Evaluation of the Effect of Acute Sibutramine in Female Rats in the Elevated T‐Maze and Elevated Plus‐Maze Tests

Sibutramine is a serotonin and norepinephrine reuptake inhibitor indicated for the treatment of obesity. A pre‐clinical study showed that acute administration of sibutramine promoted anxiolytic‐ and panicolytic‐like effects in male rats. However, in clinical reports, sibutramine favoured the onset of panic attacks in women. In this study, the effect of sibutramine on experimental anxiety in females and the relevance of different oestrous cycle phases for this effect were analysed. In experiment 1, both male and female rats were submitted to acute intraperitoneal injection of sibutramine or vehicle 30 min. before testing in the elevated T‐maze (ETM) and in the open‐field test (OF). Females in the pro‐oestrus (P), oestrus (E), early dioestrus (ED) and late dioestrus (LD) phases were tested in the ETM and OF (experiment 2) or in the elevated plus‐maze (EPM) 30 min. after the injection of sibutramine. Sibutramine impaired the escape response in the ETM in both males and females. This effect was observed for P, E and ED, but not for LD females. Sibutramine altered neither the inhibitory avoidance in the ETM nor the behaviour of females in the EPM. Thus, sibutramine promoted a panicolytic‐like effect in female rats cycling at P, E and ED, but not in the LD phase and did not alter behaviours related to anxiety in both ETM and EPM. Considering that pre‐clinical studies aiming the screening of anxiolytic drugs employ male rodents, data here obtained reinforce the importance of better understanding the effects of drugs in females.     

Factors associated with potentially inappropriate medications use by the elderly according to Beers criteria 2003 and 2012

Background Potentially inappropriate medications (PIMs) should be avoided by the elderly because they possess a significant high risk for this population when a safer alternative is available. Therefore, the identification of prevalence and factors associated with PIMs should be considered as they provide valuable information that can be used to develop strategies to ensure patients’ safety. Objective To identify the prevalence and the clinical and socioeconomic–demographic factors that may be associated with PIMs use in the elderly, according to Beers criteria 2003 and its updated version 2012. And, as a secondary objective, a comparison between both criteria was performed. Setting Pharmacy of the Basic Health District Unit of the western district of Ribeirão Preto. Methods This cross-sectional observational study was conducted with the elderly, assisted by the Brazilian public health system. Data from patients were collected through a structured interview form. Beers criteria 2003 and 2012 were used to classify PIMs. The association between PIMs used and independent variables were analyzed by odds ratios. The differences between PIMs use according to Beers criteria 2003 and 2012 were analyzed by McNemar’s test and the agreement by kappa coefficient. Main outcome measure Prevalence and factors associated with PIMs use in Brazilian elderly outpatients. Results One thousand elderly patients were interviewed. High prevalence of PIMs use was observed, 48.0 and 59.2 % according to Beers criteria 2003 and 2012, respectively. The factors associated with PIMs use, common for both criteria, are female gender, self-medication, use of over the counter drugs, complaints related to adverse drug event, psychotropic medication, polypharmacy and some categories of drugs. PIMs use is different between Beers criteria 2003 and 2012 (McNemar’s test, p < 0.01), although a substantial agreement between these classifications was observed (kappa coefficient 0.635, 95% confidence intervals (0.588, 0.681). Conclusions Our study showed a high prevalence of PIMs use, which is associated with various clinical and social–demographic factors. When comparing both criteria through McNemar’s test, PIMs use was considered different. The differences may have occurred because medications with high prevalence of use in Brazil were included in Beers criteria 2012 .     

Synthesis of diagnostic quality cancer pathology images by generative adversarial networks

Deep learning-based computer vision methods have recently made remarkable breakthroughs in the analysis and classification of cancer pathology images. However, there has been relatively little investigation of the utility of deep neural networks to synthesize medical images. In this study, we evaluated the efficacy of generative adversarial networks to synthesize high-resolution pathology images of 10 histological types of cancer, including five cancer types from The Cancer Genome Atlas and the five major histological subtypes of ovarian carcinoma. The quality of these images was assessed using a comprehensive survey of board-certified pathologists (n = 9) and pathology trainees (n = 6). Our results show that the real and synthetic images are classified by histotype with comparable accuracies and the synthetic images are visually indistinguishable from real images. Furthermore, we trained deep convolutional neural networks to diagnose the different cancer types and determined that the synthetic images perform as well as additional real images when used to supplement a small training set. These findings have important applications in proficiency testing of medical practitioners and quality assurance in clinical laboratories. Furthermore, training of computer-aided diagnostic systems can benefit from synthetic images where labeled datasets are limited (e.g. rare cancers). We have created a publicly available website where clinicians and researchers can attempt questions from the image survey ( http://gan.aimlab.ca/ ). © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Further delineation of putative ACTB loss‐of‐function variants: A 4‐patient series

ACTB encodes β‐cytoplasmic actin, an essential component of the cytoskeleton. Based on chromosome 7p22.1 deletions that include the ACTB locus and on rare truncating ACTB variants, a phenotype resulting from ACTB haploinsufficiency was recently proposed. We report putative ACTB loss‐of‐function variants in four patients. To the best of our knowledge, we report the first 7p22.1 microdeletion confined to ACTB and the second ACTB frameshifting mutation that predicts mRNA decay. A de‐novo ACTB p.(Gly302Ala) mutation affects β‐cytoplasmic actin distribution. All four patients share a facial gestalt that is distinct from that of individuals with dominant‐negative ACTB variants in Baraitser‐Winter cerebrofrontofacial syndrome. Two of our patients had strikingly thin and sparse scalp hair. One patient had sagittal craniosynostosis and hypospadias. All three affected male children have attention deficits and mild global developmental delay. Mild intellectual disability was present in only one patient. Heterozygous ACTB deletion can allow for normal psychomotor function.     

Clinical hematological and biochemical parameters in Swiss,BALB/c,C57BL/6 and B6D2F1 Mus musculus

BackgroundAnimal models are widely used in scientific research in order to obtain information from a whole organism under a specific set of experimental conditions. Various lineages of mice have been used to investigate diseases and new therapeutic strategies, and, consequently, hematological and biochemical tests in these laboratory animals are essential to validate scientific studies. Our study seeks to establish reference values for hematological and biochemical parameters of four lineages of mice.MethodsWe evaluated the hematological and biochemical profiles of 20 males and 20 females from the lineages Swiss (heterogeneous), BALB/c and C57BL/6 (isogenic), and B6D2F1 (hybrid), totaling 160 mice. Analysis were standardized using the systems pocH‐100iV Diff™ for 19 hematological parameters and VITROS^® 350 for 12 biochemical parameters.ResultsResults are shown as means and standard deviation, grouped by lineage and genre. Comparing the values obtained in this study with the values from previous studies, some variations were detected, which could be explained by differences in methodologies or individual variability.ConclusionThus our study shows that knowledge and disclosure of the values of physiological parameters of laboratory animals is necessary, and emphasises the importance of considering variations influenced by gender, lineage and genotype in the choice of the best experimental model.