Miracle-dz/UniFAR-FTUs huggingface dataset:
Drug combinations and impaired renal function -- the 'triple whammy'.

BACKGROUND Recent studies have identified the 'triple whammy' in which combinations of diuretics, nonsteroidal anti-inflammatory drugs (NSAIDs), ACE inhibitors (ACEI) and/or angiotensin receptor antagonists (ARA) may impair renal function. METHODS We performed a cross-sectional study of patients admitted to a general medical ward of a teaching hospital. Age, sex, disease status and prior consumption of the 'target' drugs, diuretics, NSAIDs (including aspirin), ACEI and ARA were correlated with creatinine and creatinine clearance on admission. RESULTS Three hundred and one patients (48% male) were included, 135 were on no prior target drugs, 87 on one, 60 on two and 19 on three such drugs. There was a significant (P < 0.01) correlation between both creatinine and creatinine clearance with male sex, age and number of target drugs. Multivariate analysis confirmed these associations but did not support associations between renal function and heart failure or total number of diagnoses. Increasing doses of diuretics, possibly because in many cases this included two drugs, but not the other drugs, were significantly (P < 0.001) associated with impaired renal function. For the other three drug groups patients on doses of any drug at lower than the defined daily dose (DDD) did not have significantly different creatinine or creatinine clearance from those on doses at or above the DDD. CONCLUSION Taking two or more of the identified drugs was associated with significant renal impairment but did not correlate with heart failure or other diseases for which the drugs might have been prescribed. Care is necessary to balance the demonstrated advantages of these medications against the risk of inducing renal failure.
HIV treatments have malaria gametocyte killing and transmission blocking activity.

BACKGROUND Millions of individuals being treated for human immunodeficiency virus (HIV) live in malaria-endemic areas, but the effects of these treatments on malaria transmission are unknown. While drugs like HIV protease inhibitors (PIs) and trimethoprim-sulfamethoxazole (TMP-SMX) have known activity against parasites during liver or asexual blood stages, their effects on transmission stages require further study. METHODS The HIV PIs lopinavir and saquinavir, the nonnucleoside reverse-transcriptase inhibitor nevirapine, and the antibiotic TMP-SMX were assessed for activity against Plasmodium falciparum transmission stages. The alamarBlue assay was used to determine the effects of drugs on gametocyte viability, and exflagellation was assessed to determine the effects of drugs on gametocyte maturation. The effects of drug on transmission were assessed by calculating the mosquito oocyst count as a marker for infectivity, using standard membrane feeding assays. RESULTS Lopinavir and saquinavir have gametocytocidal and transmission blocking activities at or approaching clinically relevant treatment levels, while nevirapine does not. TMP-SMX is not gametocytocidal, but at prophylactic levels it blocks transmission. CONCLUSIONS Specific HIV treatments have gametocyte killing and transmission-blocking effects. Clinical studies are warranted to evaluate these findings and their potential impact on eradication efforts.
Effects of cortisol on chloride cells in the gill epithelium of Japanese eel, Anguilla japonica.

The purpose of the present study was to determine the effects of cortisol on the development of the freshwater chloride cell (CC), using flow cytometry. Scanning electron microscopy was used to determine the corresponding modifications in CC apical structure. Simultaneously, biochemical analyses were conducted to determine the activities of transport ATPases, mitochondrial enzymes (succinate dehydrogenase (SDH) and Mg(2+)-ATPase) and lactate dehydrogenase (Ldh). The effects of daily i.m. injection of 2 microg/g cortisol were compared with sham-injected freshwater-, control freshwater- and seawater-adapted fish. The hormone did not affect the activities of Ca(2+)-ATPases in CCs. However, it stimulated the proliferation and differentiation of the two freshwater CC subtypes (F1, 66+/-2.18% (s.e.m. ) and F2, 34+/-2.18%), in which the relative proportion of F1 CCs was transiently reduced in the first 5 days of treatment (F1, 53+/-1.83%; F2, 47+/-1.83%) but was then restored to a higher relative percentage on day 10 (F1, 70+/-1.42%; F2, 30+/-1.42%). Biochemically, it induced the activities of Na(+)/K(+)-ATPase, Mg(2+)-ATPase, SDH and Ldh, suggesting an increase in ion pumping and its associated metabolic activities. CCs from cortisoltreated fish demonstrated recessed apical morphology, accompanied by an increase in cell density (2012 to 2413/mm(2)). Nevertheless, the extent of cell proliferation and differentiation and the biochemical changes were significantly lower than those of seawater fish. Our results indicate that cortisol alone cannot stimulate a complete differentiation of freshwater CCs to seawater CCs. However, the respective roles of the two CC subtypes in freshwater and seawater environments are indicated.
Sensitization of the submaxillary gland to chemical stimuli.

Summary. Some types of supersensitivity of the submaxillary gland cells to chemical agents have been studied quantitatively. The increased sensitivity which is obtained after section of the chorda tympani, removal of the superior cervical ganglion, injection of cocaine or prolonged treatment with atropine is shown to be un-specific. Section of the chorda and treatment with atropine seems to give rise to similar types of supersensitivity, which in many respects differ from the type produced by extirpation of the superior cervical ganglion or injection of cocaine. The expenses of this investigation have been defrayed in part by a grant to one of us (N. E.) from the Swedish Medical Research Council.
Resettling Refugees and Safeguarding their Mental Health: Lessons Learned from the Canadian Refugee Resettlement Project

The Ryerson University Refugee Resettlement Project (RRP), a decade-long study of 1348 Southeast Asian refugees who came to Canada between 1979 and 1981, is one of the largest, most comprehensive and longest-lived investigations of refugee resettlement ever carried out. Knowledge gleaned from the RRP about research methodology, about the resettlement experience, about the social costs of resettling refugees, about factors that promote or hinder integration, about risk and protective factors for refugee mental health, and about the refugees’ consumption of mental health and social services is summarized in the form of 18 “Lessons. ” The lessons are offered in order to encourage and stimulate further research, as well to suggest policy and practice innovations that could help make resettlement easier, less costly, more effective, and more humane.
A REVIEW STUDY ON MEDICINAL PLANTS AFFECTING AMNESIA THROUGH CHOLINERGIC SYSTEM

Neurotransmitter modification is an important method for the treatment of memory loss or amnesia. Cholinomimetic drugs, particularly, acetylcholine esterase inhibitors are the mainstream in pharmacotherapy of amnesia. Donepezil, tacrine, galantamine, and rivastigmine are cholinesterase inhibitors which are widely used in the treatment of amnesia, however, their therapeutic effects are not significant. Therefore, other possibilities including herbal medicine sources have been considered for memory loss therapy. There are some Medicinal plants with cholinomimetic property which mostly possess antioxidant activity, too. These plants may not only ameliorate amnesia but also can be a good source for drug discovery. In this paper other than introducing the medicinal plants and their components affective on cholinergic system and effective on memory loss, their probable advantages over synthetic drugs are discussed.
Peroxisome Proliferator-Activated Receptor-2 P 12 A Polymorphism and Risk of Coronary Heart Disease in US Men and Women

Objective—Activation of the peroxisome proliferator-activated receptor(PPAR ) improves insulin sensitivity and exerts antiatherogenic effects. A common alanine for proline substitution at codon 12 in the PPARG2 gene is related to lower receptor activity. Studies suggest that the A12 allele is associated with reduced risk of type 2 diabetes; however, data on the risk of coronary heart disease (CHD) are scarce and controversial. Methods and Results—We examined the relationship between PPARG2 P12A and CHD risk in women (Nurses’ Health Study) and men (Health Professionals Follow-Up Study) in nested case control settings. Among participants free of cardiovascular disease at baseline, 249 women and 266 men developed nonfatal myocardial infarction (MI) or fatal CHD during 8 and 6 years of follow-up, respectively. Using risk-set sampling, controls were selected 2:1 matched on age, smoking, and date of blood draw. The relative risk (RR) of nonfatal MI or fatal CHD of carriers compared with noncarriers of the A12 allele was 1.17 (95% CI, 0.82 to 1.68) among women and 1.44 (95% CI, 1.00 to 2.07) among men (pooled RR, 1.30 [95% CI, 1.00 to 1.67]). We found a significantly increased risk associated with the A12 allele among individuals with a body mass index 25 kg/m (women: RR, 1.88; 95% CI, 1.01 to 3.50; men: RR, 1.55; 95% CI, 0.92 to 2.60; pooled: RR, 1.68; 95% CI, 1.13 to 2.50) but not among those 25 kg/m (pooled RR, 0.86; 95% CI, 0.37 to 1.97; P heterogeneity overweight versus nonoverweight 0.16). Conclusions—These data do not support the hypothesis that the A12 allele is associated with a decreased risk of CHD. The potential interaction between PPARG2 P12A, overweight, and increased CHD risk needs further evaluation. (Arterioscler Thromb Vasc Biol. 2005;25:1654-1658.)
Efficacy of Povidone-Iodine Vaginal Suppositories in the Treatment of Bacterial Vaginosis

A prospective, randomized clinical trial was performed to study the efficacy of povidone iodine (Betadine®) suppositories for the treatment of bacterial vaginosis (BV) in comparison to capsules containing lactobacilli (Döderlein Med®). Seventy patients with BV included in the study were randomly assigned to be either treated with povidone iodine suppositories or lactobacilli. Patients were treated once a day for 5 days. Initial examinations took place on the first day of the study with follow-up examinations on days 8 and 15. The examinations included clinical parameters, patient evaluation, secretion screens, and quantitative and qualitative microbiological tests of vaginal flora. Both treatment groups showed improvement of clinical parameters, condition of secretions and subjective state of health. At day 15 there was a trend towards a better efficacy of the treatment with povidone iodine but this was not significant. However, patients with acute BV treated with povidone iodine had significantly better scores after 15 days. Both treatments were well tolerated. The microbiological examinations showed an increase of the mean number of lactobacilli in the vagina on day 8 after initiation of treatment with lactobacilli, but a decrease on day 15. Contrary to that the lactobacilli counts from patients treated with povidone iodine suppositories decreased after the first week but increased in the second one. Potentially pathogenic germs, e.g. Gardnerella, Bacteroides and Enterobacteria were reduced in a higher extent and with a longer lasting effect after treatment with povidone iodine suppositories than with capsules containing lactobacilli. The results of this study show that native lactobacilli rapidly re-colonize after the antiseptic treatment with povidone iodine. Therefore, there is no need to use lactobacilli in addition.
Anatomical informatics: Millennial perspectives on a newer frontier

One of the most ancient of sciences, anatomy has evolved over many centuries. Its methods have progressively encompassed dissection instruments, manual illustration, stains, microscopes, cameras and photography, and digital imaging systems. Like many other more modern scientific disciplines in the late 20th century, anatomy has also benefited from the revolutionary development of digital computers and their automated information management and analytical capabilities. By using newer methods of computer and information sciences, anatomists have made outstanding contributions to science, medicine, and education. In that regard, there is a strong rationale for recognizing anatomical informatics as a proper subdiscipline of anatomy. A high‐level survey of the field reveals important anatomical applications of computer sciences methods in imaging, image processing and visualization, virtual reality, modeling and simulation, structural database processing, networking, and artificial intelligence. Within this framework, computational anatomy is a developing field focusing on data‐driven mathematical models of bodily structures. Mastering such computer sciences and informatics methods is crucial for new anatomists, who will shape the future in research, clinical knowledge, and teaching. Anat Rec (New Anat) 269:224–235, 2002. © 2002 Wiley‐Liss, Inc.
Acarological risk of exposure to agents of tick-borne zoonoses in the first recognized Italian focus of Lyme borreliosis

Acarological risk was calculated as the probability of encountering at least one host-seeking Ixodes ricinus tick infected by the pathogen Borrelia burgdorferi sensu lato, in 100 m transects in the province of Genoa, Italy. The seasonal pattern of I. ricinus was studied using generalized estimating equations (GEE) with negative binomial error, to consider overdispersion of tick counts and repeated sampling of the same dragging sites from April 1998 to March 1999. Prevalence of infection by B. burgdorferi s.l. was evaluated by PCR and hybridization with genospecies-specific probes. Acarological risk (R) peaked in April (R=0·2, 95% CI 0·13–0·26) and November (R=0·29, 95% CI 0·10–0·46). Borrelia garinii and B. valaisiana were the most common genospecies at our study site suggesting a major role of birds as reservoirs. DNA from Anaplasma phagocytophilum, the agent of granulocytic ehrlichiosis in humans and animals, was amplified from an adult I. ricinus.
Utility and Attention - A Structural Model of Consideration

Models of consumer decision making often condition on attention to the different offers or alternatives to choose from. However, in many environments offers not only compete through their utility but also for the attention of decision makers. In this case, it is important to distinguish between attention and utility it makes a difference whether an offering is overlooked, or rejected conditional on awareness for optimal marketing control and empirical measures of competition. We show how quantity choices, in contrast to multinomial choices, facilitate the empirical distinction between attention and utility. In our illustrative application we analyze choices from simulated store shelves. We find that the number of facings of a brand on the shelf influence attention but not utility from the brand. We then formulate a parametric model that identifies attention based considerations sets. We find overwhelming support for this model compared to a model that ignores attention and motivates choices from utility only.
Effects of Electroacupuncture Pretreatment on Inflammatory Response and Acute Kidney Injury in Endotoxaemic Rats

This study investigated the effect of electroacupuncture pretreatment on the lipopolysaccharide (LPS)-induced inflammatory response and on acute kidney injury in adult male pathogen-free Wistar rats. Rats received electroacupuncture at the Zusanli (ST36) and Neiguan (PC6) acupoints, or electrical stimulation at sham points, for 30 min before stimulation with either 5 mg/kg LPS intravenously or normal saline. Plasma cytokines, plasma nitrite, renal inducible nitric oxide synthase (iNOS) and nuclear factor κB (NF-κB) activity were assessed 240 min after LPS or normal saline injection. Blood urea nitrogen (BUN), creatinine (Cr) and histopathological score for renal tubular damage were also measured. Electroacupuncture pretreatment significantly decreased LPS-induced plasma tumour necrosis factor-α and interleukin (IL)-1β, increased plasma IL-10, and decreased plasma nitrite, renal iNOS and NF-κB activity. It also significantly decreased LPS-induced BUN, Cr and the renal histopathological score. These findings suggest that electroacupuncture pretreatment at the ST36 and PC6 acupoints attenuated the LPS-induced inflammatory response and mitigated acute kidney injury.
Organization of local axon collaterals of efferent projection neurons in rat visual cortex

We have studied the laminar origins of local long‐range connections within rat primary visual cortex (area 17), by using retrograde tracing of nerve cell bodies with fluorescent markers. Injections throughout the thickness of cortex produce distinct laminar labeling patterns which indicate that a substantial number of cells in layers 2/3, 5, and 6 have wide local axon collateral arbors, while the local arbors of layer 4 cells are much narrower. Double labeling experiments which combined area 17 injections with injections into different projection targets of area 17 (opposite area 17, area 18a, and area 18b) show that many cortico‐cortically projecting cells make widespread projections within area 17. In contrast, the overwhelming majority of subcortically projecting cells have narrow collateral arbors within area 17.
THE ROLE OF PRESYNAPTIC α‐ADRENOCEPTORS IN THE REGULATION OF BLOOD PRESSURE IN THE CONSCIOUS RABBIT

1 Changes in mean arterial pressure, heart rate and plasma noradrenaline after α‐adrenoceptor blockade with several α‐adrenoceptor antagonists have been studied in the conscious rabbit in order to investigate the possible role of presynaptic α‐adrenoceptors in cardiovascular regulation. 2 Prazosin (0.05–2 mg/kg) and phentolamine (0.5–20 mg/kg) produced dose‐dependent falls in mean arterial pressure and rises in plasma noradrenaline. These changes were related to the degree of postsynaptic α‐adrenoceptor blockade determined by the pressor response to intravenous phenylephrine. 3 Similar changes in mean arterial pressure and plasma noradrenaline were observed after administration of the direct vasodilators hydralazine (1–10 mg/kg) and nitroprusside (2.5–55 μg kg−1 min−1). 4 After baroreceptor deafferentation by sinoaortic denervation the falls in mean arterial pressure were much greater and the rise in plasma noradrenaline was markedly attenuated. 5 Yohimbine (1 mg/kg) increased mean arterial pressure and plasma noradrenaline but it was not possible to exclude the possibility that central nervous effects of yohimbine underlay the increased sympathetic activity. 6 The magnitude of the baroreflex response to changes in pressure make it unlikely that the functional significance of the presynaptic α‐adrenoceptor can be readily determined by measurement of plasma noradrenaline in intact animals.
Towards a standard protocol for antimony intralesional infiltration technique for cutaneous leishmaniasis treatment

BACKGROUND Despite its recognised toxicity, antimonial therapy continues to be the first-line drug for cutaneous leishmaniasis (CL) treatment. Intralesional administration of meglumine antimoniate (MA) represents an alternative that could reduce the systemic absorption of the drug and its side effects. OBJECTIVES This study aims to validate the standard operational procedure (SOP) for the intralesional infiltration of MA for CL therapy as the first step before the assessment of efficacy and safety related to the procedure. METHODS The SOP was created based on 21 trials retrieved from the literature, direct monitoring of the procedure and consultation with experts. This script was submitted to a formal computer-aided inspection to identify readability, clarity, omission, redundancy and unnecessary information (content validation). For criterion and construct validations, the influence of critical condition changes (compliance with the instructions and professional experience) on outcome conformity (saturation status achievement), tolerability (pain referred) and safety (bleeding) were assessed. FINDINGS The median procedure length was 12 minutes and in 72% of them, patients classified the pain as mild. The bleeding was also classified as mild in 96.6% of the procedures. Full compliance with the SOP was observed in 66% of infiltrations. Despite this, in 100% of the inspected procedures, lesion saturation was observed at the end of infiltration, which means that it tolerates some degree of modification in its execution (robustness) without prejudice to the result. CONCLUSIONS The procedure is reproducible and can be used by professionals without previous training with high success and safety rates.
Enhanced exercise-induced rise of aldosterone and vasopressin preceding mountain sickness.

A possible contribution of exercise to the fluid retention associated with acute mountain sickness (AMS) was investigated in 17 mountaineers who underwent an exercise test for 30 min on a bicycle ergometer with a constant work load of 148 +/- 9 (SE) W at low altitude (LA) and with 103 +/- 6 W 4-7 h after arrival at 4,559 m or high altitude (HA). Mean heart rates during exercise at both altitudes and during active ascent to HA were similar. Exercise-induced changes at LA did not differ significantly between the eight subjects who stayed well and the nine subjects who developed AMS during a 3-day sojourn at 4,559 m. At HA, O2 saturation before (71 +/- 2 vs. 83 +/- 2%, P less than 0.01) and during exercise (67 +/- 2 vs. 72 +/- 1%, P less than 0.025) was lower and exercise-induced increase of plasma aldosterone (617 +/- 116 vs. 233 +/- 42 pmol/l, P less than 0.025) and plasma antidiuretic hormone (23.8 +/- 14.4 vs. 3.4 +/- 1.8 pmol/l, P less than 0.05) was greater in the AMS group, whereas exercise-induced rise of plasma atrial natriuretic factor and changes of hematocrit, potassium, and osmolality in plasma were similar in both groups. (ABSTRACT TRUNCATED AT 250 WORDS)
CCR4, a 3′–5′ poly(A) RNA and ssDNA exonuclease, is the catalytic component of the cytoplasmic deadenylase

The CCR4–NOT complex from Saccharomyces cerevis iae is a general transcriptional regulatory complex. The proteins of this complex are involved in several aspects of mRNA metabolism, including transcription initiation and elongation and mRNA degradation. The evolutionarily conserved CCR4 protein, which is part of the cytoplasmic deadenylase, contains a C‐terminal domain that displays homology to an Mg2+‐dependent DNase/phosphatase family of proteins. We have analyzed the putative enzymatic properties of CCR4 and have found that it contains both RNA and single‐stranded DNA 3′–5′ exonuclease activities. CCR4 displays a preference for RNA and for 3′ poly(A) substrates, implicating it as the catalytic component of the cytoplasmic deadenylase. Mutations in the key, conserved catalytic residues in the CCR4 exonuclease domain abolished both its in vitro activities and its in vivo functions. Importantly, CCR4 was active as a monomer and remained active in the absence of CAF1, which links CCR4 to the remainder of the CCR4–NOT complex components. These results establish that CCR4 and most probably other members of a widely distributed CCR4‐like family of proteins constitute a novel class of RNA–DNA exonucleases. The various regulatory effects of the CCR4–NOT complex on gene expression may be executed in part through these CCR4 exonuclease activities.