Miracle-dz/UniFAR-FTUs huggingface dataset:
Selective Na+/H+ exchange inhibition by cariporide reduces liver fibrosis in the rat

The aim of this study was to evaluate the effect of cariporide, a selective Na+/H+ exchange inhibitor, on isolated and cultured hepatic stellate cells (HSCs) and in 2 in vivo models of rat liver fibrosis. Platelet‐derived growth factor (PDGF)‐induced HSC proliferation, evaluated by measuring the percentage of bromodeoxyuridine‐positive cells, was significantly inhibited by cariporide, with a maximal effect at 10 μmol/L. Incubation with cariporide did not inhibit PDGF‐induced extracellular‐regulated kinase 1/2 (ERK1/2), Akt (a downstream component of the phosphatidylinositol [PI]‐3 kinase pathway), and protein kinase C (PKC) activation but reduced PDGF‐induced activation of the Na+/H+ exchanger, with a maximal effect at 10 μmol/L. Rats treated with dimethylnitrosamine (DMN; 10 mg/kg) for 1 and 5 weeks received a diet with or without 6 ppm cariporide. Treatment with cariporide reduced the degree of liver injury, as determined by alanine aminotransferase (ALT) values, also when administered after the induction of hepatic damage. This was associated with reduced HSC activation and proliferation and reduced collagen deposition, as determined by morphometric evaluation of α–smooth muscle actin (SMA)/proliferating cell nuclear antigen–positive cells and percentage of Sirius red–positive parenchyma, respectively. Moreover, cariporide was also able to reduce α(1)I procollagen messenger RNA (mRNA) expression. Similar effects were observed in bile duct–ligated (BDL) rats. In conclusion, selective inhibition of the Na+/H+ exchanger by cariporide may represent an effective therapeutic strategy in the treatment of hepatic fibrosis. (HEPATOLOGY 2003;37:256‐266.)
Rising incidence of hepatocellular carcinoma in the United States.

BACKGROUND AND METHODS Clinical observations have suggested that the number of cases of hepatocellular carcinoma has increased in the United States. We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) data base to determine the age-adjusted incidence of hepatocellular carcinoma from 1976 to 1995, data from the U.S. vital-statistics data base to determine age-adjusted mortality rates from 1981 to 1995, and data from the Department of Veterans Affairs to determine age-adjusted rates of hospitalization for the disease from 1983 to 1997. RESULTS The incidence of histologically proved hepatocellular carcinoma increased from 1.4 per 100,000 population (95 percent confidence interval, 1.3 to 1.4) for the period from 1976 to 1980 to 2.4 per 100,000 (95 percent confidence interval, 2.3 to 2.4) for the period from 1991 to 1995. Among black men, the incidence was 6.1 per 100,000 for the period from 1991 to 1995, and among white men, it was 2.8 per 100,000. There was a 41 percent increase in the mortality rate from primary liver cancer and a 46 percent increase in the proportion of hospitalizations attributable to this disease during the periods studied. The incidence increased significantly among younger persons (40 to 60 years old) during the period from 1991 to 1995 as compared with earlier periods. CONCLUSIONS An increase in the number of cases of hepatocellular carcinoma has occurred in the United States over the past two decades. The age-specific incidence of this cancer has progressively shifted toward younger people.
The role of rare innate immune cells in Type 2 immune activation against parasitic helminths

SUMMARY The complexity of helminth macroparasites is reflected in the intricate network of host cell types that participate in the Type 2 immune response needed to battle these organisms. In this context, adaptive T helper 2 cells and the Type 2 cytokines interleukin (IL)-4, IL-5, IL-9 and IL-13 have been the focus of research for years, but recent work has demonstrated that the innate immune system plays an essential role. Some innate immune cells that promote Type 2 immunity are relatively abundant, such as macrophages and eosinophils. However, we now appreciate that more rare cell types including group 2 innate lymphoid cells, basophils, mast cells and dendritic cells make significant contributions to these responses. These cells are found at low frequency but they are specialized to their roles – located at sites such as the skin, lung and gut, where the host combats helminth parasites. These cells respond rapidly and robustly to worm antigens and worm-induced damage to produce essential cytokines, chemokines, eicosanoids and histamine to activate damaged epithelium and to recruit other effectors. Thus, a greater understanding of how these cells operate is essential to understand how the host protects itself during helminth infection.
Improved fruit α‐tocopherol, carotenoid, squalene and phytosterol contents through manipulation of Brassica juncea 3‐HYDROXY‐3‐METHYLGLUTARYL‐COA SYNTHASE1 in transgenic tomato

Summary 3‐Hydroxy‐3‐methylglutaryl‐coenzyme A synthase (HMGS) in the mevalonate (MVA) pathway generates isoprenoids including phytosterols. Dietary phytosterols are important because they can lower blood cholesterol levels. Previously, the overexpression of Brassica juncea wild‐type (wt) and mutant (S359A) BjHMGS1 in Arabidopsis up‐regulated several genes in sterol biosynthesis and increased sterol content. Recombinant S359A had earlier displayed a 10‐fold higher in vitro enzyme activity. Furthermore, tobacco HMGS overexpressors (OEs) exhibited improved sterol content, plant growth and seed yield. Increased growth and seed yield in tobacco OE‐S359A over OE‐wtBjHMGS1 coincided with elevations in NtSQS expression and sterol content. Herein, the overexpression of wt and mutant (S359A) BjHMGS1 in a crop plant, tomato (Solanum lycopersicum), caused an accumulation of MVA‐derived squalene and phytosterols, as well as methylerythritol phosphate (MEP)‐derived α‐tocopherol (vitamin E) and carotenoids, which are important to human health as antioxidants. In tomato HMGS‐OE seedlings, genes associated with the biosyntheses of C10, C15 and C20 universal precursors of isoprenoids, phytosterols, brassinosteroids, dolichols, methylerythritol phosphate, carotenoid and vitamin E were up‐regulated. In OE‐S359A tomato fruits, increased squalene and phytosterol contents over OE‐wtBjHMGS1 were attributed to heightened SlHMGR2, SlFPS1, SlSQS and SlCYP710A11 expression. In both tomato OE‐wtBjHMGS1 and OE‐S359A fruits, the up‐regulation of SlGPS and SlGGPPS1 in the MEP pathway that led to α‐tocopherol and carotenoid accumulation indicated cross‐talk between the MVA and MEP pathways. Taken together, the manipulation of BjHMGS1 represents a promising strategy to simultaneously elevate health‐promoting squalene, phytosterols, α‐tocopherol and carotenoids in tomato, an edible fruit.
FgSnt1 of the Set3 HDAC complex plays a key role in mediating the regulation of histone acetylation by the cAMP-PKA pathway in Fusarium graminearum

The cAMP-PKA pathway is critical for regulating growth, differentiation, and pathogenesis in fungal pathogens. In Fusarium graminearum, mutants deleted of PKR regulatory-subunit of PKA had severe defects but often produced spontaneous suppressors. In this study eleven pkr suppressors were found to have mutations in FgSNT1, a component of the Set3C histone deacetylase (HDAC) complex, that result in the truncation of its C-terminal region. Targeted deletion of the C-terminal 98 aa (CT98) in FgSNT1 suppressed the defects of pkr in growth and H4 acetylation. CT98 truncation also increased the interaction of FgSnt1 with Hdf1, a major HDAC in the Set3 complex. The pkr mutant had no detectable expression of the Cpk1 catalytic subunit and PKA activities, which was not suppressed by mutations in FgSNT1. Cpk1 directly interacted with the N-terminal region of FgSnt1 and phosphorylated it at S443, a conserved PKA-phosphorylation site. CT98 of FgSnt1 carrying the S443D mutation interacted with its own N-terminal region. Expression of FgSNT1S443D rescued the defects of pkr in growth and H4 acetylation. Therefore, phosphorylation at S443 and suppressor mutations may relieve self-inhibitory binding of FgSnt1 and increase its interaction with Hdf1 and H4 acetylation, indicating a key role of FgSnt1 in crosstalk between cAMP signaling and Set3 complex.
Recombinant subunit vaccines for soil-transmitted helminths

SUMMARY Soil-transmitted helminths (STHs) collectively infect one fourth of all human beings, and the majority of livestock in the developing world. These gastrointestinal nematodes are the most important parasites on earth with regard to their prevalence in humans and livestock. Current anthelmintic drugs are losing their efficacies due to increasing drug resistance, particularly in STHs of livestock and drug treatment is often followed by rapid reinfection due to failure of the immune system to develop a protective response. Vaccines against STHs offer what drugs cannot accomplish alone. Because such vaccines would have to be produced on such a large scale, and be cost effective, recombinant subunit vaccines that include a minimum number of proteins produced in relatively simple and inexpensive expression systems are required. Here, we summarize all of the previous studies pertaining to recombinant subunit vaccines for STHs of humans and livestock with the goal of both informing the public of just how critical these parasites are, and to help guide future developments. We also discuss several key areas of vaccine development, which we believe to be critical for developing more potent recombinant subunit vaccines with broad-spectrum protection.
In vitro selection of Phytomonas serpens cells resistant to the calpain inhibitor MDL28170: alterations in fitness and expression of the major peptidases and efflux pumps

SUMMARY The species Phytomonas serpens is known to express some molecules displaying similarity to those described in trypanosomatids pathogenic to humans, such as peptidases from Trypanosoma cruzi (cruzipain) and Leishmania spp. (gp63). In this work, a population of P. serpens resistant to the calpain inhibitor MDL28170 at 70 µ m (MDLR population) was selected by culturing promastigotes in increasing concentrations of the drug. The only relevant ultrastructural difference between wild-type (WT) and MDLR promastigotes was the presence of microvesicles within the flagellar pocket of the latter. MDLR population also showed an increased reactivity to anti-cruzipain antibody as well as a higher papain-like proteolytic activity, while the expression of calpain-like molecules cross-reactive to anti-Dm-calpain (from Drosophila melanogaster) antibody and calcium-dependent cysteine peptidase activity were decreased. Gp63-like molecules also presented a diminished expression in MDLR population, which is probably correlated to the reduction in the parasite adhesion to the salivary glands of the insect vector Oncopeltus fasciatus. A lower accumulation of Rhodamine 123 was detected in MDLR cells when compared with the WT population, a phenotype that was reversed when MDLR cells were treated with cyclosporin A and verapamil. Collectively, our results may help in the understanding of the roles of calpain inhibitors in trypanosomatids.
Does Short Sleep Lead to Obesity Among Children and Adolescents? Current Understanding and Implications

Childhood obesity continues to be a major public health concern in the United States. This work reviews the current understanding of the relationship between sleep duration and obesity among children and adolescents. A systematic search was conducted for papers published between January 2000 and July 2013 using keywords: (sleep) and (overweight or obesity or obese or body mass index or BMI or adiposity or body fat or fat) and (children or child or youth or teen or pediatric or adolescent or paediatric or childhood or adolescence or boy or girl). Reference lists of relevant articles and reviews or meta-analysis articles were checked to identify additional studies. Only empirical work and longitudinal studies that focused on children and adolescents were included in this review. The search identified 22 longitudinal studies. The majority of the reviewed studies support the presence of an inverse relationship between sleep duration and obesity. However, in some studies the relationship was not significant in adjusted analyses. Differences as a function of age and gender were also noted. Despite more than a decade of research, the debate on the association between sleep duration and obesity continues. Further research with repeated assessments, valid objective measures, and better control of potential confounding variables is warranted.
Understanding the new tremor classification

Department of Neurology, Universit€ atsklinikum Schleswig-Holstein, Kiel Campus, Christian Albrechts University Kiel, Kiel, Germany Sobell Department of Motor Neuroscience and Movement Disorders, University College London Institute of Neurology, London, UK Southern Illinois University School of Medicine, Springfield, Illinois, USA Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
Intractable Epistaxis with Febuxostat

Objective To report a case of serious, intractable epistaxis warranting an emergency department (ED) visit and hospital admission for transfusion following initiation of febuxostat. Case Summary An 86-year-old female presented to the ED after onset of intractable epistaxis for the previous 24 hours. Medications included aspirin, clopidogrel, metoprolol tartrate, valsartan, rosuvastatin, levothyroxine, esomeprazole, and febuxostat. She was treated with prednisone in the ED for a gout flare 3 weeks prior to the current visit, then was started on febuxostat at her follow-up primary care visit. Ten days after starting febuxostat therapy, she had onset of epistaxis. Initial treatment did not provide hemostasis and hemoglobin, and hematocrit values decreased. She was admitted and transfused. Aspirin, clopidogrel, and febuxostat were held during hospitalization. Bleeding subsided following bedside cautery. On hospital day 3, she restarted aspirin and clopidogrel and was discharged with no recurrence of bleeding. Discussion Epistaxis is relatively common and can be caused by multiple etiologies. Patient did not have prior episodes of epistaxis and had been on all medications for more than a year, except for febuxostat. This patient was also taking aspirin and clopidogrel; however, she had been taking these agents concomitantly for at least 4 years with no prior report of bleeding. Epistaxis occurred 10 days after the first dose of febuxostat with no other reported changes. Conclusions Epistaxis due to febuxostat use cannot be ruled out. Clinicians may consider alternate gout therapy in patients at high risk or taking medications that increase their risk for bleeding.
Deciphering the metabolic pathways influencing heat and cold responses during post-harvest physiology of peach fruit.

Peaches are highly perishable and deteriorate quickly at ambient temperature. Cold storage is commonly used to prevent fruit decay; however, it affects fruit quality causing physiological disorders collectively termed 'chilling injury' (CI). To prevent or ameliorate CI, heat treatment is often applied prior to cold storage. In the present work, metabolic profiling was performed to determine the metabolic dynamics associated with the induction of acquired CI tolerance in response to heat shock. 'Dixiland' peach fruits exposed to 39 °C, cold stored, or after a combined treatment of heat and cold, were compared with fruits ripening at 20 °C. Dramatic changes in the levels of compatible solutes such as galactinol and raffinose were observed, while amino acid precursors of the phenylpropanoid pathway were also modified due to the stress treatments, as was the polyamine putrescine. The observed responses towards temperature stress in peaches are composed of both common and specific response mechanisms to heat and cold, but also of more general adaptive responses that confer strategic advantages in adverse conditions such as biotic stresses. The identification of such key metabolites, which prime the fruit to cope with different stress situations, will likely greatly accelerate the design and the improvement of plant breeding programs.
Values, necessity and the mother of invention in clinical education

McAllister’s (2005) review of the current state of play in clinical education encompasses the what, why and how of the clinical education drought faced around the world. She presents a comprehensive view of the ‘‘forces’’ at work, shaping current clinical education practices. In this paper we will amplify issues raised by McAllister (2005), including the undervaluing of clinical education by the workplace and universities and address whether innovation in clinical education is the result of necessity or educational advancement.
Magnitude and contributory factors of postnatal depression: a community-based cohort study from a rural subdistrict of Bangladesh

Background Recent evidence suggests that the prevalence of postnatal depression (PND) is highest in low-income developing countries. This study aimed to estimate the prevalence of PND and its associated risk factors among Bangladeshi women. Method The study was conducted in the Matlab subdistrict of rural Bangladesh. A cohort of 346 women was followed up from late pregnancy to post-partum. Sociodemographic and other related information on risk factors was collected on structured questionnaires by trained interviewers at 34–35 weeks of pregnancy at the woman's home. A validated local language (Bangla) version of the Edinburgh Postnatal Depression Scale (EPDS-B) was used to measure depression status at 34–35 weeks of pregnancy and at 6–8 weeks after delivery. Results The prevalence of PND was 22% [95% confidence interval (CI) 17.7–26.7%] at 6–8 weeks post-partum. After adjustment in a multivariate logistic model, PND could be predicted by history of past mental illness [odds ratio (OR) 5.6, 95% CI 1.1–27.3], depression in current pregnancy (OR 6.0, 95% CI 3.0–12.0), perinatal death (OR 14.1, 95% CI 2.5–78.0), poor relationship with mother-in-law (OR 3.6, 95% CI 1.1–11.8) and either the husband or the wife leaving home after a domestic quarrel (OR 4.0, 95% CI 1.6–10.2). Conclusions The high prevalence of PND in the study was similar to other countries in the South Asian region. The study findings highlight the need for programme managers and policy makers to allocate resources and develop strategies to address PND in Bangladesh.
Biogenic volatile emissions from the soil.

Volatile compounds are usually associated with an appearance/presence in the atmosphere. Recent advances, however, indicated that the soil is a huge reservoir and source of biogenic volatile organic compounds (bVOCs), which are formed from decomposing litter and dead organic material or are synthesized by underground living organism or organs and tissues of plants. This review summarizes the scarce available data on the exchange of VOCs between soil and atmosphere and the features of the soil and particle structure allowing diffusion of volatiles in the soil, which is the prerequisite for biological VOC-based interactions. In fact, soil may function either as a sink or as a source of bVOCs. Soil VOC emissions to the atmosphere are often 1-2 (0-3) orders of magnitude lower than those from aboveground vegetation. Microorganisms and the plant root system are the major sources for bVOCs. The current methodology to detect belowground volatiles is described as well as the metabolic capabilities resulting in the wealth of microbial and root VOC emissions. Furthermore, VOC profiles are discussed as non-destructive fingerprints for the detection of organisms. In the last chapter, belowground volatile-based bi- and multi-trophic interactions between microorganisms, plants and invertebrates in the soil are discussed.
Is stomatal conductance optimized over both time and space in plant crowns? A field test in grapevine (Vitis vinifera).

Crown carbon gain is maximized for a given total water loss if stomatal conductance (gs ) varies such that the marginal carbon product of water (∂A/∂E) remains invariant both over time and among leaves in a plant crown, provided the curvature of assimilation rate (A) versus transpiration rate (E) is negative. We tested this prediction across distinct crown positions in situ for the first time by parameterizing a biophysical model across 14 positions in four grapevine crowns (Vitis vinifera), computing optimal patterns of gs and E over a day and comparing these to the observed patterns. Observed water use was higher than optimal for leaves in the crown interior, but lower than optimal in most other positions. Crown carbon gain was 18% lower under measured gs than under optimal gs . Positive curvature occurred in 39.6% of cases due to low boundary layer conductance (gbw ), and optimal gs was zero in 11% of cases because ∂A/∂E was below the target value at all gs . Some conclusions changed if we assumed infinite gbw , but optimal and measured E still diverged systematically in time and space. We conclude that the theory's spatial dimension and assumption of positive curvature require further experimental testing.
Effect of low-level LASER and neural mobilization on nociceptive threshold in experimental sciatica

JUSTIFICATIVA E OBJETIVOS:Ha uma carencia na literatura relatando, principalmente, os efeitos do LASER associado a mobilizacao neural na ciatalgia. O objetivo deste estudo foi verificar o efeito do LASER de baixa potencia, com comprimento de onda 830nm e fluencia de 4J/cm2, da mobilizacao neural e da sua associacao, na reducao da dor.METODOS:A amostra foi composta por 28 ratas Wistar, separadas em quatros grupos: G1 (placebo); G2 (mobilizacao neural); G3 (LASER); G4 (mobilizacao neural e LASER), sendo que, todos os grupos foram submetidos a constricao do nervo isquiatico. O tratamento ocorreu no 3o, 5o, 7o, 10o, 12o e no 14o dia de pos-operatorio. Para a avaliacao da nocicepcao foi utilizado um analgesimetro, aplicado tanto no local da lesao como na regiao plantar da pata posterior direita. Os momentos de avaliacao foram: AV1 (pre-lesao); AV2 (3o dia de pos-operatorio antes do tratamento); AV3 (4o dia de pos-operatorio); AV4 (7o dia de pos-operatorio), AV5 (10o dia de pos-operatorio) e AV6 (14o dia de pos-operatorio) aconteceram antes do tratamento; e a AV7 (15o dia de pos-operatorio). RESULTADOS:Nos dois locais de avaliacao, constatou-se que nao houve diferenca estatisticamente significativa entre os grupos, mas, na comparacao entre as avaliacoes, houve diferenca significativa, cujos valores de AV1 foram maiores do que aqueles encontrados nas demais avaliacoes.CONCLUSAO:O LASER de baixa potencia com comprimento de onda de 830nm e fluencia de 4J/cm2, a mobilizacao neural e a associacao das duas tecnicas, nao foram eficazes para aumentar o limiar nociceptivo a pressao de ratas submetidas a ciatalgia experimental.