Studying Cat (Felis catus) Diabetes: Beware of the Acromegalic Imposter

Naturally occurring diabetes mellitus (DM) is common in domestic cats (Felis catus). It has been proposed as a model for human Type 2 DM given many shared features. Small case studies demonstrate feline DM also occurs as a result of insulin resistance due to a somatotrophinoma. The current study estimates the prevalence of hypersomatotropism or acromegaly in the largest cohort of diabetic cats to date, evaluates clinical presentation and ease of recognition. Diabetic cats were screened for hypersomatotropism using serum total insulin-like growth factor-1 (IGF-1; radioimmunoassay), followed by further evaluation of a subset of cases with suggestive IGF-1 (>1000 ng/ml) through pituitary imaging and/ or histopathology. Clinicians indicated pre-test suspicion for hypersomatotropism. In total 1221 diabetic cats were screened; 319 (26.1%) demonstrated a serum IGF-1>1000 ng/ml (95% confidence interval: 23.6-28.6%). Of these cats a subset of 63 (20%) underwent pituitary imaging and 56/63 (89%) had a pituitary tumour on computed tomography; an additional three on magnetic resonance imaging and one on necropsy. These data suggest a positive predictive value of serum IGF-1 for hypersomatotropism of 95% (95% confidence interval: 90-100%), thus suggesting the overall hypersomatotropism prevalence among UK diabetic cats to be 24.8% (95% confidence interval: 21.2-28.6%). Only 24% of clinicians indicated a strong pre-test suspicion; most hypersomatotropism cats did not display typical phenotypical acromegaly signs. The current data suggest hypersomatotropism screening should be considered when studying diabetic cats and opportunities exist for comparative acromegaly research, especially in light of the many detected communalities with the human disease

Regional variation in steroid anesthetic modulation of 35STBPS binding to gamma-aminobutyric acidA receptors in rat brain

Steroids that enhance gamma-aminobutyric acid (GABA)A receptor function in the central nervous system allosterically modulate the binding of the convulsant chloride channel ligand [35S]-t-butyl bicyclophosphorothionate. When assayed in membrane homogenates and in tissue sections by autoradiography, concentration-dependence curves vary with respect to both brain region and the nature of the steroid. Alphaxalone and endogenous steroid hormone metabolites inhibit the binding of [35S]-t-butyl bicyclophosphorothionate in some regions, enhance it in others and give biphasic concentration-dependence in others, apparently the result of algebraic summation of two effects involving regional-dependent enhancement or inhibition. The alphaxalone effect is additive with that produced by adding GABA to the binding assays in some regions, but synergistic in other areas. Likewise, the effect of GABA is inhibited completely by saturating concentrations of the antagonist bicuculline methochloride in some areas but only partially in others, and completely or partially reversed by the convulsant benzodiazepine Ro5-4864, depending on region. The granule cell and molecular layers of cerebellum are particularly different in these allosteric interactions. The heterogeneity of binding behavior is consistent with the presence of multiple GABAA receptor subtypes in the brain. Regional variation in subunit gene expression apparently produces a family of hetero-oligomeric GABAA receptors with different biological and pharmacological properties, including qualitative and quantitative differences in modulation by neuroactive steroids

The Impact of Social Distancing Measures Due to COVID-19 Pandemic on Sexual Function and Relationship Quality of Couples in Greece

Introduction: Recent studies have reported that the quarantine imposed in several countries around the world due to Covid-19 affected the sexual function and relationship quality. On the March 23, 2020 the Greek government imposed a national quarantine to contain the spread of the pandemic. The impact of such conditions on sexual function and relationship quality of couples is unknown. Aim: To investigate sexual function and relationship quality of couples during the quarantine. Methods: An online anonymous survey was conducted one month post-impose of the quarantine, between the April 21 and the May 3, 2020. Adult respondents in a relationship completed a questionnaire including sociodemographic characteristics, structured inquiries regarding sexual activity and quality of relationship, anxiety level, and mood during the quarantine, as well as the IIEF and FSFI indices. Outcomes: Sexual function was assessed using the Greek versions of the FSFI and IIEF for females and males respectively. Sexual activity using 5 statements regarding frequency of sexual thoughts, masturbation, and intercourse, quality of intercourse and general estimation of the level of sexual function. Participants graded their level of agreement. Relationship quality was assessed using 5 questions regarding communication, company, understanding, tension and general estimation of companionship. Participants graded their level of agreement. Two additional statements were used in order to evaluate mood and the level of anxiety. Results: A sum of 299 adult heterosexual participants in a relationship participated. Little or no negative impact on sexual function was reported. Increased anxiety and deficient mood were reported only for those with no access to their partner. Being in a steady relationship and living with their partner, but only for couples without children, resulted in satisfaction by sexual activity and enhanced emotional security. Conclusion: Sexual function and relationship quality appeared as not affected by the quarantine and by the measures of social distancing. Sotiropoulou P, Ferenidou F, Owens D, et al. The Impact of Social Distancing Measures Due to COVID-19 Pandemic on Sexual Function and Relationship Quality of Couples in Greece. Sex Med 2021;XX:XXXXXX. © 2021 The Author

Immunophenotypic analysis of the p53 gene in non-melanoma skin cancer and correlation with apoptosis and cell proliferation

Background Sunlight precipitates a series of genetic events that lead to the development of skin cancers such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The p53 tumour suppressor gene, which plays a pivotal role in cell division and apoptosis, is frequently found mutated in sunlight- induced skin turnours. Objective To investigate the immunoreactivity of the p53 gene in non-melanoma skin cancers and to correlate its expression with apoptotic and cell proliferation markers. Methods We analysed 35 non-melanoma turnours including 19 BCCs and 16 SCCs from sun-exposed skin areas. p53 protein expression was studied immunohistochemically using the DO7 monoclonal antibody against wild-type and mutant p53 forms. The percentage of p53-immunopositive nuclei was measured by image analysis. Cell proliferation and apoptosis were also assessed by image analysis following Ki-67 immunostaining and application of the TUNEL method on paraffin sections, respectively. Results The percentage of p53-expressing cells varied from 3.5 to 90 in BCCs (median value 54.4%) and from 3.7 to 94 in SCCs (median value 40.3%). The mean value of Ki-67-positive cells was comparable in both groups of tumours with a mean value of 40.6% in BCCs and 34.6% in SCCs. Conversely, the TUNEL assay showed sporadic staining of apoptotic cells within the turnours with a mean value of 1. 12% in BCCs and 1.8% in SCCs. p53 protein expression was correlated positively with cell proliferation (r = 0.75, P = 0.000001) and negatively with apoptosis (r = 0.23, P = 0.05). Conclusion p53 immunoreactivity was high in the majority of the skin carcinomas examined and correlated positively with cell proliferation and negatively with apoptosis. The p53 protein overexpression appears to be related to an inactivated protein resulting from mutations of the p53 gene or other unclear molecular mechanisms