Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical relevance of HLA-DPB locus matching for cadaver kidney retransplants: a report of the Collaborative Transplant Study.

BACKGROUND Matching for the HLA class I loci A and B and for the HLA class II locus DRB is known to influence the survival rate of kidney transplants. It is unknown whether matching for the HLA class II locus DPB also exerts an influence on graft outcome. METHODS The influence of matching for the HLA-DPB locus was analyzed based on DNA typing results obtained in more than 3600 first and 1300 repeat cadaver kidney transplants. RESULTS HLA-DPB mismatches had no deleterious influence on the outcome of first cadaver transplants. However, the influence was statistically significant for retransplants. One-year graft survival rates were 83+/-2% with no mismatch (n=345), as compared with 76+/-2% with one mismatch (n=702, P=0.02), and 73+/-3% with two mismatches (n=258, P=0.003). The deleterious influence of HLA-DPB mismatches was particularly strong in retransplant recipients with >50% reactivity of preformed lymphocytotoxic antibodies, for which the 1-year graft survival rate was 70+/-4% with no mismatch, as compared with 69+/-3% with one mismatch (P=0.05) and 61+/-5% with two mismatches (P=0.003). CONCLUSIONS These results indicate that HLA-DPB is a clinically relevant histocompatibility locus in cadaver kidney retransplantation. It is proposed that prospective typing and matching for HLA-DPB should be implemented for cadaver kidney retransplants.
Scavenger receptor class B, type I is expressed in porcine brain capillary endothelial cells and contributes to selective uptake of HDL‐associated vitamin E

It is clearly established that an efficient supply to the brain of α‐tocopherol (αTocH), the most biologically active member of the vitamin E family, is of the utmost importance for proper neurological functioning. Although the mechanism of uptake of αTocH into cells constituting the blood–brain barrier (BBB) is obscure, we previously demonstrated that high‐density lipoprotein (HDL) plays a major role in the supply of αTocH to porcine brain capillary endothelial cells (pBCECs). Here we studied whether a porcine analogue of human and rodent scavenger receptor class B, type I mediates selective (without concomitant lipoprotein particle internalization) uptake of HDL‐associated αTocH in a similar manner to that described for HDL‐associated cholesteryl esters (CEs). In agreement with this hypothesis we observed that a major proportion of αTocH uptake by pBCECs occurred by selective uptake, exceeding HDL3 holoparticle uptake by up to 13‐fold. The observation that selective uptake of HDL‐associated CE exceeded HDL3 holoparticle up to fourfold suggested that a porcine analogue of SR‐BI (pSR‐BI) may be involved in lipid uptake at the BBB. In line with the observation of selective lipid uptake, RT‐PCR and northern and western blot analyses revealed the presence of pSR‐BI in cells constituting the BBB. Adenovirus‐mediated overexpression of the human analogue of SR‐BI (hSR‐BI) in pBCECs resulted in a fourfold increase in selective HDL‐associated αTocH uptake. In accordance with the proposed function of SR‐BI, selective HDL–CE uptake was increased sixfold in Chinese hamster ovary cells stably transfected with murine SR‐BI (mSR‐BI). Most importantly stable mSR‐BI overexpression mediated a twofold increase in HDL‐associated [14C]αTocH selective uptake in comparison with control cells. In line with tracer experiments, mass transfer studies with unlabelled lipoproteins revealed that mSR‐BI overexpression resulted in a twofold increase in endogenous HDL3‐associated αTocH uptake. The results of this study indicate that SR‐BI promotes the uptake of HDL‐associated αTocH into cells constituting the BBB and plays an important role during the supply of the CNS with this indispensable micronutrient.
Antiproteinuric effect of oral paricalcitol in chronic kidney disease.

BACKGROUND Proteinuria is a marker of cardiovascular and renal disease in patients with chronic kidney disease (CKD), and reduction in proteinuria has been associated with improved cardiovascular and renal outcomes. While active vitamin D and its analogs have been shown to have renal protective effects in animals, these hormones have not been shown to reduce proteinuria in CKD patients. METHODS In three double-blind, randomized, placebo-controlled studies to evaluate the safety and efficacy of oral paricalcitol, 220 CKD stage 3 and 4 patients with secondary hyperparathyroidism (SHPT) were randomized to oral paricalcitol (N= 107, mean dose 9.5 microg/week) or placebo (N= 113) and followed for up to 24 weeks. In conjunction with other safety measures, proteinuria was measured by dipstick and read by an automated reader at the beginning and end of trial. We subsequently analyzed the dipstick data to evaluate the effect of paricalcitol on proteinuria. RESULTS At baseline, proteinuria was present in 57 patients randomized to oral paricalcitol and 61 patients randomized to placebo (NS). At the final visit, 29/57 (51%) of the paricalcitol patients compared to 15/61 (25%) placebo patients had reduction in proteinuria, P= 0.004 (odds for reduction in proteinuria 3.2 times greater for paricalcitol patients, 95% CI 1.5-6.9). For the patients who had both proteinuria at baseline and parathyroid hormone (PTH) suppression (end point defined as 2 consecutive > or =30% decreases in iPTH from baseline), 27/51 (53%) patients had a reduction in the proteinuria in the paricalcitol group and 0/7 (0%) had a reduction in proteinuria in the placebo group. Reduction of proteinuria favored patients on paricalcitol, regardless of age, sex, race, diabetes mellitus, hypertension, or use of therapies to block the renin-angiotensin-aldosterone system (RAAS). CONCLUSION Our results demonstrate that the reduction in proteinuria was associated with paricalcitol treatment, and the reduction in proteinuria was independent of concomitant use of agents that block the RAAS. Paricalcitol as a potential pharmacologic means of reducing proteinuria in CKD patients warrants further investigation.
Structural, Optical, and Magnetic Properties of Cobalt-Doped Dip Coated ZnO Films

Co-doped zinc oxide thin films (ZnCoO) have been deposited on glass substrates by sol-gel dip coating deposition method. X-ray diffractometer patterns for these thin films prove crystalline behavior with wurtzite structure. The films have lattice parameters similar to that of ZnO. When Zn is replaced by Co, more impurity levels are produced within the bandgap, and more defects are developed. However, Co-doping does not alter the wurzite structure. The bandgap of the films tends to decrease with increasing withdrawal speed. These transparent thin films possess bandgap in the ultra-violet (3.86-3.45 eV) and high transparency throughout the visible spectral region. Ellipsometry also show the same trend for bandgaps (3.83-3.45). Morphological analysis by scanning electron microscope shows surface with porous structure. Magnetic property studied shows the ferromagnetic behavior. Chemical composition of these Co-doped ZnO thin films was investigated through Fourier transform infrared analysis.
Appointment Scheduling with Limited Distributional Information

In this paper, we develop distribution-free models that solve the appointment sequencing and scheduling problem by assuming only moments information of job durations. We show that our min--max appointment scheduling models, which minimize the worst-case expected waiting and overtime costs out of all probability distributions with the given marginal moments, can be exactly formulated as tractable conic programs. These formulations are obtained by exploiting hidden convexity of the problem. In the special case where only the first two marginal moments are given, the problem can be reformulated as a second-order cone program. Based on the structural properties of this formulation, under a mild condition, we derive the optimal time allowances in closed form and prove that it is optimal to sequence jobs in increasing order of job duration variance. We also prove similar results regarding the optimal time allowances and sequence for the case where only means and supports of job durations are known. This paper was accepted by Dimitris Bertsimas, optimization.
In vitro activity of BRL 36650, a new penicillin

Compared with four beta-lactam antibiotics and amikacin, BRL 36650 and BMY-28142 were the most active against 509 Enterobacteriaceae, including cefotaxime-resistant isolates and resistant laboratory mutants. BRL 36650 was more active than aztreonam, ceftazidime, and BMY-28142 against Acinetobacter spp. , Pseudomonas aeruginosa, and other Pseudomonas spp. ; all strains were inhibited by 2 micrograms/ml or less.
Body dysmorphic disorder in the DSM-IV field trial for obsessive-compulsive disorder.

OBJECTIVE This study investigated the prevalence and phenomenology of body dysmorphic disorder in patients with obsessive-compulsive disorder. METHOD The authors studied 442 patients who participated in the DSM-IV field trial for obsessive-compulsive disorder. RESULTS Twelve percent (N = 51) of the patients had a lifetime comorbid diagnosis of body dysmorphic disorder. Patients with and without body dysmorphic disorder did not differ in demographic characteristics of obsessive-compulsive symptoms. Patients with obsessive-compulsive disorder and body dysmorphic disorder had more anxious, impulsive, and schizotypal features than patients with obsessive-compulsive disorder alone. Age at onset was similar for the two disorders, and severity correlated. However, insight was significantly more impaired for body dysmorphic disorder than for obsessive-compulsive disorder. CONCLUSIONS As previously thought, these findings suggest that the two disorders are strongly related but also have differences that require further investigation.
Determination of high Zn and Pb concentrations in polluted soils using energy-dispersive X-ray fluorescence spectrometry

A method of determination of high Zn and Pb concentrations by means of EDXRF (energy-dispersive X-ray fluorescence spectrometry) is presented. Zn and Pb concentration in soil samples from contaminated areas ranged within a limit of Zn: 800–2000ppm and Pb: 200–600ppm. Soil analysis was conducted directly after the samples had been dried and powdered, as well as in situ in polluted areas. Due to the absence of the certificate reference materials for soils with such high Zn and Pb concentrations, samples of soil with the Pb and Zn amounts determined using the AAS method were used to perform calibration. The obtained detection limits are 30ppm and 19ppm for Zn and Pb, respectively. Because of the high analytes concentration and material heterogeneity, the repeatability of the results was examined according to the sample holder’s various positions in EDXRF analyzer; repeatability the of the results while putting into the sample holder and out of it, together with the repeatability of making the calibration. The results obtained using the EDXRF method were compared to these obtained using AAS and wavelength-dispersive X-ray fluorescence spectrometry (WDXRF).
Rap1 Stabilizes β-Catenin and Enhances β-Catenin–Dependent Transcription and Invasion in Squamous Cell Carcinoma of the Head and Neck

Purpose: In head and neck squamous cell carcinoma (HNSCC) cells, Rap1 shuttles between the nucleus and cytoplasm. Prior findings suggested that Rap1 may modulate the β-catenin–independent Wnt pathway in some settings, but the role of Rap1 in β-catenin–dependent Wnt signaling remains undefined. Experimental Design and Results: We observed that β-catenin bound to active Rap1 in vitro and Rap1 activated β-catenin/T-cell factor (TCF)–dependent transcription. Immunofluorescence studies showed that ectopic expression of Rap1 increased nuclear translocation of β-catenin. Overexpression of active Rap1 facilitated an increase in β-catenin–mediated transcription that was abrogated by dominant-negative TCF4. Conversely, small interfering RNA–mediated inhibition of endogenous Rap1 expression inhibited β-catenin/TCF–mediated transcription as well as invasion of HNSCC. Furthermore, inhibition of Rap1 expression downregulated the expression of matrix metalloproteinase 7, a transcriptional target of β-catenin/TCF. In HNSCC cells stably transfected with β-catenin or treated with lithium chloride or Wnt3A to stabilize endogenous β-catenin, inhibition of Rap1 expression led to decreases in the free pool of β-catenin. Immunohistochemical studies of tissue from HNSCC patients revealed that increased β-catenin intensity correlated with higher tumor stage. Furthermore, the prognostic effect of active Rap1 on tumor N stage was found to depend on cytosolic β-catenin expression (P < 0.013). When β-catenin is high, higher Rap1GTP intensity is associated with more advanced N stage. Conclusions: The findings suggest that Rap1 enhances β-catenin stability and nuclear localization. In addition to indicating that Rap1 has a significant role in regulating β-catenin and β-catenin–dependent progression to more advanced N-stage lesions, these data highlight Rap1 as a potential therapeutic target in HNSCC. Clin Cancer Res; 16(1); 65–76
In vivo measurement of lipofuscin in Stargardt's disease--Fundus flavimaculatus.

PURPOSE Several histopathologic studies have concluded that Stargardt's disease (Fundus flavimaculatus) is associated with abnormally high levels of lipofuscin-like material in the retinal pigment epithelium. The purpose of this study was to determine whether this material has the same fluorescence characteristics as lipofuscin in vivo and whether noninvasive measurements identify a significant elevation in this material. METHODS Five patients with autosomal recessive Stargardt's disease were included in this study, as were 45 healthy controls. All patients had the angiographic dark choroid sign. The intensity and emission spectra of lipofuscin fluorescence were measured by noninvasive fundus spectrophotometry at 7 degrees temporal to the fovea. RESULTS The fluorescence intensities in the five patients with Stargardt's disease were significantly higher (P < 0.0001) than those observed in normal subjects of the same age. The emission spectra in the patients are similar in shape to those measured in normals, but flecks appear to shift the spectra toward shorter wavelengths. CONCLUSIONS The spectral characteristics of the fluorophore observed in patients with Stargardt's disease are consistent with those of retinal pigment epithelial lipofuscin. These patients have abnormally high levels of lipofuscin, confirming previous histopathologic observations. Noninvasive retinal pigment epithelial lipofuscin measurements may be a useful adjunct in the diagnosis of Stargardt's disease. -F. flavimaculatus.
Heat stability of the potato tuber ADP-glucose pyrophosphorylase: role of Cys residue 12 in the small subunit.

Most of the ADP-glucose pyrophosphorylases from different sources are stable to a heat treatment. We found that in the potato (Solanum tuberosum L.) tuber enzyme, the intermolecular disulfide bridge located between Cys12 of the small subunits is responsible for the stability at 60 degrees C. When this unique disulfide bond is cleaved the enzyme is stable up to 40 degrees C. Mutation of Cys12 in the small subunit into either Ala or Ser yielded enzymes with stability similar to the reduced form of the wild type. Concurrently, the enzyme with a truncated small subunit on the N-terminal was stable only up to 40 degrees C. Thus, the N-terminal is important for the stability of the enzyme because of the presence of a disulfide bond.
The CHARMS Study: cardiac patients’ experiences of sexual problems following cardiac rehabilitation

Background: Sexual problems are common among cardiac patients. Further information is required on patients’ experiences of sexuality and preferences for sexual counselling. Aim: To characterise sexual dysfunction and related factors among patients following cardiac rehabilitation and examine related treatment delivery. Methods: Telephone interviews with 382 patients (32% response rate) recruited from six hospital rehabilitation centres. Results: Seventy-nine per cent were male; average age was 64 years (SD 9.8). Forty-seven per cent of the total sample reported no sexual relations in the previous year, and nearly a half of sexually active respondents reported at least one sexual problem. Erectile dysfunction (reported by 33%) and lack of interest in sex (reported by 10%) were the most common problems for men and women respectively. Twenty-three per cent reported that sex had deteriorated for them since their cardiac event, and for half of these this was considered a serious problem. In logistic regression analysis, higher anxiety (Hospital Anxiety and Depression Scale) and being male were associated with reporting a sexual problem (χ2 = 37.85, p<0.001). Sixty-six per cent reported that sex was never discussed by a health professional and satisfaction with this aspect of care was low. Patients wanted these issues to be addressed and the majority (63%) claimed they would find it easy to discuss sexual problems with a health professional. Conclusions: Sexual inactivity and sexual problems are common in this group. Health professionals should address sexual issues with their patients, ideally in a private setting and within the broader context of addressing psychological wellbeing.
Environmental Hazard in the Aetiology of Somatic and Germ Cell Aneuploidy

Sources of environmental exposures to potentially aneugenic agents are many and include occupational and therapeutic exposures, and exposures associated with lifestyle habits. In this present study, some of these agents and exposure scenarios are discussed that involve potentially large population targets and/or seem to affect chromosome segregation by previously unsuspected mechanisms: metals, possibly acting by epigenetic mechanisms; nano-sized particles that might directly interact with subcellular components of the mitotic and meiotic machineries; cytostatic drugs in healthcare occupations; anticancer therapies potentially affecting the genetic integrity of gametes; continuously increasing electromagnetic field exposures with some sparse evidence of aneugenic activity; endocrine disruptors and their seemingly elusive effects in mouse oocytes, including the first evidence that prenatal exposure could affect meiotic nondisjunction in adult life. Hazards are considered for both somatic cells at risk of neoplastic transformation or tumour progression by chromosome loss and gain and germ cells at risk of heritable aneuploidies associated with spontaneous abortions or genetic diseases. Finally, possible synergistic interactions between environmental exposure and ageing or genetic predisposition are considered that could influence ultimate risks.
A Mindfulness Course Decreases Burnout and Improves Well-Being among Healthcare Providers

Objective: Healthcare providers are under increasing stress and work-related burnout has become common. Mindfulness-based interventions have a potential role in decreasing stress and burnout. The purpose of this study was to determine if a continuing education course based on mindfulness-based stress reduction could decrease burnout and improve mental well-being among healthcare providers, from different professions. Design: This was a pre-post observational study conducted in a university medical center. A total of 93 healthcare providers, including physicians from multiple specialties, nurses, psychologists, and social workers who practiced in both university and community settings, participated. The intervention was a continuing education course based on mindfulness-based stress reduction that met 2.5 hours a week for 8 weeks plus a 7-hour retreat. The classes included training in four types of formal mindfulness practices, including the body scan, mindful movement, walking meditation and sitting meditation, as well as discussion focusing on the application of mindfulness at work. The course was offered 11 times over 6 years. The main outcome measures were work-related burnout as measured by the Maslach Burnout Inventory and self-perceived mental and physical well-being as measured by the SF-12v2. Results: Maslach Burnout Inventory scores improved significantly from before to after the course for both physicians and other healthcare providers for the Emotional Exhaustion (p < 0.03), Depersonalization (p < 0.04), and Personal Accomplishment (p < 0.001) scales. Mental well-being measured by the SF12v2 also improved significantly (p < 0.001). There were no significant changes in the SF12v2 physical health scores. Conclusion: A continuing education course based on mindfulness-based stress reduction was associated with significant improvements in burnout scores and mental well-being for a broad range of healthcare providers.
Effects of the presence of hypertension on the relationship between obstructive sleep apnoea and sleepiness

Obstructive sleep apnoea (OSA) plays a significant role in increasing blood pressure. Significant decreases were reported in blood pressure of hypertensive OSA patients with sleepiness who underwent continuous positive airway pressure (CPAP) treatment, but not in non‐sleepy hypertensive OSA patients. More recently, however, significant decreases in blood pressure in non‐sleepy hypertensive OSA patients following CPAP were shown. Effects of sleepiness on hypertension in OSA patients have been investigated, but not the effects of hypertension on sleepiness in OSA patients. We investigated the relationships between hypertension and sleepiness in patients with OSA. We analysed data on 275 middle‐aged male subjects from a cross‐sectional epidemiological health survey. We measured blood pressure and sleep duration objectively using an actigraph for 7 days and the respiratory disturbance index (RDI) with a type 3 portable device for 2 nights, and assessed sleepiness using the Epworth Sleepiness Scale (ESS). The RDI correlated significantly with ESS scores in the 88 hypertensive subjects (r = 0.33, P = 0.0024), but not in the 187 non‐hypertensive subjects (r = −0.01, P = 0.91). Short sleep duration correlated significantly with ESS scores in both groups. Both the RDI and short sleep duration were related independently to sleepiness in only hypertensive subjects. Furthermore, the RDI was related negatively significantly to sleep duration in hypertensive subjects. Although short sleep duration was related significantly to sleepiness in both groups, hypertension may be important for the sleepiness in OSA patients. Detailed mechanisms of the difference in the relationship between sleepiness and the severity of OSA with or without hypertension should be studied further.
Body mass index and early CD4 T‐cell recovery among adults initiating antiretroviral therapy in North America, 1998–2010

Adipose tissue affects several aspects of the cellular immune system, but prior epidemiological studies have differed on whether a higher body mass index (BMI) promotes CD4 T‐cell recovery on antiretroviral therapy (ART). The objective of this analysis was to assess the relationship between BMI at ART initiation and early changes in CD4 T‐cell count.