Organoids as host models for infection biology – a review of methods

Infectious diseases are a major threat worldwide. With the alarming rise of antimicrobial resistance and emergence of new potential pathogens, a better understanding of the infection process is urgently needed. Over the last century, the development of in vitro and in vivo models has led to remarkable contributions to the current knowledge in the field of infection biology. However, applying recent advances in organoid culture technology to research infectious diseases is now taking the field to a higher level of complexity. Here, we describe the current methods available for the study of infectious diseases using organoid cultures.We thank Rike Zietlow for editing of the manuscript. This work was supported by the European Union’s Horizon 2020 Research and Innovation program under grant agreement No. 857491 to A.S.O., M.Sa., and S.B.; BMBF grant NUM-COVID 19 Organo-Strat 01KX2021 to S.B.; and FCT, grant CEEC, to M.Sa

De-fragmentation of space within dwellings and neighbourhoods in Al-Madinah using urban information sytems (space syntax and Arc/GIS)

This research addresses one of the major cumulative problems in Saudi Cities; the fragmented developments of urban lands. Such fragmentation is caused by wasteful standards and measures that are used during subdivision of land, and building control codes for residential units within plans after they are approved. Moreover, it is because of lack of application of urban information systems in neighbourhood planning. The main goal of this study is to draw up a guidance policy that defragments wasteful spaces and consequently reduces costs of both dwellings and neighbourhoods by adjusting consumption of space in regard to the socio-economic characteristics of the majority of the residents. The case study is Al-Madinah owing to it had unique form of traditional houses, and neighbourhoods known as `Ahwash'. They are the two main categories of units that form the city as a whole. At the end, the study draws a guidance technique as a recommendation for future planners to use Urban Information Systems as tools to study Neighbourhood Planning to de-fragment space within dwellings and neighbourhoods, and re-adjust building regulations with regard to their socio-economic characteristics and the local culture of Al-Madinah. The final results and proposals are a major contribution for the majority of residents who are still tenants to enable them to buy a plot and build on it, and the municipality can reduce the costs of their services among fragmented urban areas to upgrade their facilities within neighbourhoods, infrastructure agencies can reduce the cost of networks and improve the quality of their services and reduce the cost of service for public, and developers can understand the actual demands for housing not only for their own revenue by providing only luxury measures in dwellings but also to provide affordable dwellings that can be owned by residents with lower socio-economic characteristics.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Depression and self-esteem among Afghan school-going adolescents under the Taliban government: a cross-sectional study

Background: During the period of adolescence, several major developmental changes occur that can have significant impact on an individual’s brain structure and functioning through their entire life. Aims: The present study aimed to examine the association between depression and self-esteem alongside specific sociodemographic factors among school-going adolescents living under the rule of Taliban. Methods: A cross-sectional survey study was conducted with adolescents (n = 452) from 20 randomly selected public primary, secondary and high schools of Herat province (Afghanistan) out of the 86 schools registered in Herat Education Department. The survey included the Center for Epidemiological Studies-Depression Scale (CES-D) and Rosenberg's Self-Esteem Scale (RSES). Results: Two-thirds of adolescents reported depression symptoms (65.3%) and 86.3% reported poor self-esteem. Multiple regression analysis indicated that (i) mother's education level was significantly associated with depression symptoms and (ii) low-income economic status was significantly associated with self-esteem. Conclusion: As well as being one of the few studies in Afghanistan, the present study is one of the very few to assess the association between class group, self-esteem, and depression symptoms. These findings may be used by healthcare authorities and school administrators to raise awareness and implement strategies to facilitate self-esteem among school school-going adolescents

Depression, anxiety and quality of life of Afghan women living in urban areas under the Taliban government: a cross-sectional study

Objectives: According to the World Health Organization, depression is a common mental health illness that is characterised by a persistent feeling of sadness and loss of interest. The present study examined the association of two mental health variables (ie, depression, anxiety) with quality of life (QoL) and the sociodemographic characteristics of Afghan women living in urban areas under the rule of Taliban government in Afghanistan. Design: Cross-sectional study administered between 10 November 2021 to 25 December 2021 among women. Setting: Across major provinces of Afghanistan (Herat, Mazar-e-Sharif, Kabul and Samangan). Measurements: Data were collected using a pretested structured questionnaire. Data entry was carried out using Microsoft Excel 2016. And then exported to IBM SPSS V.26 for Microsoft Windows. Logistic regression models were used to examine the association of depression, anxiety with QoL and sociodemographic characteristics among women (N=438). Results: The prevalence of depression symptoms was 80.4%, and the prevalence of mild to extremely severe anxiety was 81.0%. Depression symptoms among Afghan women were associated with being older, having more children, lower education level, other individuals’ bad behaviour, bad events experienced in the past month, and feeling physically ill. Multiple regression analysis indicated that low monthly household income (adjusted OR, AOR 2.260; 95% CI 1.179 to 4.331, p=0.014) poor physical domain of QoL (AOR 4.436; 95% CI 1.748 to 11.256, p=0.002) and poor psychological domain of QoL (AOR 23.499; 95% CI 7.737 to 71.369, p<0.001) were significantly associated with depression. Conclusion: The prevalence of depression was high among women living under the government of the Taliban in Afghanistan. Considering the high prevalence of depression, anxiety and their impact on QoL and the overall quality of healthcare services, international health organisations should implement programmes for regular screening of depression and anxiety, and there should be psychological counselling services available for vulnerable women living under the government of the Taliban

Antenatal depression among pregnant mothers in Afghanistan: a cross-sectional study

Background: Approximately one in five pregnant women experience antenatal depression globally. The purpose of the present study was to estimate the prevalence of antenatal depression and explore its relationship between various demographic variables, recent sexual engagement, and recent adverse life events among pregnant Afghan women. Methods: A cross-sectional survey study was carried out between January, 2023 and April 2023 among 460 women aged 15–45 years who were recruited using convenience sampling from Herat province (Afghanistan). Logistic regression models were utilized to explore the relationship between antenatal depression and socio-demographic characteristics among the participants. Results: The prevalence of antenatal depression symptoms was 78.5%. Multiple regression analysis indicated that antenatal depression was significantly associated with (i) being aged 30–45 years (AOR: 4.216, 95% CI: 1.868–9.515, p = .001), (ii) being of low economic status (AOR:2.102, 95% CI: 1.051–4.202, p = .036), (iii) not being employed (AOR: 2.445, 95% CI:1.189–5.025, p = .015), (iv) not having had sex during the past seven days (AOR: 2.335, 95% CI: 1.427–3.822, p = .001), and (v) not experiencing a traumatic event during the past month (AOR:0.263, 95% CI: 0.139–0.495, p < .001). Conclusion: The present study provides insight into the factors associated with the high prevalence of antenatal depression among pregnant Afghan women (e.g., demographic variables, recent adverse life events, and recent sexual engagement). It highlights the urgency of addressing antenatal depression in Afghanistan and provides a foundation for future research and interventions aimed at improving the mental health and well-being of pregnant women in the Afghan context

P11 promoter methylation predicts the antidepressant effect of electroconvulsive therapy

Although electroconvulsive therapy (ECT) is among the most effective treatment options for pharmacoresistant major depressive disorder (MDD), some patients still remain refractory to standard ECT practise. Thus, there is a need for markers reliably predicting ECT non/response. In our study, we have taken a novel translational approach for discovering potential biomarkers for the prediction of ECT response. Our hypothesis was that the promoter methylation of p11, a multifunctional protein involved in both depressive-like states and antidepressant treatment responses, is differently regulated in ECT responders vs. nonresponders and thus be a putative biomarker of ECT response. The chronic mild stress model of MDD was adapted with the aim to obtain rats that are resistant to conventional antidepressant drugs (citalopram). Subsequently, electroconvulsive stimulation (ECS) was used to select responders and nonresponders, and compare p11 expression and promoter methylation. In the rat experiments we found that the gene promoter methylation and expression of p11 significantly correlate with the antidepressant effect of ECS. Next, we investigated the predictive properties of p11 promoter methylation in two clinical cohorts of patients with pharmacoresistant MDD. In a proof-of-concept clinical trial in 11 patients with refractory MDD, higher p11 promoter methylation was found in responders to ECT. This finding was replicated in an independent sample of 65 patients with pharmacoresistant MDD. This translational study successfully validated the first biomarker reliably predicting the responsiveness to ECT. Prescreening of this biomarker could help to identify patients eligible for first-line ECT treatment and also help to develop novel antidepressant treatment procedures for depressed patients resistant to all currently approved antidepressant treatments.Peer reviewe

SarcTrack: an adaptable software tool for efficient large-scale analysis of sarcomere function in hiPSC-cardiomyocytes

Rationale: Human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) in combination with CRISPR/Cas9 genome editing provide unparalleled opportunities to study cardiac biology and disease. However, sarcomeres, the fundamental units of myocyte contraction, are immature and nonlinear in hiPSC-CMs, which technically challenge accurate functional interrogation of contractile parameters in beating cells. Furthermore, existing analysis methods are relatively low-throughput, indirectly assess contractility, or only assess well-aligned sarcomeres found in mature cardiac tissues. Objective: We aimed to develop an analysis platform that directly, rapidly, and automatically tracks sarcomeres in beating cardiomyocytes. The platform should assess sarcomere content, contraction and relaxation parameters, and beat rate. Methods and Results: We developed SarcTrack, a MatLab software that monitors fluorescently tagged sarcomeres in hiPSC-CMs. The algorithm determines sarcomere content, sarcomere length, and returns rates of sarcomere contraction and relaxation. By rapid measurement of hundreds of sarcomeres in each hiPSC-CM, SarcTrack provides large data sets for robust statistical analyses of multiple contractile parameters. We validated SarcTrack by analyzing drug-treated hiPSC-CMs, confirming the contractility effects of compounds that directly activate (CK-1827452) or inhibit (MYK-461) myosin molecules or indirectly alter contractility (verapamil and propranolol). SarcTrack analysis of hiPSC-CMs carrying a heterozygous truncation variant in the myosin-binding protein C (MYBPC3) gene, which causes hypertrophic cardiomyopathy, recapitulated seminal disease phenotypes including cardiac hypercontractility and diminished relaxation, abnormalities that normalized with MYK-461 treatment. Conclusions: SarcTrack provides a direct and efficient method to quantitatively assess sarcomere function. By improving existing contractility analysis methods and overcoming technical challenges associated with functional evaluation of hiPSC-CMs, SarcTrack enhances translational prospects for sarcomere-regulating therapeutics and accelerates interrogation of human cardiac genetic variants

Female education ban by the Taliban: a descriptive survey study on suicidal ideation, mental health, and health-related quality of life among girls in Afghanistan

Background: Following the Taliban’s resurgence, Afghan girls were probited from attending school and university, likely causing adverse psychological effects. Therefore, the present study investigated depression, suicidal ideation, and quality of life (QoL) among Afghan girls banned from education by the Taliban. Methods: A survey study assessed depression, suicidal ideation, and QoL among 426 females prohibited from attending secondary schools, high schools, and universities by the Taliban. The study used the CES-D 20 Scale to assess depression, and the WHOQOL-Bref Questionnaire to assess QoL. Associations between variables were tested with chi-square tests, and predictors of QoL were analyzed through multivariate regression analysis. Results: Among the 426 participants, 87.6% exhibited depression symptoms and 49.8% reported suicidal thoughts. Significant predictors of overall QoL included monthly family income (B = 0.147, P = 0.001), recent others’ behavior toward participants (B = −0.247, P < 0.001), physical illness (B = 0.110, P = 0.011), experiencing a recent traumatic event (B = 0.108, P = 0.015), depression (B = −0.159, P < 0.001) and suicidal ideation (B = −0.187, P < 0.001). Conclusion: In Taliban-ruled Afghanistan, the results indicated that female students who have been prohibited from studying in classes have a high prevalence of depression and suicidal ideation. Having depression and suicidal ideation significantly predicted decreased quality of life among female students

Hypertension, depression, and health-related quality of life among hospitalized patients in Afghanistan

In recent decades, hypertension has become the foremost risk factor for disability-adjusted life years (DALYs). The present study investigated the relationship between quality of life, depression, and hypertension among hospitalized patients in Afghanistan. A cross-sectional survey was administered from September 3, 2022, to February 2, 2023, in the Herat and Mazar-e-Sharif provinces of Afghanistan (N = 2059). The prevalence of depression symptoms was 65.8%, and hypertension was 20.9%. Multiple regression analysis indicated that moderate physical functioning, poor role-physical, higher bodily pain, poor general health, poor social functioning, lower role-emotional, and poor mental health significantly predicted depression. Multiple regression analysis indicated that moderate quality of life, poor physical functioning, higher bodily pain, lower energy/fatigue, and depression significantly predicted hypertension. The findings of the present study offer valuable insights for healthcare providers, policymakers, and researchers in developing targeted interventions and policies to enhance the well-being of individuals facing the challenges of depression and hypertension. The prevalence of hypertension and depression was high among patients in the Herat and Mazar-e-Sharif provinces of Afghanistan. Patients with hypertension had poor mental and physical quality of life. Hospitals should therefore implement regular screening for depression and offer psychological counseling for vulnerable patients with hypertension