Background and aim: Mental health services in Colombia have had a complex history shaped by 50 of years armed conflict, disproportionate clinical approach and social factors such as stigma. Nevertheless, recent global tendencies and interventions have suggested basing mental health services on communities and the recovery approach and considering the social determinants of mental health during planning. Colombia has involved these approaches in its legal and practical framework in recent years, but multiple internal and external factors have retarded an accurate implementation. This systematic review aims to contribute to mental health services understanding in Colombia, offering an implementation research approach. Methods: A comprehensive strategy search was developed to include peer-reviewed studies where mental health services were mentioned or described. The review was conducted in five databases (Medline (OVID), PubMed, Scopus, Scielo and BVS), three languages (English, Spanish & Portuguese) and was limited to the last ten years. Moreover, it followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and used the Consolidated Framework for Implementation Research (CFIR) to identify barriers and facilitators during the implementation of mental health services. Results: Twelve articles were selected. The principal reported barriers were lack of coordination, workloads, and funding. Implementation differences between public and private settings were significant and repeatedly reported. On the other hand, good planning strategies and the involvement of communities, stakeholders, users, and external champions facilitated implementation. Remarkable efforts to adopt community-based mental health services were described as well. Conclusions: Overall, this review offers significant insight into current mental health services, their implementation status, and principal barriers to effective implementation. It is suggested to continue applying community and recovery approaches in mental health services, but also to improve coordination between all actors (e.g., public and private organisations, non-governmental organisations (NGOs), and users and their families).

Abstract: Antibiotic resistance is driven by selection, but how a bacterial strain’s evolutionary history shapes drug-resistance remains an open question. Here we reconstruct the genetic and evolutionary mechanisms of carbapenem resistance in a clinical isolate of Klebsiella. A combination of short and long read sequencing, machine learning, genetic and enzymatic analyses established that this carbapenem-resistant strain carries no carbapenemase-encoding genes. Genetic reconstruction of the resistance phenotype confirmed that two distinct genetic loci are necessary for the strain to acquire carbapenem resistance. Experimental evolution of the carbapenem-resistant strains in growth conditions without the antibiotic revealed that both loci confer a significant cost, and are readily lost by de novo mutation resulting in the rapid evolution of a carbapenem-sensitive phenotype. Thus, historical contingency - a patient’s treatment history - can shape the evolution of antibiotic resistance and suggests that the strategic combinations of antibiotics could direct the evolution of low-fitness, drug-resistant genotypes.

Abstract: The cell envelope is essential for the survival and adaptation of bacteria. Bacterial membrane proteins include the major porins that mediate the influx of nutrients and several classes of antimicrobial drugs. Consequently, membrane remodelling is closely linked to antimicrobial resistance (AMR). Knowledge of bacterial membrane protein biogenesis and turnover underpins our understanding of bacterial membrane remodelling and the consequences that this process has in the evolution of AMR phenotypes. At the population level, the evolution of phenotypes is a reversible process, and we can use these insights to deploy evolutionary principles to resensitize bacteria to existing antimicrobial drugs. In our opinion, fundamental knowledge is opening a new way of thinking towards sustainable solutions to the mounting crisis in AMR. Here we discuss what is known about outer-membrane remodelling in bacteria and how the process could be targeted as a means to restore sensitivity to antimicrobial drugs. Bacteriophages are highlighted as a powerful means to exert this control over membrane remodelling but they require careful selection so as to reverse, and not exacerbate AMR phenotypes.

Abstract: In mammalian females, germ cells remain arrested as primordial follicles. Resumption of meiosis is heralded by germinal vesicle breakdown, condensation of chromosomes, and their eventual alignment on metaphase plates. At the first meiotic division, anaphase-promoting complex/cyclosome associated with Cdc20 (APC/CCdc20) activates separase and thereby destroys cohesion along chromosome arms. Because cohesion around centromeres is protected by shugoshin-2, sister chromatids remain attached through centromeric/pericentromeric cohesin. We show here that, by promoting proteolysis of cyclins and Cdc25B at the germinal vesicle (GV) stage, APC/C associated with the Cdh1 protein (APC/CCdh1) delays the increase in Cdk1 activity, leading to germinal vesicle breakdown (GVBD). More surprisingly, by moderating the rate at which Cdk1 is activated following GVBD, APC/CCdh1 creates conditions necessary for the removal of shugoshin-2 from chromosome arms by the Aurora B/C kinase, an event crucial for the efficient resolution of chiasmata.

Abstract: The evolution of multidrug resistance in Klebsiella species in response to selective pressure and the extent to which this may be reversible is not fully understood. The spread of carbapenemresistant Enterobacteriaceae (CRE) is considered a public health threat by the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC). As such, more studies are needed to understand the evolution of antibiotic resistance mechanisms to determine if it is possible to reverse this trend. Highlighted In this study, a comprehensive characterisation of a clinical Klebsiella quasipneumoniae isolate called FK688 is performed. The FK688 strain is resistant to multiple antibiotics, including third-generation cephalosporins and carbapenems and caused a bloodstream infection in a hospitalised patient. A combinational approach of genomic, enzymatic, and machine learning analyses did not uncover any carbapenemase-encoding genes in FK688. Rather, this research showed that epistatic changes are necessary for FK688 to acquire a CRE phenotype. Evolution experiments demonstrated the fitness burden associated with antimicrobial resistance determinants and the reversion to a carbapenem-susceptible phenotype in an antibiotic-free environment. Fitness assays showed that a low concentration of ceftazidime selects for a ?- lactamase gene and can potentiate evolution to carbapenem resistance by a single-step mutation in the porin OmpK36. This study demonstrated the importance of epistatic events and how variation in drug exposure can shape the evolutionary pathway to antibiotic resistance in bacteria.

Abstract: Background: Although Latin American migrants (LAMs) are one of the fastest-growing migrant populations in England, they still face health barriers that make them unaware of their HIV status, leading to late HIV diagnosis, AIDS, and even death. Thus, this study aims to assess the differences in HIV outcomes among newly HIV-diagnosed LAMs compared to other England populations. Methods: Data on new HIV/AIDS diagnoses in the UK during the 2011-2020 period were obtained from the HIV and AIDS New Diagnoses and Deaths Database (HANDD) and the HIV and AIDS Reporting System (HARS). Potential associations between the region of birth and late HIV diagnosis, AIDS at HIV diagnosis, and mortality were analysed by logistic regression. Furthermore, a comparison between LAMs and the main populations living in the UK was examined. Lastly, a descriptive trend analysis was made. Results: From 2011 to 2020, 47,828 new HIV diagnoses were reported in the UK, with almost a third (29.2%) being late diagnoses. Over half of new diagnoses (52%) were made in migrants, LAMs representing 9.3% of those diagnoses. In general, newly diagnosed HIV LAMs are not more likely to be diagnosed late than UK residents (aRRR: 1.02; 95%CI: 0.90–1.15). However, some subgroups are more likely to be diagnosed late than their UK counterparts (e.g., 15-24 years old). Regarding AIDS and mortality, LAMs are less likely to be diagnosed with AIDS (aOR: 0.50; 95%CI: 0.35–0.71) or die by any cause (aOR: 0.29; 95%CI: 0.16–0.52) than UK residents. Finally, the number of new HIV diagnoses among LAMs increased in those ten years, but the number of late diagnoses remained nearly constant. Conclusions: Although the current HIV epidemiological situation of LAMs living in the UK is not troublesome, the expansion of the LAM population and their increasing number of new HIV diagnoses could become a public health challenge in the coming years. Therefore, to accomplish the 2030 zero HIV transmission goal, it is necessary to integrate the migrant community into future public policies and categorise them as the ‘sixth’ HIV key population in the UK.

Abstract: Evidence about the effectiveness of school closures as a measure to control the spread of COVID-19 is controversial. We posit that schools are not an important source of transmission; thus, we analyzed two surveillance methods: a web-based questionnaire and a telephone survey that monitored the impact of the pandemic due to COVID-19 cases in Bogotá, Colombia. We estimated the cumulative incidences for Acute Respiratory Infection (ARI) and COVID-19 for each population group. Then, we assessed the differences using the cumulative incidence ratio (CIR) and 95% confidence intervals (CI95%). The ARI incidence among students was 20.1 times higher when estimated from the telephone survey than from the online questionnaire (CIR: 20.1; CI95% 17.11–23.53). Likewise, the ARI incidence among choolteachers was 10 times higher in the telephone survey (CIR: 9.8; CI95% 8.3–11.5). The incidence of COVID-19 among schoolteachers was 4.3 times higher than among students in the online questionnarie (CIR: 4.3, CI95%: 3.8–5.0) and 2.1 times higher in the telephone survey (CIR = 2.1, CI95%: 1.8–2.6), and this behavior was also observed in the general population data. Both methods showed a capacity to detect COVID-19 transmission among students and schoolteachers, but the telephone survey estimates were probably closer to the real incidence rate. Resumen: La evidencia sobre la efectividad del cierre de las instituciones educativas como una medida para controlar la transmisión del COVID-19 es controversial. Nosotros postulamos que los colegios no son una fuente importante de transmisión, por lo tanto, se analizaron dos métodos de vigilancia: un cuestionario en línea y una encuesta telefónica que monitoreaba el impacto causado por los casos de la pandemia de COVID-19 en Bogotá, Colombia. Se estimó las incidencias acumuladas por infección respiratoria aguda (IRA) y COVID-19 para cada grupo poblacional. Posteriormente, se evaluaron las diferencias usando la tasa de incidencias acumuladas (TIA) con intervalos de confianza del 95%. La incidencia de IRA en los estudiantes fue 20.1 veces más alta cuando se estimó a partir de la encuesta telefónica frente al cuestionario en línea (TIA: 20.1; IC95% 17.11–23.53). Igualmente, la incidencia de ARI entre los docentes fue 10 veces más alta en la encuesta telefónica (TIA: 9.8; IC95% 8.3–11.5). La incidencia de COVID-19 en los docentes fue 4.3 veces más alta que la de los estudiantes de acuerdo con el cuestionario en línea (TIA: 4.3, IC95%: 3.8–5.0) y 2.1 veces más alta en la encuesta telefónica (CIR = 2.1, CI95%: 1.8–2.6), y este comportamiento también se observó en los datos de la población general. Ambos métodos de vigilancia mostraron ser capaces de detectar la transmisión del COVID-19 entre los estudiantes y los docentes, pero las estimaciones derivadas de la encuesta telefónica fueron probablemente más cercanas a las tasas de incidencia reales.

Abstract: Sexual reproduction depends on the transmission of exactly one copy of each chromosome by the maternal and paternal gametes. This is accomplished during meiosis when diploid progenitors undergo two consecutive rounds of chromosome segregation following a single round of DNA replication. In most organisms, this relies on the establishment of bivalent chromosomes consisting of replicated parental homologues physically linked at sites of meiotic recombination. In female mammals, bivalents are formed during fetal development when the lifetime stock of primordial-stage oocytes is established. However, they are not resolved until shortly before ovulation. Extending this period beyond ~35 years results in a dramatic increase in embryo aneuploidy. Depletion of the lifetime stock of oocytes during ageing culminates in menopause. Our previous studies indicate that Rec8-containing cohesin complexes also become depleted from oocyte chromosomes during female ageing. Consistent with cohesin’s role in maintaining chromosome structure, depletion of Rec8 is associated with destabilisation of bivalents chromosomes. Nevertheless, the mechanisms and timing of cohesin depletion remain unknown. Here, I investigated the possibility that age-related cohesion depletion is a consequence of leaky inhibition of the protease separase, which cleaves Rec8 during anaphase. I found that oocyte-specific deletion of separase did not prevent depletion of oocyte cohesin during female ageing. I, therefore, conclude that age-related depletion occurs by a separaseindependent mechanism. I next investigated the timing, during oogenesis, at which cohesin loss occurs. I found that cohesin is predominantly lost at the primordial stage before oocytes are recruited for growth. In addition, using an oocyte-specific deletion of Pten, I determined that this occurs independently of the decline in the ovarian stock of primordial-stage oocytes. Together, these results indicate that age-related cohesin depletion occurs at the primordial stage by a separase-independent mechanism. Other possible of mechanisms of cohesin depletion include protein damage and/or agerelated deterioration of chromatin structure. From a clinical perspective, my work suggests that “rejuvenation’ of fertility by activating the residual pool of primordial oocytes is unlikely to be successful in older women.

Abstract: Health literacy aims to improve the ability to make decisions about our health and thus improve our quality of life. This is why the project JUNTOS (TOGETHER) aimed to do everything possible to promote health literacy, on the basis of a specific sociolinguistic problem. One of the objectives of this project was to carry out a quantitative readability analysis of written medical reports received by families with a child affected by a rare disease, as a way to account for the comprehension difficulty that these texts represent for these families. To carry out this analysis, we used different readability tools that currently exist for texts written in Spanish and English. The results we obtained led us to realize that there are some limitations that do not allow this type of quantitative analysis to be completely reliable when applied to specialized texts, specifically medical texts and more specifically medical reports; and at the same time they lead us to highlight the need to carry out parallel qualitative analyses when trying to make a readability analysis of specialized texts of this nature. Hence, the results of this research provide us with new ideas to continue working on this line of research. Resumen: La alfabetización en salud pretende mejorar la capacidad para tomar decisiones sobre nuestra salud y, por lo tanto, mejorar nuestra calidad de vida. Es por eso por lo que desde el proyecto JUNTOS se planteó hacer lo posible para favorecer esta alfabetización en salud, partiendo de un problema sociolingüístico en concreto. Uno de los objetivos de este proyecto fue hacer un análisis cuantitativo de legibilidad de informes médicos escritos recibidos por familias con un niño afectado por una enfermedad rara, como mecanismo para dar cuenta de la dificultad de comprensión que estos textos suponen para dichas familias. Para llevar a cabo este análisis aprovechamos diferentes herramientas de legibilidad que existen en la actualidad para textos escritos en español y en inglés. Los resultados que obtuvimos nos llevaron a darnos cuenta de que existen algunos limitantes que no permiten que este tipo de análisis cuantitativo sea completamente fiable cuando se aplica a textos especializados, en concreto, de medicina y más específicamente de informes médicos; y al mismo tiempo nos llevan a destacar la necesidad de realizar en paralelo análisis cualitativos cuando se pretende hacer un análisis de legibilidad de textos especializados de esta índole. De aquí que los resultados de esta investigación nos planteen nuevas ideas para seguir trabajando en esta línea de investigación.

Abstract: Introduction: Children born very preterm have an immature sucking reflex at birth and are exposed to neonatal care that can impede proper palate growth. Objectives: We aimed to describe the frequency of high-arched palate and posterior crossbite at the age of 5 in children born very preterm and to identify their respective risk factors. Methods: Our study was based on the data from EPIPAGE-2, a French national prospective cohort study, and included 2,594 children born between 24- and 31-week gestation. Outcomes were high-arched palate and posterior crossbite. Multivariable models estimated by generalized estimation equations with multiple imputation were used to study the association between the potential risk factors studied and each outcome. Results: Overall, 8 % of children born very preterm had a high-arched palate and 15 % posterior crossbite. The odds of high-arched palate were increased for children with low gestational age (24–29 vs. 30–31 weeks of gestation) [adjusted odds ratio (aOR) 1.76, 95% confidence interval (CI) 1.17, 2.66], thumb-sucking habits at the age of 2 (aOR 1.53, 95% CI 1.03, 2.28), and cerebral palsy (aOR 2.18, 95% CI 1.28, 3.69). The odds of posterior crossbite were increased for children with pacifier-sucking habits at the age of 2 (aOR 1.75, 95% CI 1.30, 2.36). Conclusions: Among very preterm children, low gestational age and cerebral palsy are the specific risk factors for a high-arched palate. High-arched palate and posterior crossbite share non-nutritive sucking habits as a common risk factor. The oro-facial growth of these children should be monitored. Resumen: Introducción: Los niños que nacen muy prematuros tienen un reflejo de succión inmaduro al nacer y están expuestos a cuidados neonatales que pueden impedir el correcto crecimiento del paladar. Objetivos: Nuestro objetivo fue describir la frecuencia de paladar ojival y mordida cruzada posterior a la edad de 5 años en niños nacidos muy prematuros e identificar sus respectivos factores de riesgo. Métodos: Nuestro estudio se basó en los datos de EPIPAGE-2, un estudio de cohorte prospectivo nacional francés, e incluyó a 2 594 niños nacidos entre las semanas 24 y 31 de gestación. Los resultados fueron paladar ojival y mordida cruzada posterior. Se utilizaron modelos multivariables estimados por ecuaciones de estimación generalizadas con imputación múltiple para estudiar la asociación entre los potenciales factores de riesgo estudiados y cada desenlace. Resultados: En general, el 8% de los niños nacidos muy prematuros tenían paladar ojival y el 15% mordida cruzada posterior. Las probabilidades de paladar ojival aumentaron para niños con edad gestacional baja (24–29 vs. 30–31 semanas de gestación) [odds ratio ajustado (ORa) 1,76, intervalo de confianza (IC) del 95 % 1,17, 2,66], hábito de succión del pulgar a los 2 años (ORa 1,53, IC 95% 1,03, 2,28), y parálisis cerebral (ORa 2,18, IC 95% 1,28, 3,69). Las probabilidades de mordida cruzada posterior aumentaron para los niños con hábitos de succión del chupete a la edad de 2 años (ORa 1,75, IC del 95%: 1,30, 2,36). Conclusiones: Entre los niños muy prematuros, la baja edad gestacional y la parálisis cerebral son los factores de riesgo específicos para paladar ojival. El paladar ojival y la mordida cruzada posterior comparten hábitos de succión no nutritiva como factor de riesgo común. El crecimiento orofacial de estos niños debe ser monitoreado.