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: 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 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: 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.

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: Objective: To describe the prevalence pattern of anemia among Indigenous children in Latin America. Methods: PRISMA guidelines were followed. Records were identified from the databases PubMed, Google Scholar, and Lilacs by two independent researchers between May and June 2021. Studies were included if the following criteria were met: a) studied Indigenous people b) was about children (from 0 to 12 years old); c) reported a prevalence estimate of anemia; d) had been conducted in any of the countries of Latin America; e) was published either in English, Portuguese, or Spanish; f) is a peer-reviewed article; and g) was published at any date. Results: Out of 2,401 unique records retrieved, 42 articles met the inclusion criteria. A total of 39 different Indigenous communities were analyzed in the articles, and in 21 of them (54.0%) child anemia was a severe public health problem (prevalence ? 40%). Those communities were the Aymara (Bolivia); Aruak, Guaraní, Kamaiurá, Karapotó, Karibe, Kaxinanuá, Ma-cro-Jê, Suruí, Terena, Xavante (Brazil); Cabécar (Costa Rica), Achuar, Aguaruna, Awajún, Urarina, Yomybato (Peru); Piaroa and Yucpa (Venezuela); and Quechua (Peru and Bolivia). Children below two years had the highest prevalence of anemia (between 16.2% and 86.1%). Among Indigenous people, risk factors for anemia include nutrition, poor living conditions, access to health services, racism, and discrimination. Bolivia and Guatemala are scarcely studied, despite having the highest proportion of Indigenous communities in Latin America. Conclusions: Anemia constitutes a poorly documented public health problem among Indigenous children in 21 Indigenous communities in Bolivia, Brazil, Colombia, Costa Rica, Ecuador, Guatemala, Mexico, and Peru. In all Indigenous communities included in this study child anemia was an issue, especially in younger children. Resumen: Objetivo: Describir el patrón de prevalencia de anemia en niños indígenas de América Latina. Métodos: Se siguieron las directrices PRISMA. Los registros fueron identificados en las bases de datos PubMed, Google Scholar y Lilacs por dos investigadores independientes entre mayo y junio de 2021. Los estudios se incluyeron si cumplían los siguientes criterios: a) estudiaban a indígenas; b) eran sobre niños (de 0 a 12 años); c) reportaban una estimación de prevalencia de anemia; d) se habían realizado en cualquiera de los países de América Latina; e) se publicaron en inglés, portugués o español; f) eran artículos revisados por pares; y g) se publicaron en cualquier fecha. Resultados: De los 2.401 registros únicos recuperados, 42 artículos cumplían los criterios de inclusión. Un total de 39 comunidades indígenas diferentes fueron analizadas en los artículos, y en 21 de ellas (54,0%) la anemia infantil era un problema grave de salud pública (prevalencia ? 40%). Esas comunidades eran aymara (Bolivia); aruak, guaraní, kamaiurá, karapotó, karibe, kaxinanuá, macro- jê, suruí, terena, xavante (Brasil); cabécar (Costa Rica), achuar, aguaruna, awajún, urarina, yomybato (Perú); piaroa y yucpa (Venezuela); y quechua (Perú y Bolivia). Los niños menores de dos años presentaban la mayor prevalencia de anemia (entre el 16,2% y el 86,1%). Entre los indígenas, los factores de riesgo de la anemia son la nutrición, las malas condiciones de vida, el acceso a los servicios sanitarios, el racismo y la discriminación. Bolivia y Guatemala están escasamente estudiados, a pesar de tener la mayor proporción de comunidades indígenas de América Latina. Conclusiones: La anemia constituye un problema de salud pública poco documentado entre los niños indígenas de 21 comunidades indígenas de Bolivia, Brasil, Colombia, Costa Rica, Ecuador, Guatemala, México y Perú. En todas las comunidades indígenas incluidas en este estudio, la anemia infantil era un problema, especialmente en los niños más pequeños.

Abstract: Aim: To evaluate the reliability of the ExSel® self-questionnaire to detect an excess salt intake (≥12 g/24h) in patients consulting for hypertension and/or renal failure. Methods: Results of the ExSel® self-questionnaire were compared to 24 h sodium excretion using the Cohen’s kappa test and a Chi² test. Sensitivity, specificity, VPP and VPN were calculated. A ROC curve was realized to find an accurate cut-off.Results: Mean characteristics of the 101 patients with reliable results were: age of 67+12 years, Body Mass Index 28.4+5.6 kg/m², SBP/DBP 139+23/74+13 mmHg (98% were hypertensives. Mean salt intake was 7.5+3.1 g/24h and mean creatininuria was 13.9+20.1 mmol/24 h. An excess salt intake (≥12 g/24h) was observed in 8% of the patients. The Kappa test at 0.17 and the Chi² at 0.66 signify that the agreement was very low. Sensitivity was 37%, specificity 90%, PPV 20% and NPV 94%. The AUC under the ROC curve was too low (0.665) to determine a threshold adapted to the renal patients. Conclusions: The ExSel® auto-questionnaire is not adapted to outpatients, mainly hypertensives (98%) followed in a nephrology consultation to detect an excess salt consumption.

Abstract: This review aimed at evaluating the state of availability, accessibility and model of delivery of oral health services in prisons, globally. Five databases of peer-reviewed literature and potential sources of gray literature were systematically searched. Inclusion criteria encompassed oral health papers related to prisons globally, with exclusion of certain article types. Selection involved independent evaluations by two researchers, followed by quality assessment. Data on the availability of oral health interventions in prisons came from18 countries, while information on the model of delivery of the services is scarce. In addition, two sets of individual and organizational barriers toward oral health service uptake in prisons were revealed and discussed in the text. Lack of oral health services in prisons affects people living in prisons and jeopardizes their reintegration. Urgent and concrete international actions are required to ensure the availability, accessibility, and quality of oral health services among people living in prisons.

Resumen: Tras una cirugía de reemplazo articular, la presencia del material protésico, la intervención quirúrgica y los factores de riesgo del paciente predisponen la aparición de una infección protésica. En general las tasas de infección rondan el 1,5% en las prótesis de cadera y el 2,5% en las de rodilla. Los protocolos de tratamiento consisten en una combinación de medidas quirúrgicas junto con un tratamiento farmacológico sistémico de rifampicina y fluoroquinolonas en monoterapia o en combinación durante al menos 3-9 meses. El desarrollo de nanopartículas cargadas con antibióticos permite la administración selectiva en el lugar de la infección, reduciendo los efectos adversos sistémicos del antibiótico y logrando la liberación controlada del mismo. Por ello, el objetivo del presente trabajo fue el desarrollo de una formulación de nanopartículas poliméricas de ciprofloxacino por el método de doble emulsión (W/O/W) extracción-evaporación del solvente para su administración local en el tratamiento de infecciones protésicas. Para el desarrollo y optimización de las formulaciones se ha empleado el diseño experimental. Se ha realizado un diseño factorial completo (L12) de dos niveles para evaluar y determinar el grado de influencia de diversos parámetros del proceso de elaboración en las características de estos nanosistemas. Gracias a este diseño se determinó que la hidrofobicidad del polímero y la cantidad de ciprofloxacino fueron los únicos factores que mostraron una influencia estadísticamente significativa en el tamaño de partícula y carga de antibiótico de las nanopartículas, respectivamente. Por último, se ha estudiado el perfil de liberación del ciprofloxacino en las formulaciones seleccionadas. Con el fin de garantizar las condiciones sink, previamente se evaluó la solubilidad del fármaco en tampón fosfato a distintos valores de pH. Este estudio demostró que el ciprofloxacino presenta baja solubilidad a pH >6 y forma soluciones sobresaturadas metaestables a pH 6 y 5.5. La formulación elaborada con PLGA-502, 15mg de ciprofloxacino y NaCl en la fase externa acuosa, se seleccionó como la formulación más adecuada, mostrando un tamaño de partícula de 307 nm, un PDI de 0.28, una eficacia de encapsulación de 62.46% y una liberación controlada del ciprofloxacino durante al menos 7 días.

Abstract: At the present time, climate change and antimicrobial resistance are considered as the most critical threats, affecting human, animal, plant, and environmental health. Although these terms may initially appear different, they are interconnected and share similarities in their causes (human interventions and natural cycles), health, and societal consequences. Climate change is associated through direct and indirect pathways with an increase in infectious diseases. Nonetheless, the association between global warming and antimicrobial resistance requires a comprehensive summary of evidence exploring it. Methods: A literature review was conducted to identify and describe the association between climate change and the rapid emergence and spread of antimicrobial resistance. The search was conducted in the following databases: PubMed, Web of Science, Scopus, Embase, Epistemonikos, and Google Scholar. The search period was restricted to articles published from January 2010 to June 2021. Additionally, a snowballing approach was conducted to identify any additional papers. Data extraction included study location, weather factors, environmental elements, antibiotics, and bacteria analysed, as well as the results. Results: 29 articles were included (ten literature or systematic reviews, eight experimental, six ecological, four observational, and one quasi-experimental). In terms of location, all the studies were conducted in countries between 35° and 75° north latitude. The results suggested some evidence of the effects of climate change (alterations in temperature, precipitation, and humidity) on the emergence and rapid spread of antimicrobial resistance in different environments (water, soil, cryosphere, and air). Temperature was described as a main effect of climate change that had effects on antibiotic resistance (increasing bacteria growth, altering metabolism, inducing crossprotection, and facilitating horizontal gene transfer between bacteria). Additionally, results also described the association between altered rain patterns and humidity and antimicrobial resistance, through the runoff of antibiotic molecules or the transport of antibiotic resistance mechanisms to other areas. Conclusions: This literature review has underscored the association between climate change and antimicrobial resistance. According to the results shown in the selected studies, the alterations in weather factors resulting from climate change have varying effects on the emergence and spread of antibiotic resistance. However, further research is imperative to decipher the complex interactions between other environmental processes, pollutants, patterns of antibiotic consumption, wastewater, animal migration, and regions below the latitudes covered in this literature review.