Miracle-dz/UniFAR-FTUs huggingface dataset:
Influence of CYP2B6 and ABCB1 SNPs on nevirapine plasma concentrations in Burundese HIV-positive patients using dried sample spot devices.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Nevirapine pharmacokinetics are affected by several factors including CYP2B6 single nucleotide polymorphisms (SNPs). These genetic profiles are more common in African patients and they affect the drug clearance being associated with higher trough concentrations. Pharmacokinetic/pharmacogenetic (PK/PG) studies are difficult to perform in remote areas where refrigeration is not available, although dried plasma and dried blood methods have been validated. WHAT THIS STUDY ADDS • Dried plasma spots are useful tools for studying nevirapine PK with a good association to plasma concentrations and they can be used in rural areas since a cold chain is not necessary. Dried blood spots can be used to store and analyze patients' DNA for PG polymorphisms. Nevirapine trough concentrations in Burundese patients, not studied so far, are above the target concentration (3000 ng ml(-1) ) in 84% of patients. CYP2B6 (both at position 516 and 983) but not ABCB1 (3435 and 1236) SNPs as well as age correlate with higher nevirapine exposure. AIMS The pharmacokinetics (PK) and pharmacogenetics (PG) of nevirapine have been studied in rich and limited-resource countries. CYP2B6 single nucleotide polymorphisms (SNPs) have been associated with decreased drug clearance. We evaluated the PG determinants of nevirapine trough concentrations in a rural cohort in Burundi using easy to store and transport dried sample spot devices. METHODS A cross-sectional analysis in HIV-positive nevirapine-treated patients in Kiremba, north of Burundi, was performed in 2009. After blood withdrawal whole blood was stored on dried blood spots and plasma (after centrifugation) was placed on dried plasma spot devices and stored at room temperature. Nevirapine plasma and dried sample spot concentrations were compared to test the clinical usefulness of this method. SNPs in CYP2B6 and ABCB1 (using a real time PCR technique) were analyzed and associated with nevirapine plasma trough concentrations. RESULTS Nevirapine concentrations measured on dried plasma spot devices were highly related to plasma concentrations in 60 patients, although a negative bias was observed (-18%). Nevirapine trough concentrations were above the target concentration (3000 ng ml(-1) ) in 84% of patients and they were associated with CYP2B6 SNPs (both at position 516 and 983). No effect of ABCB1 SNPs was noted. CONCLUSIONS Dried plasma spot devices are accurate tools for measuring nevirapine concentrations in rural settings where refrigeration is not available, despite a moderate underestimation bias. They allowed the evaluation of nevirapine concentrations in a cohort of HIV-infected people in rural Burundi, confirming very good exposure and correlation with PG polymorphisms in the CYP2B6 encoding gene.
Prevalence of developmental odontogenic cysts in children and adolescents with emphasis on dentigerous cyst and odontogenic keratocyst (keratocystic odontogenic tumor)

Abstract Objective. To investigate the incidence and prevalence of developmental odontogenic cysts in children and adolescents and compare the features of the two most common types, dentigerous cyst and keratocystic odontogenic tumor (KCOT). Study design. A retrospective review in a series of 369 patients with all histological diagnoses of developmental odontogenic cysts in children (≤12 years) and adolescents (13–18 years) was conducted. Results. Among these, 361 (97.8%) patients were diagnosed as dentigerous cyst (n = 281) and KCOT (n = 80), with the male-to-female ratios of dentigerous cyst and KCOT both being 2:1. The average age of the patients with KCOT was older than that of those with dentigerous cyst (14.7 years vs 11.8 years, p < 0.001). Dentigerous cyst (59.1%) was more common in children, but KCOT (78.8%) was more common in adolescents (p < 0.001). Dentigerous cyst (57.6%) predominantly located on the maxilla, but KCOT (60.3%) predominantly located on the mandible (p = 0.010). Conclusions. Adolescent patients with lesions located on the mandible would favor KCOT over dentigerous cyst. This study aids in better knowledge of the prevalence of developmental odontogenic cysts in a large pediatric population, and shows that a well-supported early diagnosis is indispensable for a more adequate treatment.
Altered expression of connexin subtypes in mesial temporal lobe epilepsy in humans.

OBJECT The causes of epileptic events remain unclear. Much in vitro and in vivo experimental evidence suggests that gap junctions formed by connexins (Cxs) between neurons and/or astrocytes contribute to the generation and maintenance of seizures; however, few experiments have been conducted in humans, and those completed have shown controversial data. The authors designed a study to compare the level of expression of Cxs in hippocampi from epileptic and nonepileptic patients to assess whether an alteration of gap junction expression in epileptic tissue plays a role in seizure origin and propagation. METHODS The expression of Cxs32, -36, and -43 was studied in 47 consecutive samples of hippocampi obtained from epileptic patients who had undergone an amygdalohippocampectomy for the treatment of intractable seizure. These expression levels were compared with those in hippocampi obtained in nonepileptic patients during postmortem dissection. Immunostaining was performed to create one slide for each of the three Cxs. Each slide demonstrated multiple cells from each of six regions (CA1, CA2, CA3, CA4, dentate gyrus, and subiculum). Two independent reviewers rated each Cx-region combination according to an immunoreactive score. Across all three measures-that is, staining intensity, percentage of positively stained cells, and immunoreactive score-Cx32 appeared to be expressed at a significantly lower level in the epileptic patients compared with controls (p < 0.001 for each measure), whereas Cx43 appeared to be expressed more among the epileptic patients (p < 0.001 for each measure). There was no evidence of any differential expression of Cx36. There was, however, regional variation within each Cx subtype. For Cx36, the staining intensity was higher in the CA2 region in the epilepsy group. CONCLUSIONS The increase in Cx43, decrease in Cx32, and preservation of Cx36 expression in hippocampi from epileptic persons could play a role in the development of seizures in patients with temporal sclerosis. Additional studies must be completed to understand this mechanism better.
Optimizing cardiac energy substrate metabolism: a novel therapeutic intervention for ischemic heart disease

Ischemic heart diseases, encompassing and ranging from angina pectoris to acute myocardial infarction, have a major impact on both cardiac energy metabolism and cardiac function. In the normal heart, energy metabolism and function are exquisitely matched. However, during and after ischemia there are both a decrease in energy production and disturbances in the balance between use of fatty acid and of glucose by the heart. The dominance of fatty acid oxidation as a source for the generation of ATP at the expense of glucose oxidation during and after ischemia has a negative impact on both cardiac efficiency and cardiac contractile function. Thus optimizing energy substrate metabolism, such that the efficiency of both generating and utilizing ATP is maximized has emerged as a novel therapeutic intervention in various manifestations of ischemic heart disease. For example, the antianginal benefit of trimetazidine can be attributed to the partial inhibition of fatty acid oxidation and the reciprocal increase in glucose oxidation. This optimization of the balance between fatty acid and glucose metabolism results in an improvement in the efficiency of both the generation and utilization of ATP. Other pharmacological agents also exploit this plasticity and interdependence between the pathways of fatty acid and glucose oxidation. This is achieved either by altering flux through these metabolic pathways, or by altering the availability of circulating energy substrates. Thus the multitude of targets available to optimize myocardial energy metabolism may significantly increase the armamentarium of therapeutic interventions for preserving cardiac contractile function and limit the untoward effects of ischemic heart disease. Heart Metab. 2008;38:5–14.
Histologic differentiation of hepatocellular carcinoma from adenocarcinoma by a simple panel: evaluation of the pitfalls.

The histological differentiation of Hepatocellular carcinoma (HCC) from cholangiocarcinoma (CC) and metastatic adenocarcinoma (MA) of the liver is difficult in some cases and immunohistochemistry (IHC) is necessary for the diagnosis. HepPar-1 is a recently available antibody which seems to be very specific and sensitive for the diagnosis of HCC. MOC31 is an antibody directed against a cell surface glycoprotein and has been shown to be helpful in distinguishing between HCC and CC or MA as a negative marker in HCC. In this study we tried to apply these two markers for the diagnosis of HCC cases as a simple, useful and reliable panel. We selected 101 liver tumors which had proven diagnosis by several antibodies and cilinicopathologic correlation. The tumors with confirmed histologic diagnosis including 35 HCC, 58 MA, 7 CC and 1 combined HCC-CC. HepPar-1 was positive in 30 of 35 cases of HCC; none of the other tumors were reactive for HepPar1 except for a case of metastatic gall bladder adenocarcinoma which showed areas of hepatoid differentiation in the H&E slides. MOC31 was positive in 5 of the HCC cases and stained 60 of 65 cases of MA. There were 4 cases of HCC with clear cell morphology, in most of which, IHC pattern was not diagnostic and further investigation was needed. As a conclusion the combination of positive Hepar1 and negative MOC31 is highly suggestive for HCC except for the clear cell variant. These two reliable markers are recommended for the initial step of differential diagnosis between HCC and MA and for the confirmation of the histologic diagnosis.
Alcohol, low-methionine--low-folate diets, and risk of colon cancer in men.

BACKGROUND Methylation of DNA, which may have a role in the regulation of gene expression, depends on dietary folate and methionine. Because aberrant DNA methylation may contribute to the initiation or progression of colon cancer, we hypothesized that deficient intakes of folate or methionine and high consumption of alcohol, an antagonist of methyl-group metabolism, increase risk of colon neoplasia. Previously, a high-alcohol and low-methionine--low-folate (methyl-deficient) diet was shown to be related to a higher risk of colon adenomas, precursors of cancer. PURPOSE Our goal was to determine if ingestion of a high-alcohol, methyl-deficient diet is related directly to risk of colon cancer. METHODS We assessed dietary intake for a 1-year period for a cohort of 47,931 U.S. male health professionals, 40-75 years old and free of diagnosed cancer in 1986. We assessed diet by using a validated, semiquantitative food-frequency questionnaire. During 6 years of follow-up, we documented 205 new cases of colon cancer in this cohort. RESULTS Current alcohol intake was directly related to risk of colon cancer (multivariate relative risk [RR] = 2.07; 95% confidence interval [CI] = 1.29-3.32, for > 2 drinks versus < or = 0.25 drink daily; P trend = .005), and past drinkers were also at higher risk (RR = 1.95; 95% CI = 1.22-3.10). Individually, folate and methionine intakes were weakly inversely associated with risk of colon cancer. An adverse effect of a high-alcohol, low-methyl diet was not observed among regular users of aspirin, who have previously been shown to be at lower risk for colon cancer. Combinations of high alcohol and low methionine and folate intakes yielded striking associations for total colon cancer (RR = 3.30 [95% CI = 1.58-6.88] comparing high-methyl diets with low-methyl diets among nonusers of aspirin) and for cancers of the distal colon (RR = 7.44; 95% CI = 1.72-32.1). Among men with high intakes of folate or methionine, alcohol levels of > 2 drinks daily were not associated with risk of colon cancer. The increased risk of colon cancer associated with alcohol and methyl-deficient diets was not confounded by smoking; intakes of fat, red meat, and fiber; level of physical activity; multivitamin or aspirin use; and body mass index. CONCLUSIONS These findings support the hypothesis that substantial consumption of alcohol, when combined with inadequate intakes of folate and methionine, may increase risk of colon cancer and confirm similar findings in adenomas. IMPLICATIONS These data provide further support of recommendations to avoid excess alcohol consumption and to increase dietary folate to lower the risk of colon cancer.
Event-driven charge redistribution analog-to-digital converter with simultaneous sampling and conversion

The paper presents a design of the event-driven charge redistribution analog to-digital converter with accelerated conversion speed obtained by partially simultaneous realization of sampling and conversion. The maximum conversion time of the proposed converter is reduced by 25% compared to its basic version with sequential sampling and conversion. The converter with accelerated speed is predisposed especially for analog-to-digital conversion operating continuously in real-time.
Growth Control and Morphogenesis in the Development and Pathology of Arteries

&NA; We briefly review and compare the current knowledge of growth mechanisms for the mitogenic response of endothelial cells and smooth‐muscle cells to injury. For the endothelium, this focuses on the evidence that growth control involves two components: an endogenous inhibition mechanism, which can be overcome either by fibroblast growth factor (FGF) or by other agents that disrupt cell‐cell junctions, and a separate mechanism, which requires FGF to allow cells to respond to a mitogenic effect. The smoothmuscle cell story is more complex; however, there is evidence here as well of an endogenous inhibitory mechanism, which may be overcome by a wide variety of agents. Platelet‐derived growth factor, long seen as a major mitogen, does not itself now appear to be a major mitogen in vivo. In contrast, FGF also seems to play a major role in initiating smooth‐muscle replication. Other molecules, including angiotensin II, bradykinin, thrombin, and catecholamines, are beginning to appear to play major roles in control of smooth‐muscle replication in vivo as well.
A comparison of pregnancy care delivered by family physicians versus obstetricians in Lebanon.

BACKGROUND The provision of prenatal and intrapartum care is an important issue in family practice. Physician specialty as a risk factor for adverse perinatal outcome is of interest to both educators and patients. The purpose of this study is to compare perinatal care provided by family practice and obstetrics residents for low-risk women in Lebanon. METHODS A study of 400 matched pairs of low-risk pregnant women was conducted at the American University of Beirut Medical Center to compare outcomes of perinatal care provided by family physicians and obstetricians. The medical records of women admitted for delivery at the American University of Beirut Medical Center between October 1, 1986, and October 1, 1990, were reviewed. RESULTS Obstetricians used oxytocin induction significantly more frequently than family physicians (43% versus 7%, P < .01). A similar significant difference was also noted for artificial rupture of membranes. There were similar episiotomy rates (63%), with a greater number of lacerations reported among women cared for by obstetricians (28% versus 15%, P < .05). The use of forceps was similar in both groups. Vacuum extraction was not used by family physicians. Neonatal outcomes were comparable, although meconium-stained amniotic fluid was more common in the obstetrics group (21% versus 6%, P < .05). During the postpartum period, significantly more women breast-fed (62% versus 45%, P < .01) and used oral contraceptives in the family practice group. CONCLUSIONS When caring for low-risk pregnant women, family physicians appear to provide comparable care with less intervention than obstetricians.
Similarity in volatile communities leads to increased herbivory and greater tropical forest diversity.

A longstanding paradigm in ecology is that there are positive associations between herbivore diversity, specialization, and plant species diversity, with a focus on taxonomic diversity. However, phytochemical diversity is also an informative metric, as insect herbivores interact with host plants not as taxonomic entities, but as sources of nutrients, primary metabolites, and mixtures of attractant and repellant chemicals. The present research examines herbivore responses to phytochemical diversity measured as volatile similarity in the tropical genus Piper. We quantified associations between naturally occurring volatile variation and herbivory by specialist and generalist insects. Intraspecific similarity of volatile compounds across individuals was associated with greater overall herbivory. A structural equation model supported the hypothesis that plot level volatile similarity caused greater herbivory by generalists, but not specialists, which led to increased understory plant richness. These results demonstrate that using volatiles as a functional diversity metric is informative for understanding tropical forest diversity and indicate that generalist herbivores contribute to the maintenance of diversity.
Double blind randomised placebo controlled trial of adjunctive prednisolone in the treatment of effusive tuberculous pericarditis in HIV seropositive patients

OBJECTIVE To determine the effect of adjunctive prednisolone on morbidity, pericardial fluid resolution, and mortality in HIV seropositive patients with effusive tuberculous pericarditis. DESIGN Double blind randomised placebo controlled trial. SETTING Two medical school affiliated referral hospitals in Harare, Zimbabwe. PATIENTS 58 HIV seropositive patients aged 18–55 years with tuberculous pericarditis. INTERVENTIONS All patients received standard short course antituberculous chemotherapy and were randomly assigned to receive prednisolone or placebo for six weeks. MAIN OUTCOME MEASURES Clinical improvement, echocardiographic and radiologic pericardial fluid resolution, and death. RESULTS 29 patients were assigned to prednisolone and 29 to placebo. After 18 months of follow up there were five deaths in the prednisolone treated group and 10 deaths in the placebo group. Mortality was significantly lower in the prednisolone group (log rank χ2 = 8.19, df = 1, p = 0.004). Resolution of raised jugular venous pressure (p = 0.017), hepatomegaly (p = 0.007), and ascites (p = 0.015), and improvement in physical activity (p = 0.02), were significantly more rapid in the prednisolone treated patients. However, there was no difference in the rate of radiologic and echocardiographic resolution of pericardial effusion. CONCLUSIONS Adjunctive prednisolone for effusive tuberculous pericarditis produced a pronounced reduction in mortality. It is suggested prednisolone should be added to standard short course chemotherapy to treat HIV related effusive tuberculous pericarditis.
Generation of macrophage migration inhibitory activity by plasminogen activators.

Medium from cultures of simian virus 40-transformed mouse 3T3 cells (SV3T3) inhibits the migration in vitro of peritoneal exudate cells (macrophages) from guinea pigs while medium from untransformed 3T3 cultures does not [Hammond, M. E. , Robbin, R. D. , Dvorak, A. M. , Selvaggio, S. S. , Black, P. H. & Dvorak, H. F. (1974) Science 185, 955-957]. The present paper describes the generation of migration inhibitory factor (MIF)-like activity for peritoneal exudate cells from guinea pigs after incubation of a serum-free harvest fluid from SV3T3 cells with guinea pig serum. Inhibited macrophages lose a densely staining material from the cell surface coat compared with uninhibited guinea pig peritoneal exudate cells. The factor in SV3T3 harvest fluids which generates the migration inhibitory activity appears to be plasminogen activator, i.e., a serine protease, because (i) plasminogen activator activity and the factor which generates MIF-like activity copurify, and co-chromatograph on Sephadex G-200 columns, and (ii) plasminogen activator activity and capacity to generate MIF-like activity are simultaneously lost upon treatment with [3H]diisopropylfluorophosphate. In addition, a purified preparation of a known plasminogen activator, human urokinase, can also generate MIF-like activity upon reaction with guinea pig serum. Because transformation of 3T3 cells by SV40 increases their plasminogen activator secretion, enhanced secretion of plasminogen activator by SV3T3 cells may explain why formation of MIF-like activity is observed in SV3T3 but not 3T3 cultures. These results reveal a biochemical pathway whereby a product secreted by virus-transformed cells affects one function of a cell central to the host's immunological defense system.
Fmr1 knockout mice are impaired in a leverpress escape/avoidance task

Fragile X syndrome (FXS) is the most common form of inherited mental retardation (MR). FXS is typically caused by a mutation of the Fmr1 gene (Verkerk et al. 1991, Cell 65, 905–914). To better understand the role of Fmr1 and its gene product fragile X mental‐retardation protein (FMRP) in central nervous system function, researchers have turned to the use of animal model systems to generate an Fmr1 knockout (KO) mouse that is deficient in FMRP (Bakker et al. 1994, Cell 78, 23–33). Unfortunately, a number of studies have found no consistent, robust learning and memory impairment in the Fmr1 KO mice. We conducted a study to assess the performance of Fmr1 KO and wildtype (WT) animals in a leverpress escape/avoidance paradigm. Fmr1 KO and WT littermates were studied in four daily 1‐h sessions. The Fmr1 KO mice performed fewer avoidance and total responses than WT mice. The KO animals were not simply deficient in avoidance, but a within‐factor anova revealed that they did not acquire the leverpress response to any appreciable degree. Observation during the sessions indicated that the Fmr1 KO animals clearly responded to the shock, eliminating an obvious sensory explanation for the deficit. The fact that other studies have found that the KO mice displayed increased exploratory and locomotor activity compared with WT controls argues against a motoric deficit. Future studies will attempt to delineate the nature of the behavioral deficit as well as attempt to rescue the response with glutamatergic or dopaminergic agents.
Design of collaborative engineering data system (CEDS): an application case of process integration

This paper presents a collaborative engineering data system (CEDS) design for supporting semiconductor technology lifecycle management in three aspects: change impact analysis, knowledge perspective modeling, and service configuration. The design innovation lies in the generic engineering data object (GEDO), which is designed for dynamic object modeling to wrap, structuralize and integrate all disparate information along an engineering chain. A proposed CEDS lifecycle control mechanism then guarantees the operation efficiency and quality during the CEDS implementation and run-time phases. An application of CEDS to collaborative construction of process integration knowledge serves as a conveyer of ideas