Assessment of aflatoxin exposure, growth faltering and the gut microbiome among children in rural Guatemala: protocol for an observational prospective cohort and bioreactor simulations.

INTRODUCTION: Aflatoxin B1 (AFB1) is a carcinogen produced by Aspergillus flavus and Aspergillus parasiticus which grow on maize. Given the high prevalence of child stunting (ie, impaired growth) and other nutritional disorders in low-income and middle-income countries, where maize is consumed, the role of aflatoxin exposure may be significant. Observational reports have demonstrated associations between aflatoxin exposure and impaired child growth; however, most have been cross-sectional and have not assessed seasonal variations in aflatoxin, food preparation and dynamic changes in growth. Biological mechanistic data on how aflatoxin may exert an impact on child growth is missing. This study incorporates a prospective cohort of children from rural Guatemala to assess (1) temporal associations between aflatoxin exposure and child growth and (2) possible mediation of the gut microbiome among aflatoxin exposure, inflammation and child growth. METHODS AND ANALYSIS: We will prospectively evaluate aflatoxin exposure and height-for-age difference trajectories for 18 months in a cohort of 185 children aged 6-9 months at enrolment. We will assess aflatoxin exposure levels and biomarkers of gut and systemic inflammation. We will examine the faecal microbiome of each child and identify key species and metabolic pathways for differing AFB1 exposure levels and child growth trajectories. In parallel, we will use bioreactors, inoculated with faeces, to investigate the response of the gut microbiome to varying levels of AFB1 exposure. We will monitor key microbial metabolites and AFB1 biotransformation products to study nutrient metabolism and the impact of the gut microbiome on aflatoxin detoxification/metabolism. Finally, we will use path analysis to summarise the effect of aflatoxin exposure and the gut microbiome on child growth. ETHICS AND DISSEMINATION: Ethics approval was obtained from Arizona State University Institutional Review Board (IRB; STUDY00016799) and Wuqu' Kawoq/Maya Health Alliance IRB (WK-2022-003). Findings will be disseminated in scientific presentations and peer-reviewed publications.

Osimertinib and Capmatinib Combination Therapy to Overcome MET Y1003N-Mediated Resistance in EGFR-Mutant NSCLC: A Case Report.

Osimertinib, a third-generation EGFR tyrosine kinase inhibitor, is the frontline standard in the treatment of metastatic EGFR-mutant NSCLC. Although osimertinib is effective, disease progression occurs in virtually all patients, mediated by a heterogeneous array of resistance mechanisms. Activation of the MET signaling pathway by means of amplification has been implicated in resistance to osimertinib, but activation caused by point mutations in MET has not been well described. Here, we present the case of a 65-year-old female with metastatic EGFR-mutant NSCLC whose disease progressed on osimertinib owing to emergence of MET Y1003N mutation. She subsequently received capmatinib in combination with osimertinib and achieved a partial response. This case illustrates a potential role for dual EGFR/MET inhibition in EGFR-mutated NSCLC with resistance driven by activating MET mutations.

Pseudomonas putida mediates bacterial killing, biofilm invasion and biocontrol with a type IVB secretion system.

Many bacteria utilize contact-dependent killing machineries to eliminate rivals in their environmental niches. Here we show that the plant root colonizer Pseudomonas putida strain IsoF is able to kill a wide range of soil and plant-associated Gram-negative bacteria with the aid of a type IVB secretion system (T4BSS) that delivers a toxic effector into bacterial competitors in a contact-dependent manner. This extends the range of targets of T4BSSs-so far thought to transfer effectors only into eukaryotic cells-to prokaryotes. Bioinformatic and genetic analyses showed that this killing machine is entirely encoded by the kib gene cluster located within a rare genomic island, which was recently acquired by horizontal gene transfer. P. putida IsoF utilizes this secretion system not only as a defensive weapon to kill bacterial competitors but also as an offensive weapon to invade existing biofilms, allowing the strain to persist in its natural environment. Furthermore, we show that strain IsoF can protect tomato plants against the phytopathogen Ralstonia solanacearum in a T4BSS-dependent manner, suggesting that IsoF can be exploited for pest control and sustainable agriculture.

Immunotherapy in lung cancer.

Immunotherapy has emerged as an important treatment modality throughout oncology with a particularly important role in the treatment of lung cancer. Early signals showed responses could be achieved in nonsmall cell lung cancer and small cell lung cancer and these monoclonal antibodies have become standards of care for advanced stage disease. They have also shown promise in earlier-stage disease as complements to radiation or surgery, offering the potential for durable, meaningful survival gains.

Role of extracellular matrix components in the formation of biofilms and their contribution to the biocontrol activity of Pseudomonas chlororaphis PCL1606.

Pseudomonas chlororaphis PCL1606 (PcPCL1606) displays plant-colonizing features and exhibits antagonistic traits against soil-borne phytopathogenic fungi. Biofilm formation could be relevant for the PcPCL1606 lifestyle, and in this study the role of some putative extracellular matrix components (EMC; Fap-like fibre, alginate and Psl-like polysaccharides) in the biofilm architecture and biocontrol activity of this bacterium were determined. EMC such as the Fap-like fibre and alginate polysaccharide play secondary roles in biofilm formation in PcPCL1606, because they are not fundamental to its biofilm architecture in flow cell chamber, but synergistically they have shown to favour bacterial competition during biofilm formation. Conversely, studies on Psl-like polysaccharide have revealed that it may contain mannose, and that it is strongly involved in the PcPCL1606 biofilm architecture and niche competition. Furthermore, the Fap-like fibre and Psl-like exopolysaccharide play roles in early surface attachment and contribute to biocontrol activity against the white root rot disease caused by Rosellinia necatrix in avocado plants. These results constitute the first report regarding the study of the extracellular matrix of the PcPCL1606 strain and highlight the importance of a putative Fap-like fibre and Psl-like exopolysaccharide produced by PcPCL1606 in the biofilm formation process and interactions with the host plant root.

Biological role of EPS from Pseudomonas syringae pv. syringae UMAF0158 extracellular matrix, focusing on a Psl-like polysaccharide.

Pseudomonas syringae is a phytopathogenic model bacterium that is used worldwide to study plant-bacteria interactions and biofilm formation in association with a plant host. Within this species, the syringae pathovar is the most studied due to its wide host range, affecting both, woody and herbaceous plants. In particular, Pseudomonas syringae pv. syringae (Pss) has been previously described as the causal agent of bacterial apical necrosis on mango trees. Pss exhibits major epiphytic traits and virulence factors that improve its epiphytic survival and pathogenicity in mango trees. The cellulose exopolysaccharide has been described as a key component in the development of the biofilm lifestyle of the P. syringae pv. syringae UMAF0158 strain (PssUMAF0158). PssUMAF0158 contains two additional genomic regions that putatively encode for exopolysaccharides such as alginate and a Psl-like polysaccharide. To date, the Psl polysaccharide has only been studied in Pseudomonas aeruginosa, in which it plays an important role during biofilm development. However, its function in plant-associated bacteria is still unknown. To understand how these exopolysaccharides contribute to the biofilm matrix of PssUMAF0158, knockout mutants of genes encoding these putative exopolysaccharides were constructed. Flow-cell chamber experiments revealed that cellulose and the Psl-like polysaccharide constitute a basic scaffold for biofilm architecture in this bacterium. Curiously, the Psl-like polysaccharide of PssUMAF0158 plays a role in virulence similar to what has been described for cellulose. Finally, the impaired swarming motility of the Psl-like exopolysaccharide mutant suggests that this exopolysaccharide may play a role in the motility of PssUMAF0158 over the mango plant surface.

Comparação do perfil clínico-epidemiológico entre homens e mulheres na síndrome coronariana aguda / Comparison of clinical and epidemiological profiles among men and women with acute coronary syndrome

Fundamentos: A doença isquêmica do coração é a principal causa de morte entre homens e mulheres no Brasil e em vários países de diferentes continentes. Verifica-se um crescimento acelerado da mortalidade nos países em desenvolvimento, sendo esta considerada uma das questões mais relevantes em saúde pública atualmente. Objetivo: Analisar e comparar o perfil clínico-epidemiológico de homens e mulheres na síndrome coronariana aguda.Métodos: Avaliado o perfil clínico-epidemiológico de 927 pacientes (60,0% homens), com média de idade 67,0±12,0 anos com diagnóstico de síndrome coronariana aguda (SCA), internados na unidade coronariana de um hospital da rede suplementar de saúde, de referência em cardiologia, na cidade de Recife, PE, Brasil, no período de setembro de 2009 a dezembro de 2012.Resultados: Dentre os fatores de risco, a hipertensão arterial sistêmica e o sedentarismo foram mais frequentes nas mulheres (p=0,001), enquanto o tabagismo e o alcoolismo foram mais frequentes nos homens (p=0,01). Ainda nos homens foram mais frequentes: o infarto agudo do miocárdio com supradesnivelamento do segmento do ST ou cirurgia de revascularização do miocárdio prévios (p=0,011) e também os níveis de troponina (p=0,006). Durante a hospitalização, os desfechos adversos e óbito foram mais frequentes nas mulheres (p=0,177).Conclusão: As mulheres com SCA apresentaram maior prevalência de hipertensão arterial sistêmica e sedentarismo e a maior ocorrência de desfechos adversos, indicando a necessidade de intervir mais precocemente e estimular o controle nos fatores de risco, visando a reduzir as complicações e a mortalidade hospitalar.

Background: Ischemic heart disease is the leading cause of death among men and women in Brazil and in several countries on different continents. A sharp upsurge in mortality rates has been noted in the developing countries, today constituting a major public health issue.Objective: To analyze and compare the clinical and epidemiological profiles of men and women with acute coronary syndrome.Methods: We studied 927 patients (60.0% men) with an average age of 67.0±12.0 years diagnosed with acute coronary syndrome (ACS) and admitted to the coronary unit of a cardiology reference hospital in the supplementary healthcare network between September 2009 and December 2012 in the city of Recife, Pernambuco State, Brazil.Results: Among the risk factors, hypertension and sedentary lifestyles were more frequent among women (p=0.001), while smoking and alcoholism were more frequent among men (p=0.01). Men also had more frequent acute myocardial infarctions with elevation of the ST segment or previous coronary artery bypass grafting (p=0.011) and higher troponin levels (p=0.006). During hospitalization, adverse outcomes and deaths were more frequent among women (p=0.177).Conclusion: Women with ACS present higher rates for hypertension and sedentary lifestyles, with more adverse outcomes among women underscoring the need for earlier intervention and encouragement for controlling risk factors, in order to lower in-hospital mortality rates with fewer complications.

Maternal health and health-seeking behaviors among indigenous Mam mothers from Quetzaltenango, Guatemala.

OBJECTIVE: To obtain background information about maternal health and health-seeking behaviors among indigenous mothers living in rural Mam-Mayan communities of Quetzaltenango, Guatemala. METHODS: A cross-sectional analysis of 100 pregnant and breastfeeding women in four communities was performed to determine prevalence and determinants of service utilization. RESULTS: Extreme poverty, poor education, and poor access to basic resources were prevalent. Out of 100 women 14-41 years old, 33% did not use the formal health care sector for antenatal care; the majority consulted a traditional birth attendant. Only 13% delivered in a hospital. Lower socioeconomic status, lack of fluency in Spanish, and no ownership of a motorized vehicle were associated with the highest likelihood of poor utilization of services. CONCLUSIONS: A variety of factors affect utilization of maternal health services by indigenous women in rural Quetzaltenango. These include socioeconomic disparities, ethnic and linguistic differences, and poor access to basic resources. The current reproductive needs of women should be addressed to improve their health and increase their chance of having healthy children.

Maternal health and health-seeking behaviors among indigenous Mam mothers from Quetzaltenango, Guatemala / Salud materna y comportamientos relacionados con la búsqueda de asistencia sanitaria en madres indígenas mames del departamento de Quetzaltenango, Guatemala

OBJECTIVE: To obtain background information about maternal health and health-seeking behaviors among indigenous mothers living in rural Mam-Mayan communities of Quetzaltenango, Guatemala. METHODS: A cross-sectional analysis of 100 pregnant and breastfeeding women in four communities was performed to determine prevalence and determinants of service utilization. RESULTS: Extreme poverty, poor education, and poor access to basic resources were prevalent. Out of 100 women 14-41 years old, 33% did not use the formal health care sector for antenatal care; the majority consulted a traditional birth attendant. Only 13% delivered in a hospital. Lower socioeconomic status, lack of fluency in Spanish, and no ownership of a motorized vehicle were associated with the highest likelihood of poor utilization of services. CONCLUSIONS: A variety of factors affect utilization of maternal health services by indigenous women in rural Quetzaltenango. These include socioeconomic disparities, ethnic and linguistic differences, and poor access to basic resources. The current reproductive needs of women should be addressed to improve their health and increase their chance of having healthy children.

OBJETIVO: Obtener información básica acerca de la salud materna y los comportamientos relacionados con la búsqueda de asistencia sanitaria en madres indígenas residentes en comunidades rurales de la etnia maya mam en Quetzaltenango, Guatemala. MÉTODOS: Se llevó a cabo un análisis transversal de 100 mujeres pertenecientes a cuatro comunidades, embarazadas o en período de lactancia, con objeto de determinar la prevalencia y los determinantes de la utilización de servicios. RESULTADOS: La pobreza extrema, la escasa formación y el acceso limitado a los recursos básicos fueron prevalentes. De las 100 mujeres, de 14 a 41 años de edad, 33% no acudieron al sector formal de atención de salud en busca de asistencia prenatal; la mayor parte de ellas consultaron a una partera tradicional. Solo 12% dieron a luz en un hospital. El nivel socioeconómico inferior, la falta de fluidez en español y la carencia de un vehículo motorizado se asociaron con la mayor probabilidad de escasa utilización de los servicios. CONCLUSIONES: Diversos factores afectan a la utilización de los servicios de salud materna por parte de las mujeres indígenas del Quetzaltenango rural. Entre estos factores figuran las desigualdades socioeconómicas, las diferencias lingüísticas y étnicas, y el acceso limitado a los recursos básicos. Es preciso atender a las necesidades reproductivas actuales de las mujeres para mejorar su salud y aumentar sus probabilidades de tener hijos sanos.