Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effects of Normalizing Hyperhomocysteinemia on Clinical and Operative Outcomes in Patients With Critical Limb Ischemia

Purpose To assess the outcome of patients with medically treated hyperhomocysteinemia (HHC) requiring intervention for critical limb ischemia (CLI). Methods A parallel observational study was conducted to compare the clinical and revascularization outcomes of CLI patients who received standardized treatment for HHC preoperatively (folic acid and vitamin B12) vs. contemporaneous patients with normal homocysteine levels. The threshold for HHC diagnosis was 13.0 μmol/L. From 2009 to 2011, 169 patients underwent revascularization procedures for CLI. Of these, all 66 patients (40 men; mean age 69.6±11.2 years) with HHC (mean 17.3 μmol/L, range 13.5–34.9) were treated to normalize the homocysteine level prior to lower limb revascularization. The remaining 103 patients (58 men; mean age 72.7±8.1 years) had normal homocysteine levels (8.2 μmol/L, range 5–12.3) before revascularization. The primary endpoint was symptomatic and hemodynamic improvement in the treated HHC group. The secondary endpoints were all-cause survival, binary restenosis, reintervention, amputation-free survival, and major adverse events. The treated HHC cohort was compared to an age/sex-matched historical group of patients with untreated HHC from 2002 to 2006 before HHC pretreatment became routine. All interventions (endovascular, hybrid, and open) were performed by the same surgeon, and the groups were evenly matched. Results Patients with HHC were treated for a mean 12.2 days, which significantly reduced their mean homocysteine level after 3 weeks to 10.1 μmol/L (range 6.2–14.4, p<0.05). After revascularization, immediate clinical improvement was similar between normal homocysteine and medically corrected HHC groups. There was no significant difference in time to binary restenosis (p=0.822). Secondary endpoints and all-cause mortality were similar. Multivariate logistic regression showed that untreated HHC was a significant factor for graft occlusion and limb loss (p<0.0001), but medically corrected HHC was no longer predictive of adverse operative outcome. Conclusion Patients with medically corrected HHC have similar outcomes compared to those with normal homocysteine levels. Thus, aggressively treating HHC with folic acid and vitamin B12 may help enhance the clinical outcome of CLI patients undergoing revascularization.
Regional and socio-economic differences in food, nutrient and supplement intake in school-age children in Germany: results from the GINIplus and the LISAplus studies

Abstract Objective To describe regional differences between eastern and western Germany with regard to food, nutrient and supplement intake in 9–12-year-old children, and analyse its association with parental education and equivalent income. Design Data were obtained from the 10-year follow-up of the two prospective birth cohort studies – GINIplus and LISAplus. Data on food consumption and supplement intake were collected using an FFQ, which had been designed for the specific study population. Information on parental educational level and equivalent income was derived from questionnaires. Logistic regression modelling was used to analyse the effect of parental education, equivalent income and region on food intake, after adjusting for potential confounders. Setting Germany. Subjects A total of 3435 children aged 9–12 years. Results Substantial regional differences in food intake were observed between eastern and western Germany. Intakes of bread, butter, eggs, pasta, vegetables/salad and fruit showed a significant direct relationship with the level of parental education after adjusting for potential confounders, whereas intakes of margarine, meat products, pizza, desserts and soft drinks were inversely associated with parental education. Equivalent income had a weaker influence on the child's food intake. Conclusions Nutritional education programmes for school-age children should therefore account for regional differences and parental education.
Refining Molecular Pathways Leading to Calcific Aortic Valve Stenosis by Studying Gene Expression Profile of Normal and Calcified Stenotic Human Aortic Valves

Background— Calcific aortic valve stenosis (AS) is a major societal and economic burden that is rising after the current shift toward an older population. Understanding the pathobiology of AS is crucial to implementing better preventive and therapeutic options. Research conducted during the past decade clearly points to active molecular and cellular processes involved in disease pathogenesis. However, no genomic approaches were used to identify genes and pathways that are differentially regulated in aortic valves of patients with and without AS. Methods and Results— A large-scale quantitative measurements of gene expression was performed on 5 normal and 5 AS valves using Affymetrix GeneChips. A total of 409 and 306 genes were significantly up- and downregulated in AS valves, respectively. The 2 most highly upregulated genes were matrix metalloproteinase 12 and chitinase 3-like 1. The upregulation of these 2 biologically relevant genes in AS was validated by real-time polymerase chain reaction in 38 aortic valves (12 normal and 26 AS). To provide a global biological validation of the whole-genome gene expression analysis, the microarray experiment was repeated in a second set of aortic valves with (n=5) or without (n=5) AS. There was an overrepresentation of small P values among genes claimed significant in the first microarray experiment. A total of 223 genes were replicated (P<0.05 and fold change >1.2), including matrix metalloproteinase 12 and chitinase 3-like 1. Conclusions— This study reveals many unrecognized genes potentially implicated in the pathogenesis of AS. These new genes were overlaid on known pathological pathways leading to AS to refine our molecular understanding of this disease.
GABAergic disinhibition and impaired KCC2 cotransporter activity underlie tumor‐associated epilepsy

Seizures frequently accompany gliomas and often escalate to peritumoral epilepsy. Previous work revealed the importance of tumor‐derived excitatory glutamate (Glu) release mediated by the cystine‐glutamate transporter (SXC) in epileptogenesis. We now show a novel contribution of GABAergic disinhibition to disease pathophysiology. In a validated mouse glioma model, we found that peritumoral parvalbumin‐positive GABAergic inhibitory interneurons are significantly reduced, corresponding with deficits in spontaneous and evoked inhibitory neurotransmission. Most remaining peritumoral neurons exhibit elevated intracellular Cl− concentration ([Cl−]i) and consequently depolarizing, excitatory gamma‐aminobutyric acid (GABA) responses. In these neurons, the plasmalemmal expression of KCC2, which establishes the low [Cl−]i required for GABAAR‐mediated inhibition, is significantly decreased. Interestingly, reductions in inhibition are independent of Glu release, but the presence of both decreased inhibition and decreased SXC expression is required for epileptogenesis. We suggest GABAergic disinhibition renders peritumoral neuronal networks hyper‐excitable and susceptible to seizures triggered by excitatory stimuli, and propose KCC2 as a therapeutic target. GLIA 2015;63:23–36
Metacarpophalangeal Joint Orientation in Anthropoid Manual Phalanges

The proximal articular surface angle of orientation (AO) of proximal phalanges of the hand and foot has been used to infer the locomotor profile of extinct Miocene catarrhines and early hominins. Previous work has found that joint orientation distinguishes quadrupedal from suspensory anthropoids. The purpose of this study is to expand on previous research by examining this feature within and across several primate clades, allowing us to investigate the potential influences of locomotion, substrate usage, hand posture, and phylogeny. We also report AO measurements in human proximal hand phalanges, allowing us to examine human skeletal variation within a wide comparative context. The angle of orientation was measured on manual proximal third phalanges of 21 extant anthropoid species using a Microscribe digitizer. Comparisons were made between locomotor groups within hominoids, platyrrhines, and cercopithecoids. Proximal phalanges of quadrupedal species were characterized by greater dorsal orientation than those of suspensory taxa in hominoids and atelids. In addition, arboreal quadrupeds had greater AO values than terrestrial quadrupeds within the Cercopithecoidea. However, within the terrestrial locomotor group, mean AO values did not differ between palmigrade and digitigrade taxa. Thus, while there appears to be a functional signal related to substrate usage, differences in use of hand postures when moving on the ground were not reflected in proximal joint orientation of the proximal phalanx. Finally, we measured relatively low AO values in human phalanges, which might be related to integration with serially homologous pedal phalanges that are under strong selective pressure related to bipedalism. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.
Intravitreal Dexamethasone Implant versus Intravitreal Ranibizumab for the Treatment of Macular Edema Secondary to Retinal Vein Occlusion in a Chinese Population

Background: The aim of this work was to compare the efficacy of intravitreal dexamethasone implant (Ozurdex) and intravitreal ranibizumab (Lucentis) in the treatment of macular edema (ME) caused by retinal vein occlusion (RVO). Methods: Thirty-two ME cases treated with Ozurdex and 32 ME cases treated with ranibizumab were enrolled, with 26 central (C)RVO and 6 branch (B)RVO subjects in each group. We compared the results of best-corrected visual acuity (BCVA), central retinal thickness, number of injections, and intraocular pressure (IOP) at 1, 2, 3, and 6 months after injection. Results: BCVA in both groups at each follow-up were significantly increased compared to baseline with no statistical difference between the groups. Ozurdex and ranibizumab successfully reduced CMT at each follow-up. Both CRVO and BRVO patients had significant between-group differences in the mean number of injections. Among the CRVO patients, IOP in the Ozurdex group was significantly increased compared to baseline and the ranibizumab group at 1, 2, and 3 months postinjection. Conclusions: Intravitreal injection of Ozurdex and ranibizumab can effectively control ME secondary to RVO and increase a patient's BCVA. The advantages of Ozurdex are fewer injections and longer efficacy, while the advantages of ranibizumab include fewer side effects.
Human Resource Management Practices and Performance of Firms Listed on the Nairobi Securities Exchange

Most research demonstrating the link between Human Resource Management Practices (HRMP) and firm performance has focused on the private sector, yet understanding this relationship in publicly listed firms, in the Developing World setting is equally important. The role of HRMP on firm performance of the Nairobi Securities Exchange (NSE) listed firms has not been established using the selected variable, yet theory has demonstrates that HRMP can have an effect on firm performance. This study was motivated by the desire to fill this gap in knowledge. The objective of the study was to establish the relationship between HRMP and firm performance. The research design was cross sectional descriptive survey. Data was collected using a self-administered questionnaire, from a population of 60 NSE listed firms. The response rate was 60%. Simple linear regression was used to analyze the data. The results of the study show a statistically significant relationship between HRMP and performance of firms listed on the NSE. The findings of the study are consistent with the findings of other empirical studies which have established a significant link between HRMP and firm performance. It was recommended that firms have to ensure that the HRMP that they adopt assist them to attain and sustain a superior competitive advantage in their operations. Key words: Human Resource Management Practices (HRMP); firm performance
Retinol (vitamin A) maintains self‐renewal of pluripotent male germline stem cells (mGSCs) from adult mouse testis

Studies have shown that male germline stem cells (mGSCs), which are responsible for maintaining spermatogenesis in the male, could be obtained from mouse and human testis. However, the traditional cultural methods were mostly dependent on serum and feeder, and the initial mGSCs were either obtained from neonatal mice or the detailed description of its potency and origin was not provided. Here we reported a novel (retinol (RE) serum‐free and feeder‐free) system for the successful culture of adult germline stem cells from adult Kunming mice (8–24 weeks) testis. The isolated mGSCs cultured in RE serum‐free and feeder‐free medium maintained the typical morphology of undifferentiated embryonic stem cells (ESCs), and they proliferated well in RE medium analyzed by proliferation assay, RT‐PCR, microarray, and Western blotting. These cells also showed typical properties of ESCs (alkaline phosphatase (AP) positive, expressions of Oct4, Sox2, Nanog, and SSEA1, with the capacity to form teratomas and differentiate into various types of cells within three germ layers). Taken together, we conclude that RE promotes the self‐renewal of mGSCs and maintains the pluripotency of mGSCs, the RE serum‐free and feeder‐free system may be useful for the culture of pluripotent stem cell lines from adult testis tissues, which provides a new resource for tissue engineering and therapy for infertility. J. Cell. Biochem. 112: 1009–1021, 2011. © 2011 Wiley‐Liss, Inc.
Transient BK outward current enhances motoneurone firing rates during Drosophila larval locomotion

We combine in situ electrophysiology with genetic manipulation in Drosophila larvae aiming to investigate the role of fast calcium‐activated potassium currents for motoneurone firing patterns during locomotion. We first demonstrate that slowpoke channels underlie fast calcium‐activated potassium currents in these motoneurones. By conducting recordings in semi‐intact animals that produce crawling‐like movements, we show that slowpoke channels are required specifically in motoneurones for maximum firing rates during locomotion. Such enhancement of maximum firing rates occurs because slowpoke channels prevent depolarization block by limiting the amplitude of motoneurone depolarization in response to synaptic drive. In addition, slowpoke channels mediate a fast afterhyperpolarization that ensures the efficient recovery of sodium channels from inactivation during high frequency firing. The results of the present study provide new insights into the mechanisms by which outward conductances facilitate neuronal excitability and also provide direct confirmation of the functional relevance of precisely regulated slowpoke channel properties in motor control.
Studies on nutrition in severely neurologically disabled children in an institution

Severe neurological handicaps in children are frequently accompanied by growth retardation. We have studied 13 severely neurologically impaired children in an institution to see if their poor growth was related to a low intake of energy and nutrients, if this was reflected in biochemical nutritional parameters, and to modify their diet according to the results. The investigation showed low dietary intakes of energy and of several of the nutrients, with corresponding low Hb values and serum values of ferritin, selenium and vitamins E and D in some of the children. All the children were initially light for age, with catch‐up growth after intervention. We conclude that severely disabled children are at high risk for under‐ and malnutrition, and that this may partly explain the growth retardation in the study group. To avoid the potential detrimental effects of malnutrition, it is important to aim at providing an optimal diet.
Treatment of advanced pancreatic adenocarcinoma with 5-FU, leucovorin, interferon-alpha-2b, and cisplatin.

Previous laboratory and clinical studies support the ability of interferon (IFN) to enhance the antitumor properties of chemotherapy agents, including cisplatin and 5-fluorouracil (5-FU). A phase I-II clinical trial was initiated to treat several tumor types with IFN-alpha-2b, cisplatin, 5-FU, and leucovorin (LV), given daily for 5 days of a 28-day cycle. Because of preliminary results, this was continued as a phase II trial in 18 patients with metastatic adenocarcinoma of the pancreas. Each treatment day consisted of IFN 5 million u/m2 s.c. (maximum, 10 million U), CDDP 20 mg/m2 i.v. over 1 h, LV 20 mg/m2 i.v. p., and 5-FU 250-275 mg/m2 i.v. p. All patients had measurable disease with no prior chemotherapy for metastatic disease, and all had an Eastern Cooperative Oncology Group (ECOG) performance status of 1. Six of the 16 patients evaluable for response had partial responses (PRs) (37.5%) with a median response duration of 4 months, and all responding patients survived > or = 8 months. Median survival of all 18 treated patients was 5 months. Severe gastrointestinal toxicity (nausea, diarrhea, or requirement for i.v. hydration) was common. Grade 4 hematologic toxicity was seen in six patients. The response rate observed is promising and supports the concept that IFN may potentiate the effects of standard chemotherapy agents. However, the toxicities observed with this dosage schedule were considerable and further studies are needed to develop a less toxic regimen.
Ageing and the brain

Ageing causes changes to the brain size, vasculature, and cognition. The brain shrinks with increasing age and there are changes at all levels from molecules to morphology. Incidence of stroke, white matter lesions, and dementia also rise with age, as does level of memory impairment and there are changes in levels of neurotransmitters and hormones. Protective factors that reduce cardiovascular risk, namely regular exercise, a healthy diet, and low to moderate alcohol intake, seem to aid the ageing brain as does increased cognitive effort in the form of education or occupational attainment. A healthy life both physically and mentally may be the best defence against the changes of an ageing brain. Additional measures to prevent cardiovascular disease may also be important.
Endocannabinoids and stress

Endogenous cannabinoids play an important role in the physiology and behavioral expression of stress responses. Activation of the hypothalamic–pituitary–adrenal (HPA) axis, including the release of glucocorticoids, is the fundamental hormonal response to stress. Endocannabinoid (eCB) signaling serves to maintain HPA-axis homeostasis, by buffering basal activity as well as by mediating glucocorticoid fast feedback mechanisms. Following chronic stressor exposure, eCBs are also involved in physiological and behavioral habituation processes. Behavioral consequences of stress include fear and stress-induced anxiety as well as memory formation in the context of stress, involving contextual fear conditioning and inhibitory avoidance learning. Chronic stress can also lead to depression-like symptoms. Prominent in these behavioral stress responses is the interaction between eCBs and the HPA-axis. Future directions may differentiate among eCB signaling within various brain structures/neuronal subpopulations as well as between the distinct roles of the endogenous cannabinoid ligands. Investigation into the role of the eCB system in allostatic states and recovery processes may give insight into possible therapeutic manipulations of the system in treating chronic stress-related conditions in humans.
Primary/De Novo Paroxysmal Nocturnal Hemoglobinuria in a Child From North India: A Case Report With Review of Literature

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematologic disorder, characterized by intravascular hemolysis, thrombosis, or bone marrow failure. It is very rare in children. The clinical manifestations are due to deficiency of a family of membrane proteins that are anchored into the cell membrane through glycosylphosphatidylinositol (GPI). Currently, flow cytometric analysis of GPI-linked proteins has replaced the traditional Ham test (acidified-serum lysis test) and sucrose lysis test, it being a quantitative and more sensitive method. The only curative treatment of the disease is stem cell transplantation. We are reporting a case of de novo pediatric PNH, presenting with hemoglobinuria and a sizeable clone of GPI-anchor deficient blood cells, along with review of reported cases of PNH in pediatric patients. PNH can occur in children and has varied clinical and hematologic presentations; the presence of PNH should be considered in every child with an acquired bone marrow failure, unexplained hemoglobinuria and/or unexpected serious thrombosis. Pediatricians should keep this disorder in mind, when patients present with above features.
Phylogeny and Origins of Hantaviruses Harbored by Bats, Insectivores, and Rodents

Hantaviruses are among the most important zoonotic pathogens of humans and the subject of heightened global attention. Despite the importance of hantaviruses for public health, there is no consensus on their evolutionary history and especially the frequency of virus-host co-divergence versus cross-species virus transmission. Documenting the extent of hantavirus biodiversity, and particularly their range of mammalian hosts, is critical to resolving this issue. Here, we describe four novel hantaviruses (Huangpi virus, Lianghe virus, Longquan virus, and Yakeshi virus) sampled from bats and shrews in China, and which are distinct from other known hantaviruses. Huangpi virus was found in Pipistrellus abramus, Lianghe virus in Anourosorex squamipes, Longquan virus in Rhinolophus affinis, Rhinolophus sinicus, and Rhinolophus monoceros, and Yakeshi virus in Sorex isodon, respectively. A phylogenetic analysis of the available diversity of hantaviruses reveals the existence of four phylogroups that infect a range of mammalian hosts, as well as the occurrence of ancient reassortment events between the phylogroups. Notably, the phylogenetic histories of the viruses are not always congruent with those of their hosts, suggesting that cross-species transmission has played a major role during hantavirus evolution and at all taxonomic levels, although we also noted some evidence for virus-host co-divergence. Our phylogenetic analysis also suggests that hantaviruses might have first appeared in Chiroptera (bats) or Soricomorpha (moles and shrews), before emerging in rodent species. Overall, these data indicate that bats are likely to be important natural reservoir hosts of hantaviruses.
mRNA Study on Cu/Zn Superoxide Dismutase Induction by Hemodialysis Treatment

Background/Aims: There is little or no controversy about the increased oxidative stress of hemodialysis (HD) patients. Several reports show that the activity of superoxide dismutase (SOD), one of the major endogenous antioxidant enzymes, in plasma is elevated among HD patients. It is still unclear, however, whether this elevation is due to the promotion of SOD production or a decrease in renal excretion of SOD. This study was designed to investigate the cause of the SOD activation in HD patients, and we examined the expression of SOD mRNA levels in leukocytes of patients with chronic renal failure. Methods: The total plasma SOD activity was determined by the nitroblue tetrazolium method, plasma SOD contents by ELISA, and SOD mRNA levels in leukocytes by RT-PCR. Results: Our results demonstrated that contents and mRNA levels of Cu/Zn SOD in HD patients are 4.4 times and 2.0 times, respectively, as large as those in healthy controls. Furthermore, in contrast to nondialyzed chronic renal failure patients, we observed higher concentrations of Cu/Zn SOD in plasma and a more enhanced mRNA expression of Cu/Zn SOD in leukocytes of HD patients. Conclusion: Increased Cu/Zn SOD mRNA reflects enhanced antioxidant capacity of leukocytes and can be a promising oxidative stress marker in HD patients.