Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison between the protective effects of vitamin K and vitamin A on the modulation of hypervitaminosis D3 short-term toxicity in adult albino rats.

BACKGROUND/AIM Vitamin D3 has increased risk of toxicity due to its common use in multivitamin preparations. Vitamin K and vitamin A play an important role in vitamin D action. The goal of the current study was to compare the protective effects of vitamin K and vitamin A on the modulation of hypervitaminosis D3 toxicity in rats by assessing serum calcium, renal function tests, cardiac enzymes, and related histopathological changes. MATERIALS AND METHODS Eighty adult albino rats were divided into four groups; each group consisted of 20 rats. The first group received water; the second received a toxic dose of vitamin D3; the third received a toxic dose of vitamin D3 with vitamin A; and the fourth received a toxic dose of vitamin D3 with vitamin K. RESULTS Vitamin D3 toxicity led to significant abnormalities of cardiac enzymes, renal function tests, and serum calcium associated with histopathological changes in the kidney, heart, lung, adrenal gland, and aorta. Individual administration of vitamin A or vitamin K with a toxic dose of vitamin D improved the biochemical and histopathological abnormalities of hypervitaminosis D3. CONCLUSION Vitamins A and K showed the same protective effects in the modulation of hypervitaminosis D3 short-term toxicity.
EFICACIA DE LA AMIODARONA EN LA CARDIOVERSIÓN DE LA FIBRILACIÓN AURICULAR DE RECIENTE INICIO

La Fibrilacion Auricular es la arritmia mas frecuente vista en cardiologia. Los medicamentos antiarritmicos son diversos. Uno de ellos es la amiodarona. Su eficacia varia entre 40 y 80 %. Se realizo un estudio en el Hospital Militar con 40 pacientes cuyo objetivo fue establecer el porcentaje de cardioversion de pacientes portadores de Fibrilacion Auricular de reciente inicio (menos de 48 horas) usando la Amiodarona (antiarritmico de clase III ). Los resultados mostraron una cardioversion del 87,5%, en pacientes con distintas cardiopatias de fondo. No se produjeron efectos secundarios de importancia. La experiencia en este trabajo confiere, como multiples estudios en la literatura, una muy importante accion de la Amiodarona EV en la cardioversion de la FA de reciente inicio, por lo cual se recomienda, como conclusion, su uso en esta arritmia. PALABRAS CLAVES: FIBRILACION AURICULAR, CARDIOVERSION, AMIODARONA
Multiple Micronutrient Supplementation during Pregnancy in Developing-Country Settings: Policy and Program Implications of the Results of a Meta-Analysis

Background An independent Systematic Review Team performed a meta-analysis of 12 randomized, controlled trials comparing multiple micronutrients with daily iron–folic acid supplementation during pregnancy. Objective To provide an independent interpretation of the policy and program implications of the results of the meta-analysis. Methods A group of policy and program experts performed an independent review of the meta-analysis results, analyzing internal and external validity and drawing conclusions on the program implications. Results Although iron content was often lower in the multiple micronutrient supplement than in the iron–folic acid supplement, both supplements were equally effective in tackling anemia. Community-based supplementation ensured high adherence, but some mothers still remained anemic, indicating the need to concomitantly treat infections. The small, significant increase in mean birthweight among infants of mothers receiving multiple micronutrients compared with infants of mothers receiving iron-folic acid is of similar magnitude to that produced by food supplementation during pregnancy. Larger micronutrient doses seem to produce greater impact. Meaningful improvements have also been observed in height and cognitive development of the children by 2 years of age. There were no significant differences in the rates of stillbirth, early neonatal death, or neonatal death between the supplemented groups. The nonsignificant trend toward increased early neonatal mortality observed in the groups receiving multiple micronutrients may be related to differences across trials in the rate of adolescent pregnancies, continuing iron deficiency, and/or adequacy of postpartum health care and merits further investigation. Conclusions Replacing iron–folic acid supplements with multiple micronutrient supplements in the package of health and nutrition interventions delivered to mothers during pregnancy will improve the impact of supplementation on birthweight and on child growth and development.
The effect of splenectomy for hypersplenism on whole body protein turnover, resting metabolic rate and growth in sickle cell disease.

OBJECTIVE To determine whether, in the same individual, an observed fall in whole body protein turnover following splenectomy in children with hypersplenism and homozygous sickle cell (SS) disease is associated with a measurable fall in resting metabolic rate (RMR) and an increase in rate of growth. SUBJECTS Six children (5 SS disease, 1 S beta degree thalassaemia), aged 68 to 126 months, were studied before and after splenectomy for hypersplenism. DESIGN Protein turnover was measured by the end product method using prime/intermittent oral doses of 15N-glycine and RMR by indirect calorimetry before preoperative transfusion and repeated at least eight weeks after splenectomy. Height and weight velocities were measured over six month periods before and after splenectomy. SETTING University Hospital of the West Indies in Jamaica and the Medical Research Laboratories (Jamaica). RESULTS After splenectomy protein turnover fell significantly by 30% and RMR by 34 kJ/kg/d. Mean weight velocity which was below normal before surgery, z = -2.3, improved significantly after surgery, z = 0.7, (P = 0.03). Height velocity increased in two children but the mean height velocity did not change following splenectomy. The reduction in protein turnover was estimated to account for 62% of the fall in RMR. CONCLUSION This study confirms that there is a significant reduction in energy expenditure following splenectomy for hypersplenism in SS disease. A reduction in protein turnover was a major contributor to the saving in energy, although it is not clear whether it accounted for all. In the present group of children the energy saved was associated with an improvement in the wasting present before splenectomy.
Searching for Combinations of Small-Molecule Correctors to Restore F508del–Cystic Fibrosis Transmembrane Conductance Regulator Function and Processing

The mutated protein F508del–cystic fibrosis transmembrane conductance regulator (CFTR) failed to traffic properly as a result of its retention in the endoplasmic reticulum and functions as a chloride (Cl−) channel with abnormal gating and endocytosis. Small chemicals (called correctors) individually restore F508del-CFTR trafficking and Cl− transport function, but recent findings indicate that synergistic pharmacology should be considered to address CFTR defects more clearly. We studied the function and maturation of F508del-CFTR expressed in HeLa cells using a combination of five correctors [miglustat, IsoLAB (1,4-dideoxy-2-hydroxymethyl-1,4-imino-l-threitol), Corr4a (N-[2-(5-chloro-2-methoxy-phenylamino)-4′-methyl-[4,5′]bithiazolyl-2′-yl]-benzamide), VX-809 [3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid], and suberoylamilide hydroxamic acid (SAHA)]. Using the whole-cell patch-clamp technique, the current density recorded in response to CFTR activators (forskolin + genistein) was significantly increased in the presence of the following combinations: VX-809 + IsoLAB; VX-809 + miglustat + SAHA; VX-809 + miglustat + IsoLAB; VX-809 + IsoLAB + SAHA; VX-809 + miglustat + IsoLAB + SAHA. These combinations restored the activity of F508del-CFTR but with a differential effect on the appearance of mature c-band of F508del-CFTR proteins. Focusing on the VX-809 + IsoLAB cocktail, we recorded a level of correction higher at 37°C versus room temperature, but without amelioration of the thermal instability of CFTR. The level of functional rescue with VX-809 + IsoLAB after 4 hours of incubation was maximal and similar to that obtained in optimal conditions of use for each compound (i.e., 24 hours for VX-809 + 4 hours for IsoLAB). Finally, we compared the stimulation of F508del-CFTR by forskolin or forskolin + VX-770 [N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide] with cells corrected by VX-809 + IsoLAB. Our results open new perspectives for the development of a synergistic polypharmacology to rescue F508del-CFTR and show the importance of temperature on the effect of correctors and on the level of correction, suggesting that optimized combination of correctors could lead to a better rescue of F508del-CFTR function.
The effect of anti‐malarial drugs on human natural killer cells in vitro

Summary Human natural killer (NK) cell cytotoxicity against K‐562 target was found to be markedly depressed by quinacrine, mefloquine, pyrimethamine and chloroquine. The most potent were quinacrine and mefloquine. Two other drugs tested, quinine and primaquine, displayed no significant effects even after long incubation periods with effector cells. The results showed that the inhibitory effects were not related to an inhibition of effector cell binding to target or to a toxic effect on NK cells.
From Trees To Timbers: A Comparative Study Of Timber Quantities In Houses

It is over 40 years since Oliver Rackham published his paper in VA 3 on the quantities of timber in Grundle House in Suffolk and the number and sizes of trees it consumed. His methodology is often quoted, but seldom re-used; surveys of only two other houses have been published. To these is now added 1 Coppard’s Bridge, an open-hall house of 1473d in the Low Weald of East Sussex, allowing comparison of four house types and their timber requirements to demonstrate the transition in methods of conversion of trees to timber during the medieval and post-medieval periods. This analysis, based on Oliver Rackham’s enduring work, marks his passing in February 2015 and his contribution to vernacular architecture studies.
Analysis of the Heteromeric CsdA-CsdE Cysteine Desulfurase, Assisting Fe-S Cluster Biogenesis in Escherichia coli*

Biogenesis of iron-sulfur (Fe-S) cluster-containing proteins relies on assistance of complex machineries. To date three systems, NIF, ISC, and SUF, were reported to allow maturation of Fe-S proteins. Here we report that the csdA-csdE (formally ygdK) genes of Escherichia coli constitute a sulfur-generating system referred to as CSD which also contributes to Fe-S biogenesis in vivo. This conclusion was reached by applying a thorough combination of both in vivo and in vitro strategies and techniques. Yeast two-hybrid analysis allowed us to show that CsdA and CsdE interact. Enzymology analysis showed that CsdA cysteine desulfurase activity is increased 2-fold in the presence of CsdE. Mass spectrometry analysis and site-directed mutagenesis showed that residue Cys-61 from CsdE acted as an acceptor site for sulfur provided by cysteine desulfurase activity of CsdA. Genetic investigations revealed that the csdA-csdE genes could act as multicopy suppressors of iscS mutation. Moreover, both in vitro and in vivo investigations pointed to a specific connection between the CSD system and quinolinate synthetase NadA.
APIBot: Question answering bot for API documentation

As the carrier of Application Programming Interfaces (APIs) knowledge, API documentation plays a crucial role in how developers learn and use an API. It is also a valuable information resource for answering API-related questions, especially when developers cannot find reliable answers to their questions online/offline. However, finding answers to API-related questions from API documentation might not be easy because one may have to manually go through multiple pages before reaching the relevant page, and then read and understand the information inside the relevant page to figure out the answers. To deal with this challenge, we develop APIBot, a bot that can answer API questions given API documentation as an input. APIBot is built on top of SiriusQA, the QA system from Sirius, a state of the art intelligent personal assistant. To make SiriusQA work well under software engineering scenario, we make several modifications over SiriusQA by injecting domain specific knowledge. We evaluate APIBot on 92 API questions, answers of which are known to be present in Java 8 documentation. Our experiment shows that APIBot can achieve a Hit@5 score of 0.706.
New Advances in Addiction Medicine

The high prevalence rate of the drug and alcohol-related problems highlights the public health importance of this disorder. The abuses of legal and illegal drugs remain one of the major medical problems in the world today. The total number of drug users in the world is now estimated at about 200 million people, equivalent to about five percent of the global population age 15–64 (United Nations Office on Drugs and Crime. World Drug Report, 2006). Cannabis remains by far the most widely used drug, followed by amphetamine-type stimulants, opiate and cocaine users. Alcohol abuse and alcoholism affects nearly 10% of the general population both in the United States (McGinnis and Foege, 1993) and in Europe (Hupkens et al., 1993). Drug and alcohol abuse have many medical consequences. Health effects may range between cardiomyopathies, immune impairment, endocrine disorders, metabolic and nutritional disorders, liver and gastrointestinal diseases, cancer disease, neuropsychiatric complications to name a few, so all kinds of physicians could be involved in the management of these patients. Medical approaches continue to develop with new discoveries in pharmacology, molecular genetics, and immunology. Indeed, in the last three decades, our increased knowledge about the molecular, biological and behavioral aspects of addiction has enabled us to improve the management and survival of these patients. For example, the discovery of the neurobiological basis of addiction and of different neural pathways involved in drug and alcohol abuse led to identify new pharmacological approaches to treatment that can be paired with psychosocial treatments. Furthermore, there are new advances in pharmacogenetics that can bring forward to era of personalized medicine to the addictions field. New vistas in vaccine research also promise to improve both the prevention and treatment of addictive disorders. All this scientific progress was, and shall continue to be, possible due to the rapid expansion of research in the field. Frontiers in Addictive Disorders will be at the cutting-edge of publishing papers that will shape our understanding and the treatment of addictive diseases now and in the future. The scope of the journal is very broad and ranges from the laboratory bench to society.
Cardiac abnormalities in diabetic patients with mutation in the mitochondrial tRNA(Leu(UUR)) gene.

An A-to-G transition at position 3243 of the mitochondrial DNA is known to be a pathogenic factor for mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), diabetes and cardiomyopathy. This mutation causes dysfunction of the central nervous system in MELAS. Because the heart, as well as the brain and nervous system, is highly dependent on the energy produced by mitochondrial oxidation, these tissues are more vulnerable to mitochondrial defects. Cardiac abnormalities were assessed in 10 diabetic patients associated with this mutation using echocardiography and 123I-metaiodobenzylguanidine (MIBG) scintigraphy, and compared with 19 diabetic patients without the mutation. Duration of diabetes, therapy, control of blood glucose and diabetic complications, such as diabetic retinopathy and nephropathy, were not different between the 2 groups. Diabetic patients with the mutation had a significantly thicker interventricular septum (16.8+/-3.7 vs 11.0+/-1.6mm, p<0.001) than those without the mutation. Fractional shortening was lower in diabetic patients with the mutation than those without it (30.7+/-7.0 vs 42.5+/-6.6, p<0.001). MIBG uptake on the delayed MIBG image was significantly lower in diabetic patients with the mutation than in those without the mutation (mean value of the heart to mediastinum ratio: 1.6+/-0.2 vs 2.0+/-0.4, p>0.05). In conclusion, left ventricular hypertrophy with or without abnormal wall motion and severely reduced MIBG uptake may be characteristic in diabetic patients with a mutation in the mitochondrial tRNA(Leu(UUR)) gene.
Immune Surveillance, Cytokines, and Breast Cancer Risk: Genetic and Psychological Influences in African American Women

Abstract : Breast cancer cells are known to bear determinants that would allow tumor specific immune responses. However, initiation and amplification of such immune responses are critically dependent upon the balance in TH1 and TH2 cytokine profiles. This molecular epidemiological study evaluates the impact that variability in cytokine profiles, (inferred from functional polymorphisms in cytokine genes), may have on breast cancer risk among urban African-American women. In the first phase of the study, DNA collected and approved for additional study as part of a previously funded Case-Control investigation (n=1600) will be assessed for cytokine polymorphisms. Because cytokine profiles are also known to be affected by environmental factors, particularly levels of stress, this study also evaluates the relative contribution of genotype and stress influences using data collected for that purpose from a sub-sample of healthy Controls (n=400) recruited from the graduates of the larger study. Results will allow evaluation of the possibility that deficits in cytokine responses due to genetic or environmental factors may contribute to breast cancer risk. Based on these findings, women at risk for breast cancer because of polymorphisms in genes important to effective immune surveillance could be targeted for innovative prevention strategies including stress reduction and immune modulators.
Real-time telerehabilitation for the treatment of musculoskeletal conditions is effective and comparable to standard practice: a systematic review and meta-analysis

Objective: To evaluate the effectiveness of treatment delivered via real-time telerehabilitation for the management of musculoskeletal conditions, and to determine if real-time telerehabilitation is comparable to conventional methods of delivery within this population. Data sources: Six databases (Medline, Embase, Cochrane CENTRAL, PEDro, psycINFO, CINAHL) were searched from inception to November 2015 for literature which reported on the outcomes of real-time telerehabilitation for musculoskeletal conditions. Review methods: Two reviewers screened 5913 abstracts where 13 studies (n = 1520) met the eligibility criteria. Methodological quality was assessed using the Downs & Black ‘Checklist for Measuring Quality’ tool. Results were pooled for meta-analysis based upon primary outcome measures and reported as standardised mean differences and 95% confidence intervals (CI). Results: Aggregate results suggest that telerehabilitation is effective in the improvement of physical function (SMD 1.63, 95%CI 0.92-2.33, I2=93%), whilst being slightly more favourable (SMD 0.44, 95%CI 0.19-0.69, I2=58%) than the control cohort following intervention. Sub-group analyses reveals that telerehabilitation in addition to usual care is more favourable (SMD 0.64, 95%CI 0.43-0.85, I2=10%) than usual care alone, whilst treatment delivered solely via telerehabilitation is equivalent to face-to-face intervention (SMD MD 0.14, 95% CI −0.10–0.37, I2 = 0%) for the improvement of physical function. The improvement of pain was also seen to be comparable between cohorts (SMD 0.66, 95%CI −0.27–1.60, I2=96%) following intervention. Conclusions: Real-time telerehabilitation appears to be effective and comparable to conventional methods of healthcare delivery for the improvement of physical function and pain in a variety of musculoskeletal conditions.
Gene Cloning and Characterization of CDP-diacylglycerol Synthase from Rat Brain*

A cDNA encoded a 462-amino acid protein, which showed CDP-diacylglycerol synthase (CDS) activity was cloned for the first time as the vertebrate enzyme molecule from rat brain cDNA library. The deduced molecular mass of this rat CDS was 53 kDa, and putative primary structure included several possible membrane- spanning regions. At the amino acid sequence level, rat CDS shared 55.5%, 31.7%, and 20.9% identity with already known Drosophila, Saccharomyces cerevisiae, and Escherichia coli CDS, respectively. This rat CDS preferred 1-stearoyl-2-arachidonoyl phosphatidic acid as a substrate, and its activity was strongly inhibited by phosphatidylglycerol 4,5-bisphosphate. By immunoblotting analysis of COS cells overexpressed with the epitope-tagged for rat CDS, a 60-kDa band was detected. By epitope-tag immunocytochemistry, the CDS protein was mainly localized in close association with the membrane of the endoplasmic reticulum of the transfected cells. The intense mRNA expression of CDS was localized in the cerebellar Purkinje cells, the pineal body, and the inner segment of photoreceptor cells. Additionally, very intense expression was detected in postmitotic spermatocytes and spermatids.
CDKN 2 A gene mutations and genetic interactions in the pathogenesis of melanoma

BACKGROUND: Neonatal blue light phototherapy (NBLP) has been widely and successfully used for the treatment of neonatal jaundice to reduce the plasma concentration of bilirubin and, hence, to prevent kernicterus. Only a few and controversial data are available in the literature as to how NBLP influences melanocytic nevus development. OBJECTIVE: Our goal was to conduct a twin study with the aim of better understanding the role of NBLP in melanocytic nevus development. We also investigated the roles of other environmental and constitutional factors in nevus formation. METHODS: Fifty-nine monozygotic and dizygotic twins were included in this cross-sectional study. One of the twinmembers received NBLP, and the other did not. A whole-body skin examination was performed to determine the density of melanocytic skin lesions. The prevalence of benign pigmented uveal lesions was evaluated during a detailed ophthalmologic examination. A standardized questionnaire was used to assess data relating to constitutional, sun-exposure, and other variables. To search for possible gene-environmental interactions involved in the appearance of pigmented lesions, the melanocortin 1 receptor variants and the I439V polymorphismof histidine ammonia-lyase genes were also determined in the enrolled twins. RESULTS: NBLP was associated with a significantly higher prevalence of both cutaneous and uveal melanocytic lesions. No association was found between the examined gene polymorphisms and the number of pigmented alterations in the examined study group. CONCLUSIONS: Our data suggest that NBLP couldwell be a risk factor for melanocytic nevus development. Phototherapy with blue-light lamps is a standard and essential therapeutic modality in neonatal care; therefore, additional in vivo and in vitro studies are necessary to establish its potential long-term adverse effects. Pediatrics 2011;128:e856–e864 AUTHORS: Zsanett Csoma, MD, PhD,a Edit Tóth-Molnár, MD, PhD,b Klára Balogh, MD,a Hilda Polyánka, MSc,c Hajnalka Orvos, MD, PhD,d Henriette Ócsai, MD,a Lajos Kemény, MD, DSc,a,c Márta Széll, DSc,c and Judit Oláh, MD, PhDa aDepartment of Dermatology and Allergology, cDermatological Research Group of the Hungarian Academy of Sciences, and dDepartment of Obstetrics and Gynecology, University of Szeged, Szeged, Hungary; and bNovotalex Ltd, Szeged, Hungary