Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacy patronage: identifying key factors in the decision making process using the determinant attribute approach.

OBJECTIVE To use the determinant attribute approach, a research method commonly used in marketing to identify the wants of various consumer groups, to evaluate consumer pharmacy choice when having a prescription order filled in different pharmacy settings. DESIGN Cross sectional. SETTING Community independent, grocery store, community chain, and discount store pharmacies in Georgia between April 2005 and April 2006. PARTICIPANTS Convenience sample of adult pharmacy consumers (n = 175). INTERVENTION Survey measuring consumer preferences on 26 attributes encompassing general pharmacy site features (16 items), pharmacist characteristics (5 items), and pharmacy staff characteristics (5 items). MAIN OUTCOME MEASURE 26 potential determinant attributes for pharmacy selection. RESULTS 175 consumers were surveyed at community independent (n = 81), grocery store (n = 44), community chain (n = 27), or discount store (n = 23) pharmacy settings. The attributes of pharmacists and staff at all four pharmacy settings were shown to affect pharmacy patronage motives, although consumers frequenting non-community independent pharmacies were also motivated by secondary convenience factors, e.g., hours of operation, and prescription coverage. CONCLUSION Most consumers do not perceive pharmacies as merely prescription-distribution centers that vary only by convenience. Prescriptions are not just another economic good. Pharmacy personnel influence pharmacy selection; therefore, optimal staff selection and training is likely the greatest asset and most important investment for ensuring pharmacy success.
The efficacy and safety of reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: A systematic review and meta-analysis

ABSTRACT Context: Reslizumab is a humanised anti-interleukin 5 monoclonal antibody that disrupts eosinophil maturation and promotes programmed cell death. Objective: We carried out a systematic review and meta-analysis to assess the efficacy and safety of the drug in patients with inadequately controlled, eosinophilic asthma. Data sources: The search included the following databases: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. Study selection: A literature review was performed to identify all published randomized double-blind, placebo-controlled trials of reslizumab for the treatment of inadequately controlled, eosinophilic asthma. Data extraction: Two reviewers independently extracted and verified pre-defined data fields. Results: Four publications including 5 RCTs that compared reslizumab with placebo. For the comparison of reslizumab with placebo, asthma exacerbation (odds ratio (OR) = 0.46, 95% confidence interval (CI) = 0.35 to 0.59, p <0.00001); a forced expiratory volume in 1 s (FEV1) (the standardized mean difference (SMD) = 0.16, 95%CI = 0.10 to 0.23, p <0.00001); Asthma Control Questionnaire (ACQ) score (the SMD = −0.26, 95%CI= −0.36 to −0.16, p <0.00001); blood eosinophil counts (the SMD = −475.62, 95%CI = −528.41 to −422.83, p <0.00001). Safety assessments included the proportion of individuals who withdrawn due to adverse event (AE) (OR = 0.60 95%CI = 0.38 to 1.17, p = 0.16) indicated that reslizumab was well tolerated. Limitations: The article didn't research the safety, efficacy of reslizumab with longer term. Conclusions: This meta-analysis indicates that reslizumab to be an effective and safe treatment for inadequately controlled, eosinophilic asthma.
Hereditary C2 Deficiency in Sweden: Frequent Occurrence of Invasive Infection, Atherosclerosis, and Rheumatic Disease

Abstract: Although frequently asymptomatic, homozygous C2 deficiency (C2D) is known to be associated with severe infections and rheumatic disease. We describe the clinical findings in 40 persons with C2D from 33 families identified in Sweden over 25 years. Medical records covering 96% of the accumulated person-years were reviewed, giving a mean observation time of 39 years (range, 1-77 yr). Severe infection was the predominant clinical manifestation in the cohort: 23 patients had a past history of invasive infections, mainly septicemia or meningitis caused by Streptococcus pneumoniae, and 12 patients had repeated infections of this kind. Nineteen patients had at least 1 episode of pneumonia, and recurrent pneumonia was documented in 10 patients. Repeated infections occurred mainly during infancy and childhood. Systemic lupus erythematosus was found in 10 patients. Another 7 patients had undifferentiated connective tissue disease (n = 4) or vasculitis (n = 3). We found no correlation between susceptibility to invasive infection and rheumatologic disease. Cardiovascular disease occurred at a high rate, with a total of 10 acute myocardial infarctions and 5 cerebrovascular episodes in 6 patients. Causes of death among the C2D patients were infection (n = 5), acute myocardial infarction (n = 3), and cancer (n = 1). We suggest that severe infection may be the principal clinical manifestation of C2D. We also provide novel evidence for a possible role of C2D in the development of atherosclerosis consistent with findings in mannan-binding deficiency and experimental C3 deficiency. In addition, we confirm the well-known association between C2D and systemic lupus erythematosus. Abbreviations: ACR = American College of Rheumatology, AMI = acute myocardial infarction, ANA = antinuclear antibodies, C2D = homozygous C2 deficiency, MASP = MBL-associated serine protease, MBL = mannan-binding lectin, MHC = major histocompatibility complex, PCR = polymerase chain reaction, SLE = systemic lupus erythematosus.
Awareness of heart disease among female college students.

OBJECTIVE Awareness of heart disease as the leading cause of death in women has increased over the past 10 years, but little is known about the awareness level of college students. This study evaluated the level of awareness and knowledge of heart disease in women among college students. METHODS AND RESULTS Using a cross-sectional design, a sample of 320 women from a private university was queried. A 13-item survey assessed demographic information and awareness of cardiovascular disease (CVD). The mean age was 23 years; the majority were single and of Hispanic ethnicity. Almost one third believed breast cancer was the greatest problem facing women. One half recognized CVD as the leading cause of death among women. Students aged 18-24 years were significantly less likely to identify heart disease/heart attack as the leading cause of death in women compared with students aged 25-34 years. Significant ethnic differences in perceptions of risk were found. Family history and obesity were seen as major contributors to CVD; less than a fourth ever discussed CVD with their healthcare provider. Information was gained primarily from television, magazines, and the Internet. Exercise and maintenance of healthy blood pressure were viewed as priorities in prevention of CVD. CONCLUSIONS Results add to the body of research on CVD risk and the need for intervention to increase awareness and knowledge of heart disease risk among younger and ethnically diverse young women and raises questions about the role of colleges and universities in promotion of student health. Colleges and universities may provide the last opportunity to reach youth as a group to affect lifestyle changes.
pp60c-src tyrosine kinase, myristylation, and modulatory domains are required for enhanced mitogenic responsiveness to epidermal growth factor seen in cells overexpressing c-src

In previous studies examining the potential role of pp60c-src in cellular proliferation, we demonstrated that C3H10T1/2 murine embryo fibroblasts overexpressing transfected chicken genomic c-src displayed an epidermal growth factor (EGF)-induced mitogenic response which was 200 to 500% of the response exhibited by parental control cells (Luttrell et al., Mol. Cell. Biol. 8:497-501, 1988). In order to examine specific structural and functional requirements for pp60c-src in this event, 10T1/2 cells were transfected with chicken c-src genes encoding pp60c-src deficient in tyrosine kinase activity (pm430), myristylation, (pm2A), or a domain hypothesized to modulate the interaction with substrates or regulatory components (dl155). Neomycin-resistant clonal cell lines overexpressing each of the mutated c-src genes were assayed for EGF mitogenic responsiveness by measuring [3H]thymidine incorporation into acid-precipitable material or into labeled nuclei. The results were compared with those obtained with lines overexpressing the cDNA form of wild-type (wt) c-src or control cells transfected with the neomycin resistance gene only. As previously described for cells overexpressing wt genomic c-src (Luttrell et al., 1988), clones overexpressing wt cDNA c-src also exhibited enhanced EGF mitogenic responses ranging from approximately 300 to 400% of the control cell response. In contrast, clones overexpressing unmyristylated, modulation-defective, or kinase-deficient c-src not only failed to support an augmented response to EGF but also exhibited EGF responses lower than that of the control cells. Furthermore, there were no significant differences in the mitogenic responses to 10% fetal calf serum among any of the cells tested. These results indicate that pp60(c-scr) can potentiate mitogenic signaling generated by EGF but not all growth factors. This potentiation requires the utilization of pp60(c-scr) myristylation, and modulatory and tyrosine kinase domains and can me mediated by cDNA-encoded as well as by genome-encoded wt pp60(c-scr).
Overexpression of Sir2 in the adult fat body is sufficient to extend lifespan of male and female Drosophila

Sir2 is the most intensively discussed longevity gene in current aging research. Although, the gene encoding for a NAD+-dependent histone deacetylase initially was found to extend lifespan of various organisms ranging from yeast to mammals, serious doubts regarding its role in longevity have been expressed recently. In this study, we tested whether tissue-specific overexpression of Sir2 in the adult fat body can extend lifespan when compared to genetically identical controls. We also wanted to elucidate the mechanisms by which fat body Sir2 promotes longevity by studying the phenotypic and transcriptional changes in the fat body. We found that moderate (3-fold) Sir2 overexpression in the fat body during adulthood only can promote longevity in both sexes by roughly 13 %. In addition, we obtained transcriptional profiles elicited by this overexpression and propose a role for Sir2 in lipid droplet biology especially under conditions of starvation. Furthermore, our data do not support the idea of Sir2 mediating the response to dietary restriction (DR) because transcriptional profiles of fat bodies after DR or Sir2 overexpression do not match. This study provides additional independent evidence for the concept of Sir2 as a longevity gene and as a promising pharmacological target to cure age-related diseases.
Climatic influences on basal metabolic rates among circumpolar populations

This article examines evidence for elevations in basal metabolic rate (BMR) among indigenous Northern (circumpolar) populations and considers potential mechanisms and the adaptive basis for such elevations. Data on BMR among indigenous (n = 109 males; 122 females) and nonindigenous (n = 15 males; 22 females) circumpolar groups of North America and Siberia are compiled and compared to predicted BMRs based on three different references: body surface area (Consolazio et al., 1963), body mass (Schofield, 1985), and fat‐free mass (Poehlman and Toth, 1995). Regardless of which reference is used, indigenous circumpolar groups show systematic and statistically significant elevations in BMR ranging from +7% to +19% above predicted values for indigenous men and from +3 to +17% for indigenous women. Nonindigenous males also show elevations in BMR, although not to the same extent as in indigenous men (deviations = +3 to +14%), whereas nonindigenous females show no clear evidence of elevated BMRs (deviations = −7 to +5%). This pattern of variation between indigenous and nonindigenous groups suggests that both functional and genetic factors play a role in metabolic adaptation to northern climes. Recent studies on the ecology and genetics of thyroid function offer insights into the mechanisms through which indigenous circumpolar populations may regulate metabolic rates. Studies of seasonal variation in thyroid hormone levels suggest that indigenous circumpolar populations may have a greater capacity to elevate BMR during severe cold than nonindigenous groups. Recent twin studies indicate a significant genetic component of thyroid responses to environmental stressors. Further research exploring the genetics of seasonal variation in thyroid function and BMR among circumpolar groups would advance understanding of the role that selection may have played in shaping metabolic variation. Am. J. Hum. Biol. 14:609–620, 2002. © 2002 Wiley‐Liss, Inc.
Kindling‐induced overexpression of Homer 1A and its functional implications for epileptogenesis

Despite an extensive research on the molecular basis of epilepsy, the essential players in the epileptogenic process leading to epilepsy are not known. Gene expression analysis is one strategy to enhance our understanding of the genes contributing to the functional neuronal changes underlying epileptogenesis. In the present study, we used the novel MPSS (massively parallel signature sequencing) method for analysis of gene expression in the rat kindling model of temporal lobe epilepsy. Kindling by repeated electrical stimulation of the amygdala resulted in the differential expression of 264 genes in the hippocampus compared to sham controls. The most strongly induced gene was Homer 1A, an immediate early gene involved in the modulation of glutamate receptor function. The overexpression of Homer 1A in the hippocampus of kindled rats was confirmed by RT‐PCR. In order to evaluate the functional implications of Homer 1A overexpression for kindling, we used transgenic mice that permanently overexpress Homer 1A. Immunohistochemical characterization of these mice showed a marked Homer 1A overexpression in glutamatergic neurons of the hippocampus. Kindling of Homer 1A overexpressing mice resulted in a retardation of seizure generalization compared to wild‐type controls. The data demonstrate that kindling‐induced epileptogenesis leads to a striking overexpression of Homer 1A in the hippocampus, which may represent an intrinsic antiepileptogenic and anticonvulsant mechanism in the course of epileptogenesis that counteracts progression of the disease.
Chlorpyrifos, parathion, and their oxons bind to and desensitize a nicotinic acetylcholine receptor: relevance to their toxicities.

The nicotinic acetylcholine receptor (nAChR) of the electric organ of the electric ray. Torpedo sp. , the richest source of nAChR, with similar structure and pharmacology to the mammalian skeletal muscle nAChR, carries several binding sites for different ligands. Incubation of Torpedo membrane-bound nAChRs with the agonist carbamylcholine (Carb) stimulated the binding of [3H]thienyl-cyclohexylpiperidine ([3H]TCP), which binds to the receptor's noncompetitive antagonist binding site in its ionic channel, with high affinity (Kd of 196 nM). The agonist-stimulated binding of [3H]TCP (i.e., binding to activated nAChRs) was inhibited in a concentration-dependent manner by four organophosphate (OP) anticholinesterases, chlorpyrifos oxon (CPO), chlorpyrifos (CPS), parathion (PS), and paraoxon (PO) with IC50 (concentration that inhibits 50% of the effect) values of 5, 150, 200, and 300 microM, respectively. The binding of CPO was totally reversible. The OPs had no effect on equilibrium binding of [alpha-125I]bungarotoxin ([alpha-125I]BGT) to the receptor's acetylcholine (ACh)-binding site, but preincubation of the membranes with the OPs increased this site's affinity for Carb. In absence of agonist, 100 microM of the OPs increased the binding of [3H]TCP by two- to fivefold with the following order of decreasing potency: PS > CPO > CPS > PO. The data suggest that in addition to inhibition of acetylcholinesterase, these OPs bind to a site on the nAChR that is different from the sites that bind ACh or TCP and that this binding induces nAChR desensitization. The relevance of this direct action of OPs on nAChRs on their acute toxicities is discussed.
Novel Dural Closure Technique Using Polyglactin Acid Sheet Prevents Cerebrospinal Fluid Leakage after Spinal Surgery

OBJECTIVE: Extradural or subcutaneous cerebrospinal fluid (CSF) leakage is a common complication after spinal surgery and is associated with the risks of poor wound healing, meningitis, and pseudomeningocele. Numerous methods to prevent postoperative CSF leakage are available, but pressure-tight dural closure remains difficult, especially with synthetic surgical membranes. The efficacy of a novel dural closure technique was assessed by detecting extradural or subcutaneous CSF leakage on magnetic resonance imaging. METHODS: The novel dural closure technique using absorbable polyglactin acid sheet and fibrin glue and the conventional procedure using only fibrin glue were evaluated retrospectively by identifying extradural or subcutaneous CSF leakage on magnetic resonance imaging scans in the acute (2–7 d) and chronic (3–6 mo) postoperative stages after spinal intradural surgery in 53 patients. RESULTS: The incidence of extradural and subcutaneous CSF leakage was significantly lower (P < 0.05) in the acute (20%) and chronic (0%) stages using polyglactin acid sheet and fibrin glue in 15 patients compared with that in the acute (81%) and chronic (24%) stages using only fibrin glue in 38 patients. One patient in the fibrin glue-only group required repair surgery for cutaneous CSF leakage. CONCLUSION: The combination of polyglactin acid sheet and fibrin glue can achieve water-tight closure after spinal intradural surgery and can minimize the risk of intractable postoperative CSF leakage. This simple, economical technique is recommended for dural closure after spinal intradural surgery.
Recent progress towards a molecular understanding of Marfan syndrome

Marfan syndrome (MFS) is a systemic disorder of the connective tissue that is inherited as an autosomal dominant trait and which displays variable manifestations in the ocular, skeletal, and cardiovascular systems. These pleiotropic manifestations are accounted for by mutations in fibrillin‐1, the building block of extracellular microfibrils. During the past 10 years, we have witnessed significant progress in delineating the pathological events responsible for the manifestations of MFS. Much of this progress has been based on the creation and analysis of fibrillin‐1 mutant mouse lines that faithfully recapitulate the spectrum of clinical severity of MFS. These studies have established the critical contribution of fibrillin‐1 deficiency to disease progression through altered cell–matrix interactions and dysregulated TGF‐β signaling. As a result, our definition of MFS as the prototypical structural disorder of the connective tissue has changed to that of a developmental abnormality with broad and complex effects on the morphogenesis and function of multiple organ systems. Importantly, new biological targets have emerged that may yield exciting new opportunities for the development of productive treatment strategies in MFS. © 2005 Wiley‐Liss, Inc.
Glucagon physiology and pathophysiology.

THE function of pancreatic glucagon has been questioned for several decades, but it now seems probable that glucagon, like insulin, is extremely important in the moment-to-moment control of the homeostasis of glucose, of certain amino acids and perhaps of free fatty acids. Normal alpha-cell function seems essential to optimal glucoregulation, and abnormal alpha-cell function may cause, contribute to or result from a variety of metabolic disorders, the most common being diabetes mellitus. Biologic Opposition of Glucagon and Insulin Glucagon has been shown to have potent glycogenolytic1 and gluconeogenic2 , 3 activity at concentrations within the physiologic range. In addition, it may have .
Mycophenolate mofetil vs. azathioprine is associated with decreased acute rejection, late acute rejection, and risk for cardiovascular death in renal transplant recipients with pre‐transplant diabetes

Abstract: Outcomes specifically in mycophenolate mofetil (MMF)‐treated diabetic renal transplant patients have not been previously reported. This study compared acute rejection (AR), late acute rejection (LAR), patient survival [and specifically death from cardiovascular (CV), infectious and malignant causes], incidence of post‐transplant malignancies, and graft loss in MMF‐ or azathioprine (AZA)‐treated renal transplant patients with pre‐transplant diabetes. Outcomes were compared between MMF‐ (n = 14 144) and AZA‐ (n = 3001) treated diabetic patients using the Scientific Registry of Transplant Recipients data on all U.S. adult renal transplants performed between 1995 and 2002. Statistical analyses included Kaplan–Meier survival analysis, Cox multivariable regression and chi‐square tests. MMF patients had less AR compared with AZA‐treated patients (23.5% vs. 28.3%, p < 0.001) and less risk for LAR over 4 yr [hazard ratio (HR): 0.64, 95% CI 0.44, 0.92; p = 0.02]. While time to any‐cause death did not differ between the groups, MMF treatment was associated with a 20% decreased risk of CV death (HR: 0.80, 95% CI 0.67, 0.97; p = 0.020) compared with AZA treatment. MMF patients also had a lower incidence of malignancies than AZA patients (2.2% vs. 3.7%, p < 0.001). These results suggest treatment with MMF compared with treatment with AZA in diabetic transplant patients is associated with less AR, less risk of LAR, a decreased risk of CV death, and a lower incidence of malignancies.
CAESAR: A New Conformer Generation Algorithm Based on Recursive Buildup and Local Rotational Symmetry Consideration

A highly efficient conformer search algorithm based on a divide-and-conquer and recursive conformer build-up approach is presented in this paper. This approach is combined with consideration of local rotational symmetry so that conformer duplicates due to topological symmetry in the systematic search can be efficiently eliminated. This new algorithm, termed CAESAR (Conformer Algorithm based on Energy Screening and Recursive Buildup), has been implemented in Discovery Studio 1.7 as part of the Catalyst Component Collection. CAESAR has been validated by comparing the conformer models generated by the new method and Catalyst/FAST. CAESAR is consistently 5-20 times faster than Catalyst/FAST for all data sets investigated. The speedup is even more dramatic for molecules with high topological symmetry or for molecules that require a large number of conformers to be sampled. The quality of the conformer models generated by CAESAR has been validated by assessing the ability to reproduce the receptor-bound X-ray conformation of ligands extracted for the Protein Data Bank (PDB) and assessing the ability to adequately cover the pharmacophore space. It is shown that CAESAR is able to reproduce the receptor-bound conformation slightly better than the Catalyst/FAST method for a data set of 918 ligands retrieved from the PDB. In addition, it is shown that CEASAR covers the pharmacophore space as well or better than Catalyst/FAST.