Miracle-dz/UniFAR-FTUs huggingface dataset:
beta(2)-microglobulin kinetics in nocturnal haemodialysis.

BACKGROUND beta(2)-Microglobulin (beta(2)m) is a major component of dialysis-related amyloidosis. The available therapeutic options do not permit normalization of the serum beta(2)m level. In a cross-over trial, we studied the kinetics of beta(2)m during two different dialytic techniques. METHODS Ten stable, anuric end-stage renal disease patients were studied during two consecutive weeks of three conventional (CHD) and six nocturnal haemodialysis (NHD) sessions. CHD was performed for 4 h three times weekly using a polysulfone dialyser (F80, surface area of 1.8 m(2)) with a mean blood and dialysate flow rate of 401+/-91.6 and 514+/-10.9 ml/min, respectively. The NHD was done with a smaller dialyser (F40, surface area of 0.7 m(2)) and lower blood (281+/-17 ml/min) and dialysate flow rates (99+/-1.2 ml/min) for 8 h, six nights a week. RESULTS Weekly removal of urea (51.6+/-24.6 vs 43.1+/-20.5 g) and creatinine (8501+/-5204 vs 6319+/-4134 mg) were comparable with the two modalities of dialysis but the mass of beta(2)m removed was significantly higher with NHD (127+/-48 vs 585+/-309 mg, P<0.001), with a percentage reduction in serum level of 20.5+/-5.8 vs 38.8+/-7. 1% (P<0.0001) and a Kt/V(beta2m) of 0.21+/-0.09 vs 0.56+/-0.17 (P<0. 0006). The mean post-dialysis beta(2)m (20.8+/-6.3 vs 14.0+/-3.8 mg/dl, P=0.02), Tac(beta2m) (26.2+/-5.2 vs 19.8+/-3.8 mg/dl, P=0.02) and pre-dialysis beta(2)m (beta(2)m(pre)) at the end of 1 week of therapy (24.4+/-7.6 vs 19.0+/-3.4 mg/dl, P=0.02) were lower with NHD. Long-term follow-up data were available in 13 and seven patients at the end of 1 and 2 years, respectively. Serum beta(2)m(pre) levels progressively declined from 27.2+/-11.7 mg/dl at initiation of NHD to 13.7+/-4.4 mg/dl by 9 months, and they remained stable thereafter. CONCLUSIONS NHD provides a much higher clearance of beta(2)m than CHD, leading to a long-term decrease in the pre-dialysis concentration of beta(2)m.
Early dentine lead levels and subsequent cognitive and behavioural development.

While a number of studies have reported associations between lead levels and cognitive development and behaviour in cross-sectionally studied child samples, there have been relatively few studies of the long term effects of early lead exposure. This issue was studied in a birth cohort of 1265 New Zealand children who were assessed with respect to: (a) dentine lead levels at ages 6-8 years; (b) cognitive and behavioural outcomes at 12, 13 years; (c) various confounding factors. The results of the analysis show: (a) the presence of small but consistent bivariate associations (ranging in absolute size from r = .08 to .20) between early lead levels and later school performance and behaviour; (b) after adjustment for both errors of measurement in test scores and lead levels and adjustment for confounding factors these correlations reduced to between . 07 and . 14. Nonetheless these correlations remained statistically significant. The evidence is consistent with the view that early mildly elevated lead levels are associated with small but relatively long term deficits in cognitive ability and attentional behaviours.
20‐Hydroxyeicosatetraenoic acid inhibits ATP‐induced COX‐2 expression via peroxisome proliferator activator receptor‐α in vascular smooth muscle cells

20‐Hydroxyeicosatetraenoic acid (20‐HETE), formed from arachidonate by cytochrome P450, regulates vascular smooth muscle cell (VSMC) function. Because 20‐HETE may activate peroxisome proliferator activator receptors (PPARs) and may participate in inflammatory responses, we asked whether 20‐HETE may inhibit cyclooxygenase 2 (COX‐2) expression by activating PPARs in VSMC.
Effects of hand cycle training on wheelchair capacity during clinical rehabilitation in persons with a spinal cord injury

Purpose. To evaluate the effects of a structured hand cycle training programme on physical capacity in subjects with spinal cord injury (SCI) during clinical rehabilitation. Method. Twenty subjects with SCI who followed hand cycle training were compared with matched control subjects from a Dutch longitudinal cohort study, who received usual care. Primary outcomes of physical capacity were peak power output (POpeak), peak oxygen uptake (VO2peak) and oxygen pulse during a hand rim wheelchair test. Secondary outcome measures were isometric peak muscle strength of the upper extremities and pulmonary function. Hand cycle capacity (POpeak and VO2peak) was evaluated in the training group only. Results. Strong tendencies for improvement were found in wheelchair capacity, reflected by POpeak and oxygen pulse after additional hand cycle training. Significant effects on shoulder exo- and endo-rotation and unilateral elbow flexion strength were found but no improvements on pulmonary function. Conclusions. Additional hand cycle training during clinical rehabilitation seems to show similar or slightly favourable results on wheelchair capacity and muscle strength compared with regular care. The heterogeneous subject group and large variation in training period may explain the limited effects of additional hand cycle training on wheelchair capacity.
Purification and characterization of three parathion hydrolases from gram-negative bacterial strains

Three unique parathion hydrolases were purified from gram-negative bacterial isolates and characterized. All three purified enzymes had roughly comparable affinities for ethyl parathion and had broad temperature optima at ca. 40 degrees C. The membrane-bound hydrolase of Flavobacterium sp. strain ATCC 27551 was composed of a single subunit of approximately 35,000 daltons (Da) and was inhibited by sulfhydryl reagents such as dithiothreitol (DTT) and by metal salts such as CuCl2. The cytosolic hydrolase of strain B-1 was composed of a single subunit of approximately 43,000 Da and was stimulated by DTT and inhibited by CuCl2. The membrane-bound hydrolase of strain SC was composed of four identical subunits of 67,000 Da and was inhibited by DTT and stimulated by CuCl2. The substrate ranges of the three enzymes also differed, as evidenced by their relative affinities for parathion and the related organophosphate insecticide O-ethyl-O-4-nitrophenyl phenylphosphonothioate (EPN). The B-1 hydrolase displayed equal affinity for both compounds, the Flavobacterium enzyme showed twofold-lower affinity for EPN than for parathion, and the SC hydrolase displayed no activity toward EPN. The range in characteristics of these three enzymes can be exploited in different waste disposal strategies.
Prediction of obstetrical risk using maternal serum markers and clinical risk factors

Abnormal maternal serum analytes (pregnancy associated plasma protein A, total human chorionic gonadotropin, alpha fetoprotein, Inhibin A, and unconjugated estriol) measured as part of aneuploidy screening programs have been associated with adverse obstetrical outcomes in euploid pregnancies. This study aimed to determine if their predictive ability could be enhanced with additional information on obstetrical history.
Stromal cell‐derived CSF‐1 blockade prolongs xenograft survival of CSF‐1‐negative neuroblastoma

The molecular mechanisms of tumor–host interactions that render neuroblastoma (NB) cells highly invasive are unclear. Cancer cells upregulate host stromal cell colony‐stimulating factor‐1 (CSF‐1) production to recruit tumor‐associated macrophages (TAMs) and accelerate tumor growth by affecting extracellular matrix remodeling and angiogenesis. By coculturing NB with stromal cells in vitro, we showed the importance of host CSF‐1 expression for macrophage recruitment to NB cells. To examine this interaction in NB in vivo, mice bearing human CSF‐1‐expressing SK‐N‐AS and CSF‐1‐negative SK‐N‐DZ NB xenografts were treated with intratumoral injections of small interfering RNAs directed against mouse CSF‐1. Significant suppression of both SK‐N‐AS and SK‐N‐DZ NB growth by these treatments was associated with decreased TAM infiltration, matrix metalloprotease (MMP)‐12 levels and angiogenesis compared to controls, while expression of tissue inhibitors of MMPs increased following mouse CSF‐1 blockade. Furthermore, Tie‐2‐positive and ‐negative TAMs recruited by host CSF‐1 were identified in NB tumor tissue by confocal microscopy and flow cytometry. However, host‐CSF‐1 blockade prolonged survival only in CSF‐1‐negative SK‐N‐DZ NB. These studies demonstrated that increased CSF‐1 production by host cells enhances TAM recruitment and NB growth and that the CSF‐1 phenotype of NB tumor cells adversely affects survival.
Long-term follow-up of a prospective study of combined modality therapy for stage I-II indolent non-Hodgkin's lymphoma.

PURPOSE Standard therapy for patients with stage I-II indolent lymphoma has been involved-field radiation therapy (IF-XRT), which achieves 10-year disease-free survival in 40% to 50% of patients, with many of these patients cured. We investigated the potential for combined-modality therapy to increase the disease-free survival for such patients. PATIENTS AND METHODS A total of 102 eligible patients with stage I-II low grade lymphoma (International Working Formulation criteria) were enrolled from 1984 to 1992. Treatment comprised 10 cycles of risk-adapted chemotherapy (cyclophosphamide, vincristine, prednisone, bleomycin [COP-Bleo], and with doxorubicin added for some [CHOP-Bleo]) and 30 to 40 Gy IF-XRT. RESULTS The patients' median age was 56 years (range, 28 to 77), with follicular histology in 83%, bulky disease (>/= 5 cm) in 24%, and stage II in 52%. There were no treatment-related deaths and 99% of patients attained complete remission. With a median follow-up of 10 years, the 10-year time to treatment failure and overall survival were 76% and 82%, respectively. For patients with follicular lymphoma, these figures were 72% and 80%, respectively. The only factor associated with treatment failure, for follicular lymphoma patients, was stage-modified International Prognostic Factors Index score (P =.02). None of 17 patients with diffuse small lymphocytic or mucosa-associated lymphoid tissue histology have relapsed. Elevated serum beta2-microglobulin was associated with shorter survival (P <.0001). The 10-year survival after relapse was 46%. There have been two cases of myelodysplasia and 12 other new malignancies, including four arising within radiation fields. CONCLUSION With prolonged follow-up, combined-modality therapy with risk-adapted COP-/CHOP-Bleo and IF radiation has attained higher rates of disease control and survival than previously reported with IF-XRT alone. This apparent improvement is being further explored in an ongoing randomized trial.
IgG and IgM anticardiolipin antibodies following treatment with infliximab plus methotrexate in patients with early rheumatoid arthritis.

OBJECTIVE To assess the occurrence of anticardiolipin antibodies (aCL) in patients with early rheumatoid arthritis (RA) receiving treatment with infliximab plus methotrexate (MTX) versus MTX alone. METHODS The first 299 patients enrolled in the randomized, Active-Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset (ASPIRE) trial who had baseline (week 0) samples available for aCL testing were included in this study. Sera were collected at weeks 0, 30, and 54 from 110 patients taking infliximab 3 mg/kg plus MTX, 98 patients taking infliximab 6 mg/kg plus MTX, and 91 patients taking placebo plus MTX. IgG and IgM aCL were measured using an anticardiolipin assay. RESULTS IgG and IgM aCL positivity at baseline was similar in all treatment groups. Most patients were negative for IgG aCL at baseline and remained so at the last followup evaluation. One percent (2 of 208) of patients who received infliximab plus MTX and were negative for IgG aCL at baseline were positive for IgG aCL at weeks 30 and 54. A slightly higher proportion of patients who received infliximab plus MTX and were negative for IgM aCL at baseline were positive for IgM aCL at weeks 30 and 54 (4.8% [10 of 208]) as compared with patients who received placebo plus MTX (1.1% [1 of 91]), but the difference was not significant. CONCLUSION There was a low incidence of the development of aCL in patients with early RA who received infliximab in combination with MTX, and the difference was not significant compared with patients who received placebo plus MTX.
Late Ureteral Stenosis Following Renal Transplantation: Risk Factors and Impact on Patient and Graft Survival

The aim of this retrospective study of a cohort of 1787 consecutive kidney transplantations was to analyze the risk factors associated with the occurrence of ureteral stenosis and the impact of ureteral stenosis on graft and patient survival. Between January 1990 and December 2002, 1787 renal transplantations were performed at our center. Only stenosis observed after the first month, were considered. Among the parameters studied were: donor age and serum creatinine before procurement; recipient age, cold ischemia time, delayed graft function (DGF), number of arteries and the presence of a double J stent. The follow‐up parameters were the number and timing of acute rejection episodes, cytomegalovirus (CMV) infection, acute pyelonephritis, renal function and death. Ureteral stenosis occurred in 4.1% of patients and was correlated with donor age > 65 years (p = 0.001), kidneys with more than 2 arteries (p = 0.009) and DGF (p = 0.016). Ureteral stenosis did not affect 10‐year patient and graft survival rates, which were respectively 90% and 64% for the stenosis group, 86% and 63% for the no‐stenosis group (p = NS). These data suggest an important role for donor age, number of renal arteries and DGF for the occurrence of ureteral stenosis following renal transplantation.
Effects of short-term mechanical hyperventilation on cerebral blood flow and dynamic cerebral autoregulation in critically ill patients with sepsis

Abstract In sepsis, higher PaCO2 levels are associated with impaired dynamic cerebral autoregulation (dCA), which may expose the brain to hypo- and hyperperfusion during acute fluctuations in blood pressure. We hypothesised that short-term mechanical hyperventilation would dCA in critically ill patients with sepsis. Seven mechanically ventilated septic patients were included. We assessed dCA before and after 30 min of mechanical hyperventilation. Transfer function analysis of spontaneous oscillations in transcranial Doppler-based middle cerebral artery blood flow velocity (MCAv) and invasive mean arterial blood pressure was used to assess dCA. Mechanical enhance hyperventilation reduced the median PaCO2 from 5.3 (IQR, 5.0–6.5) to 4.7 (IQR, 4.2–5.1) kPa (p < 0.05). This was associated with a reduction in the median MCAv from 57 (IQR, 33–68) to 32 (IQR, 21–40) cm sec−1 (p < 0.05). Apart from a small increase in gain in the low frequency range (2.32 [IQR 1.80–2.41] vs. 2.59 (2.40–4.64) cm mmHg−1 sec−1; p < 0.05), this was not associated with any enhancement in dCA. In conclusion, cerebral CO2 vasoreactivity was found to be preserved in septic patients; nevertheless, and in contrast to our working hypothesis, short-term mechanical hyperventilation did not enhance dCA.
Establishment of field change by expression of cytokeratins 8/18, 19, and MMP-9 in an apparently normal oral mucosa adjacent to squamous cell carcinoma: A immunohistochemical study

Background: Squamous cell carcinoma is the most frequent malignancy of the oral cavity. The survival rate of this malignancy has not improved from past two decades. The major factors responsible for this could be due to loco regional and distant metastatic spread. However, the other important prognostic factor is concomitant occurrence and recurrence of multiple primary carcinomas in the head and neck region, which is explained as the concept of field cancerization. The evidence to support the field change in normal mucosa of Oral squamous cell carcinoma (OSCC) through biological markers using immunohistochemistry has always been challenging. Aim: Hence, the aim of the present research is to identify changes in the expression of CK 8/18, 19, and MMP-9 to visualize field changes in the clinically normal mucosa adjacent to OSCC and compare with non neoplastic normal oral mucosa. Materials and Methods: 20 cases of OSCC with radical resection specimens were included in the study. Lesional tissue and adjacent normal looking mucosa were taken during grossing. Ten cases of non-neoplastic normal oral mucosa are also included in the study. Markers such as CK 8/18, CK 19, and MMP-9 are used by the immunohistochemical method in this present study. Result and Conclusion: The enhance expression of CK 8/18 (80%), CK 19 (70%), and MMP 9 (90%) in ANM was noted and furthermore in six ANM showing severe dysplasia with enhance expression of CK 8/18, CK 19, and MMP 9 in the apparently normal oral mucosa can suggest a field cancerization.
The Impact of Social Connectedness and Internalized Transphobic Stigma on Self-Esteem Among Transgender and Gender Non-Conforming Adults

ABSTRACT The transgender and gender non-conforming (TGNC) community continues to represent a notably marginalized population exposed to pervasive discrimination, microaggressions, and victimization. Congruent with the minority stress model, TGNC individuals persistently experience barriers to wellbeing in contemporary society; however, research uncovering resilience-based pathways to health among this population is sparse. This study aimed to explore the impact and interaction between internalized transphobic stigma and a potential buffer against minority stress—social connectedness—on the self-esteem of TGNC identified adults. Data were collected from 65 TGNC identified adults during a national transgender conference. Multiple regression analysis reveals that self-esteem is negatively impacted by internalized transphobia and positively impacted by social connectedness. Social connectedness did not significantly moderate the relationship between internalized transphobia and self-esteem. Micro and macro interventions aimed at increasing social connectedness and decreasing internalized transphobic stigma may be paramount for enhancing resiliency and wellbeing in the TGNC community.
Comparison of Induced versus Natural Regulatory T Cells of the Same TCR Specificity for Induction of Tolerance to an Environmental Antigen

Recent evidence shows that natural CD25+Foxp3+ regulatory T cells (nTreg) and induced CD25+Foxp3+ regulatory T cells (iTreg) both contribute to tolerance in mouse models of colitis and asthma, but there is little evidence regarding their relative contributions to this tolerance. We compared the abilities of nTreg and iTreg, both from OVA-TCR–transgenic OTII mice, to mediate tolerance in OVA-asthmatic C57BL/6 mice. The iTreg were differentiated from Th2 effector T cells by exposure to IL-10–differentiated dendritic cells (DC10) in vitro or in vivo, whereas we purified nTreg from allergen-naive mice and exposed them to DC10 before use. Each Treg population was subsequently repurified and tested for its therapeutic efficacy in vitro and in vivo. DC10 engaged the nTreg in a cognate fashion in Forster (or fluorescence) resonance energy transfer assays, and these nTreg reduced in vitro OVA-asthmatic Th2 effector T cell responses by 41–56%, whereas the comparator iTreg reduced these responses by 72–86%. Neutralization of IL-10, but not TGF-β, eliminated the suppressive activities of iTreg but not nTreg. Delivery of 5 × 105 purified nTreg reduced allergen challenge–induced airway IL-4 (p ≤ 0.03) and IL-5 (p ≤ 0.001) responses of asthmatic recipients by ≤23% but did not affect airway hyperresponsiveness or IgE levels, whereas equal numbers of iTreg of identical TCR specificity reduced all airway responses to allergen challenge by 82–96% (p ≤ 0.001) and fully normalized airway hyperresponsiveness. These data confirm that allergen-specific iTreg and nTreg have active roles in asthma tolerance and that iTreg are substantially more tolerogenic in this setting.
Nfkb1 Activation by the E26 Transformation-Specific Transcription Factors PU.1 and Spi-B Promotes Toll-Like Receptor-Mediated Splenic B Cell Proliferation

ABSTRACT Generation of antibodies against T-independent and T-dependent antigens requires Toll-like receptor (TLR) engagement on B cells for efficient responses. However, the regulation of TLR expression and responses in B cells is not well understood. PU.1 and Spi-B (encoded by Sfpi1 and Spib, respectively) are transcription factors of the E26 transformation-specific (ETS) family and are important for B cell development and function. It was found that B cells from mice knocked out for Spi-B and heterozygous for PU.1 (Sfpi1+/− Spib−/− [PUB] mice) proliferated poorly in response to TLR ligands compared to wild-type (WT) B cells. The NF-κB family member p50 (encoded by Nfkb1) is required for lipopolysaccharide (LPS) responsiveness in mice. PUB B cells expressed reduced Nfkb1 mRNA transcripts and p50 protein. The Nfkb1 promoter was regulated directly by PU.1 and Spi-B, as shown by reporter assays and chromatin immunoprecipitation analysis. Occupancy of the Nfkb1 promoter by PU.1 was reduced in PUB B cells compared to that in WT B cells. Finally, infection of PUB B cells with a retroviral vector encoding p50 substantially restored proliferation in response to LPS. We conclude that Nfkb1 transcriptional activation by PU.1 and Spi-B promotes TLR-mediated B cell proliferation.
Older, Less Regulated Medical Marijuana Programs Have Much Greater Enrollment Rates Than Newer 'Medicalized' Programs.

Twenty-three states and the District of Columbia have passed laws implementing medical marijuana programs. The nineteen programs that were in operation as of October 2014 collectively had over one million participants. All states (including D.C.) with medical marijuana laws require physicians directly or indirectly to authorize the use of marijuana at their discretion, yet little is known about how medical marijuana programs vary regarding adherence to basic principles of medical practice and associated rates of enrollment. To explore this, we analyzed marijuana programs according to seven components of traditional medical care and pharmaceutical regulation. We then examined enrollment rates, while controlling for potentially confounding state characteristics. We found that fourteen of the twenty-four programs were nonmedical and collectively enrolled 99.4 percent of participants nationwide, with enrollment rates twenty times greater than programs deemed to be "medicalized. " Policy makers implementing or amending medical marijuana programs should consider the powerful relationship between less regulation and greater enrollment. Researchers should consider variations across programs when assessing programs' population-level effects.
Electronic properties of Au/Cu2O/n-type Si heterojunction for energy conversion

Au/Cu2O/n-type Si structures have been fabricated and characterized electrically. The structure yields a current rectification of almost 7 orders of magnitude. It is also shown that the structure performs as a metal/semiconductor junction when subjected to CV measurements. The Cu2O film, deposited by radio frequency magnetron sputtering is highly transparent for light of energy below the fundamental band gap, while concurrently highly absorbing of light with energy above the bandgap. It is concluded that the structure is well suited as the upper junction in a tandem junction solar cell configuration, utilizing an industrial standard Si solar cell as ‘substrate’.