Miracle-dz/UniFAR-FTUs huggingface dataset:
Rho/Rho-Kinase Pathway in Brain Stem Contributes to Blood Pressure Regulation via Sympathetic Nervous System: Possible Involvement in Neural Mechanisms of Hypertension

Abstract— Recent studies have demonstrated that the Rho/Rho-kinase pathway plays an important role in various cellular functions, including actin cytoskeleton organization and vascular smooth muscle contraction. This pathway is also present in the central nervous system and is involved in the maintenance of dendritic spines and axon outgrowth and in the regulation of neurotransmitter release. However, its role in central blood pressure regulation is unknown. In the present study, blockade of the Rho/Rho-kinase pathway in the nucleus tractus solitarii (NTS) of the brain stem by microinjection of a specific Rho-kinase inhibitor decreased blood pressure, heart rate, and renal sympathetic nerve activity in both Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). However, the magnitude of decreases in these variables was greater in SHR than in WKY rats. In addition, an adenovirus vector encoding dominant-negative Rho-kinase decreased blood pressure, heart rate, and urinary norepinephrine excretion in both WKY rats and SHR in an awake and free-moving state. The magnitude of decreases in these variables was also greater in SHR than in WKY rats. Furthermore, membrane RhoA expression and Rho-kinase activity in the NTS were enhanced in SHR compared with WKY rats. These observations indicate that the Rho/Rho-kinase pathway in the NTS contributes to blood pressure regulation via the sympathetic nervous system in vivo and suggest that activation of this pathway is involved in the central mechanisms of hypertension.
What affects organizational performance?: The linking of learning and knowledge management

Purpose – The purpose of this paper is to propose a conceptual structural equation model to investigate the relationships among self‐directed learning (SDL), organizational learning (OL), knowledge management capability (KMC) and organizational performance (OP) and to demonstrate the direct and indirect effect of SDL on OP from the perspectives of KMC and OL.Design/methodology/approach – An empirical study is conducted in 21 technological companies (N=236) in Taiwan and the collected survey data are used to test the relationships among the four dimensions expressed in the proposed structural equation model.Findings – The results show that SDL has a direct and significant impact on OL and KMC. SDL influences OP indirectly through OL and KMC. In addition, OL and KMC have direct and significant influences on OP.Research limitations/implications – The source of data collected is Taiwan, hence, the results may not be easily generalized to other areas or countries. However, the findings are valuable for manager.
Effect of non-enzymatic antioxidants in extender on post-thaw quality of buffalo (Bubalus bubalis) bull spermatozoa.

The objective of the present study was to determine the effect of non-enzymatic antioxidants (vitamin C or E) in tris-citric acid buffer (TCA) on post-thaw quality of buffalo (Bubalus bubalis) bull spermatozoa. Split pooled buffalo bull ejaculates were diluted in TCA egg yolk glycerol extender containing either vitamin C (TCAC), vitamin E (TCAE) or without antioxidant (TCAN) at 37°C. Extended semen was cooled to 4°C in 2 h and equilibrated for 4 h at 4°C. Cooled semen was then filled in 0.5 ml straws at 4°C and frozen in programmable cell freezer. Thawing of semen was performed at 37°C for 30 seconds. Sperm motility, plasma membrane integrity and sperm morphology (acrosome integrity, head, mid-piece and tail abnormalities) of each semen sample were evaluated. Percentage of post-thaw spermatozoal motility assessed visually at 0 and 6 h and the post-thaw percentage of spermatozoa with intact plasma membranes at 0 h were higher (P 0.05). In conclusion, non-enzymatic antioxidants, particularly vitamin E, in the tris citric acid extender may improve the quality of frozen-thawed buffalo bull spermatozoa.
Is Incretin-Based Therapy Ready for the Care of Hospitalized Patients With Type 2 Diabetes? Insulin therapy has proven itself and is considered the mainstay of treatment

© 2013, American Diabetes Association This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported License ( http://creativecommons.org/licenses/by/3.0/), which permits distribution of derivative works, distribution, public display, and publicly performance, making multiple copies, provided the original work is properly cited. This license requires credit be given to copyright holder and/or author, copyright and license notices be kept intact.
Race, Ethnicity, and Socioeconomic Status in Research on Child Health

An extensive literature documents the existence of pervasive and persistent child health, development, and health care disparities by race, ethnicity, and socioeconomic status (SES). Disparities experienced during childhood can result in a wide variety of health and health care outcomes, including adult morbidity and mortality, indicating that it is crucial to examine the influence of disparities across the life course. Studies often collect data on the race, ethnicity, and SES of research participants to be used as covariates or explanatory factors. In the past, these variables have often been assumed to exert their effects through individual or genetically determined biologic mechanisms. However, it is now widely accepted that these variables have important social dimensions that influence health. SES, a multidimensional construct, interacts with and confounds analyses of race and ethnicity. Because SES, race, and ethnicity are often difficult to measure accurately, leading to the potential for misattribution of causality, thoughtful consideration should be given to appropriate measurement, analysis, and interpretation of such factors. Scientists who study child and adolescent health and development should understand the multiple measures used to assess race, ethnicity, and SES, including their validity and shortcomings and potential confounding of race and ethnicity with SES. The American Academy of Pediatrics (AAP) recommends that research on eliminating health and health care disparities related to race, ethnicity, and SES be a priority. Data on race, ethnicity, and SES should be collected in research on child health to improve their definitions and increase understanding of how these factors and their complex interrelationships affect child health. Furthermore, the AAP believes that researchers should consider both biological and social mechanisms of action of race, ethnicity, and SES as they relate to the aims and hypothesis of the specific area of investigation. It is important to measure these variables, but it is not sufficient to use these variables alone as explanatory for differences in disease, morbidity, and outcomes without attention to the social and biologic influences they have on health throughout the life course. The AAP recommends more research, both in the United States and internationally, on measures of race, ethnicity, and SES and how these complex constructs affect health care and health outcomes throughout the life course.
Calcitonin gene-related peptide, heme oxygenase-1, endothelial progenitor cells and nitric oxide-dependent vasodilation relationships in a human model of angiotensin II type-1 receptor antagonism

Objective: An increased number of endothelial progenitor cells (EPCs), which correlated with heme oxygenase-1 gene expression and nitric oxide-mediated vasodilation [flow-mediated dilation (FMD)], has been recently reported by us in Bartter/Gitelman syndromes, rare diseases that represent a human model of endogenous angiotensin (Ang) II type-1 receptor antagonism and depicting an opposite picture of hypertension. Calcitonin gene-related peptide (CGRP), which prevents circulating EPCs senescence and reverses Ang II-induced EPCs senescence is reduced in hypertensive patients, its level is stimulated by heme oxygenase-1 and is related with stimulation of nitric oxide. This study reports on CGRP concentration and heme oxygenase-1 protein level in Bartter/Gitelman syndrome's patients compared with healthy individuals and analyzes their relationships with EPCs [CD34+kinase insert domain receptor (KDR+), CD133+KDR+, CD34+CD133+KDR+) as well as FMD. Methods and results: CGRP concentration (ELISA) and heme oxygenase-1 protein level (sandwich immunoassay) were higher in Bartter/Gitelman syndrome : 38.20 ± 8.23 pg/ml vs. 25.07 ± 3.51, P < 0.002 and 9.44 ± 3.1 ng/ml vs. 5.52 ± 1.1, P < 0.007, respectively. CD133+KDR+ and CD34+CD133+KDR+ (direct three-color flow cytometry analysis) and FMD (B-mode echo scan of brachial artery) were confirmed higher in Bartter/Gitelman syndrome. CGRP and heme oxygenase-1 strongly correlated (P < 0.0001) and did not differ by group. In Bartter/Gitelman syndrome, both CGRP and heme oxygenase-1 were strongly correlated with both EPCs and FMD. Conclusions: Using a human model opposite to hypertension, this study provides information on the relationships between CGRP, heme oxygenase-1, FMD, major clinical and biochemical factors involved in cardiovascular disease, and EPC-specific populations and may also serve to confirm the utility of Bartter/Gitelman syndrome patients in delineating EPCs and related factors roles in the pathophysiology of cardiovascular remodeling in humans.
Variation-Tolerant Write Completion Circuit for Variable-Energy Write STT-RAM Architecture

In this paper, we demonstrate an energy-reduction strategy that overcomes the stochastic switching characteristics of the spin-torque-transfer magnetic-RAM (STT-RAM) write operation and propose a write completion circuit needed for it. In contrast to the traditional worst case approach, which fixes the write duration for all cells, the proposed write technique terminates the write pulse after a write process finishes by monitoring the state of a cell. Since the average write duration is far shorter than the worst case duration, the average write energy is significantly reduced by the proposed architecture. We developed a write completion circuit for state change detection and bitline termination, and evaluated it using a compact STT-RAM model targeting an implementation in a 16-nm technology node. We also developed a variation-tolerant version of the design specifically suited for handling significant variation in process parameters for both FETs and magnetic tunnel junctions (MTJs), and the low value of tunnel magnetoresistance of practical MTJs. Analysis indicates that at the required write-error rate, the proposed architecture reduces write energy by 36%-97% compared with the conventional designs relying on the worst case approach.
Computer-assisted Total Knee Arthroplasty Using Patient-specific Templating

Current techniques used for total knee arthroplasty rely on conventional instrumentation that violates the intramedullary canals. Accuracy of the instrumentation is questionable, and assembly and disposal of the numerous pieces is time consuming. Navigation techniques are more accurate, but their broad application is limited by cost and complexity. We aimed to prove a new concept of computer-assisted preoperative planning to provide patient-specific templates that can replace conventional instruments. Computed tomography-based planning was used to design two virtual templates. Using rapid prototyping technology, virtual templates were transferred into physical templates (cutting blocks) with surfaces that matched the distal femur and proximal tibia. We performed 45 total knee arthroplasties on 16 cadaveric and 29 plastic knees, including a comparative trial against conventional instrumentations. All operations were performed using patient-specific templates with no conventional instrumentations, intramedullary perforation, tracking, or registration. The mean time for bone cutting was 9 minutes with a surgical assistant and 11 minutes without an assistant. Computer-assisted analyses of six random computed tomography scans showed mean errors for alignment and bone resection within 1.7° and 0.8 mm (maximum, 2.3° and 1.2 mm, respectively). Patient-specific templates are a practical alternative to conventional instrumentations, but additional clinical validation is required before clinical use.
Differential Expression of Melanopsin Isoforms Opn4L and Opn4S during Postnatal Development of the Mouse Retina

Photosensitive retinal ganglion cells (pRGCs) respond to light from birth and represent the earliest known light detection system to develop in the mouse retina. A number of morphologically and functionally distinct subtypes of pRGCs have been described in the adult retina, and have been linked to different physiological roles. We have previously identified two distinct isoforms of mouse melanopsin, Opn4L and Opn4S, which are generated by alternate splicing of the Opn4 locus. These isoforms are differentially expressed in pRGC subtypes of the adult mouse retina, with both Opn4L and Opn4S detected in M1 type pRGCs, and only Opn4L detected in M2 type pRGCs. Here we investigate the developmental expression of Opn4L and Opn4S and show a differential profile of expression during postnatal development. Opn4S mRNA is detected at relatively constant levels throughout postnatal development, with levels of Opn4S protein showing a marked increase between P0 and P3, and then increasing progressively over time until adult levels are reached by P10. By contrast, levels of Opn4L mRNA and protein are low at birth and show a marked increase at P14 and P30 compared to earlier time points. We suggest that these differing profiles of expression are associated with the functional maturation of M1 and M2 subtypes of pRGCs. Based upon our data, Opn4S expressing M1 type pRGCs mature first and are the dominant pRGC subtype in the neonate retina, whereas increased expression of Opn4L and the maturation of M2 type pRGCs occurs later, between P10 and P14, at a similar time to the maturation of rod and cone photoreceptors. We suggest that the distinct functions associated with these cell types will develop at different times during postnatal development.
Urinary tract infection in children: recurrent infections.

INTRODUCTION Up to 11% of girls and 7% of boys will have had a urinary tract infection (UTI) by the age of 16 years, and recurrence of infection is common. Vesicoureteric reflux (VUR) is identified in up to 40% of children being investigated for a first UTI, and is a risk factor for, but weak predictor of, renal parenchymal defects. METHODS AND OUTCOMES We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of prophylactic antibiotics to prevent recurrent urinary tract infection in children? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2013 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). RESULTS We found three studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS In this systematic review we present information relating to the effectiveness and safety of the following intervention: prophylactic antibiotics.
International Seminars in Surgical Oncology Prognostic Indicators in Peritoneal Carcinomatosis from Gastrointestinal Cancer

Carcinomatosisprognostic indicatorsperitonectomycytoreductive surgerycolorectal cancergastric cancerintraperitoneal chemotherapy. Abstract Peritoneal carcinomatosis from gastrointestinal cancer has new treatment options for surgical management. The approach uses cytoreductive surgery which combines peritonectomy and visceral resection in an effort to remove all visible cancer within the abdomen and pelvis. Then the peritoneal cavity is flooded with chemotherapy solution in an attempt to eradicate residual disease. In order to select patients for this approach the quantitative prognostic indicators for carcinomatosis were reviewed, compared and contrasted. Prognostic indicators to be used to select patients for this aggressive approach at the initiation of surgery and after completion of cytoreduction were studied. Four quantitative assessments to be used at the time of abdominal exploration were the Gilly staging, Japanese gastric cancer P score, peritoneal cancer index (PCI), and the simplified peritoneal cancer index (SPCI). All have value with the PCI being the most validated and most precise. Preoperative assessments include the tumor histopathology and the prior surgical score. The completeness of cytoreduction score is an assessment of residual disease after a maximal surgical effort. An opportunity for long-term survival following treatment for carcinomatosis requires a complete cytoreduction in all reports for gastrointestinal cancer. Quantitative prognostic indicators need to be knowledgeably employed when patients with carcinomatosis are being treated. Improved patient selection with greater benefit and reduced morbidity and mortality should result.
Gem1 and ERMES Do Not Directly Affect Phosphatidylserine Transport from ER to Mitochondria or Mitochondrial Inheritance

In yeast, a protein complex termed the ER‐Mitochondria Encounter Structure (ERMES) tethers mitochondria to the endoplasmic reticulum. ERMES proteins are implicated in a variety of cellular functions including phospholipid synthesis, mitochondrial protein import, mitochondrial attachment to actin, polarized mitochondrial movement into daughter cells during division, and maintenance of mitochondrial DNA (mtDNA). The mitochondrial‐anchored Gem1 GTPase has been proposed to regulate ERMES functions. Here, we show that ERMES and Gem1 have no direct role in the transport of phosphatidylserine (PS) from the ER to mitochondria during the synthesis of phosphatidylethanolamine (PE), as PS to PE conversion is not affected in ERMES or gem1 mutants. In addition, we report that mitochondrial inheritance defects in ERMES mutants are a secondary consequence of mitochondrial morphology defects, arguing against a primary role for ERMES in mitochondrial association with actin and mitochondrial movement. Finally, we show that ERMES complexes are long‐lived, and do not depend on the presence of Gem1. Our findings suggest that the ERMES complex may have primarily a structural role in maintaining mitochondrial morphology.
Pattern Classification of Large-Scale Functional Brain Networks: Identification of Informative Neuroimaging Markers for Epilepsy

The accurate prediction of general neuropsychiatric disorders, on an individual basis, using resting-state functional magnetic resonance imaging (fMRI) is a challenging task of great clinical significance. Despite the progress to chart the differences between the healthy controls and patients at the group level, the pattern classification of functional brain networks across individuals is still less developed. In this paper we identify two novel neuroimaging measures that prove to be strongly predictive neuroimaging markers in pattern classification between healthy controls and general epileptic patients. These measures characterize two important aspects of the functional brain network in a quantitative manner: (i) coordinated operation among spatially distributed brain regions, and (ii) the asymmetry of bilaterally homologous brain regions, in terms of their global patterns of functional connectivity. This second measure offers a unique understanding of brain asymmetry at the network level, and, to the best of our knowledge, has not been previously used in pattern classification of functional brain networks. Using modern pattern-recognition approaches like sparse regression and support vector machine, we have achieved a cross-validated classification accuracy of 83.9% (specificity: 82.5%; sensitivity: 85%) across individuals from a large dataset consisting of 180 healthy controls and epileptic patients. We identified significantly changed functional pathways and subnetworks in epileptic patients that underlie the pathophysiological mechanism of the impaired cognitive functions. Specifically, we find that the asymmetry of brain operation for epileptic patients is markedly enhanced in temporal lobe and limbic system, in comparison with healthy individuals. The present study indicates that with specifically designed informative neuroimaging markers, resting-state fMRI can serve as a most promising tool for clinical diagnosis, and also shed light onto the physiology behind complex neuropsychiatric disorders. The systematic approaches we present here are expected to have wider applications in general neuropsychiatric disorders.
Persistent Fluctuations in Stride Intervals under Fractal Auditory Stimulation

Stride sequences of healthy gait are characterized by persistent long-range correlations, which become anti-persistent in the presence of an isochronous metronome. The latter phenomenon is of particular interest because auditory cueing is generally considered to reduce stride variability and may hence be beneficial for stabilizing gait. Complex systems tend to match their correlation structure when synchronizing. In gait training, can one capitalize on this tendency by using a fractal metronome rather than an isochronous one? We examined whether auditory cues with fractal variations in inter-beat intervals yield similar fractal inter-stride interval variability as isochronous auditory cueing in two complementary experiments. In Experiment 1, participants walked on a treadmill while being paced by either an isochronous or a fractal metronome with different variation strengths between beats in order to test whether participants managed to synchronize with a fractal metronome and to determine the necessary amount of variability for participants to switch from anti-persistent to persistent inter-stride intervals. Participants did synchronize with the metronome despite its fractal randomness. The corresponding coefficient of variation of inter-beat intervals was fixed in Experiment 2, in which participants walked on a treadmill while being paced by non-isochronous metronomes with different scaling exponents. As expected, inter-stride intervals showed persistent correlations similar to self-paced walking only when cueing contained persistent correlations. Our results open up a new window to optimize rhythmic auditory cueing for gait stabilization by integrating fractal fluctuations in the inter-beat intervals.
Dose-response analysis of opioid cross-tolerance and withdrawal suppression during LAAM maintenance.

Levo-alpha-acetylmethadol (LAAM) currently is approved as an opioid maintenance treatment. This double-blind study was designed to characterize withdrawal suppression and opioid blockade produced by two different LAAM maintenance doses. Outpatient opioid-dependent volunteers were stabilized (5-7 weeks) on 25 (n = 8) or 75 mg (n = 8) LAAM administered every-other-day with placebo administered on intervening days. After stabilization, four inpatient, randomly ordered experimental sessions were conducted at 24, 48, 72 and 96 hr after LAAM dosing; the timing of these sessions corresponds to intervals that occur during typical thrice-weekly treatment and after a missed dose. During each session, after baseline assessments, ascending doses of hydromorphone (0, 6 and 12 mg i.m.) were administered 45 min apart; physiological, subjective and observer-rated effects were recorded throughout the session. Physiological and subjective indices of opioid withdrawal measured at session base lines increased with time since the last LAAM dose, but did not depend on the maintenance dose. Withdrawal symptoms were mild in both groups, even at 96 hr after LAAM dosing. Hydromorphone produced dose-related opioid agonist effects at all intervals in the 25 mg LAAM group; these effects were attenuated substantially in the 75 mg LAAM group. Time since last LAAM dose had little influence on hydromorphone effects in either group. Thus, 75 mg LAAM provides opioid blockade and withdrawal suppression for up to 96 hr, whereas 25 mg LAAM is relatively ineffective at producing significant opioid blockade.