Miracle-dz/UniFAR-FTUs huggingface dataset:
In vivo measurement of aldehyde dehydrogenase‐2 activity in rat liver ethanol model using dynamic MRSI of hyperpolarized [1‐13C]pyruvate

To date, measurements of the activity of aldehyde dehydrogenase‐2 (ALDH2), a critical mitochondrial enzyme for the elimination of certain cytotoxic aldehydes in the body and a promising target for drug development, have been largely limited to in vitro methods. Recent advancements in MRS of hyperpolarized 13C‐labeled substrates have provided a method to detect and image in vivo metabolic pathways with signal‐to‐noise ratio gains greater than 10 000‐fold over conventional MRS techniques. However aldehydes, because of their toxicity and short T1 relaxation times, are generally poor targets for such 13C‐labeled studies. In this work, we show that dynamic MRSI of hyperpolarized [1‐13C]pyruvate and its conversion to [1‐13C]lactate can provide an indirect in vivo measurement of ALDH2 activity via the concentration of NADH (nicotinamide adenine dinucleotide, reduced form), a co‐factor common to both the reduction of pyruvate to lactate and the oxidation of acetaldehyde to acetate. Results from a rat liver ethanol model (n = 9) show that changes in 13C‐lactate labeling following the bolus injection of hyperpolarized pyruvate are highly correlated with changes in ALDH2 activity (R2 = 0.76). Copyright © 2012 John Wiley & Sons, Ltd.
Acute ethanol suppresses glutamatergic neurotransmission through endocannabinoids in hippocampal neurons

Ethanol exposure during fetal development is a leading cause of long‐term cognitive impairments. Studies suggest that ethanol exposure have deleterious effects on the hippocampus, a brain region that is important for learning and memory. Ethanol exerts its effects, in part, via alterations in glutamatergic neurotransmission, which is critical for the maturation of neuronal circuits during development. The current literature strongly supports the growing evidence that ethanol inhibits glutamate release in the neonatal CA1 hippocampal region. However, the exact molecular mechanism responsible for this effect is not well understood. In this study, we show that ethanol enhances endocannabinoid (EC) levels in cultured hippocampal neurons, possibly through calcium pathways. Acute ethanol depresses miniature post‐synaptic current (mEPSC) frequencies without affecting their amplitude. This suggests that ethanol inhibits glutamate release. The CB1 receptors (CB1Rs) present on pre‐synaptic neurons are not altered by acute ethanol. The CB1R antagonist SR 141716A reverses ethanol‐induced depression of mEPSC frequency. Drugs that are known to enhance the in vivo function of ECs occlude ethanol effects on mEPSC frequency. Chelation of post‐synaptic calcium by EGTA antagonizes ethanol‐induced depression of mEPSC frequency. The activation of CB1R with the selective agonist WIN55,212‐2 also suppresses the mEPSC frequency. This WIN55,212‐2 effect is similar to the ethanol effects and is reversed by SR141716A. In addition, tetani‐induced excitatory post‐synaptic currents (EPSCs) are depressed by acute ethanol. SR141716A significantly reverses ethanol effects on evoked EPSC amplitude in a dual recording preparation. These observations, taken together, suggest the participation of ECs as retrograde messengers in the ethanol‐induced depression of synaptic activities.
Genetic Variation and Susceptibilities to Protease Inhibitors among Subtype B and F Isolates in Brazil

ABSTRACT The genetic variation of the human immunodeficiency virus type 1 (HIV-1) protease gene (prt) permits the classification of HIV-1 strains into five distinct protease subtypes, which follow thegag subtyping patterns. The susceptibilities of non-B-subtype strains to protease inhibitors (PIs) and other antiretroviral drugs remain largely unknown. Subtype F is the main non-B strain contributing to the Brazilian epidemic, accounting for 15 to 20% of these infections. In this work, we report the findings on 81 isolates from PI-naive Brazilian patients collected between 1993 and 1997. In addition, the relevant PI resistance mutations and their phenotypes were determined in vitro for 15 of these patients (B = 9 and F = 6). Among these, the subtype F samples evidenced high sensitivities in vitro to ritonavir and indinavir, with MICs at which 50 and 90% of the isolates are inhibited similar to those of both the Brazilian and the U.S. subtype B isolates. Analysis of the 81 Brazilianprt sequences demonstrated that the subtype F consensus sequence differs from the U.S. and Brazilian subtype B consensus in eight positions (I15V, E35D, M36I, R41K, R57K, Q61N, L63P, and L89M). The frequency of critical PI resistance substitutions (amino acid changes D30N, V82A/F/T, I84V, N88D, and L90M) among Brazilian isolates is very low (mean, 2.5%), and the associated secondary substitutions (amino acid positions 10L, 20K, 36M, 46M, 48G, 54I, 63P, 71A, and 77A) are infrequent. These observations document the relative rarity of resistance to PIs in the treatment of patients infected with HIV-1 subtype F in South America.
Translational Control by a Small RNA: Dendritic BC1 RNA Targets the Eukaryotic Initiation Factor 4A Helicase Mechanism

ABSTRACT Translational repressors, increasing evidence suggests, participate in the regulation of protein synthesis at the synapse, thus providing a basis for the long-term plastic modulation of synaptic strength. Dendritic BC1 RNA is a non-protein-coding RNA that represses translation at the level of initiation. However, the molecular mechanism of BC1 repression has remained unknown. Here we identify the catalytic activity of eukaryotic initiation factor 4A (eIF4A), an ATP-dependent RNA helicase, as a target of BC1-mediated translational control. BC1 RNA specifically blocks the RNA duplex unwinding activity of eIF4A but, at the same time, stimulates its ATPase activity. BC200 RNA, the primate-specific BC1 counterpart, targets eIF4A activity in identical fashion, as a result decoupling ATP hydrolysis from RNA duplex unwinding. In vivo, BC1 RNA represses translation of a reporter mRNA with 5′ secondary structure. The eIF4A mechanism places BC RNAs in a central position to modulate protein synthesis in neurons.
Target Cell Range of Haemophilus ducreyiHemolysin and Its Involvement in Invasion of Human Epithelial Cells

ABSTRACT Haemophilus ducreyi, the causative agent of chancroid, produces a hemolysin, whose role in virulence is not well defined. To assess the possible role of hemolysin in pathogenesis, we evaluated its target cell range by using wild-type H. ducreyi 35000, nonhemolytic mutants with the hemolysin structural gene deleted, and isogenic strains expressing different amounts of hemolytic activity. The cytotoxicity of the various cell types was assessed by quantitating the release of lactate dehydrogenase into culture supernatants as a measure of cell lysis. In these experiments, human foreskin fibroblasts, human foreskin epithelial cells, and, to a lesser extent, HEp-2 cells were lysed by H. ducreyi hemolysin. Hemolysin also lysed human blood mononuclear cells and immune system cell lines including U937 macrophage-like cells, T lymphocytes, and B lymphocytes. In contrast, human polymorphonuclear leukocytes were not sensitive to hemolysin under the conditions tested. We also analyzed the effect of hemolysin on invasion of human epithelial cells and found that H. ducreyi strains expressing cloned hemolysin genes showed a 10-fold increase in invasion compared to the control strain. These data support the hypothesis that the H. ducreyi hemolysin is important in the pathogenesis of chancroid and may contribute to ulcer formation, invasion of epithelial cells, and evasion of the immune response.
Functional recovery after rhesus monkey spinal cord injury by transplantation of bone marrow mesenchymal-stem cell-derived neurons.

BACKGROUND The treatment of spinal cord injury is still a challenge. This study aimed at evaluating the therapeutical effectiveness of neurons derived form mesenchymal stem cells (MSCs) for spinal cord injury. METHODS In this study, rhesus MSCs were isolated and induced by cryptotanshinone in vitro and then a process of RT-PCR was used to detect the expression of glutamic acid decarboxylase (GAD) gene. The induced MSCs were tagged with Hoechst 33342 and injected into the injury site of rhesus spinal cord made by the modified Allen method. Following that, behavior analysis was made after 1 week, 1 month, 2 months and 3 months. After 3 months, true blue chloride retrograde tracing study was also used to evaluate the re-establishment of axons pathway and the hematoxylin-eosin (HE) staining and immunohistochemistry were performed after the animals had been killed. RESULTS In this study, the expression of mRNA of GAD gene could be found in the induced MSCs but not in primitive MSCs and immunohistochemistry could also confirm that rhesus MSCs could be induced and differentiated into neurons. Behavior analysis showed that the experimental animals restored the function of spinal cord up to grade 2-3 of Tarlov classification. Retrograde tracing study showed that true blue chollide could be found in the rostral thoracic spinal cords, red nucleus and sensory-motor cortex. CONCLUSIONS These results suggest that the transplantation is safe and effective.
Risk Factors for Preterm Birth Subtypes

To assess epidemiologic risk factors for preterm birth subcategories in an urban population, we undertook a study of 31,107 singleton livebirths that took place at Mount Sinai Hospital in New York City between 1986 and 1994. We subdivided the preterm births into preterm premature rupture of the membranes, preterm labor, and medically induced births. We obtained information regarding the preterm subtypes and their epidemiologic risk factors from a computerized perinatal database. Adjusted odds ratios showed an increased risk for all three preterm birth subtypes in women who were black (1.9 for preterm premature rupture of membranes, 2.1 for preterm labor, and 1.7 for medically induced births) or Hispanic (1.7 for preterm premature rupture of membranes, 1.9 for preterm labor, and 1.6 for medically induced births), those who had had a previous preterm birth (3.2 for preterm premature rupture of membranes, 4.5 for preterm labor, and 3.3 for medically induced births), those who began prenatal care after the first trimester (1.4 for preterm premature rupture of membranes, 1.3 for preterm labor, and 1.3 for medically induced births), women who had been exposed to diethylstilbestrol in utero (3.1 for preterm premature rupture of membranes, 4.1 for preterm labor, and 3.7 for medically induced births), patients with preexisting diabetes mellitus (2.2 for preterm premature rupture of membranes, 2.4 for preterm labor, and 9.5 for medically induced births), and those with antepartum bleeding (2.8 for preterm premature rupture of membranes, 3.6 for preterm labor, and 3.7 for medically induced births). Other sociodemographic, constitutional, life-style, and obstetrical characteristics differed across the groups. Variation in some of the risk factors among the preterm subtypes implies that epidemiologic assessment of the more specific outcomes would be advisable. (Epidemiology 1998;9:279–285)
Carbon dioxide fixation and mixotrophic metabolism by strain DCB-1, a dehalogenating anaerobic bacterium

Fixation by strain DCB-1 of CO2 carbon into cell material and organic acids occurred during growth on pyruvate both with and without thiosulfate. By using sodium [14C]bicarbonate and sodium [2-14C]pyruvate, the isotopic composition of products and cells was investigated. Up to 70% of cell carbon was derived from CO2. CO2 carbon was also incorporated into succinate, formate, and acetate. Both carbons of acetate underwent exchange reactions with CO2, although the carboxyl-group exchange was twice as fast. Because strain DCB-1 uses CO2 as its major but not sole carbon source while deriving energy from pyruvate metabolism, we describe its metabolism as mixotrophic. Other mixotrophic conditions also supported growth. Lactate or butyrate, which could not support growth in mineral medium, could replace pyruvate as the oxidizable substrate only when acetate was added to the medium.
A systematic review of postoperative analgesia following laparoscopic colorectal surgery

Objective The use of epidural analgesia is considered fundamental in Enhanced Recovery Protocols. However its value in the perioperative management of laparoscopic colorectal surgical patients is unclear and analgesic regimens vary. The aim of this systematic review was to examine the effects of various analgesic regimes on outcomes following laparoscopic colectomy.
Consumption of added sugar among U.S. children and adolescents, 2005-2008.

Approximately 16% of children and adolescents’ total caloric intakes came from added sugars. Boys consumed more added sugars than girls. Preschool-aged children consumed the fewest calories from added sugars. Although girls consumed a smaller absolute amount of calories from added sugars than boys, their intakes were not that different from boys when the amounts are expressed as a percentage of total caloric intakes. Non-Hispanic white children and adolescents consumed a larger percentage of their calories from added sugars than Mexican-American children and adolescents. Also, Non-Hispanic black girls consumed a larger percentage of their calories from added sugars than Mexican-American girls. There was very little difference in added sugar consumption based on PIR. More of the added sugars calories came from foods as opposed to beverages. Previous research has demonstrated that sodas are the single leading food source of added sugars intakes among children, adolescents, and adults (2,4). Our results showed a little more than 40% of calories from added sugars came from beverages. Poti and Popkin (5) have suggested that eating location impacts daily energy intake in children and adolescents and that foods prepared away from home, are contributing to their increased total energy intake. Our results showed that more of the added sugars calories were consumed at home rather than away from home. A substantial percentage of calories in the diets of children and adolescents between 2005 and 2008 came from added sugars. According to the 2010 Dietary Guidelines "reducing the consumption of these sources of added sugars will lower the caloric content of the diet, without compromising its nutrient adequacy (3). " This strategy could play an important role in reducing the high prevalence of obesity in the United States (6) without compromising adequate nutrition.
Ensuring Quality of Service in a multi-tenant cloud-enabled RAN environment

To meet the communication expectations of the future, mobile networks need to evolve quicker than ever toward systems with ultra-low latency, huge traffic volume and higher data rates. Cloud-enabled radio systems have been introduced as a promising solution to meet these demands with the help of network functions virtualization techniques and network edge processing capabilities, which allow for increased resource pooling, scalability, layer interworking and spectral efficiency. Despite their potential benefits, joint radio-cloud systems pose technical challenges on the network management and orchestration, especially on ensuring the Quality of Service (QoS). To this end, having a complete loop of monitoring, decision-making and reaction is essential. However, considering the fact that the radio and the cloud parameters are inherently disparate, forming such a loop in a joint radio-cloud environment is very challenging. This challenge becomes more difficult in multi-tenant (operator) scenarios, targeted by 5G, where ensuring the QoS for one tenant should not violate the QoS of the others. This paper intends to state the problem from a 5GPPP H2020 perspective, and discusses a possible solution within the context of the SESAME project.
Guidelines for point-of-care testing : haematology Summary

This guideline provides a framework for the arrangement of point-of-care testing (POCT) services, previously known as near patient testing (patient self-testing not covered). POCT is defined as any analytical test performed outside the laboratory. Primary users are often non-laboratory healthcare workers. The guidance applies to units within hospitals as well as general practioner surgeries, community clinics and pharmacies. The head of the haematology laboratory or a point of care coordinator must take responsibility for all aspects of the POCT service, including quality and training. Depending on the size and nature of the POCT practice, a local POCT manager may also be required. Equipment selected should have received a successful independent performance evaluation. If an independent evaluation has not been performed the purchaser should assess the device according to the protocol in this document. POCT devices should generate results that are comparable to those of the local laboratory. An accredited external quality assessment programme and internal quality control system must be established. Manufacturers promoting POCT devices designed for non-laboratory sites, e.g. pharmacies, should undertake training and annual competency assessment, perhaps using a web-based system. A diagram to illustrate the stages for the implementation of a POCT service is illustrated.
Team Clinical Supervision in Acute Hospital Wards

Clinical supervision provides a strategy to mitigate nurses’ workplace stress and enhance retention, but the literature provides little guidance about its implementation beyond mental health nursing. This study explored the feasibility of implementing and evaluating ward-based team clinical supervision for general nurses on two separate wards at one public and one private hospital. Nurses completed the Work Environment Questionnaire pre- (n = 36) and postintervention (n = 27), and focus groups (n = 20) explored their perceptions of supervision. Staff were unfamiliar with clinical supervision, so information sessions were required. The questionnaire may not have been suitable to evaluate this type of intervention. Focus group findings revealed that team supervision improved communication, enhanced working relationships, and empowered nurses to challenge existing practices, which had a positive impact on their perceived stress. This study provides insights to guide implementation and evaluation of clinical supervision in acute settings.
Improvement of inflammatory and toxic stress biomarkers by silymarin in a murine model of type one diabetes mellitus

Type 1 diabetes mellitus (T1DM) is characterized by an impairment of the insulin-secreting beta cells with an immunologic base. Inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, and free radicals are believed to play key roles in destruction of pancreatic β cells. The present study was designed to investigate the effect of Silybum marianum seed extract (silymarin), a combination of several flavonolignans with immunomodulatory, anti-oxidant, and anti-inflammatory potential on streptozotocin (STZ)-induced T1DM in mouse. Experimental T1DM was induced in male albino mice by IV injection of multiplelow- doses of STZ for 5 days. Seventy-two male mice in separate groups received various doses of silymarin (20, 40, and 80 mg/kg) concomitant or after induction of diabetes for 21 days. Blood glucose and pancreatic biomarkers of inflammation and toxic stress (IL-1β, TNF-α, myeloperoxidase, lipid peroxidation, protein oxidation, thiol molecules, and total antioxidant capacity) were determined. Silymarin treatment reduced levels of inflammatory cytokines such as TNF-α and IL-1β and oxidative stress mediators like myeloperoxidase activity, lipid peroxidation, carbonyl and thiol content of pancreatic tissue in an almost dose dependent manner. No marked difference between the prevention of T1DM and the reversion of this disease by silymarin was found. Use of silymarin seems to be helpful in T1DM when used as pretreatment or treatment. Benefit of silymarin in human T1DM remains to be elucidated by clinical trials.
Silencing of polo‐like kinase (Plk) 1 via siRNA causes induction of apoptosis and impairment of mitosis machinery in human prostate cancer cells: implications for the treatment of prostate cancer

Prostate cancer (PCa) is one of the most common cancers in men. Each year ∼543,000 new cases are reported worldwide, and the disease kills 200,000 (mostly older men) in developed countries. The existing treatment approaches and surgical intervention have not been able to effectively manage this dreaded cancer and, therefore, continuing efforts are ongoing to explore novel targets and strategies for the management of PCa. The activity of polo‐like kinase 1 (Plk1) is elevated in tissues and cells with a high mitotic index, including cancer cells. An increasing body of evidence suggests that the level of Plk1 expression has prognostic value for predicting outcomes in patients with some cancers. A close correlation between Plk1 expression and carcinogenesis has been documented. However, the role of Plk1 in PCa is not known. We propagated a hypothesis that Plk1 inhibition will result in elimination of human PCa cells via a mitotic arrest followed by apoptosis (1). To define the role of Plk1 in PCa, we used the technique of RNA silencing via small interfering RNA (siRNA). First, using a series of human prostate carcinoma cells and normal human prostate epithelial (PrEC) cells, we assessed Plk1 levels in PCa. Immunoblot analyses clearly showed a significant expression of Plk1 in LNCaP, DU145, and PC3 human PCa cells. Interestingly, Plk1 was not detectable in normal PrEC cells. Next, we transfected the PCa cells with Plk 1 siRNA, which resulted in a significant inhibition in Plk1 protein in all PCa cells. Plk1 depletion resulted in a decrease in cell viability and induction of apoptosis in PCa cells but had no appreciable effect in normal PrEC cells. Our data also demonstrated that Plk1 siRNA transfection of PCa cells resulted in 1) a mitotic cell cycle arrest, 2) failure of cytokinesis, and 3) defects in centrosome integrity and maturation. Thus, our study suggested that 1) Plk1 plays a critical role in the process of PCa development and 2) gene therapeutic approaches aimed at Plk1 or the pharmacological inhibitors of Plk1 may be developed for the management of PCa.
Protection from Intestinal Inflammation by Bacterial Exopolysaccharides

Host inflammatory responses against pathogenic organisms can be abrogated by commensals; however, the molecular mechanisms by which pathogenesis is prevented are still poorly understood. Previous studies demonstrated that administration of a single dose of Bacillus subtilis prevented disease and inflammation by the enteric mouse pathogen Citrobacter rodentium, which causes disease similar to the human pathogen enteropathogenic Escherichia coli. No protection was observed when an exopolysaccharide (EPS)-deficient mutant of B. subtilis was used, suggesting that EPS are the protective factor. In this study, we isolated and characterized EPS and showed that they also prevent C. rodentium–associated intestinal disease after a single injection. Protection is TLR4 dependent because EPS-treated TLR4 knockout mice developed disease. Furthermore, protection could be conveyed to wild-type mice by adoptive transfer of macrophage-rich peritoneal cells from EPS-treated mice. We found that EPS specifically bind peritoneal macrophages, and because mice lacking MyD88 signaling in myeloid cells were not protected by EPS, we conclude that bacterial EPS prevent colitis in a TLR4-dependent manner that requires myeloid cells. These studies provide a simple means of preventing intestinal inflammation caused by enteric pathogens.