Miracle-dz/UniFAR-FTUs huggingface dataset:
Adverse drug reactions of antidepressants and antipsychotics: Experience, knowledge and attitudes among Norwegian psychiatrists

Efficient prevention of adverse drug reactions (ADRs) requires knowledge about their severity and pharmacological mechanisms and is dependent on reliable data on their frequencies and possible risk factors. The study was conducted to investigate the prescribers’ experience and understanding of the ADRs of psychotropic drugs, and their attitude towards reporting these. In a questionnaire, physicians treating adult psychiatric patients were asked which ADRs that they regarded bothersome for some of the most widely used antidepressants and antipsychotics. Questions about the relationship between blockade of drug receptors and ADRs, and about the physicians’ personal experience of and attitudes towards reporting of ADRs were also included. In total, 70 of 91 questionnaires (78%) were returned. The mean number of ADRs regarded bothersome ranged from 2.4 to 9.3 for the various drugs/drug classes. Qualified psychiatrists stated a significantly higher number of bothersome ADRs than did the residents. The percentage of physicians associating blockade of a receptor with a specific ADR varied from 76% (histamine receptor blockade and sedation) to 37% (α1-adrenergic blockade and tachycardia). Thirty-nine per cent of the physicians had never reported an ADR to the Norwegian Medicines Agency. The number of ADRs considered bothersome was relatively high. The pattern of these ADRs generally mirrored the typical ADR profiles of the drugs. The knowledge of the underlying mechanisms of ADRs was more or less incomplete. The reporting rate of ADRs to the national regulatory authorities was low.
The Influence of Cardiac Rehabilitation on Inflammation and Metabolic Syndrome in Women With Coronary Heart Disease

Background:Metabolic syndrome (MetS) and increased inflammatory markers, both predictors of future cardiovascular events, are more prevalent in women with coronary heart disease (CHD). The influence of cardiac rehabilitation (CR) on MetS and inflammatory biomarkers is not well characterized for women. Purpose:The purpose of this article was to examine the effects of a 12-week behaviorally enhanced CR exclusively for women compared with traditional CR on components of the MetS and inflammatory markers in women with CHD. Methods:The randomized clinical trial used 2 treatment groups, both receiving a comprehensive 12-week CR program, with 1 group receiving a motivationally enhanced intervention exclusively for women. A subset of 91 women (mean age, 61.6 years) from the parent study provided serum samples to examine the effects of CR on high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor &agr; (TNF-&agr;), and intercellular adhesion molecule-1 (ICAM-1). Results:After CR, the total sample of women demonstrated significant reductions in hsCRP (P =.002), IL-6 (P <.001), TNF-&agr; (P =.010), and ICAM-1 (P =.016). Women in the gender-tailored CR program significantly improved all biomarker levels compared with baseline (P <.05 for all), whereas those in the traditional group improved only hsCRP (P <.05) and IL-6 (P <.05) levels. The combined study group demonstrated improvements in several components of MetS (triglycerides, waist circumference, and systolic blood pressure) but not in others (high-density lipoprotein cholesterol, fasting glucose, and diastolic blood pressure). Conclusion:Cardiac rehabilitation promotes greater improvements in inflammatory biomarkers than in components of MetS for women with CHD. Improvements in body composition or weight may not be a precondition for the benefits of exercise because of loss of abdominal fat. Examining components of MetS as continuous variables is recommended to prevent lost information inherent in dichotomization.
Unravelling the biology of macrophage infection by gene expression profiling of intracellular Salmonella enterica

For intracellular pathogens such as Salmonellae, Mycobacteriae and Brucellae, infection requires adaptation to the intracellular environment of the phagocytic cell. The transition from extracellular to intravacuolar environment has been expected to involve a global modulation of bacterial gene expression, but the precise events have been difficult to determine. We now report the complete transcriptional profile of intracellular Salmonella enterica sv. Typhimurium following macrophage infection. During replication in murine macrophage‐like J774‐A.1 cells, 919 of 4451 S. Typhimurium genes showed significant changes in transcription. The expression profile identified alterations in numerous virulence and SOS response genes and revealed unexpected findings concerning the biology of the Salmonella–macrophage interaction. We observed that intracellular Salmonella are not starved for amino acids or iron (Fe2+), and that the intravacuolar environment is low in phosphate and magnesium but high in potassium. S. Typhimurium appears to be using the Entner–Douderoff pathway to use gluconate and related sugars as a carbon source within macrophages. Almost half the in vivo‐regulated genes were of unknown function, suggesting that intracellular growth involves novel macrophage‐associated functions. This is the first report that identifies the whole set of in vivo‐regulated genes for any bacterial pathogen during infection of mammalian cells.
Pattern of diarrheal diseases in Atwima Nwabiagya District-Ghana, 2009- 2013

Introduction Diarrheal diseases remain one of the most important public health challenges worldwide. In 2011, Ghana recorded average annual diarrheal cases of 2,218 per 100,000 populations for children under-five with Ashanti region recording the third highest. In the Atwima Nwabiagya District, summary statistics are done without detailed analysis. We analyzed diarrheal surveillance data to determine its pattern and to develop threshold levels for the disease in Atwima Nwabiagya District in the Ashanti Region of Ghana. Methods District level diarrheal morbidity data from January 2009 to December 2013 was extracted from District Health Information Management System II, cleaned and analyzed. Descriptive analysis was done and expressed as frequencies and relative frequencies. Description of the data was done in time, place and person. We calculated diarrhea threshold using the C2 method. Results Overall, 51,131 cases were reported with 55.2% being females over the five year period. The highest episode of diarrhea by age-group occurred in children under-five during the study period. Changes in disease occurrence did not conform to a seasonal pattern. District analysis showed one outbreak whilst sub-district analysis revealed more than one outbreak. Conclusion Diarrheal disease pattern did not show a seasonal trend. Only one outbreak was observed at district level but each sub-district, showed more than one outbreak. The highest number of episodes of diarrhea per year occurred in Children under- five. Data analysis should be done at lower levels to inform interventions. Interventions should be targeted towards children under-five years.
Nucleotide sequence analysis of human T‐cell lymphotropic virus type I pX and LTR regions from patients with Sicca syndrome

Human T‐cell lymphotropic virus type I (HTLV‐I) is associated with adult T‐cell leukemia (ATL) and tropical spastic paraparesis/HTLV‐I‐associated myelopathy (TSP/HAM). Other inflammatory disorders may occur in HTLV‐I‐infected patients, such as sicca syndrome resembling Sjögren's syndrome. The sicca syndrome may be the unique clinical manifestation of HTLV‐I infection, but is associated frequently with TSP/HAM, which could suggest that sicca syndrome might be an early event in disease progression to TSP/HAM in some cases. We investigated whether peculiar pX and LTR mutations could be related to sicca syndrome, or might argue the existence of clinical progression to TSP/HAM. pX, especially pXI, pXII, and pXIV ORFs corresponding to Tax cytotoxic T‐lymphocyte epitopes, and LTR regions from Caribbean patients who have sicca syndrome with or without TSP/HAM, ATL patients, and healthy carriers were sequenced. The sequences were aligned and compared with ATK‐1 prototype and published sequences. LTR sequences exhibited 1.5–2.4% of divergence with ATK‐1. pX‐sequenced regions showed a lower homology within p12I encoding sequences. Only few mutations were found within functionally important regions, but were not associated specifically with the clinical status. Finally, no mutations that could be related to sicca syndrome or argue the existence of clinical progression to TSP/HAM were found. It would be of interest to study the clinical evolution of HTLV‐I–sicca syndrome in patients and to determine HTLV‐I sequences from peripheral blood and salivary glands at different stages. J. Med. Virol. 59:245–255, 1999. © 1999 Wiley‐Liss, Inc.
Urinary bladder carcinogenicity of dimethylarsinic acid in male F344 rats.

The present study was conducted to determine the carcinogenicity of dimethylarsinic acid (DMA) administered to male F344 rats in a 2 year bioassay. A total of 144 rats (10 weeks old at the start) were divided into four groups of 36 rats each. Groups 1-4 received DMA (purity 100%) at concentrations of 200, 50, 12.5 and 0 p.p.m. in the drinking water, respectively, for 104 weeks. From weeks 97 to 104, urinary bladder tumors were observed in 12 of 31, eight of 31 and none of 33 in groups 1-3, respectively. No bladder tumors were observed in group 4. The present study demonstrated that long-term p. o. administration of DMA induced urinary bladder carcinomas in male F344 rats. Therefore, the results indicate that DMA is carcinogenic for the rat urinary bladder, which may be related to the human carcinogenicity of arsenicals.
Mixed chimerism and immunosuppressive drug withdrawal after hla-mismatched kidney and hematopoietic progenitor transplantation1

Background. Rodents and dogs conditioned with total-lymphoid irradiation (TLI), with or without antithymocyte globulin (ATG), have been shown to develop mixed chimerism and immune tolerance without graft-versus-host disease (GVHD) after the infusion of major histocompatability complex (MHC)-mismatched donor bone marrow cells given alone or in combination with an organ allograft. Methods. Four human leukocyte antigen (HLA)-mismatched recipients of living donor kidney transplants were conditioned with TLI and ATG posttransplantation and infused with cyropreserved donor granulocyte colony-stimulating factor (G-CSF) “mobilized” hematopoietic progenitor (CD34+) cells (3–5×106 cells/kg) thereafter. Maintenance prednisone and cyclosporine dosages were tapered, and recipients were monitored for chimerism, GVHD, graft function, T-cell subsets in the blood, and antidonor reactivity in the mixed leukocyte reaction (MLR). Results. Three of the four patients achieved multilineage macrochimerism, with up to 16% of donor-type cells among blood mononuclear cells without evidence of GVHD. Prolonged depletion of CD4+ T cells was observed in all four patients. Rejection episodes were not observed in the three macrochimeric recipients, and immunosuppressive drugs were withdrawn in the first patient by 12 months. Prednisone was withdrawn from a second patient at 9 months, and cyclosporine was tapered thereafter. Conclusions. Multilineage macrochimerism can be achieved without GVHD in HLA-mismatched recipients of combined kidney and hematopoietic progenitor transplants. Conditioning of the host with posttransplant TLI and ATG was nonmyeloablative and was not associated with severe infections. Recipients continue to be studied for the development of immune tolerance.
Insulin-like growth factor (IGF) I, -II, and IGF binding protein-3 and risk of ischemic stroke.

BACKGROUND Low IGF-I levels may be associated with the development of stroke; however, prospective data appear to be unavailable. METHODS This was a nested case-control study within a Danish follow-up study, including 57,053 men and women. Baseline data included circulating IGF-I, IGF-II, and IGF binding protein (IGFBP)-3 concentrations as well as lifestyle factors and medical history. We identified 254 cases with incident ischemic stroke and 254 gender- and age-matched controls. RESULTS Participants in the bottom quartiles of IGF-I and IGFBP-3 levels (median concentrations, 72 and 2937 ng/ml, respectively) were at increased risk of ischemic stroke, e.g. adjusted odds ratios (ORs) of 2.06 [95% confidence interval (CI), 1.05-4.03] and 2.29 (95% CI, 1.17-4.49), respectively, when compared with participants in the top quartiles (median concentrations, 125 and 4835 ng/ml, respectively). A negative, although weaker, association was also found for IGF-II (adjusted OR 1.44, 95% CI 0.79-2.64) when comparing the bottom quartile with the top quartile. No substantial associations were seen for IGF-I and IGF-II when also adjusting for IGFBP-3; adjusting IGFBP-3 for IGF-I and -II had only a minor impact on the risk estimates. CONCLUSION These findings give some support to the hypothesis that the IGF axis is involved in the pathogenesis of ischemic stroke.
Molecular mechanisms of Campylobacter fetus surface layer protein expression

Cells of the Gram‐negative bacteria Campylobacter fetus are covered by monomolecular arrays of surface layer proteins (SLPs) critical for both persistence in their natural hosts and for virulence. For C. fetus cells, expression of SLPs essentially eliminates C3b binding and their antigenic variation thwarts host immunological defences. Each cell possesses multiple partially homologous and highly conserved SLP gene cassettes, tightly clustered in the genome, that encode SLPs of 97–149 kDa. These attach non‐covalently via a conserved N‐terminus to the cell wall lipopolysaccharide. Recent studies indicate that C. fetus reassorts a single promoter, controlling SLP expression, and one, or more, complete open reading frame strictly by DNA inversion, and that rearrangement is independent of the distance between sites of inversion. In contrast to previously reported programmed DNA inversion systems, inversion in C. fetus is recA‐ dependent. These rearrangements permit variation in protein expression from the family of SLP genes and suggest an expanding paradigm of programmed DNA rearrangements among microorganisms.
Anti-inflammatory drugs and risk of Alzheimer's disease: an updated systematic review and meta-analysis.

BACKGROUND In the past 20 years, substantial evidence from laboratory and epidemiologic studies have suggested that anti-inflammatory medications could defer or prevent the occurrence of Alzheimer's disease (AD). However, several studies do not corroborate these findings. OBJECTIVE To evaluate the association of anti-inflammatory drug use on the incidence of AD. METHODS Pubmed, Embase, and Cochrane Library databases were searched up to March 2014. Studies evaluating the association between use of anti-inflammatory drugs and AD risk were included. Relative risks (RRs) with 95% confidence intervals (CIs) were meta-analyzed using random effects models and were grouped by anti-inflammatory type and duration of drug use. RESULTS In observational studies, use of non-steroidal anti-inflammatory drugs (NSAIDs) was significantly associated with a reduced risk of AD (RR, 0.72; 95%CI, 0.62-0.84) compared to no use of NSAIDs, especially in long term users (RR, 0.36; 95%CI, 0.17-0.74); the risks of AD were also lower in both aspirin (RR, 0.77; 95%CI, 0.63-0.95) and non-aspirin NSAID users (RR, 0.65; 95%CI, 0.47-0.88) compared with nonusers; whereas the use of corticosteroids showed no significant association (RR, 0.62; 95%CI, 0.26-1.46). In the single randomized controlled trial (RCT), NSAID use showed no significant effect on AD risk among dementia-free individuals (p > 0.05). CONCLUSION Observational studies support the use of NSAIDs for prevention of AD, but RCT do not. Well-designed studies and innovative approaches are required to illuminate the exact relationship between NSAID use and AD risk. The appropriate dosage and duration of use to benefit and the safety are also needed to determine.
PGC-1 Functions as a Transcriptional Coactivator for the Retinoid X Receptors*

Ligand-dependent gene transcription mediated by the nuclear receptors involves the recruitment of transcriptional coactivators to the ligand-binding domain (LBD), which leads to interaction with the basal transcription machinery, and ultimately with RNA polymerase II. Although most of these coactivators are ubiquitously expressed, a tissue-selective coactivator, PGC-1, has recently been characterized. Because PGC-1 and the retinoid X receptors (RXRs) possess an overlapping tissue distribution, we investigated whether PGC-1 is a coactivator for the retinoid X receptors. In a transient transfection assay, PGC-1 augments ligand-stimulated RXR transcription. Furthermore, PGC-1 efficiently enhances the RXR element-driven reporter gene transcription by all three RXR isoforms. An immunoprecipitation assay reveals that PGC-1 and RXRα interact in vivo. In addition, a glutathioneS-transferase pull-down assay showed that this interaction requires the presence of the LXXLL motif of PGC-1. We demonstrate further, in a mammalian two-hybrid assay, that this physical interaction also requires the presence of the AF-2 region of RXR to interact with the LXXLL motif of PGC-1, which is consistent with our protein·protein interaction results. A time-resolved fluorescence assay shows that a peptide within the NR box of PGC-1 is efficiently recruited by a ligand-bound RXRα in vitro. Finally, PGC-1 and TIF2 synergistically enhance ligand-activated RXRα transcriptional activity. Taken together, these results indicate that PGC-1 is a bona fide coactivator for RXRα.
The Role of Fas Ligand in the Development of Insulitis in Nonobese Diabetic Mice

The role of Fas ligand-induced lymphocyte apoptosis in the development of insulitis was studied in nonobese diabetic (NOD) mice. Fas ligand with a molecular weight of 45 kD appeared in the pancreas of NOD mice during the onset of insulitis as demonstrated by western blot analysis. In situ DNA end-labeling (ISEL) of the pancreases of NOD mice demonstrated positive cells in the islets of Langerhans, with an age-dependent increase in the density and frequency of animals with islets containing ISEL-positive cells. In the pancreatic islets of BALB/c mice, no ISEL-positive cells were observed in any of the age groups studied. In ultrastructural analysis degenerating cells with condensed or fragmented nuclei and plasma membranes detached from neighboring cells were observed both in and around the islets. In some cases, these cells were being phagocytosed by the neighboring islet cells. Degenerating cells with characteristics of lymphocytes were seen in contact with healthy lymphocytes around the islets. Neutralizing Fas ligand antibodies affected 3H-thymidine incorporation of CD3+CD28+ pancreatic lymphocytes from 12- to 30-week-old NOD mice in one of three cultures. There was no difference in the effect of neutralizing Fas ligand antibodies between pancreatic and blood lymphocytes. The present results on an increase in density of apoptotic cells in pancreatic islets of NOD mice simultaneously with the onset of insulitis and appearance of Fas ligand suggest that the pancreas infiltrating lymphocytes may be destroyed by Fas ligand-induced apoptosis.
Systemic adverse effects of inhaled corticosteroid therapy: A systematic review and meta-analysis.

OBJECTIVE To appraise the data on systemic adverse effects of inhaled corticosteroids. METHODS A computerized database search from January 1, 1966, through July 31, 1998, using MEDLINE, EMBASE, and BIDS and using appropriate indexed terms. Reports dealing with the systemic effects of inhaled corticosteroids on adrenal gland, growth, bone, skin, and eye, and reports on pharmacology and pharmacokinetics were reviewed where appropriate. Studies were included that contained evaluable data on systemic effects in healthy volunteers as well as in asthmatic children and adults. A statistical meta-analysis using regression was performed for parameters of adrenal suppression in 27 studies. RESULTS Marked adrenal suppression occurs with high doses of inhaled corticosteroid above 1.5 mg/d (0.75 mg/d for fluticasone propionate), although there is a considerable degree of interindividual susceptibility. Meta-analysis showed significantly greater potency for dose-related adrenal suppression with fluticasone compared with beclomethasone dipropionate, budesonide, or triamcinolone acetonide, whereas prednisolone and fluticasone propionate were approximately equivalent on a 10:1-mg basis. Inhaled corticosteroids in doses above 1.5 mg/d (0.75 mg/d for fluticasone propionate) may be associated with a significant reduction in bone density, although the risk for osteoporosis may be obviated by post-menopausal estrogen replacement therapy. Although medium-term growth studies showed suppressive effects with 400-microg/d beclomethasone dipropionate, there was no evidence to support any significant effects on final adult height. Long-term, high-dose inhaled corticosteroid exposure increases the risk for posterior subcapsular cataracts, and, to a much lesser degree, the risk for ocular hypertension and glaucoma. Skin bruising is most likely to occur with high-dose exposure, which correlates with the degree of adrenal suppression. CONCLUSIONS All inhaled corticosteroids exhibit dose-related systemic adverse effects, although these are less than with a comparable dose of oral corticosteroids. Metaanalysis shows that fluticasone propionate exhibits greater dose-related systemic bioactivity compared with other available inhaled corticosteroids, particularly at doses above 0.8 mg/d. The long-term systemic burden will be minimized by always trying to achieve the lowest possible maintenance dose that is associated with optimal asthmatic control and quality of life.
Demonstration of PGL-I & LAM-B antigens in paraffin sections of leprosy skin lesions.

An investigation on the demonstration of PGL-I and LAM-B antigens in thirty-four paraffin embedded skin biopsies taken from leprosy patients who covered the whole spectrum of the disease and in four control specimens was carried out. Neither the PGL-I antigen nor the LAM-B antigen was demonstrated in the normal skin specimens that were used as negative control; and only the LAM-B antigen appeared in the tuberculosis specimens in which the PGL-I antigen was negative. The PGL-I antigen was demonstrated on thirty-three leprosy samples except one TT sample and the LAM-B antigen, on all samples by immunochemical staining technique. The antigens were identified as intracytoplasmic bacillary staining, in solitary, granular as well as debris patterns; and as soluble antigenic staining, in vacuolar or amorphous pattern. In LL and BL cases, the antigens were detected predominantly from macrophages and peripheral nerves in all five staining patterns; in BB cases, from macrophages mostly in the granular as well as debris patterns, from the nerves in the vacuolar pattern; while in TT and the majority of BT cases, they were mainly from nerve remnants inside the granuloma in the vacuolar or amorphous staining pattern. In addition, it is interesting to note that the immunochemical staining was able to differentiate the foamy change from the hydropic degeneration. We also found that the antigens distributed in arrector pili muscles and the walls of muscular vessels were obviously related to the unmyelinated nerve fibers innervating the smooth muscle cells. (ABSTRACT TRUNCATED AT 250 WORDS)
L'auto-exotisme dans les littératures des Antilles françaises

Les etudes realisees sur les litteratures des Antilles francaises s'inscrivent souvent dans le cadre des relations presentes et passees entre la France et les iles. Cette approche est d'ailleurs pertinente, si l'on considere l'histoire commune. Cependant, elle a l'inconvenient de presenter toute difference avec la litterature metropolitaine comme specifique aux Antilles, gommant de la sorte les convergences ou divergences que les litteratures antillaises entretiennent entre elles. Cet ouvrage de litterature comparee aborde les œuvres antillaises d'un point de vue sociologique, "psychanalytique" et litteraire.