 MyoD+/Pax7– SC/type I fiber) or II (0.012±0.00454 MyoD+/Pax7– SC/type II fiber) fibers (P<0.05). There was also a training‐induced increase in the number of hybrid fibers containing centrally located nuclei (15.1%) compared to either type I (3.4%) or II fibers (3.6%) (P<0.01). These data are consistent with the hypothesis that SCs contribute to the remodeling of muscle fibers even in the absence of hypertrophy. —Joanisse, S. , Gillen, J. B. , Bellamy, L. M. , McKay, B. R. , Tarnopolsky, M. A. , Gibala, M. J., Parise, G. Evidence for the contribution of muscle stem cells to nonhypertrophic skeletal muscle remodeling in humans. FASEB J. 27, 4596–4605 (2013). www.fasebj. org
ER Stress Inhibits mTORC2 and Akt Signaling Through GSK-3β–Mediated Phosphorylation of Rictor

Cellular stress attenuates growth factor signaling through a phosphorylation event that blocks substrate access to the kinase complex mTORC2. No Access During Stressful Times Under conditions of cellular stress, cells tend to halt anabolic processes, such as cell growth and proliferation, to conserve resources. mTORC2 (mammalian target of rapamycin complex 2), which mediates its effects through activation of the kinase Akt, is a key signaling complex that promotes anabolic processes. Chen et al. investigated the mechanisms by which mTORC2 activity is inhibited by endoplasmic reticulum (ER) stress. They found that glycogen synthase kinase–3β (GSK-3β), which is activated by ER stress, phosphorylated rictor, a component of mTORC2 that helps to determine substrate specificity for the complex. This phosphorylation event decreased binding of Akt to mTORC2, resulting in reduced activation of Akt and cell proliferation. Furthermore, transformed cells expressing a mutant form of rictor lacking the GSK-3β phosphorylation site formed larger tumors in mice than did those expressing wild-type rictor or a rictor mutant that mimicked a constitutively phosphorylated form. These results define a pathway by which mTORC2 and Akt signaling can be attenuated by cellular stress and provide a potential therapeutic target for limiting cell proliferation (such as in cancer). In response to environmental cues, cells coordinate a balance between anabolic and catabolic pathways. In eukaryotes, growth factors promote anabolic processes and stimulate cell growth, proliferation, and survival through activation of the phosphoinositide 3-kinase (PI3K)–Akt pathway. Akt-mediated phosphorylation of glycogen synthase kinase–3β (GSK-3β) inhibits its enzymatic activity, thereby stimulating glycogen synthesis. We show that GSK-3β itself inhibits Akt by controlling the mammalian target of rapamycin complex 2 (mTORC2), a key activating kinase for Akt. We found that during cellular stress, GSK-3β phosphorylated the mTORC2 component rictor at serine-1235, a modification that interfered with the binding of Akt to mTORC2. The inhibitory effect of GSK-3β on mTORC2-Akt signaling and cell proliferation was eliminated by blocking phosphorylation of rictor at serine-1235. Thus, in response to cellular stress, GSK-3β restrains mTORC2-Akt signaling by specifically phosphorylating rictor, thereby balancing the activities of GSK-3β and Akt, two opposing players in glucose metabolism.
VEGFR-1 Regulates Adult Olfactory Bulb Neurogenesis and Migration of Neural Progenitors in the Rostral Migratory Stream In Vivo

The generation of new neurons in the olfactory bulb (OB) persists into adulthood and is a multistep process that includes proliferation, fate choice, migration, survival, and differentiation. Neural precursor cells destined to form olfactory interneurons arise in the subventricular zone (SVZ) and migrate along the rostral migratory stream (RMS) to the OB. Recently, some factors classically known from their effects on the vascular system have been found to influence different steps of adult neurogenesis. In the present study, we report a modulatory function for the vascular endothelial growth factor receptor-1 (VEGFR-1) in adult olfactory neurogenesis. We identified expression of VEGFR-1 in GFAP-positive cells within regions involved in neurogenesis of the adult mouse brain. To determine functions for VEGFR-1 in adult neurogenesis, we compared neural progenitor cell proliferation, migration, and differentiation from wild-type and VEGFR-1 signaling-deficient mice (Flt-1TK−/− mice). Our data show that VEGFR-1 signaling is involved in the regulation of proliferation of neuronal progenitor cells within the SVZ, migration along the RMS, and in neuronal differentiation and anatomical composition of interneuron subtypes within the OB. RMS migration in Flt-1TK−/− mice was altered mainly as a result of increased levels of its ligand VEGF-A, which results in an increased phosphorylation of VEGFR-2 in neuronal progenitor cells within the SVZ and the RMS. This study reveals that proper RMS migration is dependent on endogenous VEGF-A protein.