Deep Learning Techniques to Characterize the RPS28P7 Pseudogene and the Metazoa-SRP Gene as Drug Potential Targets in Pancreatic Cancer Patients.

The molecular explanation about why some pancreatic cancer (PaCa) patients die early and others die later is poorly understood. This study aimed to discover potential novel markers and drug targets that could be useful to stratify and extend expected survival in prospective early-death patients. We deployed a deep learning algorithm and analyzed the gene copy number, gene expression, and protein expression data of death versus alive PaCa patients from the GDC cohort. The genes with higher relative amplification (copy number >4 times in the dead compared with the alive group) were EWSR1, FLT3, GPC3, HIF1A, HLF, and MEN1. The most highly up-regulated genes (>8.5-fold change) in the death group were RPL30, RPL37, RPS28P7, RPS11, Metazoa_SRP, CAPNS1, FN1, H3-3B, LCN2, and OAZ1. None of their corresponding proteins were up or down-regulated in the death group. The mRNA of the RPS28P7 pseudogene could act as ceRNA sponging the miRNA that was originally directed to the parental gene RPS28. We propose RPS28P7 mRNA as the most druggable target that can be modulated with small molecules or the RNA technology approach. These markers could be added as criteria to patient stratification in future PaCa drug trials, but further validation in the target populations is encouraged.

Gastroprotective Effects of Oral Glycosaminoglycans with Sodium Alginate in an Indomethacin-Induced Gastric Injury Model in Rats.

The gastrointestinal (GI) mucosal barrier is often exposed to inflammatory and erosive insults, resulting in gastric lesions. Glycosaminoglycans (GAGs), such as hyaluronic acid (HA), chondroitin sulfate (CS), and N-acetylglucosamine (NAG) have shown potential beneficial effects as GI protectants. This study aimed to evaluate the gastroprotective effects of oral GAGs in rats with indomethacin-induced GI lesions. Forty-five Sprague-Dawley rats (8-9 weeks-old, 228 ± 7 g) were included in the study, divided into five study groups, and given, administered orally, either sucralfate (positive control group; PC), NAG (G group), sodium alginate plus HA and CS (AHC group), sodium alginate plus HA, CS, and NAG (AHCG group), or no treatment (negative control group; NC). Animals were administered 12.5 mg/kg indomethacin orally 15 min after receiving the assigned treatment. After 4 h, stomach samples were obtained and used to perform a macroscopic evaluation of gastric lesions and to allow histological assessment of the gastric wall (via H/E staining) and mucous (via PAS staining). The AHCG group showed significant gastroprotective improvements compared to the NC group, and a similar efficacy to the PC group. This combination of sodium alginate with GAGs might, therefore, become a safe and effective alternative to prescription drugs for gastric lesions, such as sucralfate, and have potential usefulness in companion animals.

Complementary mechanisms of modulation of spontaneous phasic contractions by the gaseous signalling molecules NO, H2S, HNO and the polysulfide Na2S3 in the rat colon.

OBJECTIVES: Reactive oxygen and nitrogen species may be produced during inflammation leading to the formation of NO, H2S or HNO. Enzymes such as iNOS, CSE and CBS might also be responsible for polysulfide production. Since these signalling molecules might have an impact on colonic motility, the aim of this study was to compare their effect on rat colonic slow phasic contractions (SPC). METHODS: Organ bath measurements with strips obtained from rat proximal colon were performed using the polysulfide Na2S3, sodium nitroprusside (NaNP), sodium hydrogen sulfide (NaHS), Angeli's salt as NO, H2S, and HNO donors, respectively. TTX (1 µM) was used to block neuronal activity. RESULTS: All four molecules, concentration-dependently, inhibited the amplitude and frequency of SPC both in the circular and longitudinal muscle layer. The relative potency was NaNP>Angeli's salt>NaHS>Na2S3. The inhibitory response induced by NaNP (1 µM) and Angeli's salt (50 µM) was reversed by ODQ (10 µM) whereas the inhibitory effect of NaHS (1 mM) was reversed by apamin (1 µM) and glibenclamide (10 µM). Na2S3 (1 mM) response was partially reversed by apamin (1 µM) and glibenclamide (10 µM). High concentrations of Na2S3 caused an increase in tone. Low concentrations of NaHS or Na2S3 did not potentiate NaNP responses. CONCLUSIONS: All signalling molecules inhibit SPC in both muscle layers. The effect is independent of neural activity and involves guanylyl cyclase (NO and HNO) and SKCa and KATP channels (NaHS or Na2S3). Other pathways might also be involved in Na2S3 responses. Accordingly, complementary mechanisms of inhibition might be attributable to these signalling molecules.

Stroke Outcomes in Women: A Population-Based Cohort Study.

BACKGROUND: Limited data are available on sex-related disparities in long-term outcomes after stroke. We estimated sex differences in various stroke long-term outcomes among survivors after stroke in a prospective 25-year follow-up study. METHODS: Individuals recruited to the South London Stroke Register, an ongoing multi-ethnic urban-based population stroke register, from 1995 onward were included in the analyses (n=6687). The outcomes were death, subsequent stroke, activity of daily living, instrumental activity of daily living, cognitive impairment, depression, anxiety, and health-related quality of life. Kaplan-Meier curves were generated for mortality, stroke recurrence, and recurrence-free survival by sex and Cox proportional hazards model used to model sex differences up to 25 years. Generalized estimating equation were used to model sex differences in risk of self-reported stroke outcomes over 10 years poststroke outcomes, adjusting for age, preexisting activity of daily living, case-mix, stroke subtypes, and other potential confounding risk factors. RESULTS: There were 49% women (mean age, 72 years; SD, 15.6) and 51% men (mean age, 67 years; SD, 14.3) in 6687 participants. Compared with men, women had 9% (95% CI, 3%-15%) lower covariate-adjusted risk of death and 6% (0%-13%) lower risk of stroke recurrence or death. Generally, women had significantly poorer outcomes in activity of daily living and anxiety than men, and the sex differences persisted to up to 5 years after stroke. Women also had poorer health-related quality of life in physical (ß=-2.06 [95% CI, -3.01 to -1.10]) and mental domains (ß=-1.48 [95% CI, -2.44 to -0.52]). Although not significant, there was a suggestive trend for poorer outcomes in cognitive impairment and depression in women. No significant difference in stroke recurrence were found between men and women. CONCLUSIONS: Female patients with stroke tended to have better covariate-adjusted survival but poorer outcomes among survivors than male patients, with deficits persisting to up to 5 years poststroke.

First report of tilapia lake virus emergence in fish farms in the department of Córdoba, Colombia.

BACKGROUND AND AIM: In 2016, the tilapia-producing farms in the department of Córdoba, Colombia, had witnessed outbreaks of disease with clinical signs compatible with those caused by the tilapia lake virus (TiLV). This study was conducted to confirm the presence of TiLV in some fish farms in the department of Córdoba. MATERIALS AND METHODS: A descriptive cross-sectional study was conducted in seven farms using a non-random sampling method from July 2016 to December 2017. A total of 66 fish, including 33 healthy fish and 33 fish with clinical signs, were caught, from which 178 tissue samples of spleen, liver, and brain were collected. RNA was extracted from each organ using TRIzol®. cDNA was synthesized using a retrotranscriptase and a universal amplification primer. The polymerase chain reaction was performed using primers specific to TiLV, in which the primers were amplified in a 491 bp region in segment 3 of TiLV, and the amplicons were sequenced using the Sanger method. RESULTS: Of the seven farms surveyed, 3 (42.85%) had TiLV in the collected fish. Of the 66 collected fish, 18 (27.27%) were infected with TiLV. The virus was detected in the brain (64.3%, 18/28), spleen (61.9%, 13/21), and liver (35.7%, 10/28). The sequences were recorded in GenBank with the codes MH338228, MH350845, and MH350846. Nucleotide homology analyses revealed that this study's circulating strains exhibited 97% identity with the Israeli strain (GenBank KU751816.1). CONCLUSION: This is the first official report of TiLV in the department of Córdoba, Colombia. The circulating strains detected in this study exhibited 97% identity with the Israeli strain.

Assessment of Sample Size Calculations Used in Aquaculture by Simulation Techniques.

An adequate sampling methodology is the key to knowing the health status of aquatic populations. Usually, the aims of epidemiological surveys in aquaculture are to detect an infection and estimate the disease prevalence, and different formulas are used to calculate the sample size. The main objective of this study was to assess if the sample sizes calculated using classical epidemiological formulas are valid considering the sampling methodology, the population size, and the spatial distribution of diseased animals in the population (non-clustered or clustered). However, the use of sample sizes of 30, 60, and 150 fish is widely accepted in aquaculture, due to the requirements of the World Organization for Animal Health (OIE) for epidemiological surveillance. We have developed a specific software using ASP (Active Server Pages) language and MySQL database in order to generate aquatic populations from 100 to 10 000 brown trouts infected by Aeromonas salmonicida with different levels of prevalence: 2, 5, 10, and 50%. Then we implemented several Monte Carlo simulations to estimate empirically the sample sizes corresponding to the different scenarios. Furthermore, we compared these results with the values calculated by classical formulas. We determined that simple random sampling was more accurate in detecting an infection, because it is independent of the distribution of infected animals in the population. However, if diseased animals are non-clustered it is more efficient to use systematic methods, even in the case of small populations. Finally, the formula to calculate sample size to estimate disease prevalence is not valid when the expected prevalence is far from 50%, and it is necessary to increase the sample size to reach the desired precision.

New method to estimate the sample size for calculation of a proportion assuming binomial distribution.

Nowadays the formula to calculate the sample size for estimate a proportion (as prevalence) is based on the Normal distribution, however it would be based on a Binomial distribution which confidence interval was possible to be calculated using the Wilson Score method. By comparing the two formulae (Normal and Binomial distributions), the variation of the amplitude of the confidence intervals is relevant in the tails and the center of the curves. In order to calculate the needed sample size we have simulated an iterative sampling procedure, which shows an underestimation of the sample size for values of prevalence closed to 0 or 1, and also an overestimation for values closed to 0.5. Attending to these results we proposed an algorithm based on Wilson Score method that provides similar values for the sample size than empirically obtained by simulation.

Heterotrophic microbial activity and organic matter degradation in coastal lagoons of Colombia.

In this study we measured the community respiration and the bacterial respiration as part of the overall degradation process of organic material. Additionally, the turnover rates of the pools of dissolved free glucose and acetate as representatives of the fraction of easily degradable low molecular organic solutes were determined. The study was performed in several coastal lagoons of the "Outer Delta of the Río Magdalena" in northern Colombia. The lagoons can be separated into two groups: The first group contains highly productive brackish lagoons with chl a concentrations ranging from 62-130 micrograms/l. The second group consists of less productive freshwater lagoons with chl a between 5.5-19 micrograms/l. Turnover rates of glucose and acetate were very fast in the highly productive lagoons resulting in turnover times of less than 20 min for both compounds. In the less productive systems the cycling of glucose and acetate was much slower. Here the mean values of the turnover times were 2 hr for glucose and 1.5 hr for acetate. The rates of bacterial DNA-formation measured as thymidine incorporation differed significantly between both groups of lagoons, being very high (1.86-2.76 nmol/l/hr) in the highly productive and relatively low (0.073-0.55 nmol/l/hr) in the less productive group. Water column community respiration ranged between 122 and 16 micrograms C/l/hr with means of 88 micrograms C/l/hr in the highly and 19 micrograms C/l/hr in the less productive group. In the first group the mean values of the bacterial contribution to community respiration amounted to 37% and in the second group to 18%. The bacterial respiration was determined in an indirect way via bacterial biomass production and assuming a growth efficiency of 50%. It is discussed whether this relatively high growth efficiency allows reasonable results in both groups of lagoons.

Criptococosis ocasionada por crytococcus neoformans variedad gatti / Cryptococcosis for crytococcus neoformans var. gatti

Introducción y objetivo: Cryptococcus neoformans, agente etiológico de la criptococosis presenta dos variedades (neoformans y gattii), las cuales causan diferentes formas clínicas, específicas para la variedad. Estas diferencias tienen relación con el hospedero, su respuesta inmune, los hallazgos clínicos, paraclínicos y de evolución. El objetivo del trabajo fue establecer las características clínicas y de laboratorio en pacientes colombianos afectados por la var. gattii, destacando su morbimortalidad. Diseño: estudio observacional descriptivo. Métodos: se analizaron las historias de 20 pacientes con afección sistémica por C. neoformans var. gattii diagnosticados entre 1988 y 1999. Se consignaron los datos demográficos, la procedencia, la información clínica, la evolución, las secuelas y el tratamiento. Resultados: quince pacientes fueron hombres y cinco mujeres, con edad promedio de 32 años; cuatro de ellos eran menores de 12 años. Los pacientes procedían de ocho departamentos; 12 de ellos de Norte de Santander. Los síntomas meníngeos motivaron la consulta en 18 pacientes y la afección pulmonar (criptococoma) en los dos restantes pero, posteriormente, éstos presentaron compromiso meníngeo. Los síntomas predominantes (más del 55 por ciento) fueron cefalea, vómito y fiebre. El 80 por ciento de los pacientes fueron considerados inmunocompetentes. El curso de la enfermedad fue severo ya que siete (35 por ciento) pacientes murieron un mes después del diagnóstico y otros siete sufrieron pérdida de la agudeza visual y/o de la visión. Conclusiones: se destaca la severidad de la afección por la var. gattii, su mortalidad y la morbilidad, lo cual señala la necesidad de un pronto diagnóstico de la variedad infectante de C. neoformans.