Miracle-dz/UniFAR-FTUs huggingface dataset:
Social, Environmental and Biological Determinants of Cerebral Palsy in Children with Intellectual Disabilities (ID) in India

Background Cerebral palsy (CP) is a global public health problem affecting 2.12 to 2.45 per 1000 live birth across the world. Cerebral palsy is an upper motor neuron, non-progressive disorder commonly associated with intellectual disability. The presence of cerebral palsy effects person’s overall life. Objectives This study primarily sought predictive capacity of social, environmental and biological determinants of CP in ID. Materials and Methods This is a cross-sectional study design. A total of 262 children, aged 3 to 18 years, with ID were assessed for cerebral palsy and diagnosed on basis of clinical examination in a community based rehabilitation project in Barwani, India. Information was collected by parent interviews, on social, environmental and biological determinants. A logistic regression model has been applied between determinants and CP. Results Logistic regression demonstrated that likelihood of CP in ID children can be predicted on bases of their age (odd ratio = 0.856, CI 95% - 0.76-0.95), intelligence quotients (IQ) (odd ratio = 0.782, CI 95% - 0.73-0.83) and family history of intellectual disabilities (odd ratio = 0.051, CI 95% - 2.36 -0.99) and epilepsy (odd ratio = 0.008, CI 95% - 2.58-1.28). Comorbid conditions of downs syndrome and epilepsy also predicts likelihood of CP in ID. Conclusion Likelihood of CP in ID children can be predicted by their age, IQ, family history of intellectual disability, epilepsy and comorbid conditions of downs syndrome and epilepsy. Gender, socio-economic status and population (tribal versus non-tribal) determinants have no predictive relation with CP in the group. DOI: http://dx.doi. org/10.3126/nje.v3i3. 9187 Nepal Journal of Epidemiology 2013;3(3): 262-268
GA binding protein augments autophagy via transcriptional activation of BECN1-PIK3C3 complex genes

Macroautophagy is a vesicular catabolic trafficking pathway that is thought to protect cells from diverse stressors and to promote longevity. Recent studies have revealed that transcription factors play important roles in the regulation of autophagy. In this study, we have identified GA binding protein (GABP) as a transcriptional regulator of the combinatorial expression of BECN1-PIK3C3 complex genes involved in autophagosome initiation. We performed bioinformatics analyses that demonstrated highly conserved putative GABP sites in genes that encode BECN1/Beclin 1, several BECN1 interacting proteins, and downstream autophagy proteins including the ATG12–ATG5-ATG16L1 complex. We demonstrate that GABP binds to the promoter regions of BECN1-PIK3C3 complex genes and activates their transcriptional activities. Knockdown of GABP reduced BECN1-PIK3C3 complex transcripts, BECN1-PIK3C3 complex protein levels and autophagy in cultured cells. Conversely, overexpression of GABP increased autophagy. Nutrient starvation increased GABP-dependent transcriptional activity of BECN1-PIK3C3 complex gene promoters and increased the recruitment of GABP to the BECN1 promoter. Our data reveal a novel function of GABP in the regulation of autophagy via transcriptional activation of the BECN1-PIK3C3 complex.
Japanese encephalitis virus replication is negatively regulated by autophagy and occurs on LC3-I- and EDEM1-containing membranes

Autophagy is a lysosomal degradative pathway that has diverse physiological functions and plays crucial roles in several viral infections. Here we examine the role of autophagy in the life cycle of JEV, a neurotropic flavivirus. JEV infection leads to induction of autophagy in several cell types. JEV replication was significantly enhanced in neuronal cells where autophagy was rendered dysfunctional by ATG7 depletion, and in Atg5-deficient mouse embryonic fibroblasts (MEFs), resulting in higher viral titers. Autophagy was functional during early stages of infection however it becomes dysfunctional as infection progressed resulting in accumulation of misfolded proteins. Autophagy-deficient cells were highly susceptible to virus-induced cell death. We also observed JEV replication complexes that are marked by nonstructural protein 1 (NS1) and dsRNA colocalized with endogenous LC3 but not with GFP-LC3. Colocalization of NS1 and LC3 was also observed in Atg5 deficient MEFs, which contain only the nonlipidated form of LC3. Viral replication complexes furthermore show association with a marker of the ER-associated degradation (ERAD) pathway, EDEM1 (ER degradation enhancer, mannosidase α-like 1). Our data suggest that virus replication occurs on ERAD-derived EDEM1 and LC3-I-positive structures referred to as EDEMosomes. While silencing of ERAD regulators EDEM1 and SEL1L suppressed JEV replication, LC3 depletion exerted a profound inhibition with significantly reduced RNA levels and virus titers. Our study suggests that while autophagy is primarily antiviral for JEV and might have implications for disease progression and pathogenesis of JEV, nonlipidated LC3 plays an important autophagy independent function in the virus life cycle.
Analyzing autophagy in zebrafish

The transparency, external development and simple drug administration of zebrafish embryos makes them a useful model for studying autophagy during embryonic development in vivo. Cloning of zebrafish lc3 and generation of a transgenic GFP-Lc3 fish line provide excellent tools to monitor autophagy in this organism.1 This protocol discusses several convenient autophagy assays in zebrafish, including immunoblotting of Lc3 lipidation, microscopy imaging of GFP-Lc3 and lysosomal staining.
A Literature Review on Chronic Pain: The Daily Overcoming of a Complex Problem

Introduction: Chronic pain has an impact on the working life of those affected, but what about other areas of daily living? The objective in this research paper is to review the relationship between chronic pain and engagement in instrumental activities of daily living (IADLs), sleep and family life. Method: A search in the Medline (2006–2010) and the Cumulative Index to Nursing and Allied Health (CINAHL) (2004–2010) databases using the key terms ‘chronic pain’, ‘family’, ‘sleep disorders’ and ‘occupation’ was carried out. To be included, articles had to refer to the effects of chronic pain on IADLs, on sleep or on the family. Studies in which a specific diagnosis or condition was discussed were excluded to provide a more general view of the effects of chronic pain. Quality was assessed using the STROBE statement scale (for descriptive studies, from Strengthening the Reporting of Observational studies in Epidemiology), the Qualitative Research Guidelines Project (for qualitative studies) and the PRISMA statement scale (for systematic reviews, from Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Results: Of the 256 articles obtained from the search, 13 met the inclusion criteria. The articles show that chronic pain indeed has an impact on the lives of those affected in other areas besides work rehabilitation. Conclusion: Occupational therapists must consider levels of performance and engagement in all occupational domains of an individual, even when focusing on a single domain due to the work setting or commissioning process.
The Gordian knot of interim 18-fluorodeoxyglucose positron emission tomography for Hodgkin lymphoma: a meta-analysis and commentary on published studies

Abstract We assessed the diagnostic performance of interim 18-fluorodeoxyglucose positron emission tomography (FDG-PET) with regard to the final outcome of adult patients with newly diagnosed Hodgkin lymphoma (HL). The predefined outcome was treatment failure at the end of follow-up. Bivariate meta-analysis of diagnostic data was used to calculate combined (pooled) estimates. Demographics, quality data and study characteristics were used as potential moderators of outcome in subgroup analysis and meta-regression. A total of 14 studies (16 arms stratified by staging or therapy, 1328 evaluable patients) were deemed eligible for final analysis, after excluding intention-to-treat studies (i.e. those where treatment decision was based on interim PET). The combined effect (95% confidence interval) for sensitivity was 0.67 (0.57–0.76) and specificity 0.89 (0.84–0.93). The corresponding likelihood ratios (LRs) were 6.2 (3.9–10.0) for LR + and 0.37 (0.27–0.50) for LR −, with moderate heterogeneity (I2 =67%). The estimated negative predictive value was 0.93 (0.85–1.00). The diagnostic performance was influenced by most covariates tested, including age, duration of follow-up, criteria used and time of interim PET. Interim PET retains a high specificity for final outcome, but the sensitivity is low. The use of a PET + study as a surrogate marker is hampered by inconsistent interpretation criteria and study populations. However, the high negative predictive value may permit treatment stratification based on a negative outcome.
The marriage of quantitative genetics and cell biology

Microtubules play a central role in many essential cellular processes, including chromosome segregation, intracellular transport, and cell polarity. As these dynamic polymers are crucial components of eukaryotic cellular architecture, we were surprised by our recent discovery that a common human genetic difference leads to variation in microtubule stability in cells from different people. A single nucleotide polymorphism (SNP) near the TUBB6 gene, encoding class V β-tubulin, is associated with the expression level of this protein, which reduces microtubule stability at higher levels of expression. We discuss the novel cellular GWAS (genome-wide association study) platform that led to this discovery of natural, common variation in microtubule stability and the implications this finding may have for human health and disease, including cancer and neurological disorders. Furthermore, our generalizable approach provides a gateway for cell biologists to help interpret the functional consequences of human genetic variation.
Optimization Study on Supercritical Electrodeposition of Nickel Nanowire Arrays Using AAO Template

Highly ordered and nanometer-scaled nickel wire arrays were successfully prepared by supercritical electrodeposition method using anodized aluminum oxide (AAO) template. The results show that the well-ordered and free-standing nickel nanowire arrays can be constructed uniformly on a titanium-coated silicon wafer after removing the AAO template. The diameter and length of the nickel nanowire in the arrays can be obtained, about 100 nm and 10 um, respectively. Based on Box-Behnken design and Response Surface Methodology (RSM), a regression model was built by fitting the experimental results with a polynomial equation. The current density, pressure, and temperature are critical important factors of the growth mechanism of deposited nanowires. The optimal length of nanowires, 10.03 μm, can be achieved at the following conditions: current density 0.23 A/cm2, pressure 107 bar, and temperature 53°C.
Delusions with Religious Content in Patients with Psychosis: How They Interact with Spiritual Coping

Delusions with religious content have been associated with a poorer prognosis in schizophrenia. Nevertheless, positive religious coping is frequent among this population and is associated with a better outcome. The aim of this study was to compared patients with delusions with religious content (n = 38), patients with other sorts of delusions (n = 85) and patients without persistent positive symptoms (n = 113) clinically and spiritually. Outpatients (n = 236) were randomly selected for a quantitative and qualitative evaluation of religious coping. Patients presenting delusions with religious content were not associated with a more severe clinical status compared to other deluded patients, but they were less likely to adhere to psychiatric treatment. For almost half of the group (45%), spirituality and religiousness helped patients cope with their illness. Delusional themes consisted of: persecution (by malevolent spiritual entities), influence (being controlled by spiritual entities), and self-significance (delusions of sin/guilt or grandiose delusions). Both groups of deluded patients valued religion more than other patients, but patients presenting delusions with religious content received less support from religious communities. In treating patients with such symptoms, clinicians should go beyond the label of “religious delusion,” likely to involve stigmatization, by considering how delusions interact with patients' clinical and psychosocial context.
Epidemiology and molecular characterization of chikungunya virus involved in the 2008 to 2009 outbreak in Malaysia

The 2008 to 2009 outbreak of chikungunya was considered as the huge and worst outbreak of CHIKV (Chikungunya virus) infections in history of the country affecting all states in both Peninsular and East Malaysia. This was unlike the first outbreak in late 1998, which was only restricted to Klang district in Selangor and six years later the second outbreak which only involved the state of Perak. The objective of the study was to detect the presence of chikungunya antibody and antigen by immunofluorescence technique and RT-PCR from the sera samples. A total of 2,692 sera samples were received in 2008, in which 19.2% were positive by antibody detection and 42.6% were positive by RT-PCR. The following year in 2009, the samples size increased to 3,592, only 16.3% sample were positive by antibody detection and 31.7% were positive by RT-PCR. Majority of the hospitalized cases were adults between 30 to 60 years of age and the highest incidence rate was amongst patients’ age between 40 to 49 year old. In 2008, most of the confirmed CHIKV infection cases were female but the opposite was seen in 2009, where more male cases were reported. In this outbreak, the prominent ethnic group affected was the Malays. CHIKV involved in the 2008 to 2009 outbreaks was the new Central/East African genotype which was found to be similar with strains causing the outbreaks in the India Ocean and main CHIKV genotype circulating in the European countries from 2006 to 2009. Key words:
WHO Manual on Animal Influenza Diagnosis and Surveillance

This document is not a formal publication of the World Health Organization (WHO), and all rights are reserved by the Organization. The document may, however, be freely reviewed, abstracted, reproduced and translated, in part or in whole, but not for sale nor for use in conjunction with commercial purposes. For authorization to reproduce or translate the work in full, and for any use by commercial entities, applications enquiries should be addressed to the Global Influenza Programme, World Health Organization, Geneva, Switzerland, which will be glad to provide the latest information on any changes made to the text, plans for new editions and the reprints, regional adaptions and translations that are already available. The views expressed in documents by named authors are solely the responsibility of those authors. Each member was assigned one or more chapters for revision. The introduction and background information on surveillance for animal influenza orients the trainee in these areas and sets out the overall goals of the proposed WHO Animal Influenza Network. The laboratory procedures for the isolation and antigenic characterization of influenza viruses from humans and lower animals are essentially the same and the present manual reflects these similarities. However, there are a significant number of differences in sampling and field strategies. The chapters on the neuraminidase assay and neuramini-dase inhibition assay that were not previously included in the Human Influenza Manual were developed specifically for this Animal Influenza Training Manual. The chapters on the identification of influenza viruses by Reverse Transcriptase – Polymerase Chain Reaction, the intravenous pathogenicity tests for influenza viruses and Newcastle Disease Virus were developed for this manual as was the chapter on the agar gel precipitation tests for the detection of antibodies for avian influenza. This is the second edition of the WHO Animal Influenza Training Manual and it must be emphasized that the work was done on a voluntary basis and the manual should be considered a work in progress. We fully acknowledge that there is room for improvement and that errors may be present. We request that any omissions and errors be brought to the attention of members of the Animal Influenza Network.
β-adrenoceptor Blockade and Pulmonary Function in Patients Suffering from Chronic Obstructive Lung Disease

: Pulmonary function can be reduced by beta-blockers. It has been established that no beta-blocker is entirely safe in patients with chronic obstructive lung disease. An alternative medication not expected to influence pulmonary function should first be considered. This side effect of beta-blockers develops mostly in patients with reversible bronchial obstruction, and it is much less pronounced in those with irreversible bronchial obstruction. Translated into terms of clinical diagnosis, this means that problems should be expected in patients with bronchial asthma and with asthmatic bronchitis, whereas those with chronic bronchitis and emphysema are much less likely to develop relevant symptoms. It has been demonstrated that beta-blockers with intrinsic sympathomimetic activity (ISA), such as pindolol, and beta 1-selective blockers have a less marked effect on pulmonary function than nonselective beta-blockers without ISA, such as propranolol. The untoward effect can be compensated by combination with a beta-mimetic agent; this mechanism is most effective during beta 1-selective blockade.
Commentary on “Transference as a Therapeutic Instrument”: Transference in Plain Old Therapy

© 2014 Washington School of Psychiatry Jon G. Allen, PhD, is Senior Staff Psychologist, The Menninger Clinic; and Helen Malsen Palley Chair in Mental Health Research and Professor of Psychiatry, Menninger Department of Psychiatry and Behavioral Science, Baylor College of Medicine, Houston, Texas. Address correspondence to Jon G. Allen, The Menninger Clinic, 12301 Main Street, Houston, TX 77035. E-mail: jallen@menninger.edu Commentary on “Transference as a Therapeutic Instrument” Allen
Assessing Disability and Change on Individual Patients: A Report of a Patient Specific Measure

The purpose of this study was to assess a patient specific measure for eliciting and recording patients' problems. While the notion was to develop a measure that would be applicable to a number of conditions or disabilities, this study assessed the measure's performance on 63 out-patients with mechanical low back pain. Patients were asked to identify up to five important activities they were having difficulty with as a result of their back pain. Patients rated difficulty on an 11-point numerical scale. At subsequent reassessments patients were informed of the activities and corresponding difficulty scores identified at the previous assessment and asked to provide a current difficulty score. Concurrent validity of the patient-specific measure was assessed using the Roland-Morris Questionnaire. Sensitivity to valid change over time was determined by comparing the measure's score to the average patient/clinician global rating of change. Moderate to excellent reliability, validity, and sensitivity to change c.
Primary open angle glaucoma in Nepal: Exploring the unknown

Background: Dealing with blindness related to primary open angle glaucoma (POAG) has always been challenging due to late detection as POAG can remain asymptomatic until end stage. Most eye hospitals in Nepal conduct opportunistic screening programs for glaucoma, but no reports confirm whether screening programs achieve their goals in preventing blindness. Also, no report tells us the status of glaucoma awareness among Nepalese population. Aims: This Thesis explored previously uninvestigated facts about POAG that are essential in preventing glaucoma blindness. It aimed to investigate the association of POAG with hypertension and diabetes. It further aimed to investigate the visual damage of POAG patients at the time of first diagnosis. This Thesis also explored knowledge about POAG, hypertension, and diabetes in a periurban community. Methods: This Thesis used a mixed method approach that combined both quantitative and qualitative methods. A hospital-based case-control study investigated the association between POAG, hypertension, and diabetes. Simultaneously, we conducted a descriptive study to illustrate the clinical findings and visual damage observed at the time of POAG diagnosis. Our qualitative approach explored the knowledge of glaucoma, hypertension, and diabetes in the community. Results: This Thesis shows an association between POAG, hypertension, and diabetes. It also reveals that very few patients knew they were high-risk for POAG when they visited a hospital. Opportunistic screening detected late-stage POAG with moderate to severe visual damage. People’s in-depth knowledge of glaucoma was poor. Gender inequity was persistent in regard to knowledge, attitude, and practice of health in Nepal, and women additionally faced cultural health barriers, depriving them of adequate health care. Nepalese communities need more health awareness programs that emphasize women. Conclusion: Studies presented in this Thesis demonstrate an association between POAG, hypertension, and diabetes. In addition, it shows that the existing glaucoma screening strategy frequently results in late detection of POAG. This Thesis also explored the gap in health literacy regarding glaucoma and gender inequity in health care, indicating a need for tailored communitybased health awareness programs.
Identification of Two Functionally Distinct Endosomal Recycling Pathways for Dopamine D2 Receptor

Dopamine D2 receptor (DRD2) is important for normal function of the brain reward circuit. Lower DRD2 function in the brain increases the risk for substance abuse, obesity, attention deficit/hyperactivity disorder, and depression. Moreover, DRD2 is the target of most antipsychotics currently in use. It is well known that dopamine-induced DRD2 endocytosis is important for its desensitization. However, it remains controversial whether DRD2 is recycled back to the plasma membrane or targeted for degradation following dopamine stimulation. Here, we used total internal reflection fluorescent microscopy (TIRFM) to image DRD2 with a superecliptic pHluorin tagged to its N terminus. With these technical advances, we were able to directly visualize vesicular insertion events of DRD2 in cultured mouse striatal medium spiny neurons. We showed that insertion of DRD2 occurs on neuronal somatic and dendritic surfaces. Lateral diffusion of DRD2 was observed following its insertion. Most importantly, using our new approach, we uncovered two functionally distinct recycling pathways for DRD2: a constitutive recycling pathway and a dopamine activity-dependent recycling pathway. We further demonstrated that Rab4 plays an important role in constitutive DRD2 recycling, while Rab11 is required for dopamine activity-dependent DRD2 recycling. Finally, we demonstrated that the two DRD2 recycling pathways play distinct roles in determining DRD2 function: the Rab4-sensitive constitutive DRD2 recycling pathway determines steady-state surface expression levels of DRD2, whereas the Rab11-sensitive dopamine activity-dependent DRD2 recycling pathway is important for functional resensitization of DRD2. Our findings underscore the significance of endosomal recycling in regulation of DRD2 function.