Miracle-dz/UniFAR-FTUs huggingface dataset:
Hypoproteinemia in Patients with Diabetes Undergoing Continuous Ambulatory Peritoneal Dialysis is Attributable to High Permeability of Peritoneal Membrane

Background The present study used the newly developed personal dialysis capacity (PDC) peritoneal function test to investigate differences in individual peritoneal membrane transport function and nutritional status in non diabetic (non DM) and diabetic (DM) patients on continuous ambulatory peritoneal dialysis (CAPD). Patients and Methods To clarify the differences in peritoneal function that determine plasma protein levels, we carried out PDC tests in non DM and DM patients. Between May 1995 and May 1999, in multicenter study in Japan, we carried out 232 PDC tests on 232 non DM patients and 47 PDC tests on 47 DM patients who had been on CAPD for 1 – 210 months. Results Plasma levels of total protein and albumin in DM patients were significantly lower than those in non DM patients (total protein: 6.5 ± 0.1 g/dL non DM vs. 5.9 ± 0.1 g/dL DM, p < 0.0001; albumin: 3.5 ± 0.1 g/dL non DM vs. 2.9 ± 0.1 g/dL DM, p < 0.0001). The mean membrane area in the DM group was significantly larger than that in the non DM group (21943 ± 608 cm/1.73 m2 non DM vs. 26 304 ± 1699 cm/1.73 m2 DM, p = 0.0076). The mean plasma loss through the large pores in the DM group was significantly greater than that in the non DM group (0.095 ± 0.004 mL/min/1.73 m2 non DM vs. 0.119 ± 0.008 mL/min/1.73 m2 DM, p = 0.0113). Protein loss into dialysate in DM patients was significantly greater than that in non DM patients. We observed a significant correlation between total protein or albumin and plasma loss from dialysis solution in non DM and DM patients on CAPD. Conclusions The study demonstrated that peritoneal function, including peritoneal membrane transport and peritoneal permeability to protein was significantly higher in DM patients than in non DM patients. Hypoproteinemia in DM patients might be associated with high permeability of peritoneal membrane in CAPD.
HIV infection does not affect active case finding of tuberculosis in South African gold miners.

RATIONALE Gold miners in South Africa undergo annual radiological screening for tuberculosis in an occupational health center of a gold mining company, but the optimal screening algorithm is unclear. OBJECTIVES To evaluate methods for active case detection of tuberculosis. METHODS A sequential sample of miners attending annual medical examination was screened for tuberculosis using a symptom questionnaire, chest radiograph, and two sputum specimens for microscopy and culture. MEASUREMENTS AND MAIN RESULTS There were 1,955 miners included in this study; all were male with a median age of 41 years (range, 20-61 yr). Presence of at least one of a trio of symptoms (new or worsening cough, night sweats, or weight loss) had similar sensitivity (29.4%) to either chest radiograph (25.5%) or sputum smear (25.5%). These sensitivities did not differ by HIV status. Presence of one or more elements of the symptom trio and/or new radiological abnormality substantially increased sensitivity to 49.0%. Specificity of the symptom trio was higher in HIV-uninfected (91.8%) than in HIV-infected persons (88.2%; P = 0.018). Specificity of chest radiography and smear were similar (98.7% and 99.0%, respectively) and did not differ by HIV status (both P values > 0.8). CONCLUSIONS In a population of gold miners who undergo regular radiological screening, the addition of chest radiography to symptom screening substantially improved the sensitivity and positive predictive value. HIV infection did not alter the sensitivity of the screening tool.
The specific antibacterial proliferation of reactive arthritis synovial T cells is not due to their higher proportion of CD45RO+ cells compared to peripheral blood.

OBJECTIVE To determine the role of synovial fluid (SF) compared to peripheral blood (PB) CD45RO+ T cells in patients with reactive arthritis (ReA) and undifferentiated oligoarthritis. METHODS We examined SF and PB of 8 patients with a specific lymphocyte proliferation to Yersinia enterocolitica (n = 5) and Chlamydia trachomatis (n = 3). After depletion of the CD45RA+ T cell subset by dynabeads, the remaining T cells (> 95% CD45RO+) from PB and SF of these patients were again stimulated with these bacterial antigens. RESULTS The mean stimulation index (SI) of these 8 patients with ReA (n = 5) and undifferentiated oligoarthritis (n = 3) was 30.3 +/- 21.86 in SF compared to 1.36 +/- 0.75 in PB. The enrichment of CD45RO+ cells influenced the antigen specific proliferative response of T cells neither in PB (SI = 1.75 +/- 1.35) nor in SF (26.1 +/- 24.05); the initial difference remained unchanged. CONCLUSION Our findings suggest that the antigen specific lymphocyte proliferation obtained with SF cells is not due to abundance of nonspecific CD45RO+ T cells but can rather be taken as an indication of specific recognition of local bacterial antigens in ReA.
One-Time Programmable Memory Based on ${\rm ZrTiO}_{x}$ Antifuse for Crossbar Memory Application Featuring High Speed Operation and Low Power Consumption

TaN/ZrTiOx/Pt metal-insulator-metal structure was employed as the platform to evaluate the eligibility for antifuse one-time programmable (OTP) memory applications, and the impact of O2 plasma on device performance was also discussed. Owing to the oxygen radicals that enhance the dielectric integrity, the voltage for state switching increases with O2 plasma treatment. Memory cells without plasma treatment demonstrate promising characteristics for OTP memory applications in terms of a low dc switching voltage of 2 V, high programming speed of 60 ns, high read endurance up to 106 reading cycles, and desirable retention time and low switching power density of 6.4 mW/cm2. The memory cell technology not only exhibits the prominent performance which is advantageous over other dielectrics reported in the literature, but it also possesses the capability to from stackable 3-D architecture.
Heritability of urinary traits that contribute to nephrolithiasis.

BACKGROUND AND OBJECTIVES Kidney stones and their risk factors aggregate in families, yet few studies have systematically estimated heritabilities and genetic correlations of the numerous urinary traits associated with risk of kidney stones. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Twenty-four-hour urine samples were collected from the Genetic Epidemiology Network of Arteriopathy cohort of families in Rochester, Minnesota, to measure urinary determinants of supersaturation. Diet was assessed using the Viocare food frequency questionnaire. Heritabilities and genetic correlations among the urinary traits were estimated using variance components methods. RESULTS Samples were available from 811 individuals (344 men, 467 women; mean age 66 ± 9 years). Age, sex, and weight were significantly correlated with the majority of urinary traits. Many urine excretions (calcium, magnesium, citrate excretion) had strong evidence for heritability (P<0.01) both before and after adjusting for the identified covariates. Among significantly heritable urinary traits, genetic factors explained 20%-36% of interindividual variation after adjustment for covariates. Urinary calcium excretion was significantly genetically correlated with urinary magnesium and with urinary citrate excretion (P<0.05). Although eGFR influenced many urinary traits, controlling for eGFR did not greatly affect estimated heritabilities. CONCLUSIONS Evidence from this cohort suggests a strong heritable component to many urinary nephrolithiasis risk factors. Further study of genetic influences on urinary traits relevant for kidney stone pathogenesis is warranted.
Epidemiological characteristics and medical follow-up of 61 patients with acute hepatitis C identified through the hepatitis C surveillance system in France

SUMMARY This study aimed to describe current epidemiological and clinical characteristics, medical follow-up and outcome in the real practice of acute hepatitis C (AHC) patients. AHC cases were retrospectively identified through the French Hepatology Reference Centres Surveillance system and additional data were collected. Sixty-one patients with AHC were identified (sex ratio: M/F 1·7/1; mean age 39 years). Forty-four (72%) had documented seroconversion within a 6-month period. Main reported risk exposures were intravenous or nasal drug use (35%), invasive medical procedures (25%) and sexual contact with a HCV-positive partner (20%). Spontaneous clearance of HCV RNA was observed in seven out of 16 patients followed without therapy. This study confirms the major role of drug use in HCV transmission and highlights the role of invasive medical procedures and occupational exposure.
Enhanced sensitivity to N‐methyl‐D‐aspartate receptor activation in transgenic and knockin mouse models of Huntington's disease

We used two mouse models of Huntington's disease (HD) to examine changes in glutamate receptor sensitivity and striatal electrophysiology. One model, a transgenic, consisted of mice expressing exon 1 of the human HD gene and carrying 141–157 CAG repeat sequences (R6/2 line). The second model, a CAG repeat “knockin,” consisted of mice with different lengths of CAG repeats (CAG71 and CAG94 repeats). The effects of glutamate receptor activation were examined by visualizing neurons in brain slices with infrared videomicroscopy and differential interference contrast optics to determine changes in somatic area (cell swelling). Striatal and cortical neurons in both models (R6/2 and CAG94) displayed more rapid and increased swelling to N‐methyl‐D‐aspartate (NMDA) than those in controls. This effect was specific as there were no consistent group differences after exposure to α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) or kainate (KA). Intracellular recordings revealed that resting membrane potentials (RMPs) in the R6/2 transgenics were significantly more depolarized than those in their respective controls. RMPs in CAG94 mice also were more depolarized than those in CAG71 mice or their controls in a subset of striatal neurons. Confirming previous results, R6/2 mice expressed behavioral abnormalities and nuclear inclusions. However, CAG71 and CAG94 knockins did not, suggesting that increased sensitivity to NMDA may occur early in the disease process. These findings imply that NMDA antagonists or compounds that alter sensitivity of NMDA receptors may be useful in the treatment of HD. J. Neurosci. Res. 58:515–532, 1999. © 1999 Wiley‐Liss, Inc.
The bacterial nucleoid: A highly organized and dynamic structure

Recent advances in bacterial cell biology have revealed unanticipated structural and functional complexity, reminiscent of eukaryotic cells. Particular progress has been made in understanding the structure, replication, and segregation of the bacterial chromosome. It emerged that multiple mechanisms cooperate to establish a dynamic assembly of supercoiled domains, which are stacked in consecutive order to adopt a defined higher‐level organization. The position of genetic loci on the chromosome is thereby linearly correlated with their position in the cell. SMC complexes and histone‐like proteins continuously remodel the nucleoid to reconcile chromatin compaction with DNA replication and gene regulation. Moreover, active transport processes ensure the efficient segregation of sister chromosomes and the faithful restoration of nucleoid organization while DNA replication and condensation are in progress. © 2005 Wiley‐Liss, Inc.
HCV in Patients With End-Stage Renal Disease

Chronic hepatitis C virus (HCV) infection remains an important cause of liver disease in patients with end-stage renal disease (ESRD) and conversely, renal failure has a significant impact on morbidity and mortality throughout the natural history of chronic HCV and its treatment. With improved awareness within dialysis units of the potential for spread and the institution of preventative measures, the prevalence of HCV infection in the hemodialysis-dependent population has continued to decline since 1995. Use of HCV (+) donor kidneys is associated with an increase in the prevalence of liver disease, but when compared with continued hemodialysis, transplantation using these kidneys is associated with improved survival. Overall, survival in patients with chronic HCV infection appears to be better after renal transplantation when compared with maintenance hemodialysis, and transplant should be considered for these patients. Data support the use of interferon and the improved efficacy of pegylated interferon formulations for treatment of chronic HCV infection in ESRD patients, although tolerability continues to be troublesome. The newest and most promising data regarding the treatment of HCV in ESRD involve the combination of reduced dose ribavirin with interferon or pegylated interferon suggesting similar enhancements in sustained virologic response (SVR) as seen in non-ESRD patients, but caution is advised, as all studies to date used ribavirin plasma concentration monitoring in patient with ESRD. Finally, with regard to postrenal transplant treatment of HCV infection, there is no evidence to support treatment with interferon-based therapy and pretransplant treatment remains the best option whenever possible.
Deep sequencing of uveal melanoma identifies a recurrent mutation in PLCB4

Next generation sequencing of uveal melanoma (UM) samples has identified a number of recurrent oncogenic or loss-of-function mutations in key driver genes including: GNAQ, GNA11, EIF1AX, SF3B1 and BAP1. To search for additional driver mutations in this tumor type we carried out whole-genome or whole-exome sequencing of 28 tumors or primary cell lines. These samples have a low mutation burden, with a mean of 10.6 protein changing mutations per sample (range 0 to 53). As expected for these sun-shielded melanomas the mutation spectrum was not consistent with an ultraviolet radiation signature, instead, a BRCA mutation signature predominated. In addition to mutations in the known UM driver genes, we found a recurrent mutation in PLCB4 (c.G1888T, p.D630Y, NM_000933), which was validated using Sanger sequencing. The identical mutation was also found in published UM sequence data (1 of 56 tumors), supporting its role as a novel driver mutation in UM. PLCB4 p.D630Y mutations are mutually exclusive with mutations in GNA11 and GNAQ, consistent with PLCB4 being the canonical downstream target of the former gene products. Taken together these data suggest that the PLCB4 hotspot mutation is similarly a gain-of-function mutation leading to activation of the same signaling pathway, promoting UM tumorigenesis.
Acetyl-CoA carboxylase 2 mutant mice are protected against obesity and diabetes induced by high-fat/high-carbohydrate diets

Malonyl-CoA, generated by acetyl-CoA carboxylases ACC1 and ACC2, is a key metabolite in the control of fatty acid synthesis and oxidation in response to dietary changes. ACC2 is associated to the mitochondria, and Acc2-/- mice have a normal lifespan and higher fatty acid oxidation rate and accumulate less fat. Mutant mice fed high-fat/high-carbohydrate diets weighed less than their WT cohorts, accumulated less fat, and maintained normal levels of insulin and glucose, whereas the WT mice became type-2 diabetic with hyperglycemic and hyperinsulinemic status. Fatty acid oxidation rates in the soleus muscle and in hepatocytes of Acc2-/- mice were significantly higher than those of WT cohorts and were not affected by the addition of insulin. mRNA levels of uncoupling proteins (UCPs) were significantly higher in adipose, heart (UCP2), and muscle (UCP3) tissues of mutant mice compared with those of the WT. The increase in the UCP levels along with increased fatty acid oxidation may play an essential role in the regulation of energy expenditure. Lowering intracellular fatty acid accumulation in the mutant relative to that of the WT mice may thus impact glucose transport by higher GLUT4 activity and insulin sensitivity. These results suggest that ACC2 plays an essential role in controlling fatty acid oxidation and is a potential target in therapy against obesity and related diseases.
Obtaining Coagulation Blood Samples From Central Venous Access Devices: A Review of the Literature.

BACKGROUND Central venous access devices are used for chemotherapy and other medication administration, blood product administration, parenteral nutrition, and for obtaining blood samples in patients where the vasculature is difficult to access. Patients may need additional blood samples prior to invasive procedures and when clinical situations arise during cancer care. In addition, monitoring coagulability through ongoing blood testing is common in patients with cancer and requires repeated sampling to adjust anticoagulant medications. OBJECTIVES The purpose of this review of the literature is to determine the best practices for collecting coagulation test samples from central venous access devices. METHODS The authors conducted a systematic review of the literature. FINDINGS The only method for obtaining reliable coagulation test results from central venous access devices is the flush then waste/discard method. This method has only been studied with peripherally inserted central catheters. Additional randomized, controlled trials with larger sample sizes are needed to determine the most appropriate method for drawing coagulation test results from central venous access devices.
Formulation and Stability Testing of Itraconazole Crystalline Nanoparticles

Itraconazole (ITZ) crystalline nanoparticles were prepared using relatively simple, low-cost sonoprecipitation technique, in which both the solvent and antisolvent were organic in nature. The effect of stabilizer type (hydroxypropyl methylcellulose, hydroxypropyl cellulose, Inutec SP1®, and pluronic F127), drying method (oven and freeze drying) and matrix former used (Avicel PH101, and Aerosil®200) on the dissolution performance as a key characteristic of nanocrystals was evaluated. In 10 min, all of the prepared nanocrystals showed 3.77−8.59 times improvement in percent drug dissolved compared to pure ITZ. Concerning the effect of stabilizer type, the following rank order can be given: pluronic F127 ≥ hydroxypropyl cellulose ≥ hydroxypropyl methylcellulose (HPMC) > inutec SP1. Freeze-dried ITZ nanocrystals containing Avicel PH 101 showed better dissolution rate compared to other nanocrystals. The chemical structure of itraconazole nanocrystals was not changed as revealed by Fourier transform infrared. Stability study of selected nanocrystals (F5, F7, and F8) revealed physical and chemical stability of F7 and F8, while a decrease in dissolution rate of F5 was observed (although being chemically stable) when stored under high relative humidity conditions. Although inutec is less potent than pluronic F127 and HPMC regarding their effect on dissolution rate enhancement, it is equipotent to pluronic F127 in preserving the rapid drug dissolution.
A randomized, double blind, placebo-controlled multicenter trial comparing the effects of three doses of orally administered sodium oxybate with placebo for the treatment of narcolepsy.

STUDY OBJECTIVES To evaluate and compare the efficacy and safety of three doses of sodium oxybate and placebo for the treatment of narcolepsy symptoms. DESIGN A multicenter, double blind, placebo-controlled trial. SETTING N/A. PARTICIPANTS Study subjects were 136 narcolepsy patients with 3 to 249 (median 21) cataplexy attacks weekly. INTERVENTIONS Prior to baseline measures, subjects discontinued anticataplectic medications. Stable doses of stimulants were permitted. Subjects were randomized in blinded fashion to receive 3, 6, or 9 g doses of sodium oxybate or placebo taken in equally divided doses upon retiring to bed and 2.5-4 hours later for 4 weeks. MEASUREMENTS AND RESULTS Disease symptoms and adverse events were recorded in daily diaries. The primary measure of efficacy was the change from baseline in weekly cataplexy attacks. Secondary measures included daytime sleepiness using the Epworth Sleepiness Scale (ESS), inadvertent daytime naps/sleep attacks and nighttime awakenings. Investigators assessed changes in disease severity using Clinical Global Impression of Change (CGI-c). Compared to placebo, weekly cataplexy attacks were decreased by sodium oxybate at the 6 g dose (p=0.0529) and significantly at the 9 g dose (p=0.0008). The ESS was reduced at all doses, becoming significant at the 9 g dose (p=0.0001). The CGI-c demonstrated a dose-related improvement, significant at the 9 g dose (p=0.0002). The frequency of inadvertent naps/sleep attacks and the nighttime awakenings showed similar dose-response trends, becoming significant at the 9 g dose (p=0.0122 and p=0.0035, respectively). Sodium oxybate was generally well-tolerated at all three doses. Nausea, headache, dizziness and enuresis were the most commonly reported adverse events. CONCLUSIONS Sodium oxybate significantly improved symptoms in patients with narcolepsy and was well tolerated.
Platelets enhance CD4+ lymphocyte adhesion to extracellular matrix under flow conditions: Role of platelet aggregation, integrins, and non-integrin receptors

Summary The purpose of this study was to examine the role of platelets in CD4+ T lymphocyte adhesion to subendothelial extracellular matrix (ECM). Herpesvirus saimiri (HVS)-infected CD4+ T cells were incubated on ECM. An image analysis was used to evaluate T cell adhesion. Under static condition, T cell activation with 4-α-Phorbol 12-myristate 13-acetate (PMA) resulted in a 2.6-fold increase in cell adhesion. However, adhesion was not affected by platelets. In contrast, under flow (200s−1), platelets markedly enhanced both resting and PMA-activatedT cell adhesion (33- and 48-fold), forming lymphocyte-platelet co-aggregates that contain approximately 90% of the adherent T cells. Abrogation of platelet aggregation with tirofiban inhibited formation of platelet-T cell co-aggregates under flow and reduced T cell adhesion by 74%. Separate and combined blockade of CD40L and P-selectin glycoprotein-1 (PSGL-1) on PMA-activated lymphocytes reduced adhesion under flow in the presence of platelets by 28%, 33%, and 55%, respectively. Blockade of β1-integrins decreased adhesion under both static and flow conditions (by 35% and 44%, respectively), while blockade of β2-integrin reduced adhesion only under static condition (by 23%). A similar adhesion pattern was observed using CD4+ T cells isolated from normal donor peripheral blood. In conclusion, platelets support CD4+ lymphocyte adhesion to ECM under flow by formation of heterotypic platelet-lymphocyte co-aggregates involving αIIbβ3 integrin and β1-related integrins, as well as CD40L and PSGL-1.