Miracle-dz/UniFAR-FTUs huggingface dataset:
Appropriateness of antiepileptic drug level monitoring.

OBJECTIVES To develop explicit, reliable appropriateness criteria for antiepileptic drug level monitoring and to assess the appropriateness of monitoring in one tertiary care institution. DESIGN Appropriateness criteria derived from the literature and through expert opinion were used to evaluate a stratified random sample of antiepileptic drug level determinations obtained from chart review. SETTING Tertiary care center performing more than 10,000 antiepileptic drug level determinations per year. PATIENTS A total of 330 inpatients in whom antiepileptic drug levels were measured a total of 855 times. METHODS Drug levels were assessed at least 200 times for each of four antiepileptic drugs (phenytoin, carbamazepine, phenobarbital, and valproic acid). MAIN OUTCOME MEASURES The proportion of antiepileptic drug levels with an appropriate indication and, of those, the proportion sampled appropriately. RESULTS Overall, 27% (95% confidence interval, 24% to 30%) of levels had an appropriate indication. Interrater agreement for appropriateness was substantial (kappa = 0.61). There was no significant difference in the appropriateness rate among the four drugs (range, 25% to 29%). Of the 624 antiepileptic drug level determinations considered inappropriate (73%), only four (0.6%) were more than 20% higher than the upper limit of normal, and none of the four patients had clinical signs of drug toxicity. A median of six levels (range, one through 69) was determined per patient, and the median interval between level determinations was 24 hours. Of the 27% of level determinations with an appropriate indication, 51% were sampled correctly, resulting in an overall appropriateness rate of 14%. CONCLUSIONS Only 27% of antiepileptic drug level determinations had an appropriate indication, and half of these were not sampled correctly. Routine daily monitoring without pharmacological justification accounted for most of the inappropriate drug level determinations. Efforts to decrease inappropriate monitoring may result in substantial cost reductions without missing important clinical results.
Chemical Kinetics and Mass Action in Coexisting Phases

The kinetics of chemical reactions are determined by the law of mass action, which has been successfully applied to homogeneous, dilute mixtures. At nondilute conditions, interactions among the components can give rise to coexisting phases, which can significantly alter the kinetics of chemical reactions. Here, we derive a theory for chemical reactions in coexisting phases at phase equilibrium. We show that phase equilibrium couples the rates of chemical reactions of components with their diffusive exchanges between the phases. Strikingly, the chemical relaxation kinetics can be represented as a flow along the phase equilibrium line in the phase diagram. A key finding of our theory is that differences in reaction rates between coexisting phases stem solely from phase-dependent reaction rate coefficients. Our theory is key to interpreting how concentration levels of reactive components in condensed phases control chemical reaction rates in synthetic and biological systems.
Optical Detection of Lead(II) Ions Using DNA-Based Nanosensor

Lead (Pb) is a highly toxic metal that tends to accumulate in the body. The complexes of lead are very stable within the body and cannot be metabolized or degraded rapidly, leading to lead toxicity. Therefore, it is important to detect low levels of lead in the environment to prevent lead poisoning in humans. The detection of <formula formulatype="inline"><tex Notation="TeX">${\rm Pb}^{2+}$</tex></formula> ions at the nanomolar and micromolar level is achieved using DNA aptamers and quantum dots. <formula formulatype="inline"><tex Notation="TeX">${\rm Pb}^{2+}$</tex></formula> ions can be detected using a DNA aptamer known as thrombin binding aptamer (TBA), which folds into a G-quadruplex structure when lead is present. The conjugation of a quantum dot and a gold nanoparticle (AuNP) to the TBA allows for optical detection via fluorescence resonant energy transfer. In the aptamer probe discussed herein, the excited quantum dot fluoresces when the DNA is in a random coil configuration. Once the <formula formulatype="inline"><tex Notation="TeX">${\rm Pb}^{2+}$</tex></formula> ion-induced folding occurs, the fluorescence is reduced through energy transfer to the AuNP. The quenching efficiency observed with the liquid assay probe and the filter paper probe at 1-ţM <formula formulatype="inline"><tex Notation="TeX">${\rm Pb}^{2+}$</tex></formula> ions is 41% and 71%, respectively.
Etude phénotypique et fonctionnelle des lymphocytes intra-hépatiques dans l'hépatite chronique virale C et le carcinome hépatocellulaire

L'hepatite chronique virale C est associee a une defaillance du systeme immunitaire. Nous nous sommes interesses aux cellules NK et aux lymphocytes Treg, partenaires de la reponse immunitaire innee. Le nombre des NK, particulierement les CD56dim, est significativement diminue chez les patients infectes, dans le foie plus que dans le sang, et s'accentue avec la fibrogenese. Le nombre de CD3-CD56+brightNKG2A+ circulantes est correle a la severite de l'inflammation et de la fibrose et celui des CD3-CD56+dimNKG2A+ inversement correle a la charge virale. Les NK sont fonctionnelles, en capacite de produire de l'IFN-γ et d'engager un processus de cytolyse. L'expression de CD158 est significativement diminuee a la surface des NK hepatiques mais conservee dans les NK circulantes. L'expression de NKG2A,C,D dans les NK circulantes et hepatiques est identique a celles de patients non infectes. Les Treg intrahepatiques FoxP3+ sont quasi-exclusivement de phenotype CD4+. En analyse multivariee, le nombre de FoxP3+ est independamment associe a celui de CD8+, surtout dans les lesions necrotico-inflammatoires et une correlation forte est observee entre les transcrits CD8, FoxP3, IL-10 et TGF-β, suggerant que les Treg bloquent l'expansion et la cytotoxicite des TCD8 par contact cellulaire ou par le biais de cytokines immunosuppressives. L'equilibre entre FoxP3 et CD8 est rompu dans les grades et stades Metavir A>2 et F>3, avec un effondrement du rapport FoxP3/CD8. L'inflammation hepatique chronique s'accompagne de fibrose, aboutissant a la cirrhose, principale cause de CHC. Dans les cirrhoses virales C avec ou sans CHC, les lymphocytes CD3+, CD4+, CD8+, CD20+, CD56+, TCRγδ +, FoxP3+ sont plus nombreux dans la fibrose que dans le parenchyme. Le nombre de CD20+, CD3+, CD4+, CD8+ et l'expression d'IFN-γ et RANTES sont plus eleves dans les cirrhoses qui developpent un CHC. En analyse multivariee, CD8 est le seul facteur independament associe a la recidive tumorale et a une diminution de la survie sans recidive a 5 ans. Les CD20+, CD3+, CD4+, CD8+, CD56+, TCRγδ+, FoxP3+ sont significativement moins nombreux dans le CHC que dans la cirrhose. Mais les FoxP3+ sont significativement plus nombreux et les CD56+ moins nombreux dans le CHC que dans le nodule parenchymateux, sans modification des LT, conduisant a une augmentation du rapport FoxP3/CD8 dans la tumeur. Les CD56+ diminuent de la cirrhose au CHC. Aucune correlation n'est observee entre la densite intra-tumorale des lymphocytes etudies et la recidive carcinomateuse. Conclusion. Un infiltrat inflammatoire dense au sein de la cirrhose C, particulierement riche en CD8, favorise le developpement et/ou la recidive du CHC.
Effects of endothelin-1 on fibroblasts from type 2 diabetic patients: Possible role in wound healing and tissue repair

Endothelin-1 (ET-1) promotes the contractile ability of fibroblasts, essential for wound closure and reconstitution of the dermis. Wound healing is impaired in type 2 diabetic patients (D). We compared the effect of ET-1 on proliferative transforming growth factor (TGFβ1) expression, fibronectin and laminin release), differentiative [α-smooth muscle actin (α-SMA) expression] and inflammatory [monocyte chemo-attractant protein (MCP-1) and interleukin-6 (IL-6) expression] responses in skin fibroblasts of healthy subjects (C) and D, testing the relative role of ETA and ETB receptors in mediating these responses. ET-1 did not influence TGFβ1, fibronectin or laminin production. α-SMA was more abundant and more stimulated in D, as well as MCP-1 and IL-6 expression and release. These effects were prevented by BMS-182874, selective antagonist of ETA, more abundant than ETB in both cell strains and whose expression rose more in D than C upon stimulation with ET-1. This peculiar pattern of responses to ET-1, presumably acquired during the chronic in vivo exposure to hyperglycemia along the natural history of the disease, may partially explain the increased susceptibility of D to chronic ulcerations.
Opioids Compared With Placebo or Other Treatments for Chronic Low Back Pain: An Update of the Cochrane Review

Study Design. Systematic review and meta-analysis. Objective. To assess the efficacy of opioids in adults with chronic low back pain (CLBP). Summary of Background Data. Opioids for CLBP has increased dramatically. However, the benefits and risks remain unclear. Methods. We updated a 2007 Cochrane Review through October 2012 of randomized controlled trials from multiple databases. Use of noninjectable opioids in CLBP for at least 4 weeks was compared with placebo or other treatments; comparisons with different opioids were excluded. Outcomes included pain and function using standardized mean difference (SMD) or risk ratios with 95% confidence intervals (CIs), and absolute risk difference with 95% CI for adverse effects. Study quality was evaluated using Grading of Recommendations Assessment, Development, and Evaluation criteria. Results. Fifteen trials (5540 participants), including twelve new, met the criteria. Tramadol was better than placebo for pain (SMD, −0.55; 95% CI, −0.66 to −0.44) and function (SMD, −0.18; 95% CI, −0.29 to −0.07). Compared with placebo, transdermal buprenorphine decreased pain (SMD, −2.47; 95% CI, −2.69 to −2.25), but not function (SMD, −0.14; 95% CI, −0.53 to 0.25). Strong opioids (morphine, hydromorphone, oxycodone, oxymorphone, and tapentadol), were better than placebo for pain (SMD, −0.43; 95% CI, −0.52 to −0.33) and function (SMD, −0.26; 95% CI, −0.37 to −0.15). One trial demonstrated little difference with tramadol compared with celecoxib for pain relief. Two trials (272 participants) found no difference between opioids and antidepressants for pain or function. Reviewed trials had low to moderate quality, high drop-out rates, short duration, and limited interpretability of functional improvement. No serious adverse effects, risks (addiction or overdose), or complications (sleep apnea, opioid-induced hyperalgesia, hypogonadism) were reported. Conclusion. There is evidence of short-term efficacy (moderate for pain and small for function) of opioids to treat CLBP compared with placebo. The effectiveness and safety of long-term opioid therapy for treatment of CLBP remains unproven. Level of Evidence: 1
Studies of the “Chain Reversal Regions” of the Avian Sarcoma/Leukosis Virus (ASLV) and Ebolavirus Fusion Proteins: Analogous Residues Are Important, and a His Residue Unique to EnvA Affects the pH Dependence of ASLV Entry

ABSTRACT Most class I fusion proteins exist as trimers of dimers composed of a receptor binding and a fusion subunit. In their postfusion forms, the three fusion subunits form trimers of hairpins consisting of a central coiled coil (formed by the N-terminal helices), an intervening sequence, and a region containing the C helix (and flanking strands) that runs antiparallel to and packs in the grooves of the N-terminal coiled coil. For filoviruses and most retroviruses, the intervening sequence includes a “chain reversal region” consisting of a short stretch of hydrophobic residues, a Gly-Gly pair, a CX6CC motif, and a bulky hydrophobic residue. Maerz and coworkers (A. L. Maerz, R. J. Center, B. E. Kemp, B. Kobe, and P. Poumbourios, J. Virol. 74:6614-6621, 2000) proposed a model for this region of human T-cell leukemia virus type 1 (HTLV-1) Env in which expulsion of the final bulky hydrophobic residue is important for early conformational changes and specific residues in the chain reversal region are important for forming the final, stable trimer of hairpins. Here, we used mutagenesis and pseudovirus entry assays to test this model for the avian retrovirus avian sarcoma/leukosis virus (ASLV) and the filovirus ebolavirus Zaire. Our results are generally consistent with the model proposed for HTLV-1 Env. In addition, we show with ASLV EnvA that the bulky hydrophobic residue following the CX6CC motif is required for the step of prehairpin target membrane insertion, whereas other residues are required for the foldback step of fusion. We further found that a His residue that is unique to the chain reversal region of ASLV EnvA controls the pH at which ASLV entry occurs.
Automated Determination of Brain Parenchymal Fraction in Multiple Sclerosis

BACKGROUND AND PURPOSE: Brain atrophy is a manifestation of tissue damage in MS. Reduction in brain parenchymal fraction is an accepted marker of brain atrophy. In this study, the approach of synthetic tissue mapping was applied, in which brain parenchymal fraction was automatically calculated based on absolute quantification of the tissue relaxation rates R1 and R2 and the proton attenuation. MATERIALS AND METHODS: The BPF values of 99 patients with MS and 35 control subjects were determined by using SyMap and tested in relationship to clinical variables. A subset of 5 patients with MS and 5 control subjects were also analyzed with a manual segmentation technique as a reference. Reproducibility of SyMap was assessed in a separate group of 6 healthy subjects, each scanned 6 consecutive times. RESULTS: Patients with MS had significantly lower BPF (0.852 ± 0.0041, mean ± SE) compared with control subjects (0.890 ± 0.0040). Significant linear relationships between BPF and age, disease duration, and Expanded Disability Status Scale scores were observed (P < .001). A strong correlation existed between SyMap and the reference method (r = 0.96; P < .001) with no significant difference in mean BPF. Coefficient of variation of repeated SyMap BPF measurements was 0.45%. Scan time was <6 minutes, and postprocessing time was <2 minutes. CONCLUSIONS: SyMap is a valid and reproducible method for determining BPF in MS within a clinically acceptable scan time and postprocessing time. Results are highly congruent with those described using other methods and show high agreement with the manual reference method.
Cancer patients use of nonproven therapy: a 5-year follow-up study.

PURPOSE To investigate the prospective pattern of use of alternative medicine, here called nonproven therapy (NPT), among oncologic patients during a 5-year period, and the relationship between this use and survival, a questionnaire-based follow-up study was performed at the Department of Oncology, University of Tromsø, from 1990 to 1996. PATIENTS AND METHODS Two-hundred fifty-two patients answered the first questionnaire during the period July 1990 to July 1991. Eligible patients were mailed follow-up questionnaires after 4, 12, 24 and 60 months. A telephone interview performed after the last follow-up questionnaire showed little disagreement with the prospective collected information as regards the number of patients reported as users of NPT (kappa, 0.92). RESULTS The number of patients who reported ever using NPT in each cross-sectional part of the study varied between 17.4% and 27.3%. However, the estimated cumulative risk of being a user of NPT during the follow-up period was 45%. Seventy-four percent of NPT users in this north Norwegian study population used faith healing or healing by hand (spiritual NPT) alone or in combination with other forms of NPT. The proportion of patients who used spiritual versus nonspiritual forms of NPT was consistent throughout the follow-up period. Women were more often users than men (50% v 31%, P = .002). Patients older than 75 years of age seldomly used NPT. The 5-year observed survival rate was not influenced by the use of NPT. Adjusted for sex, age, and diagnosis, patients with a high educational level had a borderline higher 5-year survival rate than patients with less education (P = .06). CONCLUSION Our results demonstrate that cross-sectionally designed studies will underestimate the number of ever-users of NPT in a cancer patient population. The use of NPT does not influence observed survival among cancer patients seen in north Norway.
Protective effect of chrysin on carbon tetrachloride (CCl4)—induced tissue injury in male Wistar rats

Chrysin, a natural flavonoid has been reported to possess potent anti-inflammatory, anti-cancer and antioxidation properties. In the present study, we aimed to evaluate the putative protective effect of chrysin, an isoflavone, on carbon tetrachloride (CCl4)-induced toxicity in male Wistar rats. Intraperitoneal administration of CCl4 (2 ml/kg) to rats for 4 days resulted in significantly elevated (p < 0.05) serum levels of glutamic oxaloacetic transaminase (SGOT), glutamic pyruvate transaminase (SGPT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), when compared to normal rats. In addition, the tissues (liver, kidney and brain) and haemolysate samples showed considerable increase in levels (p < 0.05) of malondialdehyde (MDA) and lowered levels (p < 0.05) of reduced glutathione (GSH), vitamin C and E when compared to values in normal rats. Quantitative analysis of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (Gpx) exhibited lower activities of these antioxidant enzymes in the tissues and haemolysate of CCl4-administered rats. The protective action of chrysin on CCl4-induced rat was demonstrated with SGPT, SGOT, ALP and LDH resuming to near normal levels, while the mean levels of GSH and of vitamin C and E were elevated, the mean activities of CAT, SOD and Gpx were enhanced and the mean level of MDA was lowered in the tissue and haemolysate samples when compared to the CCl4-exposed untreated rats. The expression of the iNOS gene appeared to be up-regulated in the liver and kidney samples of CCl4-exposed untreated rats, whereas in CCl4-exposed chrysin-treated rats, the mRNA transcript levels of iNOS approximated normal levels. These results strongly suggest that chrysin is able to prevent the oxidative damage induced by CCl4 in the liver, brain, kidney and haemolysate of male Wistar rats.
Enhanced adherence of human uremic erythrocytes to vascular endothelium: role of phosphatidylserine exposure.

BACKGROUND The exposure of phosphatidylserine (PS) on the outer leaflet of erythrocyte membrane may have several pathophysiological consequences including increased erythrocyte adherence to endothelial cells, a finding that seems relevant in pathologies with reported vascular injury. METHODS Because PS externalization increases in erythrocytes from patients suffering from chronic uremia, which is frequently associated with vascular damage, the adherence of uremic erythrocytes to human umbilical vein endothelial cell (HUVEC) monolayers and the role of PS exposure on such cell-cell interaction were studied. RESULTS The number of uremic erythrocytes adhering to HUVEC was markedly greater than with normal erythrocytes and significantly correlated (r = 0.88) with the percentage of PS-exposing erythrocytes in the population. Adhesion to the monolayers was significantly decreased when uremic erythrocytes were preincubated with either annexin V or PS-containing liposomes, and was strongly greater for PS-positive than PS-negative fluorescence-activated cell sorter (FACS)-sorted uremic erythrocytes. Binding occurred preferentially in the gaps of HUVEC monolayers and was enhanced by matrix exposure. Uremic erythrocytes adhered to immobilized thrombospondin, and binding to endothelial cells was significantly reduced when monolayers were incubated with antibodies to thrombospondin. CONCLUSIONS These findings suggest that PS externalization may promote increased uremic erythrocyte adhesion to endothelium, possibly via a direct interaction with matrix thrombospondin.
13C nuclear magnetic resonance studies of Pseudomonas putida fatty acid metabolic routes involved in poly(3-hydroxyalkanoate) synthesis

The formation of poly(3-hydroxyalkanoates) (PHAs) in Pseudomonas putida KT2442 from various carbon sources was studied by 13C nuclear magnetic resonance spectroscopy, gas chromatography, and gas chromatography-mass spectroscopy. By using [1-13C]decanoate, the relation between beta-oxidation and PHA formation was confirmed. The labeling pattern in PHAs synthesized from [1-13C]acetate corresponded to the formation of PHAs via de novo fatty acid biosynthesis. Studies with specific inhibitors of the fatty acid metabolic pathways demonstrated that beta-oxidation and de novo fatty acid biosynthesis function independently in PHA formation. Analysis of PHAs derived from [1-13C]hexanoate showed that both fatty acid metabolic routes can function simultaneously in the synthesis of PHA. Furthermore, evidence is presented that during growth on medium-chain-length fatty acids, PHA precursors can be generated by elongation of these fatty acids with an acetyl coenzyme A molecule, presumably by a reverse action of 3-ketothiolase.
Phenotypic and Genotypic Characterization of Provisional Serotype Shigella flexneri 1c and Clonal Relationships with 1a and 1b Strains Isolated in Bangladesh

ABSTRACT The serotypes of 144 strains of Shigella flexneri serotype 1 (serotypes 1a, 1b, and 1c) isolated from patients attending the Dhaka treatment center of the International Centre for Diarrhoeal Disease Research, Bangladesh, between 1997 and 2001 were serologically confirmed by using commercially available antisera and a panel of monoclonal antibodies specific for S. flexneri group and type factor antigen (MASF). Among serotype 1 isolates, the prevalence of provisional serotype S. flexneri 1c increased from 0 to 56% from 1978 to 2001 in Bangladesh. Detailed biochemical studies revealed that none of the strains of serotype 1 produced indole, while all the strains fermented mannose, mannitol, and trehalose. Twenty percent of the serotype 1c and all the serotype 1a strains fermented maltose and 53% of the serotype 1c strains and 60% of the serotype 1a strains fermented arabinose, whereas all serotype 1b strains were negative for fermentation of these sugars. Only 18% of serotype 1b strains were resistant to nalidixic acid, and most of the serotype 1c and 1b strains were resistant to ampicillin, tetracycline, and trimethoprim-sulfamethoxazole. All the strains of serotypes 1a and 1b and about 88% of the serotype 1c strains were found to be invasive by the Sereny test, had a 140-MDa plasmid, and had Congo red absorption ability. Plasmid profile analysis showed that 26% of the strains of serotype 1 contained identical patterns. Most of the serotype 1c strains (72%) had the 1.6-MDa plasmid, which was not found in either serotype 1a or 1b strains. A self-transmissible middle-range plasmid (35 to 80 MDa) was found in some strains carrying the multiple-antibiotic-resistance gene. Pulsed-field gel electrophoresis analysis yielded three types (types A, B, and C) with numerous subtypes among the serotype 1c strains, whereas serotypes 1b and 1a yielded only one type for each serotype, and those types were related to the types for serotype 1c strains. Ribotyping analysis yielded three patterns for serotype 1c strains and one pattern each for serotype 1a and 1b strains which were similar to the patterns for the serotype 1c strains. Overall analysis of the results concluded that subserotype 1c is closely related to serotypes 1a and 1b. Furthermore, the high rate of prevalence of serotype 1c necessitates the commercial production of antibody against this subserotype to allow the determination of the actual burden of shigellosis caused by provisional serotype 1c.