Immune-related transcriptomic and epigenetic reconfiguration in BV2 cells after lipopolysaccharide exposure: an in vitro omics integrative study.

BACKGROUND: Molecular alterations affecting microglia have been consistently associated with the inflammatory response. These cells can have pro- or anti-inflammatory activity, phenotypes thought to be regulated by epigenetic mechanisms. Still, little is known about the details on how epigenetic marks regulate the expression of genes in the context of an inflammatory response. METHODS: Through CUT&RUN, we profiled four genome-wide histone marks (HM) (H3K4me1, H3K4me3, H3K27ac, and H3K27me3) in lipopolysaccharide-exposed cells and compared their distributions to control cells. Transcriptomic profiles were determined through RNA-seq and differentially expressed genes were identified and contrasted with the epigenetic landscapes. Other downstream analyses were also included in this study. RESULTS: Our results illustrate an effectively induced M1 phenotype in microglial cells derived from LPS exposure. We observed differential bound regions associated with the genes classically involved in the inflammatory response in the expected direction according to each histone modification. Consistently, our transcriptomic analysis yielded a conspicuous illustration of the LPS-induced immune activity showing the up-regulation of Nf-κB-induced mRNAs (TNF-α, nfκbiz, nfκbia) and other important genes (Marco, Il-6, etc.). Furthermore, we integrated both omics profiles and identified an important reconfiguration of the genome induced by LPS. The latter was depicted by 8 different chromatin states that changed between conditions and that associated with unique clusters of differentially expressed genes, which not only represented regulatory elements, but also underlined distinct biological functions (inhibition of morphogenesis; changes in metabolism, homeostasis, and cytokine regulation; activation of the inflammatory response). CONCLUSION: This study exhibits important differences in the distribution of histone modifications in treated and control BV2 cells, constituting an epigenetic reconfiguration that leads to the inflammatory response. Also, it highlights the importance of these marks' regulatory role in gene expression and provides possible targets for further studies in the context of inflammation.

Transcriptional dissection of symptomatic profiles across the brain of men and women with depression.

Major depressive disorder (MDD) is one of the most important causes of disability worldwide. While recent work provides insights into the molecular alterations in the brain of patients with MDD, whether these molecular signatures can be associated with the expression of specific symptom domains remains unclear. Here, we identified sex-specific gene modules associated with the expression of MDD, combining differential gene expression and co-expression network analyses in six cortical and subcortical brain regions. Our results show varying levels of network homology between males and females across brain regions, although the associations between these structures and the expression of MDD remain highly sex specific. We refined these associations to several symptom domains and identified transcriptional signatures associated with distinct functional pathways, including GABAergic and glutamatergic neurotransmission, metabolic processes and intracellular signal transduction, across brain regions associated with distinct symptomatic profiles in a sex-specific fashion. In most cases, these associations were specific to males or to females with MDD, although a subset of gene modules associated with common symptomatic features in both sexes were also identified. Together, our findings suggest that the expression of distinct MDD symptom domains associates with sex-specific transcriptional structures across brain regions.

Adherence to use of blood cultures according to current national guidelines and their impact in patients with community acquired pneumonia: A retrospective cohort.

BACKGROUND: Community acquired pneumonia (CAP) is the most frequent cause of mortality secondary to infectious etiologies. Recommendations about the use of blood cultures in the diagnosis and treatment of CAP has been a contentious topic of debate and ever-changing recommendations. METHODS: A cohort study was conducted in a community teaching hospital. All the patients that were admitted with a diagnosis of CAP, between January and December of 2019 were included. Sociodemographic and clinical characteristics were obtained. Blood cultures results were obtained, and it was evaluated if they were done in compliance with current recommendations by the Infectious Disease Society of America (IDSA). RESULTS: 721 patients were included in the study. Median age was 68 years and 50% of the patients were male (n = 293). Patients presented from home (84%) and the most common comorbidities were hypertension and diabetes (68% and 31%). 96 patients had positive blood culture and 34% (n = 247) of all the blood cultures were adequately ordered. 80 patients died or went to hospice and the median length of hospital stay in our cohort was 7 days. The multivariate model showed that mortality was associated with positive blood cultures (OR = 3.1 95%CI 1.63-5.87) and appropriateness of blood cultures (OR = 2.96 95% CI 1.2-5.7). CONCLUSION: Adequate use of blood cultures in patients with CAP might have some association with the outcomes of this disease. However, a prospective study evaluating the utility of this test following current IDSA recommendations is needed to understand their impact in mortality and morbidity.

Stakeholder perspectives on a patient-centred intervention (DIALOG+) for adolescents with common mental disorders in Colombia: A qualitative study.

BACKGROUND: Patient and stakeholders' involvement in the development of mental health interventions is a central part of the research process as end-user's input can improve the design of patient-centered interventions. This is particularly important when developing interventions directed towards improving the mental health of children and adolescents. The rising prevalence of mental health disorders in this population requires special attention and the development of interventions that include them as active participants is crucial. OBJECTIVE: Our aim is to explore the perspectives and opinions of adolescents, parents, educators/youth workers, and clinicians regarding the appeal and usability of an existing patient-centered digital intervention (DIALOG+), which aims to improve quality of life. METHODS: As part of a broader study aiming to adapt and test DIALOG+, we conducted Online Focus Groups (OFGs) with adults and adolescents in two cities in Colombia. The existing DIALOG+ intervention was introduced to participants, followed by a structured discussion regarding the opinions and views of stakeholders. A framework approach was used to identify the main themes followed by content analysis to aid adaptation. RESULTS: We conducted 10 OFGs with a total of 45 participants. A positive feature highlighted by all groups was the innovation of including a digital intervention in a traditional medical visit. Additionally, participants considered that the active role that adolescents have when using the intervention empowers them. Barriers identified included concerns from clinicians related to the time required during consultations and confusion with terminology. Furthermore, additional domains that are particularly relevant for the adolescent population were suggested. CONCLUSIONS: Data obtained suggest that overall, the DIALOG+ intervention and supporting app are seen as innovative and appealing to adolescents as well as adult stakeholders. However, concerns raised about the availability of time to apply the intervention, the app interface and the language and terminology require modification.

Psychodermatologic pathology in adolescents: findings from the Colombian National Mental Health Survey.

BACKGROUND: Associations between mental health and dermatology have generated a new branch of study called psychodermatology, which includes relevant conditions to the adolescent population. However, there is limited research focusing on this field and this specific population. OBJECTIVE: To estimate the prevalence of dermatological pathologies in the Colombian adolescent population and their possible associations with mental health conditions. METHODS: We performed a secondary analysis of the Colombian National Mental Health Survey results. A representative sample of the adolescent Colombian population answered questions regarding dermatological conditions and mental health disorders. We estimated the prevalence and evaluated associations using the chi squared independence test. RESULTS: Of 1753 adolescents, 8.3% (CI95%=[6.8-10.1]) had dermatitis or skin allergies and 4.5% (CI95%=[3.3-6.1]) acne. For dermatitis, we found associations with age, education, and family dysfunction (p-Values=0.024; <0.001; 0.046 respectively). Acne was associated with age, sex, educational level, the number of social groups involved in, alcohol consumption, psychoactive substances use and previous violent experiences (respective p-Values=0.007; 0.004; 0.005; 0.036; 0.002; 0.003; 0.044). Regarding mental health, dermatological conditions were associated with depression, affective disorders, suicide attempt and suicide ideation. CONCLUSION: Our results are the first to describe the prevalence of these disorders in Colombia. This is an exploratory study; nonetheless, it is of great value since it is the first to describe these associations in adolescents in a middle-income country, which should be considered during clinical examinations. Further longitudinal studies evaluating possible causal relationship between psychiatric and dermatological conditions are fundamental to establish causal links.

Adapting a Mental Health Intervention for Adolescents During the COVID-19 Pandemic: Web-Based Synchronous Focus Group Study.

BACKGROUND: Although focus groups are a valuable qualitative research tool, face-to-face meetings may be difficult to arrange and time consuming. This challenge has been further compounded by the global COVID-19 pandemic and the subsequent lockdown and physical distancing measures implemented, which caused exceptional challenges to human activities. Online focus groups (OFGs) are an example of an alternative strategy and require further study. At present, OFGs have mostly been studied and used in high-income countries, with little information relating to their implementation in low- and middle-income countries (LMICs). OBJECTIVE: The aim of this study is to share our experiences of conducting OFGs through a web conferencing service and provide recommendations for future research. METHODS: As part of a broader study, OFGs were developed with adults and adolescents in Colombia during the COVID-19 pandemic. Through a convenience sampling method, we invited eligible participants via email in two different cities of Colombia to participate in OFGs conducted via Microsoft Teams. Researcher notes and discussion were used to capture participant and facilitator experiences, as well as practical considerations. RESULTS: Technical issues were encountered, but various measures were taken to minimize them, such as using a web conferencing service that was familiar to participants, sending written instructions, and performing a trial meeting prior to the OFG. Adolescent participants, unlike their adult counterparts, were fluent in using web conferencing platforms and did not encounter technical challenges. CONCLUSIONS: OFGs have great potential in research settings, especially during the current and any future public health emergencies. It is important to keep in mind that even with the advantages that they offer, technical issues (ie, internet speed and access to technology) are major obstacles in LMICs. Further research is required and should carefully consider the appropriateness of OFGs in different settings.

Access barriers, self-recognition, and recognition of depression and unhealthy alcohol use: A qualitative study.

INTRODUCTION: Access to healthcare services involves a complex dynamic, where mental health conditions are especially disadvantaged, due to multiple factors related to the context and the involved stakeholders. However, a characterisation of this phenomenon has not been carried out in Colombia, and this motivates the present study. OBJECTIVES: The objective of this study was to explore the causes that affect access to health services for depression and unhealthy alcohol use in Colombia, according to various stakeholders involved in the care process. METHODS: In-depth interviews and focus groups were conducted with health professionals, administrative professionals, users, and representatives of community health organisations in five primary and secondary-level institutions in three regions of Colombia. Subsequently, to describe access to healthcare for depression and unhealthy alcohol use, excerpts from the interviews and focus groups were coded through content analysis, expert consensus, and grounded theory. Five categories of analysis were created: education and knowledge of the health condition, stigma, lack of training of health professionals, culture, and structure or organisational factors. RESULTS: We characterised the barriers to a lack of illness recognition that affected access to care for depression or unhealthy alcohol use according to users, healthcare professionals and administrative staff from five primary and secondary care centres in Colombia. The groups identified that lack of recognition of depression was related to low education and knowledge about this condition within the population, stigma, and lack of training of health professionals, as well as to culture. For unhealthy alcohol use, the participants identified that low education and knowledge about this condition, lack of training of healthcare professionals, and culture affected its recognition, and therefore, healthcare access. Neither structural nor organisational factors seemed to play a role in the recognition or self-recognition of these conditions. CONCLUSIONS: This study provides essential information for the search for factors that undermine access to mental health in the Colombian context. Likewise, it promotes the generation of hypotheses that can lead to the development and implementation of tools to improve care in the field of mental illness.

Implementing a Redcap-based research data collection system for mental health.

BACKGROUND: The implementation of new technologies in medical research, such as novel big storage systems, has recently gained importance. Electronic data capture is a perfect example as it powerfully facilitates medical research. However, its implementation in resource-limited settings, where basic clinical resources, internet access, and human resources may be reduced might be a problem. METHODS: In this paper we described our approach for building a network architecture for data collection to achieve our objectives using a REDCap® tool in Colombia and provide guidance for data collection in similar settings. CONCLUSIONS: REDCap is a feasible and efficient electronic data capture software to use in similar contexts to Colombia. The software facilitated the whole data management process and is a way to build research capacities in resourced-limited settings.

Mental health in adolescents displaced by the armed conflict: findings from the Colombian national mental health survey.

BACKGROUND: Colombia has one of the largest populations of internally displaced individuals by an armed conflict. However, there is no data demonstrating its effect on health, particularly in adolescents. PURPOSE: To describe the prevalence and associations of mental illness in the adolescent population displaced by violence in Colombia. METHODS: We conducted a secondary analysis of the 2015 National Mental Health Survey (NMHS), which provides data of mental health issues (SRQ), mental health disorders (CIDI-CAPI) and sociodemographic characteristics. RESULTS: Of the 1754 adolescents interviewed 5.3% (95% CI 4.1 to 6.9) mentioned a change in residence due to violence. Among them 38.5% lived in poverty compared to 23.6% of those non-displaced by the conflict. Suicidal thoughts and suicide attempt were present in 19.8% and 9.1% of displaced adolescents respectively, compared to 5.8% and 2.1% of non-displaced adolescents. The prevalence of post-traumatic stress disorder (PTSD) and any mental health disorder (measured with the CIDI-CAPI) was higher in the displaced population 12.3%, 11% respectively, in contrast to 2.1% and 7% of those non-displaced. Finally, anxiety and depressive disorders were more common among displaced adolescents. CONCLUSION: A higher prevalence of mental health conditions and disorders is observed among displaced adolescents.