Bi-allelic genetic variants in the translational GTPases GTPBP1 and GTPBP2 cause a distinct identical neurodevelopmental syndrome.

The homologous genes GTPBP1 and GTPBP2 encode GTP-binding proteins 1 and 2, which are involved in ribosomal homeostasis. Pathogenic variants in GTPBP2 were recently shown to be an ultra-rare cause of neurodegenerative or neurodevelopmental disorders (NDDs). Until now, no human phenotype has been linked to GTPBP1. Here, we describe individuals carrying bi-allelic GTPBP1 variants that display an identical phenotype with GTPBP2 and characterize the overall spectrum of GTP-binding protein (1/2)-related disorders. In this study, 20 individuals from 16 families with distinct NDDs and syndromic facial features were investigated by whole-exome (WES) or whole-genome (WGS) sequencing. To assess the functional impact of the identified genetic variants, semi-quantitative PCR, western blot, and ribosome profiling assays were performed in fibroblasts from affected individuals. We also investigated the effect of reducing expression of CG2017, an ortholog of human GTPBP1/2, in the fruit fly Drosophila melanogaster. Individuals with bi-allelic GTPBP1 or GTPBP2 variants presented with microcephaly, profound neurodevelopmental impairment, pathognomonic craniofacial features, and ectodermal defects. Abnormal vision and/or hearing, progressive spasticity, choreoathetoid movements, refractory epilepsy, and brain atrophy were part of the core phenotype of this syndrome. Cell line studies identified a loss-of-function (LoF) impact of the disease-associated variants but no significant abnormalities on ribosome profiling. Reduced expression of CG2017 isoforms was associated with locomotor impairment in Drosophila. In conclusion, bi-allelic GTPBP1 and GTPBP2 LoF variants cause an identical, distinct neurodevelopmental syndrome. Mutant CG2017 knockout flies display motor impairment, highlighting the conserved role for GTP-binding proteins in CNS development across species.

Liposuction and port site nipple sparing mastectomy: an alternative method for the operative treatment of gynecomastia at Alexandria main university hospital.

BACKGROUND: Gynecomastia is characterized by unusually large masses that radiate concentrically from the base of the nipple and is caused by abnormal growth of the glandular tissue of the male breast. An alternative strategy for the surgical treatment of gynecomastia was used in this experimental study, which aims to use liposuction and port site nipple sparing mastectomy. METHODS: The study was conducted in the surgical oncology unit at Alexandria Main University Hospital included 103 patients with a mean age of 27 and no medical history. 100 patients had bilateral gynecomastia, and three patients had unilateral gynecomastia,with two having it on the right side and one on the left. RESULTS: Among the 103 participants, 83 had grade II gynecomastia and 20 had grade I. Only one of the three patients who participated in the study had an expanding hematoma on one side that needed to be surgically evacuated in the operating room. None of our patients experienced an infection or seroma following surgery. Furthermore, only three of our patients experienced nipple areolar complicated superficial epidermolysis, which need regular dressings until recovery. Of the 103 patients, 97 (94.17%) were pleased with the outcomes. CONCLUSION: Liposuction and port site nipple sparing mastectomy are viable options for treating grade I to II gynecomastia, particularly if the patient prefers a more aesthetically pleasing chest contour; no scars equals better patient satisfaction. TRIAL REGISTRATION: retrospectively registered.

Loss of symmetric cell division of apical neural progenitors drives DENND5A-related developmental and epileptic encephalopathy.

Developmental and epileptic encephalopathies (DEEs) are a heterogenous group of epilepsies in which altered brain development leads to developmental delay and seizures, with the epileptic activity further negatively impacting neurodevelopment. Identifying the underlying cause of DEEs is essential for progress toward precision therapies. Here we describe a group of individuals with biallelic variants in DENND5A and determine that variant type is correlated with disease severity. We demonstrate that DENND5A interacts with MUPP1 and PALS1, components of the Crumbs apical polarity complex, which is required for both neural progenitor cell identity and the ability of these stem cells to divide symmetrically. Induced pluripotent stem cells lacking DENND5A fail to undergo symmetric cell division during neural induction and have an inherent propensity to differentiate into neurons, and transgenic DENND5A mice, with phenotypes like the human syndrome, have an increased number of neurons in the adult subventricular zone. Disruption of symmetric cell division following loss of DENND5A results from misalignment of the mitotic spindle in apical neural progenitors. A subset of DENND5A is localized to centrosomes, which define the spindle poles during mitosis. Cells lacking DENND5A orient away from the proliferative apical domain surrounding the ventricles, biasing daughter cells towards a more fate-committed state and ultimately shortening the period of neurogenesis. This study provides a mechanism behind DENND5A-related DEE that may be generalizable to other developmental conditions and provides variant-specific clinical information for physicians and families.

Sleep Disturbances among Caregivers of Home-Isolated and Hospitalized COVID-19 Patients: A Multi-National Cross-Sectional Study.

Background: Since the coronavirus (COVID-19) pandemic began, several studies were published on the possible prevention and treatment of the disease caused by severe acute respiratory syndrome coronavirus (SARSCoV-2), and its complications. However, one aspect that was overlooked is the impact on the mental health of the caregivers of COVID-19 patients. The current study endeavors to investigate sleep quality disturbances in the caregivers of COVID-19 patients in different countries. Material and Methods: This cross-sectional multi-center study was performed between August 1, 2021, and August 30, 2022, across 11 countries. A total of 2411 responses meeting the inclusion criteria (being a family member or caregiver involved in patient care) were collected. The sleep quality was assessed using the self-reported Pittsburgh Sleep Quality Index (PSQI) 12. Total scores ranged from 0 to 21. A ≥5 indicated poor sleep quality with 89.6% sensitivity and 86.5% specificity. Results: A total of 2411 responses meeting the inclusion criteria showed that mean PSQI scores (P = 0.3604) were higher in caregivers of hospitalized patients than in patients isolated at home. Approximately 62.4% of caregivers reported sleep quality problems while caring for their patients. Conclusion: The results showed that the majority of caregivers of patients with COVID-19 reported disturbances in sleep quality and impaired sleep was more common among caregivers of hospitalized patients, perhaps because hospitalization is associated with a more severe course of the disease. There is a pressing need to take measures to improve the mental health of these caregivers. There should be treatment programs set up to reverse sleep disturbances in this population sufficiently.

Psychological Assessment of Family Caregivers of Patients With COVID-19 in the United States of America and India.

Background and objective The coronavirus disease 2019 (COVID-19) pandemic has highlighted the shortcomings worldwide in terms of preparedness protocols related to epidemics. A key area of research that is evidently overlooked across the globe is the mental health of family caregivers taking care of patients with COVID-19. In light of this, this study aimed to engage in a comparative analysis between the two worst affected countries, India and the United States of America (USA), which differ considerably in their demography, socio-epidemiological factors, and health system efficiency. Methods A cross-sectional study was conducted among 1,250 family caregivers of patients with COVID-19 in India and the USA to assess their stress, anxiety, and sleep disturbance levels using the 10-item Perceived Stress Scale (PSS-10), the 7-item Generalized Anxiety Disorder (GAD-7) scale, and the Pittsburgh Sleep Quality Index (PSQI), respectively. Psychological assessment questionnaires were administered through online mode, which gathered demographic information and responses on several self-reporting scales. The main outcome measures were self-reported ratings on PSS, GAD-7 scale, and PSQI. Results We found that 75.4% of the family members of COVID-19 patients suffered from mental health issues. The scores of all three scales were higher in caregivers from the USA than in India, more evident and pronounced in caregivers of hospitalized patients. The test scores were statistically significant (p<0.05) indicating a negative impact of having a dependent member in the family, being married, being of younger age, and having a longer duration of COVID-19 infection. Vaccines were found to have a life-enhancing effect. Conclusion Our findings highlight that the mental health of family caregivers is an ignored aspect and must be addressed. We recommend the implementation of well-researched and appropriate legislation, treatment programs, and health policies that involve not only the patients but also their families.