Targeting the Oxytocin System: New Pharmacotherapeutic Approaches

Deficits in social behavioral domains, such as interpersonal communication, emotion recognition, and empathy, are a characteristic symptom in several neuropsychiatric disorders, including schizophrenia and autism spectrum disorder (ASD). The neuropeptide oxytocin (OT) has emerged as a key regulator of diverse social behaviors in vertebrates and, thus, has been identified as a potential therapeutic target for improving social dysfunction. In recent years, the field of OT research has seen an explosion of scientific inquiry, producing a more comprehensive picture of oxytocinergic signaling and the pathways that regulate its release and degradation in the brain. In this review, we provide an analysis of how this information is being exploited to accelerate the discovery of novel oxytocinergic therapeutics

Gestational diabetes mellitus in Cameroon: prevalence, risk factors and screening strategies

Copyright \ua9 2024 Sobngwi, Sobngwi-Tambekou, Katte, Echouffo-Tcheugui, Balti, Kengne, Fezeu, Ditah, Tchatchoua, Dehayem, Unwin, Rankin, Mbanya and Bell.Background: The burden of gestational diabetes (GDM) and the optimal screening strategies in African populations are yet to be determined. We assessed the prevalence of GDM and the performance of various screening tests in a Cameroonian population. Methods: We carried out a cross-sectional study involving the screening of 983 women at 24-28 weeks of pregnancy for GDM using serial tests, including fasting plasma (FPG), random blood glucose (RBG), a 1-hour 50g glucose challenge test (GCT), and standard 2-hour oral glucose tolerance test (OGTT). GDM was defined using the World Health Organization (WHO 1999), International Association of Diabetes and Pregnancy Special Group (IADPSG 2010), and National Institute for Health Care Excellence (NICE 2015) criteria. GDM correlates were assessed using logistic regressions, and c-statistics were used to assess the performance of screening strategies. Findings: GDM prevalence was 5\ub79%, 17\ub77%, and 11\ub70% using WHO, IADPSG, and NICE criteria, respectively. Previous stillbirth [odds ratio: 3\ub714, 95%CI: 1\ub727-7\ub776)] was the main correlate of GDM. The optimal cut-points to diagnose WHO-defined GDM were 5\ub79 mmol/L for RPG (c-statistic 0\ub762) and 7\ub71 mmol/L for 1-hour 50g GCT (c-statistic 0\ub776). The same cut-off value for RPG was applicable for IADPSG-diagnosed GDM while the threshold was 6\ub75 mmol/L (c-statistic 0\ub761) for NICE-diagnosed GDM. The optimal cut-off of 1-hour 50g GCT was similar for IADPSG and NICE-diagnosed GDM. WHO-defined GDM was always confirmed by another diagnosis strategy while IADPSG and GCT independently identified at least 66\ub79 and 41\ub70% of the cases. Interpretation: GDM is common among Cameroonian women. Effective detection of GDM in under-resourced settings may require simpler algorithms including the initial use of FPG, which could substantially increase screening yield

Nanowire Metal-Insulator-Metal Plasmonic Devices

In this paper we theoretically study the responsivity of Metal-Insulator-Metal nanostructures to light illumination over a broad wavelength band (1 - 25 microns) and we examine the role of a local field enhancement and electrostatic field on the responsivity

An evolutionary conserved region (ECR) in the human dopamine receptor D4 gene supports reporter gene expression in primary cultures derived from the rat cortex

Background: detecting functional variants contributing to diversity of behaviour is crucial for dissecting genetics of complex behaviours. At a molecular level, characterisation of variation in exons has been studied as they are easily identified in the current genome annotation although the functional consequences are less well understood; however, it has been difficult to prioritise regions of non-coding DNA in which genetic variation could also have significant functional consequences. Comparison of multiple vertebrate genomes has allowed the identification of non-coding evolutionary conserved regions (ECRs), in which the degree of conservation can be comparable with exonic regions suggesting functional significance. - Results: we identified ECRs at the dopamine receptor D4 gene locus, an important gene for human behaviours. The most conserved non-coding ECR (D4ECR1) supported high reporter gene expression in primary cultures derived from neonate rat frontal cortex. Computer aided analysis of the sequence of the D4ECR1 indicated the potential transcription factors that could modulate its function. D4ECR1 contained multiple consensus sequences for binding the transcription factor Sp1, a factor previously implicated in DRD4 expression. Co-transfection experiments demonstrated that overexpression of Sp1 significantly decreased the activity of the D4ECR1 in vitro. - Conclusion: bioinformatic analysis complemented by functional analysis of the DRD4 gene locus has identified a) a strong enhancer that functions in neurons and b) a transcription factor that may modulate the function of that enhancer

Assessment of the agreement between the Framingham and DAD risk equations for estimating cardiovascular risk in adult Africans living with HIV infection: a cross-sectional study

Abstract Background The Absolute cardiovascular disease (CVD) risk evaluation using multivariable CVD risk models is increasingly advocated in people with HIV, in whom existing models remain largely untested. We assessed the agreement between the general population derived Framingham CVD risk equation and the HIV-specific Data collection on Adverse effects of anti-HIV Drugs (DAD) CVD risk equation in HIV-infected adult Cameroonians. Methods This cross-sectional study involved 452 HIV infected adults recruited at the HIV day-care unit of the Yaoundé Central Hospital, Cameroon. The 5-year projected CVD risk was estimated for each participant using the DAD and Framingham CVD risk equations. Agreement between estimates from these equations was assessed using the spearman correlation and Cohen’s kappa coefficient. Results The mean age of participants (80% females) was 44.4 ± 9.8 years. Most participants (88.5%) were on antiretroviral treatment with 93.3% of them receiving first-line regimen. The most frequent cardiovascular risk factors were abdominal obesity (43.1%) and dyslipidemia (33.8%). The median estimated 5-year CVD risk was 0.6% (25th-75th percentiles: 0.3-1.3) using the DAD equation and 0.7% (0.2-2.0) with the Framingham equation. The Spearman correlation between the two estimates was 0.93 (p < 0.001). The kappa statistic was 0.61 (95% confident interval: 0.54-0.67) for the agreement between the two equations in classifying participants across risk categories defined as low, moderate, high and very high. Conclusion Most participants had a low-to-moderate estimated CVD risk, with acceptable level of agreement between the general and HIV-specific equations in ranking CVD risk

Histopathology of resected tissue from repair of anomalous aortic origin of a coronary artery: Potential mechanism of coronary artery compressionCentral MessagePerspective

Objective: This study aimed to describe the histomorphologic characteristics of resected (unroofed) common wall tissue from repair of anomalous aortic origin of a coronary artery and to determine whether the histologic features correlate with clinical and imaging findings. Methods: The histology of resected tissue was analyzed and reviewed for the presence of fibrointimal hyperplasia, smooth muscle disarray, mucoid extracellular matrix accumulation, mural fibrosis, and elastic fiber disorganization and fragmentation using hematoxylin and eosin and special stains. Clinical, computed tomography imaging, and surgical data were correlated with the histopathologic findings. Results: Twenty specimens from 20 patients (age range, 7-18 years; 14 males) were analyzed. Anomalous aortic origin of a coronary artery involved the right coronary in 16 (80%), and a slit-like ostium was noted in 18 (90%). By computed tomography imaging, the median proximal coronary artery eccentricity index was 0.4 (range, 0.20-0.90). The median length of intramural course was 8.2 mm (range, 2.6-15.2 mm). The anomalous vessel was determined to be interarterial in 14 patients (93%, 15 had evaluable images). The median distance from a commissure was 2.5 mm above the sinotubular junction (STJ) (range: 2 mm below the STJ–14 mm above the STJ). Prominent histopathologic findings included elastic fiber alterations, mural fibrosis, and smooth muscle disarray. The shared wall of the aorta and intramural coronary artery is more similar to the aorta histologically. Mural fibrosis and elastic fiber abnormalities tended to be more severe in patients >10 years of age at the time of surgery, but this did not reach statistical significance. The extent of vascular changes did not appear to have a clear relationship with the imaging features. Conclusions: The findings confirm the aortic wall–like quality of the intramural segment of the coronary artery and the presence of pathologic alterations in the wall microstructure