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Supplemental Digital Content is available in the text., In patients with resistant or poorly controlled hypertension and advanced chronic kidney disease, mineralocorticoid receptor antagonists are recommended; however, hyperkalemia limits their use. BLOCK-CKD was a phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group study that evaluated the safety, efficacy, and pharmacokinetics of KBP-5074, a nonsteroidal mineralocorticoid receptor antagonist, for uncontrolled hypertension in patients with stage 3b/4 chronic kidney disease. The study tested the hypothesis that addition of KBP-5074 to standard treatment lowers blood pressure without increased risk of hyperkalemia. Patients (N=162) were randomly assigned 1:1:1 to once-daily oral treatment with placebo, KBP-5074 0.25 mg, or KBP-5074 0.5 mg. The primary end point was systolic blood pressure change from baseline at day 84. Baseline mean (SD) systolic blood pressure was 155.3 (13.55) mm Hg. After 84 days, the placebo-subtracted treatment mean difference (SE) was −7.0 (3.37) mm Hg with KBP-5074 0.25 mg (P=0.0399) and −10.2 (3.32) mm Hg with KBP-5074 0.5 mg (P=0.0026). Hyperkalemia incidence, ≥5.6

Made available in DSpace on 2021-06-25T10:46:44Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-05-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Alcoholic injury can alter the hormonal signaling pathway and lead to glucose and lipid metabolism disorders. In this study, we investigated whether the strength training could exert protective effects against the alterations caused by ethanol consumption on prostatic metabolism. A UChB, ethanol-preferring rats were used in this study. Strength training was conducted for 3 days per week for 13 weeks, rats performed jumps in water carrying a weight load strapped to their chests as part of a strength training protocol. The reduced alcohol consumption by strength training was accompanied by increased glucose, serum lipid profile, total protein levels, and reduced hormonal levels. The results of protein expression of prostatic tissues in the ethanol- and strength training-treated groups indicated that “steroidal hormone receptors,” “fatty acid translocation,” and “cell regulation” were significantly different between ethanol- and strength training-treated groups. Taken together, these findings show that strength training effectively ameliorated prostatic injuries in alcoholic rats at least partially by acting on lipids receptors and steroidal hormone receptors pathway, suggesting the strength training as a potential novel therapeutic strategy for treating prostate injuries caused by ethanol. Department of Physical Education School of Technology and Sciences UNESP Campus of Presidente Prudente Postgraduate Program in Multicentric Physiological Sciences São Paulo State University—UNESP Campus of Aracatuba Postgraduate Program in Movement Sciences São Paulo State University—UNESP Campus of Presidente Prudente Department of Anatomy Institute of Biosciences São Paulo State University UNESP Postgraduate Program in Animal Science Postgraduate Program in Health Sciences University of Western São Paulo—UNOESTE Department of Plant Agriculture University of Guelph Department of Structural and Functional Biology Institute of Biology State University of Campina—UNICAMP State University of Western Paraná Department of Veterinary Hygiene and Public Health Faculty of Veterinary Medicine and Animal Science São Paulo State University UNESP Department of Physical Education School of Technology and Sciences UNESP Campus of Presidente Prudente Postgraduate Program in Multicentric Physiological Sciences São Paulo State University—UNESP Campus of Aracatuba Postgraduate Program in Movement Sciences São Paulo State University—UNESP Campus of Presidente Prudente Department of Anatomy Institute of Biosciences São Paulo State University UNESP Department of Veterinary Hygiene and Public Health Faculty of Veterinary Medicine and Animal Science São Paulo State University UNESP CAPES: 001 FAPESP: 08/00479-6 FAPESP: 13/25927-0

Neurological complications after transcatheter aortic valve replacement (TAVR) may be reduced with transcatheter cerebral embolic protection (TCEP).This study evaluated the safety and efficacy of TCEP during TAVR.Nineteen centers randomized 363 patients undergoing TAVR to a safety arm (n = 123), device imaging (n = 121), and control imaging (n = 119). The primary safety endpoint consisted of major adverse cardiac and cerebrovascular events (MACCE) at 30 days, and the primary efficacy endpoint was reduction in new lesion volume in protected brain territories on magnetic resonance imaging scans at 2 to 7 days. Patients underwent neurocognitive assessments, and the debris captured was analyzed.The rate of MACCE (7.3%) was noninferior to the performance goal (18.3%, pTCEP was safe, captured embolic debris in 99% of patients, and did not change neurocognitive function. Reduction in new lesion volume on magnetic resonance scans was not statistically significant. (Cerebral Protection in Transcatheter Aortic Valve Replacement [SENTINEL]; NCT02214277).

Made available in DSpace on 2019-10-06T16:46:22Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-10-15 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Obesity has a positive relation to non-alcoholic fatty liver disease (NAFLD) and studies have demonstrated that strength training can regulate lipid accumulation in the hepatocytes of obese rats. Aims: Our aim is to evaluate the effects of high fat diet and strength training on markers of oxidation and lipogenesis in the liver of Wistar rats. Main methods: Forty Wistar rats were divided into four groups (n = 10): control (CTL), strength training (TR), high fat diet consumption (HF) and high fat diet consumption with strength training (HFT). Animals were subjected to physical strength training and high fat diet consumption for 12 weeks, 3 session per week. Then, the animals were euthanized, and liver markers were evaluated via immunolabeling. Key findings: Our results indicated that strength training reduced the expression of adiposity as well as the accumulation of glycogen and lipids in the liver. This reduction of fatty acid (FA) stored in hepatocytes is related to reduction of proteins linked to β-oxidation such as Fas/CD95, LIMP-II and CD36, as well as other proteins linked to lipogeneses such as SREBP-1. Significance: Finally, we observed that high fat diet can alter lipogenesis and reduce β-oxidation promoted hepatic fat accumulation. In conclusion, there was a reduction of obesity-related hepatic lipogenesis after 12 weeks of strength training. Postgraduate Program in Movement Sciences São Paulo State University-UNESP, campus of Presidente Prudente Department of Physiotherapy School of Technology and Sciences UNESP, campus of Presidente Prudente Graduated Physical Education São Paulo State University-UNESP, campus of Presidente Prudente Department of Plant Agriculture University of Guelph Postgraduate Program in Movement Sciences São Paulo State University-UNESP, campus of Presidente Prudente Department of Physiotherapy School of Technology and Sciences UNESP, campus of Presidente Prudente Graduated Physical Education São Paulo State University-UNESP, campus of Presidente Prudente CAPES: 001

Introduction: Ovariectomy (OVX) results in bone loss caused by increased bone resorption. RANKL is an essential mediator of bone resorption. We examined whether the RANKL inhibitor osteoprotegerin (OPG) would preserve bone volume, density, and strength in OVX rats. Materials and Methods: Rats were OVX or sham-operated at 3 mo of age. Sham controls were treated for 6 wk with vehicle (Veh, PBS). OVX rats were treated with Veh or human OPG-Fc (10 mg/kg, 2/wk). Serum RANKL and TRACP5b was measured by ELISA. BMD of lumbar vertebrae (L1–L5) and distal femur was measured by DXA. Right distal femurs were processed for bone histomorphometry. Left femurs and the fifth lumbar vertebra (L5) were analyzed by μCT and biomechanical testing, and L6 was analyzed for ash weight. Results: OVX was associated with significantly greater serum RANKL and osteoclast surface and with reduced areal and volumetric BMD. OPG markedly reduced osteoclast surface and serum TRACP5b while completely preventing OVX-associated bone loss in the lumbar vertebrae, distal femur, and femur neck. Vertebrae from OPG-treated rats had increased dry and ash weight, with no significant differences in tissue mineralization versus OVX controls. μCT showed that trabecular compartments in OVX-OPG rats had significantly greater bone volume fraction, vBMD, bone area, trabecular thickness, and number, whereas their cortical compartments had significantly greater bone area (p < 0.05 versus OVX-Veh). OPG improved cortical area in L5 and the femur neck to levels that were significantly greater than OVX or sham controls (p < 0.05). Biomechanical testing of L5 and femur necks showed significantly greater maximum load values in the OVX-OPG group (p < 0.05 versus OVX-Veh). Bone strength at both sites was linearly correlated with total bone area (r2 = 0.54–0.74, p < 0.0001), which was also significantly increased by OPG (p < 0.05 versus OVX). Conclusions: OPG treatment prevented bone loss, preserved trabecular architecture, and increased cortical area and bone strength in OVX rats.

Artemin (ART) signals through the GFR α—3/RET receptor complex to support sympathetic neuron development. Here we show that ART also influences autonomic elements in adrenal medulla and enteric and pelvic ganglia. Transgenic mice over-expressing Art throughout development exhibited systemic autonomic neural lesions including fusion of adrenal medullae with adjacent paraganglia, adrenal medullary dysplasia, and marked enlargement of sympathetic (superior cervical and sympathetic chain ganglia) and parasympathetic (enteric, pelvic) ganglia. Changes began by gestational day 12.5 and formed progressively larger masses during adulthood. Art supplementation in wild type adult mice by administering recombinant protein or an Art-bearing retroviral vector resulted in hyperplasia or neuronal metaplasia at the adrenal corticomedullary junction. Expression data revealed that Gfr α—3 is expressed during development in the adrenal medulla, sensory and autonomic ganglia and their projections, while Art is found in contiguous mesenchymal domains (especially skeleton) and in certain nerves. Intrathecal Art therapy did not reduce hypalgesia in rats following nerve ligation. These data (1) confirm that ART acts as a differentiation factor for autonomic (chiefly sympathoadrenal but also parasympathetic) neurons, (2) suggest a role for ART overexpression in the genesis of pheochromocytomas and paragangliomas, and (3) indicate that ART is not a suitable therapy for peripheral neuropathy.

The trend towards massive parallel computing has necessitated the need for an On-Chip communication framework that can scale well with the increasing number of cores. At the same time, technology scaling has made transistors susceptible to a multitude of reliability issues (NBTI, HCI, TDDB). In this work, we propose an HCI-Tolerant microarchitecture for an NoC Router by manipulating the switching activity around the circuit. We find that most of the switching activity (the primary cause of HCI degradation) are only concentrated in a few parts of the circuit, severely degrading some portions more than others. Our techniques increase the lifetime of an NoC router by balancing this switching activity. Compared to an NoC without any reliability techniques, our best schemes improve the switching activity distribution, clock cycle degradation, system performance and energy delay product per flit by 19%, 26%, 11% and 17%, respectively, on an average.

This is a descriptive report of the management techniques used effectively in the emergency department (ED) treatment of acute congestive heart failure (CHF) in renal dialysis patients. Study design included a prospective case series of consecutive renal dialysis patients who presented to the ED of a regional dialysis center in acute CHF. Clinical presentation, ED management, and outcome were recorded. Forty-six patients (38 hemodialysis and 8 peritoneal dialysis) were included in this study. Presentation classifications for these patients were minimal distress (13 patients), moderate distress (16 patients), and severe distress (17 patients). In addition to supplemental oxygen, treatment focused on pharmacological preload and afterload reduction. Patients received sublingual nitroglycerin (NTG) (30 patients), transdermal NTG (36 patients), captopril sublingual (10 patients) nifedipine oral (nine patients), nitroprusside (four patients), morphine sulfate (one patient), NTG infusion (one patient), and clonidine (one patient). There were no deaths in the study group, and 32 of the patients were able to be dialyzed and discharged, including seven patients in the severe group. Six patients required intubation, one of whom was extubated and discharged from the ED after dialysis. Intravascular access was obtained in 29 patients but was used in only six. All patients on nitroprusside drips were weaned during the course of their dialysis. Effective ED management of acute CHF in renal dialysis patients can be accomplished through preload reduction with nitrates and afterload reduction with captopril, nifedipine, and, in severe cases, nitroprusside.

During our initial attempts to produce transgenic rats, we found that an anaesthetic combination typically used for embryo transfer (intramuscular injection of ketamine [90 mg/kg] with xylazine [10 mg/kg]) yielded extensive variation in both the depth and length of anaesthesia. In the present prospective study, we compared the reproductive outcomes afforded by using either isoflurane (5% for induction, 2% for maintenance, carried in 2 l/min of oxygen) with morphine (5 mg/kg s.c., given immediately after isoflurane induction) or ketamine/xylazine in adult (250–300 g), pseudopregnant Sprague-Dawley rats. Each animal was anaesthetized with either isoflurane/morphine or ketamine/xylazine, after which 30 microinjected eggs were transferred into the left uterine horn. The mean pregnancy rate for isoflurane/morphine (15%) was 50% greater than that achieved with ketamine/xylazine (10%). The mean number of live pups (just over five per litter) was comparable for both regimens. All rats given isoflurane/morphine quickly achieved a surgical depth of anaesthesia and experienced a rapid postoperative recovery (3–5 min). In contrast, 25% of rats injected with ketamine/xylazine did not reach a depth of anaesthesia within 10 min that was sufficient for laparotomy, and all that were anaesthetized successfully required an extended postoperative recovery period (60–90 min). These data show that isoflurane/morphine is well tolerated by microinjected embryos and suggest that its use during embryo transfer may provide a means for both reducing the number of pseudopregnant females used and increasing the speed with which rat transgenic projects are completed.