Rebamipide Does Not Protect Against Naproxen-induced Gastric Damage: A Randomized Double-blind Controlled Trial

Rebamipide is a gastroprotective agent with promising results against gastric damage induced by non-steroidal anti-inflammatory drugs. The present study evaluated if rebamipide protects against naproxen-induced gastric damage in healthy volunteers. Changes in gastric PGE2 tissue concentration were also evaluated. Methods: After a preliminary endoscopy to rule out previous gastric macroscopic damage, twenty-four healthy volunteers of both sexes were divided into 2 groups. One group received sodium naproxen 550 mg b.i.d. plus placebo for 7 days, while the other group received sodium naproxen 550 mg b.i.d. plus rebamipide 100 mg b.i.d. At the end of treatment, a new endoscopy was performed. Gastric macroscopic damage was evaluated by the Cryer score and by the modified Lanza score. The primary outcome measure of the trial was the macroscopic damage observed in each treatment group at the end of treatment. Biopsies were collected at both endoscopies for PGE2 quantification and histopathological analysis (secondary outcomes). Tissue PGE2 was quantified by ELISA. The randomization sequence was generated using 3 blocks of 8 subjects each. Volunteers and endoscopists were blind to whether they were receiving rebamipide or placebo. Results: All recruited volunteers completed the trial. Sodium naproxen induced gastric damage in both groups. At the end of the study, median Cryer score was 4 in both groups (Difference = 0; 95% CI = -1 to 0; p = 0.728). In the placebo group, the mean tissue PGE2 concentration was 1005 +/- 129 pg/mL before treatment and 241 +/- 41 pg/mL after treatment (p < 0.001). In the rebamipide group, the mean tissue PGE2 concentration was 999 +/- 109 pg/mL before treatment, and 168 +/- 13 pg/mL after treatment (p < 0.001). There was no difference in mean tissue PGE2 between the two groups (difference = 5; 95% CI from -334.870 to 345.650; p = 0.975). No significant change was observed at the histopathological evaluation, despite the evident macroscopic damage induced by naproxen. Conclusion: Rebamipide does not protect against naproxen-induced gastric damage in healthy volunteers.1658Biolab Industria Farmaceutica Ltd

Comparison of Apoptotic Cells Between Cryopreserved Ejaculated Sperm and Epididymal Sperm in Stallions

AbstractThe development of a reliable technique to freeze epididymal semen would provide a unique opportunity to preserve valuable genetic material from unexpectedly lost stallions. The aim of this study was to compare the apoptotic indices of sperm obtained from ejaculate, sperm recently recovered from the epididymides (EP), and sperm recovered from epididymides stored at 5°C for 24 hours (EP-stored). For the first category, two ejaculates from seven stallions were collected and then submitted to cryopreservation using an egg yolk-based extender. One week after the last semen collection, the stallions were submitted to bilateral orchiectomy, and sperm from one of the cauda epididymis was harvested immediately after castration (EP). The remaining testicle was stored in a passive refrigeration container at 5°C for 24 hours before the cauda epididymal sperm was harvested (EP-stored). Sperm harvesting from the epididymis for EP and EP-stored was performed by retrograde flushing of the caudal portion of the epididymis using a skim milk-based extender. The recovered sperm was then cryopreserved using the egg yolk-based extender. Sperm motility parameters were studied by computer-assisted semen analysis, and apoptosis was estimated by measuring caspase activity and membrane phospholipid translocation using epifluorescence microscopy. The samples were evaluated immediately (0 hour) and 8 hours after thawing. At 0 hour, no differences in sperm parameters were observed among the groups, but after 8 hours, significant statistical differences were observed in sperm motility parameters and plasma membrane integrity among the treatment groups. In addition, viable cells with no apoptotic signs were more prevalent in EP and EP-stored, suggesting that epididymal sperm is less sensitive to the cold shock caused by sperm cryopreservation

Accurate Atmospheric Parameters at Moderate Resolution Using Spectral Indices: Preliminary Application to the MARVELS Survey

Studies of Galactic chemical and dynamical evolution in the solar neighborhood depend on the availability of precise atmospheric parameters (Teff, [Fe/H] and log g) for solar-type stars. Many large-scale spectroscopic surveys operate at low to moderate spectral resolution for efficiency in observing large samples, which makes the stellar characterization difficult due to the high degree of blending of spectral features. While most surveys use spectral synthesis, in this work we employ an alternative method based on spectral indices to determine the atmospheric parameters of a sample of nearby FGK dwarfs and subgiants observed by the MARVELS survey at moderate resolving power (R~12,000). We have developed three codes to automatically normalize the observed spectra, measure the equivalent widths of the indices and, through the comparison of those with values calculated with pre-determined calibrations, derive the atmospheric parameters of the stars. The calibrations were built using a sample of 309 stars with precise stellar parameters obtained from the analysis of high-resolution FEROS spectra. A validation test of the method was conducted with a sample of 30 MARVELS targets that also have reliable atmospheric parameters from high-resolution spectroscopic analysis. Our approach was able to recover the parameters within 80 K for Teff, 0.05 dex for [Fe/H] and 0.15 dex for log g, values that are lower or equal to the typical external uncertainties found between different high-resolution analyzes. An additional test was performed with a subsample of 138 stars from the ELODIE stellar library and the literature atmospheric parameters were recovered within 125 K for Teff, 0.10 dex for [Fe/H] and 0.29 dex for log g. These results show that the spectral indices are a competitive tool to characterize stars with the intermediate resolution spectra.Comment: Accepted for publication in AJ. Abstract edited to comply with arXiv standards regarding the number of character

Exploring the brown dwarf desert : new substellar companions from the SDSS-III MARVELS survey

Planet searches using the radial velocity technique show a paucity of companions to solar-type stars within ∼5 au in the mass range of ∼10–80 MJup. This deficit, known as the brown dwarf desert, currently has no conclusive explanation. New substellar companions in this region help assess the reality of the desert and provide insight to the formation and evolution of these objects. Here, we present 10 new brown dwarf and 2 low-mass stellar companion candidates around solar-type stars from the Multi-object APO Radial Velocity Exoplanet Large-Area Survey (MARVELS) of the Sloan Digital Sky Survey III. These companions were selected from processed MARVELS data using the latest University of Florida Two Dimensional pipeline, which shows significant improvement and reduction of systematic errors over previous pipelines. The 10 brown dwarf companions range in mass from ∼13 to 76 MJup and have orbital radii of less than 1 au. The two stellar companions have minimum masses of ∼98 and 100 MJup. The host stars of the MARVELS brown dwarf sample have a mean metallicity of [Fe/H] = 0.03 ± 0.08 dex. Given our stellar sample we estimate the brown dwarf occurrence rate around solar-type stars with periods less than ∼300 d to be ∼0.56 per cent

Avaliação do quadro clínico e perfil bioquímico de bovinos durante indução e tratamento de hipocalcemia

O presente trabalho objetivou estudar o quadro sintomatológico, algumas variáveis bioquímicas e a resposta ao tratamento com cálcio de bovinos com hipocalcemia induzida experimentalmente. Foram utilizadas 12 novilhas distribuídas nos grupos controle (n = 5) e tratado (n = 7). Foi infundida solução de EDTA a 5% até o animal apresentar sinais clínicos de hipocalcemia, quando então era iniciado o tratamento com solução contendo cálcio, fósforo, magnésio e glicose, na dose de 1 mL/kg/PV, em 30 minutos, enquanto que o grupo controle recebia apenas solução fisiológica na mesma dose. Exame clínico e coleta de amostras sanguíneas foram realizados nos tempos T0 (basal), T1 (Fase I, caracterizada por tremores musculares), T2 (ao final da infusão com EDTA), T3 (ao final do tratamento) e T4 (24 horas após o término do experimento). Todas as novilhas mostraram diminuição temporária da concentração de cálcio total e livre, fósforo, e apresentaram quadro clássico de hipocalcemia. A taquicardia, a hipofonese e a atonia ruminal desapareceram no decorrer do tratamento, sendo observado aumento no cálcio livre e total e fósforo. O medicamento usado no tratamento dos animais foi eficaz na recuperação do quadro clínico de hipocalcemia dentro de 30 minutos, promovendo retorno das principais variáveis do perfil bioquímico aos valores basais.The present work aims to study the clinical picture, biochemical profile and treatment response in cattle with induced hypocalcaemia. Were utilized 12 heifers randomly distributed in treated (n = 7) and control (n = 5) groups. The induction model was carried on by continuous EDTA infusion into jugular vein until the animals present clinical signs of hypocalcaemia. After that, the treated group received a calcium (Ca) solution enriched with phosphorus, magnesium and glucose with a dose of 1 mL/kg/BW in 30 minutes, meanwhile, the control group was treated with the same dose of physiologic solution. Clinical examination were performed and blood samples were obtained in times T0 (basal time), T1 (beginning of hypocalcaemia); T2 (end of EDTA infusion); T3 (end of treatment) and T4 (24 hours after the induction). All the heifers present temporary blood calcium and phosphorus reduction and demonstrated classical clinical picture of hypocalcaemia. The treated group present full clinical recovery and blood calcium and phosphorus increase. Most evident clinical signs were increasing heart beat, hypophonesis and rumenal atony. Those symptoms were reversed after calcium treatment. The solution used for treatment was efficient on clinical recovery within thirty minutes, promoting the return to basal levels of the most of biochemical's variables

Skin color and severe maternal outcomes: evidence from the brazilian network for surveillance of severe maternal morbidity

Taking into account the probable role that race/skin color may have for determining outcomes in maternal health, the objective of this study was to assess whether maternal race/skin color is a predictor of severe maternal morbidity. This is a secondary analysis of the Brazilian Network for Surveillance of Severe Maternal Morbidity, a national multicenter cross-sectional study of 27 Brazilian referral maternity hospitals. A prospective surveillance was performed to identify cases of maternal death (MD), maternal near miss (MNM) events, and potentially life-threatening conditions (PLTC), according to standard WHO definition and criteria. Among 9,555 women with severe maternal morbidity, data on race/skin color was available for 7,139 women, who were further divided into two groups: 4,108 nonwhite women (2,253 black and 1,855 from other races/skin color) and 3,031 white women. Indicators of severe maternal morbidity according to WHO definition are shown by skin color group. Adjusted Prevalence Ratios (PRadj - 95%CI) for Severe Maternal Outcome (SMO=MNM+MD) were estimated according to sociodemographic/obstetric characteristics, pregnancy outcomes, and perinatal results considering race. Results. Among 7,139 women with severe maternal morbidity evaluated, 90.5% were classified as PLTC, 8.5% as MNM, and 1.6% as MD. There was a significantly higher prevalence of MNM and MD among white women. MNMR (maternal near miss ratio) was 9.37 per thousand live births (LB). SMOR (severe maternal outcome ratio) was 11.08 per 1000 LB, and MMR (maternal mortality ratio) was 170.4 per 100,000 LB. Maternal mortality to maternal near miss ratio was 1 to 5.2, irrespective of maternal skin color. Hypertension, the main cause of maternal complications, affected mostly nonwhite women. Hemorrhage, the second more common cause of maternal complication, predominated among white women. Nonwhite skin color was associated with a reduced risk of SMO in multivariate analysis. Nonwhite skin color was associated with a lower risk for severe maternal outcomes. This result could be due to confounding factors linked to a high rate of Brazilian miscegenation.2019CNPQ - Conselho Nacional de Desenvolvimento Científico e Tecnológico402702/2008-

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders