Miracle-dz/UniFAR-FTUs huggingface dataset:
The uremic retention solute p-cresyl sulfate and markers of endothelial damage.

BACKGROUND Cardiovascular disease is highly prevalent in patients with chronic kidney disease. In hemodialysis patients, the protein-bound uremic retention solute p-cresol is independently associated with cardiovascular disease. The underlying mechanisms have not been elucidated. STUDY DESIGN (1) Prospective observational study of humans and (2) in vitro study in human umbilical vein endothelial cells. SETTING Hemodialysis patients. FACTOR p-Cresol and its main derivative p-cresyl sulfate. OUTCOMES Endothelial dysfunction. MEASUREMENTS We studied: (1) the relation between p-cresol and blood markers of endothelial dysfunction, including soluble P-selectin and endothelial microparticles; and (2) direct effects of p-cresol and p-cresyl sulfate on endothelial cell cultures. RESULTS (1) In a cohort of 100 maintenance hemodialysis patients, free serum p-cresol concentrations (median, 11.7 micromol/L; interquartile range, 15.2) were directly associated with circulating endothelial microparticles (P = 0.007), but not with soluble P-selectin (mean, 37.7 +/- 14.4 [SD] pg/mL). Other independent determinants of the degree of circulating microparticles were greater serum phosphorus (mean, 4.8 +/- 1.5 mg/dL; P = 0.008) and serum calcium concentrations (mean, 9.3 +/- 0.8 mg/dL; P = 0.03), whereas treatment with active vitamin D (P = 0.008) and vintage (median, 25 months; P = 0.04) were inversely associated. (2) In vitro, p-cresyl sulfate induced a dose-dependent increase in the shedding of endothelial microparticles (P < 0.001) by human umbilical vein endothelial cells. Shedding was reduced, but not completely aborted, in the presence of albumin, whereas the selective Rho kinase inhibitor Y-27632 abrogated the p-cresyl sulfate-induced generation of endothelial microparticles. LIMITATIONS The relationship between p-cresyl sulfate and shedding of endothelial microparticles in vivo was not mechanistically explored. CONCLUSION p-Cresyl sulfate induces shedding of endothelial microparticles in the absence of overt endothelial damage in vitro and is independently associated with the number of endothelial microparticles in hemodialysis patients. These findings suggest that p-cresyl sulfate alters endothelial function in hemodialysis patients.
Minimization of immunosuppression in kidney transplantation

Purpose of reviewIn an effort to reduce the long-term toxicities of immunosuppressant drugs, corticosteroid and calcineurin inhibitor-sparing immunosuppression protocols have become increasingly popular in managing kidney transplant recipients. This article focuses on outcomes of these strategies described in recently published trials. Recent findingsThe use of induction antibody therapy and potent residual immunosuppressants has increased the safety of steroid-free regimens, resulting in a paradigm shift towards earlier elimination of steroids after kidney transplantation. Even in the modern era, results of randomized trials generally indicate that steroid elimination increases the risk of rejection compared with maintenance steroid therapy. Among calcineurin inhibitor-sparing strategies, withdrawal of these agents after their initial use in stable patients, or conversion to either mycophenolate mofetil or sirolimus in patients with early renal dysfunction appears to yield the greatest benefit in preserving renal function. The outcomes of calcineurin inhibitor avoidance protocols have been mixed and have fallen into disfavor. SummaryThe benefits of minimizing immunosuppression in kidney transplant recipients must be weighed against the risks of precipitating acute rejection or chronic allograft dysfunction. Additional research is needed to identify clinical and immune parameters that will enable selection of patients for whom the benefits outweigh the risks.
Isolation improvement of MIMO antenna for wideband applications

In this letter, a dual element MIMO antenna with orthogonally polarized feed is presented. Isolation between antennas in MIMO systems are considered to be predominant for its mutual coupling effect. The proposed antenna size of 32mm × 64mm × 1.6mm is constructed and its operating frequency is from 2.3 GHz to 6 GHz. The isolation characteristics of MIMO antenna are compared with orthogonally feed elements with the adjacent feed elements. The antenna element consists of a circle slot and continuous meander line slot to delay the current path in order to attain a wideband. The modified ground structure of semi circle ground plane helps to achieve wideband with high isolation. Envelope Correlation Coefficient (ECC) of orthogonally polarized feed achieves less than 0.006 due to its Polarization Diversity characteristics.
Testosterone‐unresponsiveness of existing immunity against Plasmodium chabaudi malaria

Summary Testosterone (Te) is known to suppress immunity and to increase host susceptibility to many parasites. This study investigates the action of Te on immunity acquired against blood‐stages of the malaria parasite Plasmodium chabaudi in female mice of the inbred strain C57BL/10. Our data show: (i) About 90% of mice infected with 106 P. chabaudi‐infected erythrocytes are able to develop protective immune mechanisms which become evident in self‐healing the infection. The capability of self‐healing is lost when mice are pretreated with Te for 3 weeks. (ii) Mice which have self‐healed infections acquire immunity to homologous rechallenge. Concomitantly, mice become Te‐unresponsive in that their acquired immunity is not suppressible by Te‐treatment. (iii) Flow cytometry reveals that Te‐pretreatment entails an increase of CD8+ cells and a decrease of Ig+ cells by about 4% in spleens of non‐immune mice. In immune mice, however, there is a Te‐unresponsiveness of the percental distribution of splenic cell populations. (iv) Adoptive transfer experiments indicate that immunity is conferred by spleen cells, presumably non‐T‐cells. These cells are Te‐unresponsive, since they exert their effect in Te‐pretreated mice in the presence of Te. (v) Teunresponsive immunity can be also transferred by serum, especially the IgG‐fraction, obtained from immune mice. Our data demonstrate that Te prevents the development of protective immunity against P. chabaudi infections. However, when once established, protective immunity becomes unresponsive to Te. Our data suggest that the effector mechanisms of protective immunity involve Teunresponsive B cells secreting protective IgG‐antibodies.
Syndecan‐1 and angiogenic cytokines in multiple myeloma: correlation with bone marrow angiogenesis and survival

Angiogenesis is a complex process involved in the proliferation and metastasis of malignant tumours, and partly triggered by the secretion of various angiogenic factors by tumour cells or cells in the stromal environment. We investigated the correlation between bone marrow angiogenesis, estimated as microvessel density (MVD), and interleukin‐6 (IL‐6), basic fibroblastic growth factor (bFGF), hepatocyte growth factor (HGF) and syndecan‐1 in 67 patients with newly diagnosed multiple myeloma, and evaluated the prognostic value of these parameters. Circulating levels of IL‐6, bFGF, HGF and syndecan‐1 were significantly higher in patients than in controls. Moreover, in patients, bone marrow levels of bFGF, HGF and syndecan‐1 were higher than peripheral blood levels. Positive correlations were found between MVD and syndecan‐1 blood levels (r = 0·33, P = 0·017), syndecan‐1 bone marrow levels (r = 0·49, P = 0·046) and HGF blood levels (r = 0·36, P = 0·008) respectively. High MVD and high blood levels of IL‐6, HGF and syndecan‐1 were predictive of a shorter survival. In a multivariate survival analysis MVD and blood levels of IL‐6 retained independent prognostic significance, while in a survival analysis without MVD the peripheral blood levels of HGF and syndecan‐1 were strong independent prognostic factors.
Retrospective multicenter cohort study of the clinical performance of 2-stage implants in South Korean populations.

PURPOSE To evaluate long-term follow-up clinical performance of dental implants in use in South Korean populations. MATERIALS AND METHODS A retrospective multicenter cohort study design was used to collect long-term follow-up clinical data from dental records of 224 patients treated with 767 2-stage endosseous implants at Ajou University Medical Center and Bundang Jesaeng Hospital in South Korea from June 1996 through December 2003. Exposure variables such as gender, systemic disease, location, implant length, implant diameter, prosthesis type, opposing occlusion type, and date of implant placement were collected. Outcome variables such as date of implant failure were measured. RESULTS Patient ages ranged from 17 to 71.7 years old (mean age, 45.6 years old). Implants were more frequently placed in men than in women (61% versus 39%, or 471 men versus 296 women). Systemic disease was described by 9% of the patients. All implants had hydroxyapatite-blasted surfaces. Most of the implants were 3.75 mm in diameter. Implant lengths 10 mm, 11.5 mm, 13 mm, and 15 mm were used most often. Differences of implant survival among different implant locations were observed. Implants were used to support fixed partial dentures for the majority of the restorations. The opposing dentition was natural teeth for about 50% of the implants. A survival rate of 97.9% (751 of 767) was observed after 4.5 years (mean, 1.95 +/- 1.2 years). CONCLUSION Clinical performance of 2-stage dental implants demonstrated a high level of predictability. The results achieved with a South Korean population did not differ from results achieved with diverse ethnic groups.
Efficacy and safety of pegylated interferon combined with ribavirin for the treatment of older patients with chronic hepatitis C.

BACKGROUND The present study evaluated the efficacy and safety of pegylated interferon (PegIFN)/ribavirin treatment in elderly patients with hepatitis C virus (HCV) infection. METHODS Seventy elderly patients with hepatitis C virus (HCV) infection (group A; age, > or = 65 years) and 140 sex- and HCV genotype-matched controls (group B; age, 50-64 years) were allocated to receive a PegIFN-alpha-2a/ribavirin standard-of-care regimen. RESULTS Group A had a significantly higher rate of treatment discontinuation (21.4% vs 6.4%; P = .001) and grade 3 or 4 adverse events (34.3% vs 20%; P = .002) than group B. In intention-to-treat analysis, the sustained virologic response (SVR) rate was substantially lower in group A than in group B (67.1% vs 78.6%; P = .07). The inferiority of the SVR rate in group A was observed among patients with HCV genotype 1 (HCV-1) (51.9% vs 75.9%; P = .03) but not among patients with HCV genotype 2 or 3 (HCV-2/3) (76.7% vs 80.2%; P = .65). Among patients in group A who had a rapid virologic response, those infected with HCV-1 and those infected with HCV-2/3 had similar SVR rates (80% and 87.9%, respectively). For patients receiving treatment for >80% of its expected duration, SVR rates were similar between the 2 groups (80.4% vs 82.6%, respectively), regardless of viral genotype. CONCLUSIONS Older patients with HCV infection, especially those in the subgroup infected with HCV-1, had a greater frequency of adverse events and poorer adherence to the standard-of-care regimen, which may be the major reason for treatment inferiority. TRIAL REGISTRATION Clinicaltrials.gov identifier NCT00629824 .
Thoracic Aortas from Multiorgan Donors Are Suitable for Obtaining Resident Angiogenic Mesenchymal Stromal Cells

The clinical use of endothelial progenitor cells is hampered by difficulties in obtaining an adequate number of functional progenitors. This study aimed to establish whether human thoracic aortas harvested from healthy multiorgan donors can be a valuable source of angiogenic progenitors. Immunohistochemical tissue studies showed that two distinct cell populations with putative stem cell capabilities, one composed of CD34+ cells and the other of c‐kit+ cells, are present in between the media and adventitia of human thoracic aortas. Ki‐67+ cells with high growth potential were located in an area corresponding to the site of CD34+ and c‐kit+ cell residence. We thus isolated cells (0.5 ∼ 2.0 × 104 aortic progenitors per 25 cm2) which, upon culturing, coexpressed molecules of mesenchymal stromal cells (i.e., CD44+, CD90+, CD105+) and showed a transcript expression of stem cell markers (e.g., OCT4, c‐kit, BCRP‐1, Interleukin‐6) and BMI‐1. Cell expansion was adequate for use in a clinical setting. A subset of cultured cells acquired the phenotype of endothelial cells in the presence of vascular endothelial growth factor (e.g., increased expression of KDR and von Willebrand factor positivity), as documented by flow cytometry, immunofluorescence, electron microscopy, and reverse transcription‐polymerase chain reaction assays. An in vitro angiogenesis test kit revealed that cells were able to form capillary‐like structures within 6 hours of seeding. This study demonstrates that thoracic aortas from multiorgan donors yield mesenchymal stromal cells with the ability to differentiate in vitro into endothelial cells. These cells can be used for the creation of an allogenic bank of angiogenic progenitors, thus providing new options for restoring vascularization at ischemic sites.
Discontinuing venom immunotherapy

The decision to discontinue venom immunotherapy requires a great deal of clinical judgement because of the potential for a life-threatening reaction to a sting. The risk of recurrence is a combination of the frequency of reaction and the severity of reaction. Early studies reported a relapse rate of 8-14% in radioallergosorbent test-negative patients when therapy was stopped after 3 years. Unfortunately, the venom skin test or radioallergosorbent test becomes negative in only 25% of patients after 5 years of treatment. An alternative criterion for stopping treatment after 5 years regardless of the skin test has been equally successful, with most post-treatment reactions being much milder than pre-treatment reactions. There was no evidence of a rebound of venom sensitivity when therapy was stopped, even when patients were stung. The level of venom-specific IgE antibodies is better suppressed by 5 than by 3 years of treatment. The risk of relapse is higher in honeybee-allergic patients and in patients who had a systemic reaction (to a sting or an injection) during therapy. The frequency of reaction may be low, but patients who had very severe pre-treatment reactions have a greater chance of the reaction being severe again, and should remain on therapy for life. Long-term observations show that the incidence of systemic reaction to a sting remains 10% for each sting that occurs, even 10-15 years after stopping treatment. Because patients may not react to one sting and then subsequently react to another sting, the cumulative frequency of sting reactions is approximately 17% after 10 years off treatment. Moreover, negative venom skin tests are not a guarantee of safety because there is almost the same 10% frequency of reaction in patients who appear to lose sensitivity. It is not yet clear whether some low-risk patients (children, mild reactors) could discontinue treatment after just 3 years.
Optogenetic stimulation of adrenergic C1 neurons causes sleep state-dependent cardiorespiratory stimulation and arousal with sighs in rats.

RATIONALE The rostral ventrolateral medulla (RVLM) contains central respiratory chemoreceptors (retrotrapezoid nucleus, RTN) and the sympathoexcitatory, hypoxia-responsive C1 neurons. Simultaneous optogenetic stimulation of these neurons produces vigorous cardiorespiratory stimulation, sighing, and arousal from non-REM sleep. OBJECTIVES To identify the effects that result from selectively stimulating C1 cells. METHODS A Cre-dependent vector expressing channelrhodopsin 2 (ChR2) fused with enhanced yellow fluorescent protein or mCherry was injected into the RVLM of tyrosine hydroxylase (TH)-Cre rats. The response of ChR2-transduced neurons to light was examined in anesthetized rats. ChR2-transduced C1 neurons were photoactivated in conscious rats while EEG, neck muscle EMG, blood pressure (BP), and breathing were recorded. MEASUREMENTS AND MAIN RESULTS Most ChR2-expressing neurons (95%) contained C1 neuron markers and innervated the spinal cord. RTN neurons were not transduced. While the rats were under anesthesia, the C1 cells were faithfully activated by each light pulse up to 40 Hz. During quiet resting and non-REM sleep, C1 cell stimulation (20 s, 2-20 Hz) increased BP and respiratory frequency and produced sighs and arousal from non-REM sleep. Arousal was frequency-dependent (85% probability at 20 Hz). Stimulation during REM sleep increased BP, but had no effect on EEG or breathing. C1 cell-mediated breathing stimulation was occluded by hypoxia (12% FIO2), but was unchanged by 6% FiCO2. CONCLUSIONS C1 cell stimulation reproduces most effects of acute hypoxia, specifically cardiorespiratory stimulation, sighs, and arousal. C1 cell activation likely contributes to the sleep disruption and adverse autonomic consequences of sleep apnea. During hypoxia (awake) or REM sleep, C1 cell stimulation increases BP but no longer stimulates breathing.
Multilocus Sequence Analysis Reveals that Vibrio harveyi and V. campbellii Are Distinct Species

ABSTRACT Identification and classification of Vibrio species have relied upon band pattern methods (e.g., amplified fragment length polymorphism) and DNA-DNA hybridization. However, data generated by these methods cannot be used to build an online electronic taxonomy. In order to overcome these limitations, we developed the first standard multilocus sequence scheme focused on the ubiquitous and pathogenic Vibrio harveyi species group (i.e., V. harveyi, V. campbellii, V. rotiferianus, and a new as yet unnamed species). We examined a collection of 104 isolates from different geographical regions and hosts using segments of seven housekeeping genes. These two species formed separated clusters on the basis of topA, pyrH, ftsZ, and mreB gene sequences. The phylogenetic picture obtained by the other three loci, i.e., gyrB, recA, and gapA, was more complex though. V. campbellii appeared nested within V. harveyi in the recA trees, whereas V. harveyi formed a tight nested cluster within V. campbellii by gapA. The gyrB gene had no taxonomic resolution and grouped the two species together. The fuzziness observed in these three genes seems not be related to recombination but to low divergence due to the accumulation of only a few substitutions. In spite of this, the concatenated sequences provided evidence that the two species form two separated clusters. These clusters did not arise by recombination but by accumulation of point mutations. V. harveyi and V. campbellii isolates can be readily identified through the open database resource developed in this study (http://www.taxvibrio.lncc.br/ ). We argue that the species should be defined by evolutionary criteria. Strains of the same species will share at least 95% concatenated sequence similarity using the seven loci, and, most importantly, cospecific strains will form cohesive readily recognizable phylogenetic clades.
Distinguishing four fundamental approaches to the evolution of helping

The evolution and stability of helping behaviour has attracted great research efforts across disciplines. However, the field is also characterized by a great confusion over terminology and a number of disagreements, often between disciplines but also along taxonomic boundaries. In an attempt to clarify several issues, we identify four distinct research fields concerning the evolution of helping: (1) basic social evolution theory that studies helping within the framework of Hamilton’s inclusive fitness concept, i.e. direct and indirect benefits, (2) an ecological approach that identifies settings that promote life histories or interaction patterns that favour unconditional cooperative and altruistic behaviour, e.g. conditions that lead to interdependency or interactions among kin, (3) the game theoretic approach that identifies strategies that provide feedback and control mechanisms (protecting from cheaters) favouring cooperative behaviour (e.g. pseudo‐reciprocity, reciprocity), and (4) the social scientists’ approach that particularly emphasizes the special cognitive requirements necessary for human cooperative strategies. The four fields differ with respect to the ‘mechanisms’ and the ‘conditions’ favouring helping they investigate. Other major differences concern a focus on either the life‐time fitness consequences or the immediate payoff consequences of behaviour, and whether the behaviour of an individual or a whole interaction is considered. We suggest that distinguishing between these four separate fields and their complementary approaches will reduce misunderstandings, facilitating further integration of concepts within and across disciplines.
The Role of Hydralazine Therapy for Pulmonary Arterial Hypertension of Unknown Cause

Hydralazine was administered acutely to 12 patients who had pulmonary arterial hypertension of unknown cause. All of the patients were studied at rest and nine during exercise. On the basis of hydralazine response at rest, the patients were divided in two groups. In six patients (group A), pulmonary arteriolar resistance (Rp) decreased from 8.4 ± 1.4 to 4.8 ± 1.4 U/in (p < 0.001), cardiac index (CI) increased from 3.47 i 0.3 to 5.86 ± 0.5 1/min/m' (p < 0.005) and systemic resistance (Rs) decreased from 25 4 to 14 ± 2 U/mi (p < 0.01). The Rp/Rs ratio did not change significantly after hydralazine (0.32 ± 0.03 vs 0.33 ± 0.07, NS). In the other six patients (group B), Rs decreased from 25 ± 2 to 17.0 ± 1 U/mi (p < 0.01), but the other variables did not change significantly. Our results suggest that the pulmonary vasodilatory effect of hydralazine caused a marked reduction in right ventricular afterload in group A. In group B, a marked systemic vasodilatory effect occurred and right ventricular afterload was not reduced. On the basis of the previous hemodynamic response, only group A patients were treated with oral hydralazine (50 mg every 6 hours). Hemodynamic measurements were repeated 48 hours after hydralazine, both at rest and during exercise, as well as 8 months later in five of the six patients in whom the beneficial hemodynamic effects persisted. These data suggest that hydralazine can reduce Rp in selected patients (pulmonary arterial pressure < 60 mm Hg, Rp < 15 U/Mi and Rp/Rs ratio < 0.7) with pulmonary hypertension of unknown cause.
Evidence for Simultaneous Protein Interactions between Human Rad51 Paralogs*

In yeast, the Rad51-related proteins include Rad55 and Rad57, which form a heterodimer that interacts with Rad51. Five human Rad51 paralogs have been identified (XRCC2, XRCC3, Rad51B/Rad51L1, Rad51C/Rad51L2, and Rad51D/Rad51L3), and each interacts with one or more of the others. Previously we reported that HsRad51 interacts with XRCC3, and Rad51C interacts with XRCC3, Rad51B, and HsRad51. Here we report that in the yeast two-hybrid system, Rad51D interacts with XRCC2 and Rad51C. No other interactions, including self-interactions, were found, indicating that the observed interactions are specific. The yeast Rad51 interacts with human Rad51 and XRCC3, suggesting Rad51 conservation since the human yeast divergence. Data from yeast three-hybrid experiments indicate that a number of the pairs of interactions between human Rad51 paralogs can occur simultaneously. For example, Rad51B expression enhances the binding of Rad51C to XRCC3 and to HsRad51D, and Rad51C expression allows the indirect interaction of Rad51B with Rad51D. Experiments using 6xHis-tagged proteins in the baculovirus system confirm several of our yeast results, including Rad51B interaction with Rad51D only when Rad51C is simultaneously expressed and Rad51C interaction with XRCC2 only when Rad51D is present. These results suggest that these proteins may participate in one complex or multiple smaller ones.