Miracle-dz/UniFAR-FTUs huggingface dataset:
The obesity pandemic--implications for Pakistan.

BACKGROUND Adverse health outcomes are associated with overweight and obesity. In February 2000, the WHO Regional Office for the Western Pacific, the International Association for the Study of Obesity and the International Obesity Task Force published provisional recommendations for adults for the Asia-Pacific region: overweight at Body Mass Index (BMI) > or = 23 and obesity at BMI > or = 25. METHODS Data from the National Health Survey of Pakistan, 1990-94 were reanalyzed using BMI cut-offs recommended for Asians to reassess prevalence of overweight and obesity in the adult Pakistani population. RESULTS Prevalence of obesity (BMI > or = 25) in 25-44 year olds in rural areas was 9% for men and 14% for women; in urban areas, prevalence was 22% and 37% for men and women, respectively. For 45-64 year olds, prevalence was 11% for men and 19% for women in rural areas, and 23% and 40% in urban areas for men and women, respectively. Obesity prevalence was directly associated with SES, regardless of residence. CONCLUSION In South Asia, including Pakistan, social and environmental changes are occurring rapidly, with increasing urbanization, changing lifestyles, higher energy density of diets, and reduced physical activity. The coexistence of underweight in early life with obesity in adults may presage both a higher prevalence and incidence for noncommunicable diseases (NCDs) such as hypertension and diabetes. Use of BMI > or = 23 for overweight, and BMI > or = 25 for obesity, may provide a more accurate determination of the health of Pakistanis, especially in those with more than one risk factor for NCDs.
What we truly know about occupation as a risk factor for ALS: A critical and systematic review

Occupational and environmental exposures may contribute to the risk of developing sporadic amyotrophic lateral sclerosis (ALS). To summarize the available evidence, a systematic review of the literature on occupation as a potential determinant of ALS was performed according to the MOOSE guidelines. From MEDLINE, EMBASE, CINAHL, and Cochrane databases, selected studies were methodologically appraised according to Armon's classification system for ALS risk factor studies. Each occupation studied was reclassified according to the International Standard Classification of Occupations (ISCO-88). The vote-counting method was applied to summarize the data. Of 3773 potentially relevant studies, 51 were initially included. Of these, 12 studies provided risk estimates for individual occupations – one case-control, two register-based case-control, and nine register-based cohort studies. All studies fell into Armon's level of evidence class IV, indicating methodological limitations. Due to the heterogeneity of study methodology, data could not be pooled. The vote-counting method revealed several candidate occupations: veterinarians and other health workers, athletes, hairdressers, power-production plant, electrical and military workers. However, well designed studies with standardized assessment of occupation are needed to provide a more definitive answer about exogenous risk factors of ALS.
Event detection and sub‐state discovery from biomolecular simulations using higher‐order statistics: Application to enzyme adenylate kinase

Biomolecular simulations at millisecond and longer time‐scales can provide vital insights into functional mechanisms. Because post‐simulation analyses of such large trajectory datasets can be a limiting factor in obtaining biological insights, there is an emerging need to identify key dynamical events and relating these events to the biological function online, that is, as simulations are progressing. Recently, we have introduced a novel computational technique, quasi‐anharmonic analysis (QAA) (Ramanathan et al., PLoS One 2011;6:e15827), for partitioning the conformational landscape into a hierarchy of functionally relevant sub‐states. The unique capabilities of QAA are enabled by exploiting anharmonicity in the form of fourth‐order statistics for characterizing atomic fluctuations. In this article, we extend QAA for analyzing long time‐scale simulations online. In particular, we present HOST4MD—a higher‐order statistical toolbox for molecular dynamics simulations, which (1) identifies key dynamical events as simulations are in progress, (2) explores potential sub‐states, and (3) identifies conformational transitions that enable the protein to access those sub‐states. We demonstrate HOST4MD on microsecond timescale simulations of the enzyme adenylate kinase in its apo state. HOST4MD identifies several conformational events in these simulations, revealing how the intrinsic coupling between the three subdomains (LID, CORE, and NMP) changes during the simulations. Further, it also identifies an inherent asymmetry in the opening/closing of the two binding sites. We anticipate that HOST4MD will provide a powerful and extensible framework for detecting biophysically relevant conformational coordinates from long time‐scale simulations. Proteins 2012. © 2012 Wiley Periodicals, Inc.
Genetic variants of eNOS gene may modify the susceptibility to idiopathic male infertility

Abstract In testis, eNOS is responsible for synthesis of nitric oxide (NO) which is an essential gas message regulator in spermatogenesis, suggesting that eNOS gene plays a role in normal spermatogenesis and the genetic variants of eNOS gene may be potential genetic risk factors of spermatogenesis impairment. In this study, the polymorphic distributions of three common polymorphism loci including T-786C, 4A4B and G894T in eNOS gene were investigated in 355 Chinese infertile patients with azoospermia or oligozoospermia and 246 healthy fertile men and a meta-analysis was carried in order to explore the possible relationship between the three loci of eNOS gene and male infertility with spermatogenesis impairment. As a result, allele -786C of T-786C (11.4% versus 6.5%, p = 0.004) and 4A of 4A4B (11.0% versus 6.3%, p = 0.005) as well as genotype TC of T-786C (22.8% versus 13.0%, p = 0.002) and AB of 4A4B (18% versus 11%, p = 0.015) were significantly associated with idiopathic male infertility. The haplotypes T-4A-G (7.4% versus 4.1%, p = 0.015) and C-4B-G (7.6% versus 4.4%, p = 0.028) could increase the susceptibility to male infertility, whereas haplotype T-4B-G (67.0% versus 75.2%, p = 0.002) might be a protective factor for male infertility. The results of meta-analysis revealed that the polymorphism of T-786C was associated with male infertility. These findings suggested that the variants of eNOS gene may modify the susceptibility to male infertility with impaired spermatogenesis.
Role of nodal involvement and the periductal soft-tissue margin in middle and distal bile duct cancer.

OBJECTIVE To determine the pattern of middle (Bm) and distal (Bi) bile duct cancers in an attempt to optimize surgical treatment. SUMMARY BACKGROUND DATA Lymph node involvement and neural plexus invasion are the prognostic factors most amenable to surgery in Bm and Bi disease. However, a detailed analysis of these factors has not been conducted. METHODS Fifty patients with Bm and Bi disease (Bm 14 patients, Bi 36 patients) were examined histopathologically. A precise determination was made of lymph node involvement and neural plexus invasion. Important prognostic factors were examined by clinicopathologic study to apply these findings to surgical management. RESULTS Frequencies of nodal involvement for Bm and Bi disease were 57% and 71%, respectively. The inferior periductal and superior pancreaticoduodenal lymph nodes were most commonly involved. Neural plexus invasion occurred in 20% of patients, particularly involving the plexus in the hepatoduodenal ligament and pancreatic head. Tumor was present at the surgical margin in 50% and 14% of patients with Bm and Bi disease, respectively. Five-year survival rates were 65% in the absence of nodal metastasis and 21% with nodal metastasis. A significant correlation existed between absence of tumor at the surgical margin and survival. A Cox proportional hazard model projected absence of tumor at the surgical margin, followed by nodal involvement, as the strongest prognostic variables. CONCLUSIONS Absence of tumor at the surgical margin and nodal involvement are important independent prognostic factors in Bm and Bi disease. Skeletonization of the hepatoduodenal ligament, including portal vein resection, is necessary for patients with Bm disease, and a wide nodal dissection is essential in all patients.
Identification of novel regions of altered DNA copy number in small cell lung tumors

Identification of the genetic alterations that occur in tumors is an important approach to understanding tumorigenesis. We have used comparative genomic hybridization (CGH), a novel molecular cytogenetic method, to identify the gross DNA copy number changes that commonly occur in small cell lung cancer (SCLC). We analyzed ten SCLC tumors (seven primary tumors and three metastases) from eight patients. We found frequent increases in DNA copy number on chromosome arms Sp, 8q, 3q, and Xq and frequent decreases in copy number on chromosome arms 3p. 17p, Sq, 8p, 13q, and 4p. The increase in copy number at 8q24 (MYC) and decreases at 17p 13 (TP53), 13q 14 (RB), and 3p have previously been identified in SCLC with other methods. Many of the other regions in which we detected common copy number changes have not been reported to be regions of common alteration in SCLC tumors. Comparison of copy number changes between a primary tumor and a metastasis from the same patient showed that they were more closely related to each other than to any of the other tumors. The results of direct CGH analysis of SCLC tumors reported here confirm the existence of copy number changes that we identified previously by using cell lines. © 1995 Wiley‐Liss, Inc.
Epilepsy and vaccinations: Italian guidelines

Reports of childhood epilepsies in temporal association with vaccination have had a great impact on the acceptance of vaccination programs by health care providers, but little is known about this possible temporal association and about the types of seizures following vaccinations. For these reasons the Italian League Against Epilepsy (LICE), in collaboration with other Italian scientific societies, has decided to generate Guidelines on Vaccinations and Epilepsy. The aim of Guidelines on Vaccinations and Epilepsy is to present recent unequivocal evidence from published reports on the possible relationship between vaccines and epilepsy in order to provide information about contraindications and risks of vaccinations in patients with epilepsy. The following main issues have been addressed: (1) whether contraindications to vaccinations exist in patients with febrile convulsions, epilepsy, and/or epileptic encephalopathies; and (2) whether any vaccinations can cause febrile seizures, epilepsy, and/or epileptic encephalopathies. Diphtheria‐tetanus‐pertussis (DTP) vaccination and measles, mumps, and rubella vaccination (MMR) increase significantly the risk of febrile seizures. Recent observations and data about the relationships between vaccination and epileptic encephalopathy show that some cases of apparent vaccine‐induced encephalopathy could in fact be caused by an inherent genetic defect with no causal relationship with vaccination.
Neurotrophic growth factor response to lower body resistance training in older adults

Multimodal cognitive interventions (resistance training + cognitive training; RT + CT) may synergistically improve cognitive function in older adults. RT stimulates the release of neurotrophic growth factors (NGF) which orchestrate structural and functional brain plasticity in the aging brain, while CT increases regional cerebral blood flow. Timing the administration of CT following a bout of RT, when NGF levels are at their highest, may maximize the blood‐borne dose of NGF delivered to active brain tissue. We refer to this as the ‘anabolic window’. Currently, when and how much NGF levels in the blood increase following a bout of RT is poorly understood. The purpose of this work was to characterize the timing and magnitude of insulin like growth factor‐1 (IGF‐1) and brain derived neurotrophic factor (BDNF) levels in venous blood for 2 hours following an acute bout of RT.
Depletion of natural killer cells in the colonic lamina propria of viraemic HIV-1-infected individuals

Background:HIV-1 infection is known to have a detrimental impact on peripheral blood natural killer cell phenotype and function. Chronic HIV-1 also causes a substantial depletion of CD4+ T cells in the gastrointestinal tract and the blood. Objective:To investigate the impact of chronic HIV-1 infection with on natural killer cell populations in the gastrointestinal tract and the effect of suppression of plasma viraemia with antiretroviral therapy. Methods:Lymphocyte populations were extracted from the lamina propria of biopsies taken from the sigmoid colon of HIV-1-infected and uninfected individuals. The proportions of natural killer cell subsets were compared in viraemic (n = 15) and aviraemic HIV-1-positive, HAART-treated individuals (n = 27) and HIV-1 negative control individuals (n = 26) using flow cytometry on gated subsets. Results:Natural killer cells are depleted in colonic biopsies from HIV-1-infected individuals with detectable plasma virus in comparison with HIV-1-negative individuals. A significant increase in the proportion of both natural killer and CD4+ T cells in the colonic lamina propria is observed in aviraemic individuals compared to viraemic individuals. Conclusions:Chronic HIV-1 infection results in depletion of both natural killer cells and CD4+ T cells in colonic tissue and antiretroviral therapy results in a recovery of these subsets in individuals with undetectable plasma viral load.
Overexpression of histone deacetylase HDAC1 modulates breast cancer progression by negative regulation of estrogen receptor α

The interaction between 17β‐estradiol and estrogen receptor alpha (ER‐α) plays an important role in breast carcinogenesis and breast cancer treatment. ER‐α is a critical growth regulatory gene in breast cancer and its expression level is tightly linked to the prognosis and treatment outcomes of breast cancer patients. Loss of ER‐α expression in breast epithelial cells is critical for breast cancer progression. The underlying molecular mechanisms for this loss, however, are poorly defined. Histone deacetylases (HDACs) are implicated in the alteration of chromatin assembly and tumorigenesis. We show that histone deacetylase 1 (HDAC1) interacts with ER‐α in vitro and in vivo and suppresses ER‐α transcription activity. The interaction of HDAC1 with ER‐α was mediated by the AF‐2 and DBD domains of ER‐α. We observed an endogenous interaction of HDAC1 with ER‐α in breast cancer cells, which was decreased in the presence of estrogen. Interestingly, overexpression of HDAC1 in stable transfected MCF‐7 clones induced loss of ER‐α and significantly increased cell proliferation and colony formation, as compared to the control MCF‐7 cells, whereas treatment of stable MCF‐7 clones with the HDAC specific inhibitor trichostatin A (TSA) induced re‐expression of ER‐α mRNA and protein. Our findings strongly suggest that HDAC1 affects breast cancer progression by promoting cellular proliferation in association with a reduction in both ER‐α protein expression and transcriptional activity. Thus, HDAC1 may be a potential target for therapeutic intervention in the treatment of a subset of ER‐negative breast cancers. © 2003 Wiley‐Liss, Inc.
Risk of asthma in relation to occupation: A hospital-based case-control study.

BACKGROUND Asthma is a common occupational lung disease and is preventable by removing identifiable allergens. OBJECTIVES (1) To assess the relationship between occupation and asthma (2) To determine the agents associated with asthma. METHODS In this hospital-based, case-control study 153 cases from the Asthma Clinic and 306 non-asthmatic controls from Srinagarind Hospital, Thailand were interviewed. Crude odds ratios (COR), 95% confidence intervals (95% CI) and adjusted ORs (AOR) for multiple logistic regression were calculated. RESULTS Of the 153 cases, 70.6% were females with median age of 53 (IQR-14). Of the 306 controls, 62.4% were females with median age of 56 (IQR-16). The highest risk of asthma was family history of asthma and history of atopy [AOR 11.68 (95% CI 4.52, 30.24) and AOR 8.03 (95% CI 5.07, 13.60)], respectively. If only occupations were considered, healthcare workers had the highest risk [AOR 4.08 (95% CI 1.35, 12.30)], followed by textile workers [AOR 3.34 (95% CI 1.07, 10.47)] and school workers AOR 2.40 (95% CI 1.31, 4.41). When subgroups of non-atopy were considered, school workers had a significant association with asthma [COR 3.18 (95% CI 1.48, 6.83)]. When no family history of asthma was considered, school and textile workers had the most significant association with asthma [COR 3.10 (95% CI 1.87, 5.13) and COR 3.06 (95% CI 1.15, 8.13), respectively]. Inorganic dust was the agent most significantly associated with asthma COR 1.89 (95% CI 1.25, 2.82). CONCLUSION School, textile and healthcare workers have the greatest risk of asthma. Family history of asthma and being atopic would also promote asthma in relation to occupation.
A Markov Chain Monte Carlo Method for Estimating Population Mixing Using Y‐chromosome Markers: Mixing of the Han People in China

We present a new approach for estimating mixing between populations based on non‐recombining markers, specifically Y‐chromosome microsatellites. A Markov chain Monte Carlo (MCMC) Bayesian statistical approach is used to calculate the posterior probability distribution of population parameters of interest, including the effective population size and the time to most recent common ancestor (MRCA). To test whether two populations are homogeneously mixed we introduce a “mixing” statistic defined for each coalescent event that weights the contribution of that ancestor's descendants to the two subpopulations, and an associated population “purity” statistic. Using simulated data with low levels of migration between two populations, we demonstrate that our method is more sensitive than other commonly used distance‐based methods such as RST and DSW. To illustrate our method, we analysed mixing between 11 pre‐defined Chinese ethnic/regional populations, using 5 microsatellite markers from the non‐recombining region of the Y‐chromosome (NRY), demonstrating a significant clustering of a subset of subpopulations with a high mutual relative degree of mixing (homogeneous mixing with support >0.99). Our analysis suggests that there is a strong correlation between effective population size and mixing with other subpopulations. Thus, despite considerable mixing between these groups, the purity statistic still identifies significant heterogeneity, suggesting that periods of historical isolation continue to leave a recoverable signal despite modern introgression.
Regulation of adiponectin in adipocytes upon exposure to HIV‐1

Adipose dysregulation, dyslipidemia, and insulin resistance are hallmarks of HIV‐related lipodystrophy. The precise mechanisms behind these disturbances are unknown. In HIV‐infected patients, we previously demonstrated a strong relationship between lipodystrophy and levels of adiponectin, an adipose peptide implicated in regulation of glucose and lipid metabolisms. In this study we investigated the effect of HIV on adipocytes, to determine whether HIV can directly infect adipocytes and/or alter the regulation and secretion of the adipocyte‐derived hormone adiponectin.
UD-TDMA: A distributed TDMA protocol for underwater acoustic sensor network

This paper presents a distributed and robust time slot scheduling algorithm, which is suitable for underwater acoustic sensor network (UASN). The information of nodes' 2-hop neighbors is needed to be collected and then be used to calculate nodes' initial time slot by a distributed algorithm. A maximal independent set is formed by the nodes which were assigned with the same initial slot. Some theorems were proved to reveal that in an interference graph the size of this maximal independent set is at least of the size of the maximum independent set of the nodes. The simulation compares UD-TDMA with other three MAC protocols. The results show that the proposed protocol is effective in the UASN with random deployment, especially in high-density underwater acoustic sensor network.
Recently patented and promising ORL-1 ligands: where have we been and where are we going?

Importance of the field: The interactions of nociceptin/orphanin FQ (N/OFQ) and the opioid receptor-like receptor 1 (nociceptin opioid peptide – NOP) have been implicated in a variety of systems including cardiovascular, respiratory, immune, and the central and peripheral nervous systems. Areas covered in this review: To elucidate the endogenous role of the N/OFQ–NOP system through the use of knockout and knockdown animal preparations, though most advances have been made using a host of synthetic agonists and antagonists. This review gives a brief history of the receptor–ligand discovery, the development of these agonists and antagonists within the last 10 years as published, and the therapeutic indications thereof focusing on pain. What the reader will gain: The use of NOP ligands in pain has been controversial at best; however, there are indications that both agonists and antagonists have a place in the clinical setting for acute and chronic pain. NOP ligands have potential as novel therapeutics, interestingly, when incorporated into a rationally-designed multi-target agent. Take home message: The discovery of N/OFQ and NOP opened a new option for the treatment of pain with the potential for a decreased side effect profile. Numerous compounds have been designed to target this system, the most promising of which have mixed profiles.
Age, Sex, and Pubertal Phase Influence Mentalizing About Emotions and Actions in Adolescents

This study examined (1) emotional versus cognitive developmental trajectories and (2) the influence of age-extrinsic factors (i.e., sex and puberty). Using a cross-sectional design, adolescents (N = 252) divided into four age-groups (ages 13, 15, 17, 19) performed two versions of a mentalizing task, about emotions and actions, as well as the Tower task. First, performance on all tasks improved linearly into late adolescence (age 19). Thus no differential trajectories were found for emotional versus cognitive development. Second, girls outperformed boys in mentalizing speed regarding both emotions and actions. In boys, a later pubertal phase was associated with increased mentalizing speed after controlling for age-group.
Negative affect and barriers to exercise among early stage breast cancer patients.

OBJECTIVE To assess the relative frequency of and barriers to exercise among women with breast cancer while controlling for cancer-relevant and demographic factors. DESIGN The present study employed concurrent samples, correlational research design. MAIN OUTCOME MEASURES Exercise frequency and its association with negative affect and barriers to exercise, independent of cancer treatment, among women (N=176) with Stage I or II breast cancer who were 3, 6, and 12 months postsurgery. RESULTS After accounting for cancer-relevant and control variables, degree of negative affect and frequency of perceived barriers were significantly inversely associated with exercise. CONCLUSION These findings suggest that attention to both emotional factors and psychosocial barriers to exercise may be warranted to further understand exercise among women with early stage breast cancer.