Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of vitamin K in vascular calcification of patients with chronic kidney disease

Patients with chronic kidney disease (CKD) are prone to vascular calcification. Pathogenetic mechanisms of vascular calcifications have been broadly studied and discussed such as the role of hyperphosphatemia, hypercalcemia, parathormone, and vitamin D. In recent years, new insights have been gained pointing to vitamin K as a main actor. It has been discovered that vitamin K is an essential cofactor for the activation of matrix Gla protein (MGP), a calcification inhibitor in the vessel wall. Patients with CKD often suffer from vitamin K deficiency, resulting in low active MGP and eventually a lack of inhibition of vascular calcification. Vitamin K supplementation and switching warfarin to new oral anticoagulants are potential treatments. In addition, MGP may have a role as a non-invasive biomarker for vascular calcification.
Neuropeptide Release from Dental Pulp Cells by RgpB via Proteinase-Activated Receptor-2 Signaling

Dental pulp inflammation often results from dissemination of periodontitis caused mostly by Porphyromonas gingivalis infection. Calcitonin gene-related peptide and substance P are proinflammatory neuropeptides that increase in inflamed pulp tissue. To study an involvement of the periodontitis pathogen and neuropeptides in pulp inflammation, we investigated human dental pulp cell neuropeptide release by arginine-specific cysteine protease (RgpB), a cysteine proteinase of P. gingivalis, and participating signaling pathways. RgpB induced neuropeptide release from cultured human pulp cells (HPCs) in a proteolytic activity-dependent manner at a range of 12.5–200 nM. HPCs expressed both mRNA and the products of calcitonin gene-related peptide, substance P, and proteinase-activated receptor-2 (PAR-2) that were also found in dental pulp fibroblast-like cells. The PAR-2 agonists, SLIGKV and trypsin, also induced neuropeptide release from HPCs, and HPC PAR-2 gene knockout by transfection of PAR-2 antisense oligonucleotides inhibited significantly the RgpB-elicited neuropeptide release. These results indicated that RgpB-induced neuropeptide release was dependent on PAR-2 activation. The kinase inhibitor profile on the RgpB-neuropeptide release from HPC revealed a new PAR-2 signaling pathway that was mediated by p38 MAPK and activated transcription factor-2 activation, in addition to the PAR-2-p44/42 p38MAPK and -AP-1 pathway. This new RgpB activity suggests a possible link between periodontitis and pulp inflammation, which may be modulated by neuropeptides released in the lesion.
early evidence from a randomized Trial

In this paper, we examine the impact of New York City's School-Wide Performance Bonus Program (SPBP) on student outcomes and the school learning environment. e SPBP is a pay-for-performance program that was implemented in approximately 200 K-12 public schools midway into the 2007-08 school year. Participating schools can earn bonus awards of up to $3,000 per full-time union member working at the school if the school meets performance targets defined by the city's accountability program. Our sample includes 186 SPBPeligible elementary, K-8, and middle schools and 137 control-condition schools in New York City over a two-year period. Overall, we find that the SPBP had little impact on student proficiency or school environment it its first year. However, it is important to remember the short-run results reported in this study provide only very limited evidence of the SPBP's effectiveness. An evaluation of the program's impact aer two years should provide more meaningful information about the impact of the SPBP
Adherence to antiretroviral medication in older adults living with HIV/AIDS: a comparison of alternative models

Abstract The CDC estimates that by 2015, half of all persons living with HIV/AIDS in the USA will be over the age of 50. Despite increasing HIV seroprevalence rates in older adults, most research examining adherence to antiretroviral therapy (ART) has focused on young HIV-infected persons and, in general, has been atheoretical in nature. This study examined two ART adherence conceptual frameworks to determine whether these models generalize to HIV-seropositive older adults. Two hundred and forty-four HIV-positive adults 50-plus years of age were recruited through AIDS service organizations in Ohio and New York. Participants completed a neuropsychological battery and an audio computer-assisted self-interview. FIML SEM analyses revealed that neuropsychological functioning was not associated with adherence. Fit indices supported a stress and coping model, with negative affect mediating the effects of social support and maladaptive coping on ART adherence. Results were consistent with stress and coping models and suggest that interventions intending to increase adherence to ART in HIV-infected older adults may be more effective if they address negative affect and enhance adaptive coping and social support.
Successes, failures and new perspectives of idiotypic vaccination for B-cell non-Hodgkin lymphomas

The idiotype of B-cell non-Hodgkin lymphomas has been intensively investigated for its proven immunogenicity as a promising cancer vaccine. Indeed, available data clearly indicate that these vaccines are able to induce tumor-specific immune responses and molecular remissions in patients with follicular lymphoma. However, only one of the three phase III trials performed so far demonstrated a prolonged disease-free survival in vaccinated patients. The observed failures have been mainly ascribed to defects in the study design and not to the limited efficacy of idiotype vaccines per se. Therefore, innovative and optimized idiotype-based vaccine formulations are being developed in order to overcome current limitations and improve the clinical benefit of this immunotherapeutic strategy. Among the most promising advances, the development of “off-the-shelf” vaccines appears of particular relevance, being potentially able to overcome the limitations related to the complex, time-consuming and expensive production of the individualized idiotypic vaccines currently used. Moreover, there is a pressing need to identify biomarkers suitable for the identification of the subset of patients who are most likely to benefit from vaccination. Recent findings also indicate that idiotypic vaccines may be safely and successfully used in additional clinical settings, including lymphoma patients after high-dose chemotherapy and autologous stem cell transplantation.
The Prox1–Vegfr3 feedback loop maintains the identity and the number of lymphatic endothelial cell progenitors

The lack of Prox1 activity results in the complete absence of lymphatic endothelial cells (LECs). Here, Srinivasan et al. identified Vegfr3, the cognate receptor of the lymphangiogenic growth factor Vegfc, as a dosage-dependent, direct in vivo target of Prox1. Vegfr3 regulates Prox1 by establishing a feedback loop necessary to maintain the identity of LEC progenitors, and Vegfc-mediated activation of Vegfr3 signaling is necessary to maintain Prox1 expression in LEC progenitors.
Evaluation of Nucleic Acid Amplification Tests in the Absence of a Perfect Gold-Standard Test: A Review of the Statistical and Epidemiologic Issues

During the past 10 years, medical diagnostic testing for sexually transmitted infections (STIs) has changed markedly as a result of the rapid expansion and marketing of nucleic acid amplification tests (NAATs). Among such new DNA/RNA-amplification techniques are the polymerase chain reaction (PCR), the ligase chain reaction (LCR), and the transcription-mediated amplification (TMA) tests. Regrettably, the test evaluation process undergone by these tests has not always been rigorous or scientifically sound. Here, we review the controversy surrounding the statistical evaluation of these NAATs. We also review some of the traditional and recent statistical methods developed to estimate test sensitivity and specificity parameters in the absence of reliable gold-standard tests. In particular, we review the traditional latent class modeling approach that requires the assumption of independence between diagnostic tests conditional on the true disease status, and the more recent procedures that relax the conditional independence assumption. Finally, we apply some of these statistical modeling techniques to real data to estimate the sensitivity and specificity of a NAAT for Chlamydia trachomatis. On the basis of the latent class modeling approach with a pessimistic prior for culture sensitivity, the NAAT specificity estimate was 97.6% and, on the basis of an optimistic prior, the specificity was 95.3%. Similarly, the sensitivity estimates ranged from 88.1% to 89.6%.
Serum soluble CD23 levels and CD23 expression on peripheral blood mononuclear cells in juvenile chronic arthritis.

OBJECTIVE To assess the CD23 status in patients with juvenile chronic arthritis (JCA), as defined by serum soluble CD23 (sCD23) and the expression of CD23 on peripheral blood mononuclear cells. METHODS Serum sCD23 levels were measured by ELISA in 22 patients with systemic JCA (s-JCA), in 40 patients with antinuclear antibody positive pauciarticular JCA (ANA+ p-JCA), and in 38 healthy controls. CD23 expression on T cells, B cells, and monocytes was determined by flow cytometry analysis of double fluorescence staining. RESULTS Serum sCD23 levels were increased in both ANA+ p-JCA and s-JCA; no relation with disease activity or severity was found. In patients with ANA+ p-JCA, serum sCD23 levels were correlated with an increased percentage of B cells expressing CD23, while in patients with s-JCA the serum sCD23 levels were correlated with an increased percentage of monocytes expressing CD23. CONCLUSION Serum sCD23 levels are elevated both in systemic and ANA+ pauciarticular JCA: different cell subset CD23 expression in s-JCA and ANA+ p-JCA (i.e. monocyte or B cell, respectively) suggests that in pauciarticular JCA CD23 may be implicated in B cell activation and autoantibody production, while in systemic JCA may be involved in monocyte activation and in the release of inflammatory mediators.
Identification of Apolipoprotein AI as a serum biomarker of chronic kidney disease in liver transplant recipients, using proteomic techniques

Chronic kidney disease (CKD) is a common complication post‐orthotopic liver transplantation (OLT). Development of CKD is detected by monitoring serum urea and creatinine, however disease can occasionally be at an advanced stage before they become abnormal. Therefore, more accurate parameters are required. In order to identify novel biomarkers of CKD, serum was obtained from 47 OLT recipients with CKD (glomerular filtration rate <60 mL/min) and 23 with normal renal function (glomerular filtration rate >90 mL/min). Using the proteomic technique SELDI‐TOF‐MS, three protein biomarkers (55.6 kDa, 9.5 kDa and 11.4 kDa) were identified that, together, could stratify patients into cases or controls with a sensitivity and specificity of 93.6 and 91.3%, respectively. The area under the curve was 0.94. The primary splitter of the groups at 55.6 kDa was an alternative version of a molecule at 27.8 kDa, which was subsequently identified by 1‐D SDS‐PAGE and LC‐ESI‐MS/MS to be Apolipoprotein AI. Protein expression was shown to be reduced in CKD, by both ELISA (p = 0.057) and Western blot analysis (p = 0.003). Apolipoprotein AI is a novel, accurate marker of CKD post‐OLT. It does require further validation in a large, more diverse patient population but could potentially improve detection of CKD.
Alveolar macrophage dysregulation in Hermansky-Pudlak syndrome type 1.

RATIONALE Individuals with Hermansky-Pudlak syndrome type 1 (HPS-1), an autosomal recessive disorder characterized by defective biogenesis of lysosome-related organelles, develop an accelerated form of progressive fibrotic lung disease. The etiology of pulmonary fibrosis associated with HPS-1 is unknown. OBJECTIVES To investigate the potential pathogenesis of pulmonary fibrosis in HPS-1, lung cells and proteins from individuals with HPS-1 were studied. METHODS Forty-one subjects with HPS-1 with and without pulmonary fibrosis were evaluated with pulmonary function tests, high-resolution computed tomography scan, and bronchoscopy. Bronchoalveolar lavage cells and analytes were analyzed. MEASUREMENTS AND MAIN RESULTS Concentrations of total bronchoalveolar lavage cells and alveolar macrophages were significantly higher in epithelial lining fluid from subjects with HPS-1 with and without pulmonary fibrosis compared with healthy research volunteers. Concentrations of cytokines and chemokines (i.e., monocyte chemoattractant protein-1, macrophage inflammatory protein-1alpha, and granulocyte-macrophage colony-stimulating factor) in alveolar epithelial lining fluid were significantly higher in subjects with HPS-1 with and without pulmonary fibrosis compared with healthy research volunteers (P < 0.001). In vitro, HPS-1 pulmonary fibrosis alveolar macrophages, which did not express HPS1 mRNA, secreted significantly higher concentrations of monocyte chemoattractant protein-1, macrophage inflammatory protein-1alpha, and regulated upon activation, normal T cell expressed and secreted (RANTES) protein compared with normal cells (P = 0.001, P = 0.014, and P = 0.011, respectively). Pirfenidone suppressed HPS-1 alveolar macrophage cytokine and chemokine secretion in vitro in a dose-dependent manner. CONCLUSIONS In HPS-1, alveolar inflammation predominantly involves macrophages and is associated with high lung concentrations of cytokines and chemokines. HPS-1 alveolar macrophages provide a model system in which to study the pathogenesis and treatment of HPS pulmonary fibrosis.
Probiotics supplementation for athletes – Clinical and physiological effects

Abstract Probiotic supplementation has traditionally focused on gut health. However, in recent years, the clinical applications of probiotics have broadened to allergic, metabolic, inflammatory, gastrointestinal and respiratory conditions. Gastrointestinal health is important for regulating adaptation to exercise and physical activity. Symptoms such as nausea, bloating, cramping, pain, diarrhoea and bleeding occur in some athletes, particularly during prolonged exhaustive events. Several studies conducted since 2006 examining probiotic supplementation in athletes or highly active individuals indicate modest clinical benefits in terms of reduced frequency, severity and/or duration of respiratory and gastrointestinal illness. The likely mechanisms of action for probiotics include direct interaction with the gut microbiota, interaction with the mucosal immune system and immune signalling to a variety of organs and systems. Practical issues to consider include medical and dietary screening of athletes, sourcing of recommended probiotics and formulations, dose–response requirements for different probiotic strains, storage, handling and transport of supplements and timing of supplementation in relation to travel and competition.
Treatment of human immunodeficiency virus 1-infected infants and children with the protease inhibitor nelfinavir mesylate.

An open-label study was conducted of nelfinavir mesylate, given with reverse transcriptase inhibitors to human immunodeficiency virus 1 (HIV-1)-infected infants and children 3 months to 13 years of age. Doses of nelfinavir mesylate of 20-30 mg/kg yielded drug exposures comparable to those seen in adults. The drug was well tolerated; mild diarrhea was the primary toxic effect observed. Seventy-one percent (39) of the 55 evaluable subjects had an initial decrease in plasma HIV-1 RNA, of at least 0.7 log10 copies/mL; suppression of plasma HIV-1 RNA levels to < 400 copies/mL was observed in 15. Children who began taking at least one new reverse transcriptase inhibitor near the time when nelfinavir mesylate was started, and those with a > or = 24% proportion of CD4 lymphocytes, had a greater chance of achieving and maintaining a decline in plasma HIV-1 RNA to < 400 copies/mL. Suppression of viremia was achieved in children as young as 3 months of age.
Genotyping the ‐521C/T functional polymorphism in the promoter region of dopamine D4 receptor (DRD4) gene

The ‐521C/T single nucleotide polymorphism (SNP) in the promoter region of the dopamine D4 receptor gene (DRD4) has recently been detected in oriental (Japanese) individuals and related to novelty seeking and schizophrenia. Here, we report the analysis of the ‐521C/T polymorphism in a Caucasian (Hungarian) population using two independent genotyping methods. The polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) procedure utilized the FspI restriction site around the ‐521 position. An additional, nonpolymorphic cleavage site was also included into the amplified region to serve as an internal standard for verifying the completion of the digestion. As another independent method, a tetraprimer system for single‐tube allele‐specific PCR (SAS‐PCR) was developed to generate ‐521C and ‐521T specific PCR products with different fragment sizes. Consequently, genotyping with SAS‐PCR is based on the gel‐electrophoretic separation of the allele‐specific double‐stranded DNA (dsDNA) fragments. 119 healthy Hungarian individuals were genotyped for ‐521C/T polymorphism of the dopamine D4 promoter region, using both methods. Similar allele frequencies were found (‐521C allele: 0.43; ‐521T allele: 0.57) as reported earlier for the Japanese population.
Endotoxin promotes adhesion of human erythrocytes to human vascular endothelial cells under conditions of flow

Objective To investigate the effects of endotoxin on adhesion of human red blood cells to human vascular endothelial cells under conditions of flow. Design Prospective, randomized, controlled in vitro study. Settings University-affiliated cell biology laboratory. Subjects Human erythrocytes and human vascular endothelial cells. Interventions Fresh human erythrocytes and human vascular endothelial cells grown as monolayers were incubated with either saline or endotoxin. After incubation, endothelial monolayers were superfused with erythrocytes, and the number of erythrocytes adhering to the endothelial monolayer was quantified. Measurements and Main Results Adhesion of erythrocytes to vascular endothelium was measured under conditions of continuous flow in different settings: a) exposure of both endothelial cells and erythrocytes to saline; b) incubation of both erythrocytes and endothelial cells with endotoxin; c) exposure of erythrocytes only to endotoxin; d) incubation of endothelial cells only to endotoxin; and e) both the endothelial cells and erythrocytes incubated with different concentrations of endotoxin. Erythrocyte adhesion in the saline control group was 71 ± 8 cells/mm2. Incubation of both components with endotoxin increased the number of adhesive erythrocytes to 172 ± 9 cells/mm2 (p < .05). When only the endothelial cells were treated with endotoxin, 142 ± 8 cells/mm2 adhered to the endothelial monolayer, whereas the incubation of the erythrocytes only to endotoxin resulted in adhesion of 102 ± 3 cells/mm2. Decreasing concentrations of endotoxin reduced adhesion from 172 ± 9 cells/mm2 (endotoxin, 75 &mgr;g/mL) to 165 ± 9 cells/mm2 (endotoxin, 25 &mgr;g/mL), 153 ± 4 cells/mm2 (endotoxin, 1 &mgr;g/mL), and 146 ± 6.1 cells/mm2 (endotoxin, 5 ng/mL). Conclusions Exposure of human erythrocytes and human venous vascular endothelial cells to an inflammatory stimulus such as endotoxin promotes a dose-dependent adhesion of erythrocytes to endothelium in a dynamic environment. These adhesive erythrocyte-endothelium interactions can be produced by exposure of either red blood cells or endothelial cells to endotoxin, with a higher degree of adhesion after activation of the endothelial cell component.
Spontaneous Pneumothorax: A Retrospective Review of Aetiology, Pathogenesis and Management

A retrospective analysis was made of all spontaneous pheumothoraces admitted to a Respiratory Unit between 1976 and 1981. There were 117 individuals responsible for 148 admissions, with a male to female ratio of 2: 1, giving a higher incidence amongst females than has been previously reported. Significantly fewer admissions were noted during May, June and July. Of the total survey population 89 per cent had smoked and in 40 per cent there was pre-existing lung disease. There was a history of two or more pneumothoraces in 36 per cent. Tetracycline pleurodesis, while attempted in 19 patients, was successful in only ten. Twelve patients underwent thoracotomy with a preponderance following right sided lesions. The duration of admission was more than 20 days for 17 per cent of the population. The aetiology, pathogenesis and management of pneumothorax is discussed.
Mitochondrial complex I impairment in leukocytes from polycystic ovary syndrome patients with insulin resistance.

CONTEXT Insulin resistance is a feature of polycystic ovary syndrome (PCOS) and is related to mitochondrial function. OBJECTIVE Our objective was to assess mitochondrial function by evaluating mitochondrial oxygen (O(2)) consumption, reactive oxygen species (ROS) production, levels of glutathione (GSH), the oxidized glutathione/GSH ratio, TNFalpha levels, and membrane potential. Additionally, we have evaluated mitochondrial complex I as a target of the oxidative stress responsible for PCOS in polymorphonuclear cells. DESIGN AND SETTING This was a prospective controlled study conducted in an academic medical center. PATIENTS The study population consisted of 20 lean reproductive-age women with PCOS and 20 body composition-matched controls. MAIN OUTCOME MEASURES We evaluated mitochondrial O(2) consumption using the Clark-type O(2) electrode; levels of ROS, GSH, and membrane potential by means of fluorescence microscopy; TNFalpha levels by ELISA; and complex I activity by spectrophotometric assay. RESULTS An impairment in mitochondrial function was observed in PCOS patients, evident by a decrease in mitochondrial O(2) consumption; an increase in ROS production, oxidized glutathione/GSH ratio, and TNFalpha levels; a drop in GSH levels; and an undermining of membrane potential. Furthermore, an impairment of mitochondrial complex I was identified. CONCLUSION This study supports the hypothesis of an association between insulin resistance and an impaired mitochondrial oxidative metabolism. We also propose that the oxidative stress responsible for PCOS takes place at complex I. These abnormalities may contribute to the increased risk of type 2 diabetes among women with PCOS.
Incidence and clinical manifestations of rheumatic fever: a 6 year community-based survey.

BACKGROUND Most data on the incidence of rheumatic fever come from hospital records. We presumed that there may be cases of RF that do not require hospitalization, especially in countries with high quality community health care. OBJECTIVES To explore the incidence and characteristics of RF using community-based data. METHODS A retrospective descriptive study was conducted among the members (more than 450,000) of the Clalit Health Services, Central district, during 2000-2005. The electronic medical files of members up to 40 years old with a diagnosis of RF in hospital discharge letters or during community clinic visits were retrieved. Patients with a first episode of RF according to the modified Jones criteria were included. RESULTS There were 44 patients with a first episode of RF. All patients were under the age of 29. The annual incidence among patients aged 0-30 years was 3.2:100,000; the highest incidence was among children aged 5-14 years (7.5:100,000), and in males the incidence was 2.26 times higher than in females. The incidence was higher among patients from large families, of non-Jewish ethnicity, and from rural areas. Twenty-five percent of the patients were both diagnosed and treated in an ambulatory care setting. CONCLUSIONS Although the incidence of RF in the western world and in Israel is low, the disease still occurs and mainly affects children. Any future estimates of disease incidence should take into account that RF is becoming an ambulatorily treated disease.