Macro level system mapping of the provision of mental health services to young people living in a conflict context in Colombia

Colombia has one of the longest running internal armed conflicts, which has significantly impacted the mental health of the population. This article is the first to present a national level mapping of the provision of mental health services to young people living in Colombia, through detailed review of documentation, interviews with key stakeholders and quantitative analysis of existing data on mental health and suicide. It explores the existing public mental health provision in the country, focussing on where mental health resources are concentrated and how these are implemented. We use this mapping to understand how the current mental health system in Colombia fits with international approaches to youth mental health. We show that whilst mental health policy is variously framed (biomedical, biosocial, psychologically or through human rights), Colombian policy clearly focusses on a differential approach. This differential approach shapes service provision to target support at those in need, consequently neglecting whole population level mental health support. This means that not all stakeholders were clearly articulated or included in policy and that key institutional stakeholders, such as the education sector, were not linked to implementation plans or activity. Policy approaches were also over-centralised with little cross-institutional collaboration. Youth were specifically missing from services, as was explicit understanding of the intergenerational effects and impact of conflict. This was exacerbated by unequal distribution of mental health care services concentrated in populous, urban areas away from conflict-affected regions. Suicide is the second most prevalent cause of death with 10% of population who were recorded as dying by violence, dying from completed suicide. Triangulation implies a strong relationship between suicide and poorer access to professional support in conflict-affected areas and suggests that international frameworks and policy approaches to supporting youth mental health have been insufficiently adapted for conflict and post conflict contexts

Mapping mental health care services for children and youth population in Colombia’s Pacific:potential for boundary spanning between community and formal services

Background: Conflict and violence can impact on the mental health of children and young people, who are in a crucial stage of their personal growth. Not much is known about the provision of mental health care to young people in conflict-affected areas. Community-based care can be essential, as state-led services are often scarce in conflict contexts, like Colombia’s Pacific region where this research was conducted. According to the WHO, such care is ideally provided in the form of a network of interconnected services, offered by different actors beyond the formal health sector. This article describes the relationship between the formal and community mental health systems in Colombia’s Pacific region, and identifies ways of improving their interaction.Methods: Qualitative data were collected through 98 semi-structured interviews with community organisations, schools, international organisations and state institutions. These interviews aimed to identify the strategies used to promote young people’s mental health and the interactions between the different providers. Boundary spanning theory was used to analyse how different actors and forms of mental health care provision could coordinate better.Results: Community organisations and schools use a wide array of strategies to attend to the mental health of children and young people, often of a collective and psychosocial nature. State institutions offer more clinically focused strategies, which are however limited in terms of accessibility and continuity. International organisations aim to strengthen state capacity, but often struggle due to high staff turnover. Although mental health care pathways exist, their effectiveness is limited due to ineffective coordination between actors.Conclusions: To make sure that the variety of strategies to improve young people’s mental health effectively reach their beneficiaries, better coordination is needed between the different actors. Mental health care pathways should therefore integrate community organisations, while community connectors can help to manage the coordination between different actors and forms of clinical and psychosocial support

Bases genéticas y moleculares de la preeclampsia

La preeclampsia es una enfermedad compleja, exclusiva de la gestación humana y responsables de una alta morbimortalidad perinatal. Ha sido denominada la enfermedad de las múltiples teorÍas, en la cual tanto factores medioambientales como genéticos se han asociado al desarrollo de la misma. para la identificación de los genes candidatos asociados con la PE, se han empleado dos tipos de metodologÍa, los estudios de asociación y los estudios de ligamiento.[Serrano NC, Páes MC, MartÍnez MP, Casas JP, Gil L, Nvarro AA. Bases genéticas y moleculares de la preeclampsia. MedUNAB 2002; 5(15):185-94].Palabras clave: Genética, preeclampsia, polimorfismos, estudios de ligamiento, estudios de asociación, metileneterahidrofolato reductasa, lipoprotein lipasa, óxidonitrico sintasa endotelial, factor V de Leiden, angiotesinógeno, HLA-G, y factor denecrosis tumoral alfa.Preeclampsia is a complex disease, exclusive of human pregnancy and responsible for high perinatal morbidity and mortality. It has been called the disease of multiple theories, in which both environmental and genetic factors have been associated with its development. For the identification of candidate genes associated with PE, two types of methodology have been used, association studies and linkage studies. This article explains the rationale for both studies and reviews the main candidate genes within the pathophysiology of the disease, including those that code for the enzymes methylene tetrahydrofolate reductase, lipoprotein lipase and endothelial nitric oxide synthase; factor V Leiden, angiotensinogen, HLA-G, and necrotumor factor alph

Actions of hormone replacement therapy through the L-arginine nitiric oxide pathway on the cardiovascular and nervous systems of menopausal women

La administración de estrógenos como terapia hormonal sustitutiva (THS) en mujeres menopáusicas mejora la función mental y el estado emocional, efectos que pueden ser dados por el acción favorable en la función endotelial que se manifiesta por aumento del flujo sanguíneo cerebral mediado por óxido nítrico (NO). Sin embargo, la inducción de la síntesis no se limita a las células endoteliales ya que otros tejidos también son estimulados, como el cerebro, así que la mejora observada con suplencia estrogénica de las funciones encefálicas superiores de la mujer menopáusica puede deberse a un doble efecto de la THS, uno por aumento del flujo sanguíneo y otro por incremento de No en el propio sistema nervioso central (SNC). La THS induce la síntesis de No en mujeres menopáusicas, lo que se refleja a nivel sistémico en aumento de los niveles plasmáticos de nitritos y nitratos. El incremento de los metabolitos estables probablemente refleja una mejor producción de No en endotelio vascular, que representa mejoría de la VMF. A nivel del SNC el efecto es selectivo y asimétrico.1. OBJETIVO GENERAL 1 1.1 OBJETIVOS ESPECÍFICOS 1 2. PLANTEAMIENTO DEL PROBLEMA Y JUSTIFICACIÓN 3 3. IMPACTO 1 4. MARCO TEÓRICO 13 4.1 DEFINICIÓN DE TÉRMINOS 13 4.2 MENOPAUSIA Y SISTEMA CARDIOVASCULAR 14 4.3 ACCIONES DE LOS ESTRÓGENOS SOBRE EL SISTEMA CARDIOVASCULAR. 17 4.4 METODOLOGÍA DE LA VASOD1LATAC1ÓN MEDIADA POR FLUJO 20 4.4.1 Prueba 22 4.4.2 Factores de Control en el Momento de Selección de Pacientes 24 4.5 MENOPAUSIA Y SISTEMA NERVIOSO 25 4.5.1 Menopausia y Alteraciones del Estado de Ánimo 25 4.5.2 Menopausia y Alteraciones en la Memoria 26 4.5.3 Terapia Estrogénica, Producción de ON y Sistema Nervioso 27 4.5.4 Inventario de Depresión de Beck (IDB) 28 4.6 TOMOGRAFÍA CON EMISIÓN DE FOTÓN ÚNICO (SPECT) 29 4.6.1 Estudio de Perfusión Normal 29 4.6.2 SPECT con Neuroactivación 30 5. METODOLOGÍA 32 5.1 CARACTERÍSTICAS DEL ENSAYO CLÍNICO 32 5.2 PRUEBAS REALIZADAS 34 6. ANÁLISIS ESTADÍSTICO 37 7. RESULTADOS 39 7.2 SELECCIÓN DE PACIENTES 39 7.2 CARACTERÍSTICAS DE LAS PACIENTES INCLUIDAS 40 7.3 METABOLITOS DEL ÓXIDO NÍTRICO 44 7.4 PRUEBAS DE FLUJO VASCULAR 45 7.4.1 Vasodilatación Mediada por Flujo 45 7.4.2 Variadón de la Velocidad Pico 50 7.5 PRUEBAS DE NEUROPSICOLOGÍA 52 7.5.1 Inventario de Depresión de Beck 52 7.5.2 Prueba de Memoria Reciente 53 7.6 PRUEBAS DE ACTIVIDAD CEREBRAL POR SPECT 55 8. DISCUSIÓN 60EspecializaciónThe administration of estrogens as hormone replacement therapy (HRT) in menopausal women improves mental function and emotional state, effects that may be due to the favorable action on endothelial function that is manifested by an increase in cerebral blood flow mediated by nitric oxide ( NO). However, the induction of synthesis is not limited to endothelial cells as other tissues are also stimulated, such as the brain, so the improvement seen with estrogen supplementation in higher brain functions in menopausal women may be due to a dual effect. of HRT, one due to increased blood flow and the other due to an increase in No in the central nervous system (CNS) itself. HRT induces the synthesis of No in menopausal women, which is reflected at the systemic level in increased plasma levels of nitrites and nitrates. The increase in stable metabolites probably reflects a better production of No in the vascular endothelium, which represents an improvement in VMF. At the CNS level, the effect is selective and asymmetric

Prognostic Value of D-dimer to Lymphocyte Ratio (DLR) in Hospitalized Coronavirus Disease 2019 (COVID-19) Patients: A Validation Study in a National Cohort

Background: This study aimed to validate the role of the D-dimer to lymphocyte ratio (DLR) for mortality prediction in a large national cohort of hospitalized coronavirus disease 2019 (COVID-19) patients. Methods: A retrospective, multicenter, observational study that included hospitalized patients due to SARS-CoV-2 infection in Spain was conducted from March 2020 to March 2022. All biomarkers and laboratory indices analyzed were measured once at admission. Results: A total of 10,575 COVID-19 patients were included in this study. The mean age of participants was 66.9 (+/- 16) years, and 58.6% (6202 patients) of them were male. The overall mortality rate was 16.3% (n = 1726 patients). Intensive care unit admission was needed in 10.5% (n = 1106 patients), non-invasive mechanical ventilation was required in 8.8% (n = 923 patients), and orotracheal intubation was required in 7.5% (789 patients). DLR presented a c-statistic of 0.69 (95% CI, 0.68-0.71) for in-hospital mortality with an optimal cut-off above 1. Multivariate analysis showed an independent association for in-hospital mortality for DLR > 1 (adjusted OR 2.09, 95% CI 1.09-4.04; p = 0.03); in the same way, survival analysis showed a higher mortality risk for DLR > 1 (HR 2.24; 95% CI 2.03-2.47; p < 0.01). Further, no other laboratory indices showed an independent association for mortality in multivariate analysis. Conclusions: This study confirmed the usefulness of DLR as a prognostic biomarker for mortality associated with SARS-CoV-2 infection, being an accessible, cost-effective, and easy-to-use biomarker in daily clinical practice

AG5 is a potent non-steroidal anti-inflammatory and immune regulator that preserves innate immunity

12 pages, 5 figures.-- This is an open access article under the CC BY-NC-ND licenseAn archetypal anti-inflammatory compound against cytokine storm would inhibit it without suppressing the innate immune response. AG5, an anti-inflammatory compound, has been developed as synthetic derivative of andrographolide, which is highly absorbable and presents low toxicity. We found that the mechanism of action of AG5 is through the inhibition of caspase-1. Interestingly, we show with in vitro generated human monocyte derived dendritic cells that AG5 preserves innate immune response. AG5 minimizes inflammatory response in a mouse model of lipopolysaccharide (LPS)-induced lung injury and exhibits in vivo anti-inflammatory efficacy in the SARS-CoV-2-infected mouse model. AG5 opens up a new class of anti-inflammatories, since contrary to NSAIDs, AG5 is able to inhibit the cytokine storm, like dexamethasone, but, unlike corticosteroids, preserves adequately the innate immunity. This is critical at the early stages of any naïve infection, but particularly in SARS-CoV-2 infections. Furthermore, AG5 showed interesting antiviral activity against SARS-CoV-2 in humanized miceThis work has been supported by NextGenerationEU Recovery and Resilience Facility (RRF) through the PTI+ Global Health Platform of Spanish National Research Council, grants SGL2103023 (PBA), SGL2103053 (MMA) and SGL2103015 (MM); by Spanish National Research Council through the program “Ayudas extraodinarias a proyectos de investigacion en el marco de las medidas urgentes extraodinarias para hacer frente al impacto económico y social del COVID-19”, grants CSIC-COV19-093 (PBA) and CSIC-COV19-117 (MM); by Generalitat Valenciana through the program “Ayudas urgentes para proyectos de investigación, desarrollo tecnológico e innovación (I+D+i) por la COVID-19”, grant GVA-COVID19/2021/059 (PBA); by the Conference of Rectors of the Spanish Universities, Spanish National Research Council and Banco Santander through the FONDO SUPERA COVID-19, grant CAPriCORn (JSM, JMB); by Severo Ochoa center of excellence program (grant CEX2021-001230-S) (PBA)Peer reviewe

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p &lt; 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation