Search

Mutations in the family of genes encoding the tubulin subunits of microtubules are associated with a spectrum of human brain malformations known as tubulinopathies. How these mutations impact tubulin activity to give rise to distinct developmental consequences is poorly understood. Here we report two patients exhibiting brain malformations characteristic of tubulinopathies and heterozygous T178M missense mutations in different β-tubulin genes, TUBB2A or TUBB3. RNAseq analysis indicates that both TUBB2A and TUBB3 are expressed in the brain during development, but only TUBB2A maintains high expression in neurons into adulthood. The T178 residue is highly conserved in β-tubulins and located in the exchangeable GTP-binding pocket of β-tubulin. To determine the impact of T178M on β-tubulin function we created an analogous mutation in the β-tubulin of budding yeast and show that the substitution acts dominantly to produce kinetically stabilized microtubules that assemble and disassemble slowly, with fewer transitions between these states. In vitro experiments with purified mutant tubulin demonstrate that T178M decreases the intrinsic assembly activity of β-tubulin and forms microtubules that rarely transition to disassembly. We provide evidence that the T178M substitution disrupts GTPase-dependent conformational changes in tubulin, providing a mechanistic explanation for kinetic stabilization. Our findings demonstrate the importance of tubulin’s GTPase activity during brain development, and indicate that tubulin isotypes play different, important roles during brain development.

Abstract Background The integration of sex and gender aspects into the research process has been recognized as crucial to the generation of valid data. During the coronavirus pandemic, a great deal of research addressed the mental state of hospital staff, as they constituted a population at risk for infection and distress. However, it is still unknown how the gender dimension was included. We aimed to appraise and measure qualitatively the extent of gender sensitivity. Methods In this scoping review, we searched MEDLINE, EMBASE, CINAHL PsycINFO and Social Sciences Citation Index (SSCI) from database inception to November 11, 2021. All quantitative studies with primary data published in English, German, or Spanish and based in the European Union were selected. Included studies had to have assessed the mental health of hospital staff using validated psychometric scales for depression, anxiety, PTSD symptoms, distress, suicidal behavior, insomnia, substance abuse or aggressive behavior. Two independent reviewers applied eligibility criteria to each title/abstract reviewed, to the full text of the article, and performed the data extraction. A gender sensitivity assessment tool was developed and validated, consisting of 18 items followed by a final qualitative assessment. Two independent reviewers assessed the gender dimension of each included article. Results Three thousand one hundred twelve studies were identified, of which 72 were included in the analysis. The most common design was cross-sectional (75.0%) and most of them were conducted in Italy (31.9%). Among the results, only one study assessed suicidal behaviors and none substance abuse disorders or aggressive behaviors. Sex and gender were used erroneously in 83.3% of the studies, and only one study described how the gender of the participants was determined. Most articles (71.8%) did not include sex/gender in the literature review and did not discuss sex/gender-related findings with a gender theoretical background (86.1%). In the analysis, 37.5% provided sex/gender disaggregated data, but only 3 studies performed advanced modeling statistics, such as interaction analysis. In the overall assessment, 3 papers were rated as good in terms of gender sensitivity, and the rest as fair (16.7%) and poor (79.2%). Three papers were identified in which gender stereotypes were present in explaining the results. None of the papers analyzed the results of non-binary individuals. Conclusions Studies on the mental health of hospital staff during the pandemic did not adequately integrate the gender dimension, despite the institutional commitment of the European Union and the gendered effect of the pandemic. In the development of future mental health interventions for this population, the use and generalizability of current evidence should be done cautiously.

Introduction: The novel coronavirus SARS-CoV-2 belongs to the coronavirus family, a group of viruses that can cause upper respiratory infections in humans. Among other symptoms, it can present as an asymptomatic infection or as a more severe disease requiring hospitalization. Neuropsychiatric symptoms have been described in the acute phase of the illness and as long-term repercussions. We describe the characteristics and interventions in those COVID-19 patients referred to our liaison psychiatry service.Materials and Methods: This is a cross-sectional descriptive study. This study was carried out within the Department of Psychiatry of Cruces University Hospital (Basque Country, Spain). Data from each psychiatric consultation within our consultation-liaison service were consecutively obtained for 1 month from March 17 to April 17, 2020. We recruited data regarding clinical and referral characteristics and psychiatric interventions.Results: Of a total of 721 SARS-CoV-2 hospitalizations, 43 (5.6%) patients were referred to our psychiatry liaison service. The median age was 61 years old, and 62.8% were women. The infectious disease department was the most frequent petitioner (37.2%), and the most common reason for referral was patient anxiety (25.6%). A total of 67.4% of patients received psychological counseling and 55.8% received some pharmacological approach, with a median of 3.7 visits/calls per patient. In addition, 20.3% needed a medication switch due to potential interactions between psychotropics and drugs used to treat SARS-CoV-2.Discussion: In our study, up to 5.6% of SARS-CoV-2 hospitalized patients needed a psychiatric evaluation, especially for anxiety and mood symptoms. Psychosocial factors associated with the pandemic, drugs used to treat the infection, or a direct causative effect of the virus may explain our findings.

Purpose: This study aims to analyze from a gender perspective the psychological distress experienced by the medical workforce during the peak of the pandemic in Spain.Methods: This is a single-center, observational analytic study. The study population comprised all associated health workers of the Cruces University Hospital, invited by email to participate in the survey. It consisted of a form covering demographic data, the general health questionnaire-28 (GHQ-28), and the perceived stress scale (PSS-14). We used multivariant regression analysis to check the effect of gender on the scores. We used gender analysis in both design and interpretation of data following SAGER guidelines.Results: Females made 74.6% of our sample, but their proportion was higher in lower-paid positions such as nursery (89.9%) than in higher-paid ones. The percentage of women categorized as cases with the GHQ-28 was 78.4%, a proportion significantly higher than in the male population (61.3%, p < 0.001). The multivariant regression analysis showed that being women, working as orderly hospital porters, and having a past psychiatric history were risk factors for higher scores in both the GHQ-28 and PSS-14.Conclusion: Women and those with lower-paid positions were at risk of higher psychological distress and worse quality of life within the medical workforce during the first wave of the pandemic. Gender analysis must be incorporated to analyze this fact better.

Antipsychotic long-acting formulations (LAI-AP) have emerged as a new therapeutic choice to treat patients presenting a severe mental disorder. Despite that, to date, there is a lack of safety data and studies regarding the use of LAI-AP formulations in pregnant women. Here we present the first six-case series of pregnant women with schizophrenia treated with aripiprazole-LAI reported in the literature. All patients remained psychopathologically stable through pregnancy and the postpartum period, and all of them were in treatment with aripiprazole-LAI. To date, all infants remain healthy with normal developmental milestones, without the presence of congenital malformations or adverse effects. Lack of information on safety data regarding the use of new antipsychotic formulations remains important in treating women with mental illness who desire to become pregnant. Further studies in this clinical population with a larger number of patients included remains necessary.

Background: Eating disorders (EDs) are serious and life-threatening mental diseases characterized by abnormal or altered eating habits. The prevalence is variable, being influenced by diverse sociocultural factors. Historically, the prevalence of EDs has been higher in women (90%), although the incidence of these disorders in men appears to be increasing. In daily medical practice, when considering the presentation of other medical complications associated to the development of an ED, few is known about its real prevalence in men. Among them, some severe gastrointestinal complications that are rarely presented, such as the superior mesenteric artery syndrome (SMAS), can produce life-threatening results. Despite that, very few cases of men presenting this pathology are reported in literature.Case Presentation: A 38-year-old man without a history of psychiatric disease was admitted to the emergency department with nausea, abdominal pain, and severe malnutrition (body mass index 15.7 kg/m2). He was diagnosed with SMAS and was studied by multiple specialists on suspicion of a probable organic origin of his thinning. The suspected diagnosis of ED was rejected for months by some professionals, as well as by the patient and his family, until it was finally diagnosed with unspecified feeding and eating disorder (USFED).Conclusion: This case represents an example of diagnostic challenge where a delayed diagnosis of an ED in a male patient was made probably due to gender bias in clinical research and practice. In the literature, numerous reports were described in women diagnosed with SMAS with a previous diagnosis of an ED; however, few cases were found in men. In this clinical case, the patient suffered a significant diagnostic delay, probably due to the lack of diagnostic suspicion given by the differences in the prevalence and clinical presentation of EDs in women and men.