Clean Water Facility as a Communal Space in Fishermen Settlement of Galsesong

Clean water facilities in fishermen settlement Galesong there were three types, namely public wells, public toilets, and public taps. The drinking water service was one of the main places visited by the surrounding residents. The primary function as a place clean water supply for surrounding residents, and social functions as a communal space, where people conduct social interaction. The impact of these interactions promote tolerance and togetherness communities, as well as improving the security environment. The purpose of the research was to determine the intensity of the interaction of the three types clean water facility, and social interaction distance of communication was established, and its effect on people's social lives. The method used was field exploration of behavioral mapping combined with time activity. That was done to help researchers determine the level and the depth of social interaction. The result was to identify differences in the frequency of social interactions that occur in the third water facilities and social distance that occur based on user age

Country-level gender inequality is associated with structural differences in the brains of women and men

Significance Gender inequality is associated with worse mental health and academic achievement in women. Using a dataset of 7,876 MRI scans from healthy adults living in 29 different countries, we here show that gender inequality is associated with differences between the brains of men and women: cortical thickness of the right hemisphere, especially in limbic regions such as the right caudal anterior cingulate and right medial orbitofrontal, as well as the left lateral occipital, present thinner cortices in women compared to men only in gender-unequal countries. These results suggest a potential neural mechanism underlying the worse outcome of women in gender-unequal settings, as well as highlight the role of the environment in the brain differences between women and men. Abstract Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women’s worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7,876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women’s brains and provide initial evidence for neuroscience-informed policies for gender equality

Investigating the association between diabetes mellitus, depression and psychological distress in a cohort of South African teachers

Background. Diabetes mellitus (DM) may increase the risk of depression as a result of a sense of threat of debilitating complications or because of associated lifestyle changes. Depression may increase the risk of type 2 diabetes as a result of poor health behaviours.Objective. To determine the association between diabetes mellitus, depression and psychological distress in a cohort of South African (SA) teachers.Methods. Teachers from 111 public schools in the Metro South District of the Cape Metropolitan area, SA, were invited to participate in this study. The Center for Epidemiologic Studies Depression Scale (CES-D) and the Kessler Psychological Distress Scale (K10) were used to assess depression and psychological distress, respectively. A professional nurse completed a physical examination and collected blood for measurement of glucose, cholesterol and serum creatinine.Results. Of the 388 teachers who completed the questionnaires, 67.5% were female and the average age was 46.2 years (standard deviation 8.7). Psychological distress was identified in 28.1% of the cohort and depression in 15.5%, and 7.7% were found to fulfil criteria for DM. A diagnosis of DM was associated with an increased risk of depression (adjusted odds ratio (AOR) 3.90; 95% confidence interval (CI) 1.33 - 11.37) and psychological distress (AOR 3.62; 95% CI 1.31 - 10.00).Conclusion. The high prevalence of obesity and DM in this cohort of SA teachers is of concern. A diagnosis of DM was strongly associated with an increased risk of depression and psychological distress

Associations of premorbid adjustment with type and timing of childhood trauma in first-episode schizophrenia spectrum disorders

CITATION: Smit, A. M. et al. 2021. Associations of premorbid adjustment with type and timing of childhood trauma in first-episode schizophrenia spectrum disorders. South African Journal of Psychiatry, 27:a1639, doi:10.4102/sajpsychiatry.v27i0.1639.The original publication is available at https://sajp.org.zaBackground: Childhood trauma may contribute to poorer premorbid social and academic adjustment which may be a risk factor for schizophrenia. Aim: We explored the relationship between premorbid adjustment and childhood trauma, timing of childhood trauma’s moderating role as well as the association of clinical and treatment-related confounders with premorbid adjustment. Setting: We conducted a secondary analysis in 111 patients with first-episode schizophrenia (FES) disorders that formed part of two parent studies, EONKCS study (n =73) and the Shared Roots study (n =38). Methods: Type of childhood trauma was assessed with the Childhood Trauma Questionnaire, short-form and premorbid adjustment using the Premorbid Adjustment Scale. Timing of childhood trauma was assessed using the Life Events Checklist and life events timeline. Linear regression analyses were used to assess the moderating effect of timing of childhood trauma. Clinical and treatment-related confounders were entered into sequential hierarchical regression models to identify independent predictors of premorbid adjustment across key life stages. Results: Childhood physical neglect was associated with poorer premorbid academic functioning during childhood and early adolescence, and poorer premorbid social functioning during early and late adolescence. By hierarchical regression modelling (r2 = 0.13), higher physical neglect subscale scores (p = 0.011) independently predicted poorer premorbid social adjustment during early adolescence. Timing of childhood trauma did not moderate the relationship between childhood trauma and premorbid functioning. Conclusion: In patients with FES, childhood physical neglect may contribute to poorer premorbid social functioning during early adolescence. This may provide us with an opportunity to identify and treat at-risk individuals earlier.https://sajp.org.za/index.php/sajp/article/view/1639Publisher's versio

A Signature in HIV-1 Envelope Leader Peptide Associated with Transition from Acute to Chronic Infection Impacts Envelope Processing and Infectivity

Mucosal transmission of the human immunodeficiency virus (HIV) results in a bottleneck in viral genetic diversity. Gnanakaran and colleagues used a computational strategy to identify signature amino acids at particular positions in Envelope that were associated either with transmitted sequences sampled very early in infection, or sequences sampled during chronic infection. Among the strongest signatures observed was an enrichment for the stable presence of histidine at position 12 at transmission and in early infection, and a recurrent loss of histidine at position 12 in chronic infection. This amino acid lies within the leader peptide of Envelope, a region of the protein that has been shown to influence envelope glycoprotein expression and virion infectivity. We show a strong association between a positively charged amino acid like histidine at position 12 in transmitted/founder viruses with more efficient trafficking of the nascent envelope polypeptide to the endoplasmic reticulum and higher steady-state glycoprotein expression compared to viruses that have a non-basic position 12 residue, a substitution that was enriched among viruses sampled from chronically infected individuals. When expressed in the context of other viral proteins, transmitted envelopes with a basic amino acid position 12 were incorporated at higher density into the virus and exhibited higher infectious titers than did non-signature envelopes. These results support the potential utility of using a computational approach to examine large viral sequence data sets for functional signatures and indicate the importance of Envelope expression levels for efficient HIV transmission

Betibeglogene Autotemcel Gene Therapy for Non-β⁰/β⁰ Genotype β-Thalassemia

BACKGROUND: Betibeglogene autotemcel (beti-cel) gene therapy for transfusion-dependent β-thalassemia contains autologous CD34+ hematopoietic stem cells and progenitor cells transduced with the BB305 lentiviral vector encoding the β-globin (βA-T87Q) gene. METHODS: In this open-label, phase 3 study, we evaluated the efficacy and safety of beti-cel in adult and pediatric patients with transfusion-dependent β-thalassemia and a non-β0/β0 genotype. Patients underwent myeloablation with busulfan (with doses adjusted on the basis of pharmacokinetic analysis) and received beti-cel intravenously. The primary end point was transfusion independence (i.e., a weighted average hemoglobin level of ≥9 g per deciliter without red-cell transfusions for ≥12 months). RESULTS: A total of 23 patients were enrolled and received treatment, with a median follow-up of 29.5 months (range, 13.0 to 48.2). Transfusion independence occurred in 20 of 22 patients who could be evaluated (91%), including 6 of 7 patients (86%) who were younger than 12 years of age. The average hemoglobin level during transfusion independence was 11.7 g per deciliter (range, 9.5 to 12.8). Twelve months after beti-cel infusion, the median level of gene therapy-derived adult hemoglobin (HbA) with a T87Q amino acid substitution (HbAT87Q) was 8.7 g per deciliter (range, 5.2 to 10.6) in patients who had transfusion independence. The safety profile of beti-cel was consistent with that of busulfan-based myeloablation. Four patients had at least one adverse event that was considered by the investigators to be related or possibly related to beti-cel; all events were nonserious except for thrombocytopenia (in 1 patient). No cases of cancer were observed. CONCLUSIONS: Treatment with beti-cel resulted in a sustained HbAT87Q level and a total hemoglobin level that was high enough to enable transfusion independence in most patients with a non-β0/β0 genotype, including those younger than 12 years of age. (Funded by Bluebird Bio; HGB-207 ClinicalTrials.gov number, NCT02906202.)

Factors moderating the relationship between childhood trauma and premorbid adjustment in first-episode schizophrenia

CITATION: Kilian, S. et al. 2017. Factors moderating the relationship between childhood trauma and premorbid adjustment in first-episode schizophrenia. PLoS ONE, 12(1):e0170178, doi:10.1371/journal.pone.0170178.The original publication is available at http://journals.plos.org/plosoneChildhood trauma is a recognised risk factor for schizophrenia. It has been proposed that childhood trauma interferes with normal neurodevelopment, thereby establishing a biological vulnerability to schizophrenia. Poor premorbid adjustment is frequently a precursor to schizophrenia, and may be a manifestation of neurodevelopmental compromise. We investigated the relationship between childhood trauma and premorbid adjustment in 77 patients with first-episode schizophrenia spectrum disorders. We also investigated possible mediating roles for other selected risk factors in the relationship. We found several significant correlations between different trauma types and both social and academic premorbid adjustment from childhood to late adolescence. There were no significant moderating effects for family history of schizophrenia or family history of psychiatric disorder. History of obstetric complications, substance abuse and poor motor coordination weakened some of the associations between childhood trauma and premorbid adjustment, while poor sequencing of motor acts strengthened the association. Our results confirm previous studies indicating an association between childhood trauma and premorbid adjustment. Results indicate a general rather than specific association, apparent with different types of trauma, and affecting both social and academic components of premorbid adjustment across childhood, early and late adolescence. Further, our results suggest a complex interplay of various risk factors, supporting the notion of different pathways to psychosis.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0170178Publisher's versio

Serpin Induced Antiviral Activity of Prostaglandin Synthetase-2 against HIV-1 Replication

The serine protease inhibitors (serpins) are anti-inflammatory proteins that have various functions. By screening a diverse panel of viruses, we demonstrate that the serpin antithrombin III (ATIII) has a broad-spectrum anti-viral activity for HIV-1, HCV and HSV. To investigate the mechanism of action in more detail we investigated the HIV-1 inhibition. Using gene-expression arrays we found that multiple host cell signal transduction pathways were activated by ATIII in HIV-1 infected cells but not in uninfected controls. Moreover, the signal pathways initiated by ATIII treatment, were more than 200-fold increased by the use of heparin-activated ATIII. The most up-regulated transcript in HIV-1 infected cells was prostaglandin synthetase-2 (PTGS2). Furthermore, we found that over-expression of PTGS2 reduced levels of HIV-1 replication in human PBMC. These findings suggest a central role for serpins in the host innate anti-viral response. Host factors such as PTGS2 elicited by ATIII treatment could be exploited in the development of novel anti-viral interventions

Expression profile of human Fc receptors in mucosal tissue: implications for antibody-dependent cellular effector functions targeting HIV-1 transmission

The majority of new Human Immunodeficiency Virus (HIV)-1 infections are acquired via sexual transmission at mucosal surfaces. Partial efficacy (31.2%) of the Thai RV144 HIV-1 vaccine trial has been correlated with Antibody-dependent Cellular Cytotoxicity (ADCC) mediated by non-neutralizing antibodies targeting the V1V2 region of the HIV-1 envelope. This has led to speculation that ADCC and other antibody-dependent cellular effector functions might provide an important defense against mucosal acquisition of HIV-1 infection. However, the ability of antibody-dependent cellular effector mechanisms to impact on early mucosal transmission events will depend on a variety of parameters including effector cell type, frequency, the class of Fc-Receptor (FcR) expressed, the number of FcR per cell and the glycoslyation pattern of the induced antibodies. In this study, we characterize and compare the frequency and phenotype of IgG (CD16 [FcγRIII], CD32 [FcγRII] and CD64 [FcγRI]) and IgA (CD89 [FcαR]) receptor expression on effector cells within male and female genital mucosal tissue, colorectal tissue and red blood cell-lysed whole blood. The frequency of FcR expression on CD14+ monocytic cells, myeloid dendritic cells and natural killer cells were similar across the three mucosal tissue compartments, but significantly lower when compared to the FcR expression profile of effector cells isolated from whole blood, with many cells negative for all FcRs. Of the three tissues tested, penile tissue had the highest percentage of FcR positive effector cells. Immunofluorescent staining was used to determine the location of CD14+, CD11c+ and CD56+ cells within the three mucosal tissues. We show that the majority of effector cells across the different mucosal locations reside within the subepithelial lamina propria. The potential implication of the observed FcR expression patterns on the effectiveness of FcR-dependent cellular effector functions to impact on the initial events in mucosal transmission and dissemination warrants further mechanistic studies