Miracle-dz/UniFAR-FTUs huggingface dataset:
Production of Monoclonal Antibodies to Tropheryma whipplei and Identification of Recognized Epitopes by Two-Dimensional Electrophoresis and Mass Spectrometry

ABSTRACT Tropheryma whipplei, the agent of Whipple's disease, is a gram-positive rod-shaped bacterium that belongs to the group of actinobacteria. In order to produce monoclonal antibodies (MAbs) against this bacterium, we inoculated mice with two different strains, Slow2 and Endo5. We produced 13 and 10 MAbs against Slow2 and Endo5, respectively. Nine of the Slow2 MAbs and seven of the Endo5 MAbs recognized a 58-kDa epitope. In addition, three other Endo5 MAbs detected a unique 84-kDa epitope. These MAbs were species specific, as they did not react with a selection of 22 different bacterial species, but they were not strain specific, as they did react with six other strains of T. whipplei. Two-dimensional gel electrophoresis (2-DE) was combined with mass spectrometry (MS) to identify the 58-kDa and 84-kDa epitopes recognized by MAbs. After trypsin in-gel digestion of the spot, the 58-kDa protein was identified as an ATP synthase F1 complex beta chain, whereas the 84-kDa protein was identified as a polyribonucleotide nucleotidyltransferase by MS with matrix-assisted laser desorption ionization-time of flight. In an in vitro model, one of these MAbs allowed good detection of T. whipplei in stool samples, contrary to a rabbit polyclonal antibody, which led to high fluorescent background. In the prospective studies, the produced MAb will be tested for detection of T. whipplei in clinical samples, and the gene coding for identified 58-kDa and 84-kDa antigens will be tentatively cloned and then tested for its use in a diagnostic enzyme-linked immunosorbent assay for Whipple's disease.
Stromal cell‐derived factor 1 (SDF1) genetic polymorphism in a sample of healthy individuals, seronegative individuals exposed to human immunodeficiency virus type 1 (HIV‐1) and patients infected with HIV‐1 from the Brazilian population

The interaction of viral and host factors is believed to determine not only the risk for initial human immunodeficiency virus type 1 (HIV‐1) acquisition but also the course of the infection. Genetic polymorphisms in the chemokine receptors and their ligands were related to the susceptibility and resistance to HIV‐1 infection. A polymorphism in the conserved 3′ untranslated region of the stromal cell‐derived factor‐1 (SDF1) gene, which encodes a ligand of the CXCR4 receptor, has been related either to delayed progression to AIDS or to rapid disease progression and death. Global, regional, and ethnic distributions of frequencies of SDF1 genotypes and of the SDF1–3′A allele vary significantly. Although the HIV‐1 epidemic is increasing in Brazil, little information about the frequencies of host genetic mutations related to HIV/AIDS resistance in the Brazilian population has been reported. To address this question, this study was carried out in order to determine the frequencies of the SDF1 polymorphism and the SDF1‐3′A allele on 1061 genomic DNA samples purified from peripheral blood cells of 136 healthy individuals (group 1), 147 HIV‐1‐exposed seronegative individuals (group 2), 161 HIV‐1‐infected asymptomatic individuals and with CD4+ T‐cells count 350 mm−3 (group 3), and 617 HIV‐1‐infected individuals with AIDS and/or CD4+ T‐cells count < 350 mm−3 (group 4). The frequencies of the SDF1–3′A homozygous mutation were 3.7%, 6.1%, 4.3%, and 5.3% among groups 1, 2, 3, and 4, respectively (P = 0.5120). The overall frequency of the SDF1‐3′A allele was 0. 1984 and did not differ among the four groups (P = 0.2744). The results underscore the global distribution of the SDF1 polymorphism and the hypothesis that the SDF1‐3′A allele, itself, may not be sufficient to prevent the risk of HIV‐1 infection and may be not related to the progression of the disease in the Brazilian population.
Inaccurate Communications in Telephone Calls to an Antimicrobial Stewardship Program

Background. Antimicrobial stewardship programs (ASPs) decrease unnecessary antimicrobial use, decrease antimicrobial resistance, and improve patient outcomes. The effectiveness of a prior approval system—that is, the requirement that approval be obtained from ASP practitioners before certain antimicrobials can be used—depends on the accuracy of the patient data communicated from the primary service. Objectives. To determine the incidence of inaccurate communication of patient data during ASP interactions, describe examples of inaccurate communications, and identify risk factors for inaccurate communication. Design. We used a retrospective cohort design. We evaluated the communicated patient data for clinically important inaccuracies, using the patients' medical records as the gold standard. Setting. A tertiary care medical center that has a prior approval system for restricted antimicrobials. Patients. Inpatients discussed in telephone ASP interactions. Intervention. Observational study. Results. Of telephone calls requesting prior approval from ASP practitioners, 39% (95% confidence interval [CI], 31%-48%) contained an inaccuracy in at least 1 type of patient data (eg, current antimicrobial therapy); the incidence varied widely between data types. Examples of inaccuracies are given to demonstrate their clinical relevance. In multivariable analysis, inaccurate communications were more common for telephone calls from surgical services (versus calls from nonsurgical services: odds ratio, 2.1 [95% CI, 1.1-3.9]) and for calls received by Infectious Diseases fellows (versus pharmacists: odds ratio, 2.0 [95% CI, 1.1-3.8]). Conclusions. A high proportion of ASP calls requesting prior approval included patient data inaccuracies, which have the potential to affect the prescribing of antimicrobials. Although risk factors were identified, these communication errors were common across the different types of ASP interactions. Inaccurate communications may compromise the utility of ASPs that use a prior approval system for optimizing antimicrobial use.
Characterization of chondrocyte alkaline phosphatase as a potential mediator in the dissolution of calcium pyrophosphate dihydrate crystals.

OBJECTIVE To characterize chondrocyte alkaline phosphatase (ALP) distribution and expression in cartilage and monolayer cultures. METHODS Sections of bovine articular cartilage or chondrocyte monolayer cultures were stained for ALP activity. Surface ALP was released with bacterial phosphatidylinositol specific phospholipase C (PI-PLC). The levels of ALP mRNA were determined by Northern blot analysis using a cDNA probe to bovine ALP. RESULTS Chondrocyte ALP activity dissolves calcium pyrophosphate dihydrate (CPPD) crystals. About 5% of the total chondrocytes contained ALP activity. The ALP positive cells were present only in the deep layers of articular cartilage adjacent to the subchondral bone. Thirty to forty percent of the total ALP activity was present on the chondrocyte surface and was released by PI-PLC. Both chondrocyte ALP activity and mRNA levels decreased with time in culture. However, continuous dexamethasone treatment stimulated the expression of ALP in ALP positive chondrocytes, sufficiently to replace all of the chondrocyte surface ALP released following PI-PLC treatment. CONCLUSION Since ALP hydrolyzes pyrophosphate and dissolves CPPD crystals, our data suggest that regulation of chondrocyte ALP activity and expression in cartilage may prove useful for the development of a specific therapy CPPD arthropathy.
Regional Citrate Anticoagulation in Continuous Hemodialysis – Acid-Base and Electrolyte Balance at an Increased Dose of Dialysis

Background: Citrate anticoagulation is an excellent alternative to heparin anticoagulation for patients at high risk of bleeding requiring continuous renal replacement therapy. However, citrate anticoagulation has some potential adverse effects such as metabolic alkalosis and acidosis, hypernatremia, hypo- and hypercalcemia. Thus, most citrate anticoagulation protocols use specially designed dialysis fluids to compensate for most of these disarrangements. This study aimed at establishing a citrate anticoagulation protocol designed for a dialysate flow rate of about 2 l/h. Methods: Based on theoretical considerations we composed a dialysis fluid suitable for a 2 l/h dialysis flow rate. The dialysate contained 133 mmol/l sodium, 2 mmol/l potassium, 1.1 mmol/l magnesium, 25 mmol/l lactate, and 112.2 mmol/l chloride. Results: Twenty-three patients were included in the study. During the treatments minor flow rate adaptations were needed and the treatments were well tolerated. Filter life was appropriate (51.3 ± 24.6 h). Thirteen patients developed a mild metabolic alkalosis (pH > 7.45 plus BE > +3) which was easily counteracted by increasing the dialysis fluid flow (by increments of 500 ml). Acid-base values returned to normal within 24 h after increasing the dialysate flow. The maximum dialysate flow was 3,000 ml/h. Hypernatremia and hypocalcemia were not observed. The systemic ionized calcium concentration was successfully controlled by adjustments of a continuous calcium infusion made with respect to the results of 6-hourly measurements. Conclusion: The analyzed citrate anticoagulation protocol was well tolerated and filter lifetime was appropriate. Regional anticoagulation with trisodium citrate in combination with a customized calcium-free dialysate is a safe and effective alternative to a heparin-based anticoagulation regimen.
Novel targets for valproic acid: up‐regulation of melatonin receptors and neurotrophic factors in C6 glioma cells

Valproic acid (VPA) is a potent anti‐epileptic and effective mood stabilizer. It is known that VPA enhances central GABAergic activity and activates the mitogen‐activated protein kinase–extracellular signal‐regulated kinase (MAPK–ERK) pathway. It can also inhibit various isoforms of the enzyme, histone deacetylase (HDAC), which is associated with modulation of gene transcription. Recent in vivo studies indicate a neuroprotective role for VPA, which has been found to up‐regulate the expression of brain‐derived neurotrophic factor (BDNF) in the rat brain. Given the interaction between the pineal hormone, melatonin, and GABAergic systems in the central nervous system, the effects of VPA on the expression of the mammalian melatonin receptor subtypes, MT1 and MT2, were examined in rat C6 glioma cells. The effects of VPA on the expression of glial cell line‐derived neurotrophic factor (GDNF) and BDNF were also examined. RT‐PCR studies revealed a significant induction of melatonin MT1 receptor mRNA in C6 cells following treatment with 3 or 5 mm VPA for 24 h or 5 mm VPA for 48 h. Western analysis and immunocytochemical detection confirmed that the VPA‐induced increase in MT1 mRNA results in up‐regulation of MT1 protein expression. Blockade of the MAPK–ERK pathway by PD98059 enhanced the effect of VPA on MT1 expression, suggesting a negative role for this pathway in MT1 receptor regulation. In addition, significant increases in BDNF, GDNF and HDAC mRNA expression were observed after treatment with VPA for 24 or 48 h. Taken together, the present findings suggest that the neuroprotective properties of VPA involve modulation of neurotrophic factors and receptors for melatonin, which is also thought to play a role in neuroprotection. Moreover, the foregoing suggests that combinations of VPA and melatonin could provide novel therapeutic strategies in neurological and psychiatric disorders.
The affective aspect of subjective well-being among Chinese people with and without spinal cord injuries

Purpose. The purpose of this study was two-fold: (a) To examine differences in affective aspects of subjective well-being between people with and without spinal cord injuries (SCI), and (b) to explore relationships among perceived health, social support, self-efficacy beliefs, and the affective aspect of subjective well-being in these groups. Method. A cross-sectional survey was conducted in China. A total of 119 out-patients with SCI and 109 college students without a disability participated in the study. Main outcome measures included: (a) The Index of Psychological Well-Being, (b) the Self-Rated Health Status Scale, (c) the Self-Efficacy Scale, and (d) the Social Support Scale. Results. A multiple analysis of the variance indicated that participants with SCI had lower affective subjective well-being, social support, social self-efficacy beliefs, and poor health compared to participants without SCI [F (5, 211) = 22.37, p < 0.001]. A hierarchical multiple linear regression analysis was conducted separately for each SCI and non-SCI group. Results indicated that the combination of perceived health, social support, and social self-efficacy accounted for 25% of the variance in affective subjective well-being [F (8, 104) = 4.22, p < 0.001] among participants with SCI. For participants without SCI, social support and social self-efficacy were related to the affective subjective well-being [F (7, 97) = 4.77, p < 0.001]. They accounted for 27% of the variance in affective subjective well-being. Conclusions. People with SCI may have lower affective subjective well-being than those without SCI, and the perceptions of one's health, social skills, and social support may play important roles in achieving affective subjective well-being in people with SCI.
[Expression of chemokine like factor-1 in nephridial tissue of lupus nephritis].

OBJECTIVE To investigate the influence of chemokine like factor-1(CKLF-1) on the genesis and development of lupus nephritis. METHODS Immunohistochemistry stain was employed on the 34 lupus nephridial tissues and 10 nephridial tissues of control group. And light microscopy was applied to observe the percentage of CKLF-1 positive cells of renal gromerulus and tubule. RESULTS The percentages of CKLF-1 positive cells of renal gromerulus and tubule were 10.4%+/-1.5% and 48.9%+/-4.3% in the lupus nephritis group, and the percentages of control group were 4.6%+/-1.1% and 4.3%+/-0.9%. There was significant difference between 2 groups (P<0.01). And there was positive correlation between the percentage of CKLF-1 positive cells of renal gromerulus and tubule and lupus active index (r=0.74 and r=0.53, respectively, P<0.05). CONCLUSION CKLF-1 plays a role in the genesis and development of lupus nephritis.
Effects of in vitro exposure to hay dust on expression of interleukin-17, -23, -8, and -1beta and chemokine (C-X-C motif) ligand 2 by pulmonary mononuclear cells isolated from horses chronically affected with recurrent airway disease.

OBJECTIVE To examine effects of in vitro exposure to solutions of hay dust, lipopolysaccharide (LPS), or beta-glucan on cytokine expression in pulmonary mononuclear cells isolated from healthy horses and horses with recurrent airway obstruction (RAO). ANIMALS 8 RAO-affected and 7 control horses (experiment 1) and 6 of the RAO-affected and 5 of the control horses (experiment 2). PROCEDURES Bronchoalveolar lavage cells were isolated from horses that had been stabled and fed dusty hay for 14 days. Pulmonary mononuclear cells were incubated for 24 (experiment 1) or 6 (experiment 2) hours with PBS solution or solutions of hay dust, beta-glucan, or LPS. Gene expression of interleukin (IL)-17, IL-23(p19 and p40 subunits), IL-8, IL-1beta, and chemokine (C-X-C motif) ligand 2 (CXCL2) was measured with a kinetic PCR assay. RESULTS Treatment with the highest concentration of hay dust solution for 6 or 24 hours increased expression of IL-23(p19 and p40), IL-8, and IL-1beta in cells from both groups of horses and increased early expression of IL-17 and CXCL2 in RAO-affected horses. Lipopolysaccharide upregulated early expression of IL-23(p40) and IL-8 in cells from both groups of horses but only late expression of these cytokines in cells from RAO-affected horses. Treatment with beta-glucan failed to increase cytokine expression at 6 or 24 hours. CONCLUSIONS AND CLINICAL RELEVANCE Cells from RAO-affected horses were not more responsive to the ligands tested than were cells from control horses, which suggests a minimal role of mononuclear cells in propagation of airway neutrophilia in horses with chronic RAO.
Prognostic value of right ventricular dysfunction and pulmonary obstruction index by computed tomographic pulmonary angiography in patients with acute pulmonary embolism.

OBJECTIVE To quantify right ventricular dysfunction (RVD) and pulmonary obstruction index assessed by computed tomographic pulmonary angiography (CTPA) to assess the predictive value of these CT parameters for mortality after the initial diagnosis of acute pulmonary embolism (APE). MATERIAL AND METHOD In 81 consecutive patients with proved APE, two readers assessed the extent of RVD, the shape of the interventricular septum, and the extent of obstruction to the pulmonary artery on CTPA images. The readers were blinded for clinical outcome in consensus reading. RESULTS During follow-up, 20 patients died (25%). CT signs of RVD (RV/LV ratio > 1.0) were seen in 47 patients (58%). The RV/LV ratio, the shape of interventricular septum, and the obstruction index were shown to be significant risk factors for mortality (p < 0.001, p = 0.04, p < 0.001, respectively). The negative predictive value for mortality with an RV/LV ratio < or = 1.0 and the obstruction index of < 40% were 100%. CONCLUSION CTPA quantification of RVD and pulmonary vascular obstruction index are potential useful tools to predict mortality in patients with APE.
Experience with a Large Dose (500 MG) of Intravenous Iron Dextran and Iron Saccharate in Peritoneal Dialysis Patients

Objective To compare efficacy in anemia correction and side effects of large doses of intravenous (IV) iron dextran and iron saccharate preparations in peritoneal dialysis (PD) patients. Setting Tertiary-care teaching hospital of University of Toronto. Design Retrospective analysis of 379 PD patients who attended PD clinics in past 5 years. Of these 379 patients, 62 were selected to receive IV iron based on ferrokinetic markers of iron deficiency, noncompliance to or ineffectiveness of oral iron, or increased erythropoietin (EPO) requirement. Intervention Sixty-one patients received two IV iron injections of 500 mg each, 1 week apart, 33 patients received iron dextran, 23 received iron saccharate, and 5 received both iron dextran and iron saccharate. One patient developed anaphylaxis to a test dose of iron dextran and was excluded from further therapy. Blood samples were collected before and 3 and 6 months after iron infusions. Results At 3 months, the group's average hemoglobin rose from 98.3 ± 18.3 g/L to 110.6 ± 16.4 g/L (p < 0.0001). Ferritin rose from 104.9 ± 115.4 μg/L to 391.5 ± 294.1 μg / L (p < 0.0001), and iron saturation from 0.17 ± 0.07 to 0.26 ± 0.19 (p < 0.0001). Erythropoietin requirements fell from 7278.7 IU/week to 5900 IU/week (p < 0.01). Five of the 34 patients who received iron dextran developed minor side effects and 1 patient had anaphylaxis to the test dose. Of the 23 patients who received iron saccharate, 1 had an anaphylactic reaction and 2 had transient chest pain, which subsided without therapy. Overall, there were more side effects with iron dextran (7.4% of injections) compared to the iron saccharate group (4.3% of injections), but this difference was statistically insignificant. Although statistically insignificant, there was an increase in the number of peritonitis episodes during the 6 months after IV iron infusion, especially with iron dextran, compared to the peritonitis episodes during the 6 months before iron infusions. Conclusion Our study indicates that IV iron in PD patients is effective in restoring iron stores and in decreasing EPO requirements. One anaphylactic reaction occurred in each group. Our data suggest that as much caution be exercised with iron saccharate as with iron dextran. The slight trend toward increased peritonitis rates after iron infusions needs to be investigated in a larger group of patients.
Factors determining non-compliance to mass drug administration for lymphatic filariasis elimination in endemic districts of Nepal.

BACKGROUND Mass drug administration (MDA) has been implemented in Nepal since 2003 for elimination of Lymphatic Filariasis (LF). The objective of this study was to explore the factors that determine the non-compliance to MDA for Lymphatic Filariasis elimination in endemic districts of Nepal. METHODS A cross-sectional descriptive study was carried out in three endemic districts namely Dhading, Kapilvastu and Kailali. A total of 900 people were interviewed with structured questionnaire. RESULTS The result shows that the respondents who knew the DEC contains Albendazole (84.9% vs 42.5%, P<0.001, Adjusted OR=2.89(1.946-4.29) at 95% CI), who were aware of MDA campaign (78.2% vs 33.8% P<0.001, Adjusted OR=2.87(1.73-4.74) at 95% CI), who were visited by health workers at their home during MDA campaign (75.9% vs 24.1% P<0.001, Adjusted OR=4.85(2.448-9.594) at 95% CI) had significantly higher compliance. The respondents who had knowledge of side effects during MDA campaign had lower prevalence of non-compliance as compared who did not have (9.4% vs 33.2%, P<0.001). CONCLUSIONS Advanced age, primary or below education, ever married, inadequate knowledge on drug, inadequate awareness on MDA, no home visit by health workers during MDA, no belief on MDA drugs were significantly associated with higher non-compliance to MDA. In future, MDA program should focus on awareness campaigns related to composition of drugs, side effects of drugs and compulsory home visit during the campaign.
Currency crash risk in the carry trade

This thesis provides a systematic study of currency crash risk and funding liquidity risk in carry trade strategy in the foreign exchange (FX) market. Carry trade, which involves longing currencies with high interest rate and shorting currencies with low interest rate, is a popular currency trading strategy in the FX market for obtaining annualized excess return as high as 12%. This thesis studies exchange rates of 9 currencies over 13 years from a microstructure perspective. We identify a global skewness factor and use it to measure the currency crash risk. Applying a portfolio approach in cross-sectional asset pricing, we find that global skewness factor explains more than 80% of carry trade excess returns. On the other hand, funding liquidity is effective in predicting the future currency crash risk. Funding liquidity explains more than 70% of carry trade excess returns. We also use the coefficient of price impact from customer order flows to measure the liquidity, which reveals heterogeneous information content possessed by different types of customers. We find that the order flow implied liquidity risk factor can explain a fraction of carry trade excess returns but with small risk premium on quarterly basis. We provide empirical evidence to show that the excess return and crash risk in carry trade is endogenous; i.e., the crash risk premium is inherent in carry trade process. As the natural condition widely affects all investors, we argue that funding constraints are effective in explaining the excess returns of carry trade. When capital moves smoothly in a liquid condition and investor have sufficient funding supply, carry trade is prosperous in the FX market. When investors hit their funding constraints, market-wide liquidity drop, which force the carry trade positions diminishing. The exchange rates respond as that the low interest rate currencies appreciate and high interest rate currencies depreciate, which exacerbates currency crash risk and induces large loss to carry traders. Our cross-sectional analysis provides empirical evidence to show that funding constraints helps to explain the forward premium puzzle and push the exchange rate shift back to the direction the UIP expects.