Implementing precision oncology in Latin America to improve patient outcomes: the status quo and a call to action for key stakeholders and decision-makers.

Background: The advent of precision oncology (PO) has revolutionised diagnostic and follow up strategies and improved clinical outcomes for cancer patients. However, socio-economic inequalities in the level of implementation of PO in different countries is a prevailing issue. To improve this situation, the Latin America Patients Academy has gathered the recommendations of healthcare professionals and social civil members experienced in cancer management from Mexico, Guatemala, Costa Rica, Dominican Republic, Panama, Colombia, Chile, Ecuador, Peru and Argentina regarding the areas that need to be prioritised to improve the access to PO in Latin American (LATAM) countries. Methods: This manuscript is the culmination of a series of educational campaigns and panel discussion aimed at improving the implementations of PO in LATAM that took place from June 2021 to January 2022. The status of PO in Latin America: the level of PO implementation is generally low with some exceptions. The number of clinical trials and articles published with keywords related to PO from LATAM countries is drastically lower than in Europe and the United States. Despite sharing many complex challenges, progress is taking place in some countries in the region. Focus areas defined by the expert panel: The expert panel determined the areas of PO that should be improved by LATAM countries to improve its implementation through cancer care plans, educational programs and collaborative strategies. These initiatives should increase awareness about PO in the region and eventually improve cancer control in the region.

The S/S Genotype of the 5-HTTLPR (Serotonin-Transporter-Linked Promoter Region) Variant of the SLC6A4 Gene Decreases the Risk of Pre-Eclampsia.

Pre-eclampsia (PE) is a disorder characterized by hypertension in the second trimester of pregnancy that results from abnormal placentation affecting fetal development and maternal health. Previous studies have shown the role of serotonin (5-HT) that leads to poor placental perfusion, where S/S and S/L polymorphisms promote the solute carrier family 6 member 4 (SLC6A4) gene associated with the risk of developing changes in the microvasculature of the placenta. This study looked at the association between the gene variant 5-HTTLPR (serotonin-transporter-linked promoter region) of the SLC6A4 gene and the occurrence of PE. A total of 200 women were included: 100 cases (pregnant with PE) and 100 controls (pregnant without complications). Genotyping of the 5-HTTLPR variant was performed using polymerase chain reaction (PCR). Associations between the presence of the genetic variant of interest and PE and other clinical features were evaluated statistically. The frequencies of S/S, S/L, and L/L genotypes were 32%, 53%, and 15% for the cases and 55%, 25%, and 20% in the control group. Compared to the controls, the genotype frequencies S/S vs. S/L + L/L (recessive model) in the cases group were different (p = 0.002). The S/S genotype decreased the probability of PE (OR = 0.39, 95% IC: 0.22-0.69, p = 0.002) and PE with severity criteria (OR = 0.39, 95% IC: 0.17-0.91, p = 0.045). The 5-HTTLPR gene variant of the SLC6A4 gene modifies the risk of PE development among the studied population.

Fierce poison to others: the phenomenon of bacterial dependence on antibiotics.

Beyond the development of resistance, the effects of antibiotics on bacteria and microbial communities are complex and far from exhaustively studied. In the context of the current global antimicrobial resistance crisis, understanding the adaptive and physiological responses of bacteria to antimicrobials is of paramount importance along with the development of new therapies. Bacterial dependence on antibiotics is a phenomenon in which antimicrobials instead of eliminating the pathogens actually provide a boost for their growth. This trait comprises an extreme example of the complexities of responses elicited by microorganisms to these drugs. This compelling evolutionary trait was readily described along with the first wave of antibiotics use and dependence to various antimicrobials has been reported. Nevertheless, current molecular characterizations have been focused on dependence on vancomycin, linezolid and colistin, three critically important antibiotics frequently used as last resource therapy for multi resistant pathogens. Outstanding advances have been made in understanding the molecular basis for the dependence to vancomycin, including specific mutations involved. Regarding linezolid and colistin, the general physiological components affected by the dependence, namely ribosomes and membrane function respectively, have been established. Nonetheless the implications of antibiotic dependence in clinically relevant features, such as virulence, epidemics, relationship with development of resistance, diagnostics and therapy effectiveness require clarification. This review presents a brief introduction of the phenomenon of bacterial dependence to antibiotics and a summary on early and current research concerning the basis for this trait. Furthermore, the available information on the effect of dependence in key clinical aspects is discussed. The studies performed so far underline the need to fully disclose the biological and clinical significance of this trait in pathogens to successfully assess its role in resistance and to design adjusted therapies.

Consumo colectivo de alcohol en jóvenes universitarios en Colombia: análisis desde una perspectiva etnográfica / Collective consumption of alcohol among young university students in Colombia: Analysis from an ethnographical perspective

Objetivo: reconocer los escenarios de consumo de alcohol como fenómeno colectivo, y las interrelaciones que se dan en estos espacios. Metodología: estudio cualitativo con enfoque etnográfico, realizado en dos etapas: cartografía y mapeo de lugares de consumo de alcohol y observación no participante, donde participaron jóvenes universitarios de ciencias de la salud. Se realizó análisis de contenido en ATLAS.Ti. Resultados: Emergieron 8 categorías: 1) Características del lugar de consumo 2) Motivaciones juveniles para beber, 3) Autonomía y autocontrol sobre el consumo, 4) Características del consumo, 5) Efectos del consumo de alcohol en el organismo, 6) Conocimiento de riesgo asociado al consumo, 7) Diferencias basadas en la división sexo-genérica,8) Rupturas por pandemia. Conclusión: Los sitios de consumo de alcohol usan la iluminación, muebles, pantallas, espectáculos, variedad de bebidas alcohólicas, diferentes formas de pago y estrategias de seguridad para atraer a los jóvenes. Las observadoras reportan que los jóvenes reconocen como motivos para consumir alcohol: las rupturas de pareja, desinhibirse, ser aceptados por el grupo, disfrutar con sus pares, eventos deportivos, celebraciones, liberar tensión provocada por responsabilidades académicas, laborales, familiares y sentimentales. Utilizan como mecanismos para enfrentar la presión social en los escenarios de consumo, el autocontrol y autoconocimiento, que les permiten establecer estrategias de cuidado antes, durante y después del consumo.(AU)

Objective: to recognize the scenarios of alcohol consumption as a collective phenomenon, and the interrelationships that occur in these spaces. Methodology: qualitative with an ethnographic approach, carried out in two stages: cartography and mapping of alcohol consumption study sites and non-participant observation, where young health sciences university students participated. A content analysis was performed in ATLAS.Ti. Results: Eight categories emerged: 1) Characteristics of the place of consumption, 2) Youth motivations to drink, 3) Autonomy and self-control over consumption, 4) Characteristics of consumption, 5) Effects of alcohol consumption on the body, 6) Knowledge of risk associated with consumption, 7) Differences based on the gender-sex division, 8) Pandemic ruptures. Conclusion: Consumption sites use lighting, furniture, screens, shows, a variety of alcoholic beverages, different forms of payment, and security strategies to attract young people. Observers report that young people recognize as reasons for consuming alcohol: breakups, loss of inhibition, being accepted by the group, enjoying with their peers, sporting events, celebrations, releasing tension caused by academic, work, family and sentimental responsibilities. They use self-control and self-knowledge as mechanisms to face social pressure in consumption scenarios, which allow them to establish care guidelines before, during and after consumption.(AU)

Severe coronavirus HCoV-NL63 pneumonia in a patient receiving blinatumomab with secondary antibody deficiency in COVID-19 times.

Introduction: Human coronavirus NL63 (HCoV-NL63) is one of four common human respiratory coronaviruses. It causes lower respiratory tract infections in young children, elderly and immunosuppressed people, which could result in fatal outcomes. In this time of pandemic, we want to highlight the importance of other coronaviruses infection besides SARS-CoV-2, especially in a patient with underlying conditions like acute lymphoblastic leukemia, receiving immunosuppressive therapy that could result in humoral secondary immunodeficiencies. Case report: We present the case of a 44-year-old Colombian man with acute lymphoblastic leukemia who developed HCoV-NL63 pulmonary infection after the first month of treatment with blinatumomab complicated with severe secondary hypogammaglobulinemia. HCoV-NL63 was detected by multiplex PCR, and HCoV-NL63 viral pneumonia was diagnosed. Hypogammaglobulinemia was studied by determining serum immunoglobulins levels and protein electrophoresis. The treatment consisted of supportive therapy and replacement with intravenous immunoglobulins. After therapy, the patient improved his oxygenation, and the infection was resolved in a few days. Conclusions: This case highlights the relevance of other coronaviruses infections besides SARS-CoV-2 in patients receiving immunosuppressive therapy who develop secondary antibody deficiency, and the importance of replacement therapy with intravenous immunoglobulins at early stage of infection with HCoV-NL63.

Identification of Differentially Expressed Genes in Nocardia brasiliensis Induced by Progesterone and Dihydrotestosterone Using Differential Display PCR.

Sex steroid hormones have an important physiological role in humans. They can also affect the gene expression of many organisms, including bacteria. In Mexico, Nocardia brasiliensis is the main causative agent of actinomycetoma, a granulomatous disease more frequent in men than women, which is thought to be related to a higher occupational risk in men. Therefore, it has been suggested that differences in clinical presentation could be related to sex steroid hormone levels. Attempting to explain the differences in actinomycetoma prevalence between men and women, in this work, the effect of progesterone and dihydrotestosterone on the genetic expression of N. brasiliensis was investigated using a differential display polymerase chain reaction assay. The results showed that both hormones affected the expression of genes encoding proteins related to central metabolism and hypothetical proteins with unknown functions. This study also demonstrated the utility of differential display in this modern era and provided a first approach to the effect of sex hormones on N. brasiliensis gene expression.

Artificial intelligence as an analytic approximation to evaluate associations between parental feeding behaviours and excess weight in Colombian preschoolers.

Parental practices can affect children's weight and BMI and may even be related to a high prevalence of obesity. Therefore, the aim of this study was to evaluate the relationship between parents' practices related to feeding their children and excess weight in preschoolers in Bucaramanga, Colombia, using artificial intelligence. A cross-sectional study was carried out between September and December 2017. The sample included preschoolers who attended child development institutions belonging to the Colombian Institute for Family Wellbeing in Bucaramanga and the metropolitan area (n 384). The outcome variable was excess weight and the main independent variable was parental feeding practices. Confounding variables analysed included sociodemographic characteristics, food consumption, and children's physical activity. All equipment for the anthropometric measurements was calibrated. Logistic regression was used to predict the effect of parental practices on the excess weight of the children, and the AUC was used to measure performance. The parental practices with the greatest association with excess weight in the children involved using food to control their behaviour and restricting the amount of food they offered (use of food to control emotions (OR 1·77; 95 % CI 1·45, 1·83; P = 0·034) and encouraging children to eat less (OR 1·22; 95 % CI 1·14, 1·89; P = 0·045)). Childrearing practices related to feeding were found to be an important predictor of excess weight in children. The results of this study represent implications for public health considering this as a baseline for the design of nutrition education interventions focused on parents of preschoolers.

The Hcp-like protein HilE inhibits homodimerization and DNA binding of the virulence-associated transcriptional regulator HilD in Salmonella.

HilD is an AraC-like transcriptional regulator that plays a central role in Salmonella virulence. HilD controls the expression of the genes within the Salmonella pathogenicity island 1 (SPI-1) and of several genes located outside SPI-1, which are mainly required for Salmonella invasion of host cells. The expression, amount, and activity of HilD are tightly controlled by the activities of several factors. The HilE protein represses the expression of the SPI-1 genes through its interaction with HilD; however, the mechanism by which HilE affects HilD is unknown. In this study, we used genetic and biochemical assays revealing how HilE controls the transcriptional activity of HilD. We found that HilD needs to assemble in homodimers to induce expression of its target genes. Our results further indicated that HilE individually interacts with each the central and the C-terminal HilD regions, mediating dimerization and DNA binding, respectively. We also observed that these interactions consistently inhibit HilD dimerization and DNA binding. Interestingly, a computational analysis revealed that HilE shares sequence and structural similarities with Hcp proteins, which act as structural components of type 6 secretion systems in Gram-negative bacteria. In conclusion, our results uncover the molecular mechanism by which the Hcp-like protein HilE controls dimerization and DNA binding of the virulence-promoting transcriptional regulator HilD. Our findings may indicate that HilE's activity represents a functional adaptation during the evolution of Salmonella pathogenicity.

Concepciones del embarazo en adolescentes gestantes de la ciudad de Bucaramanga / Concepções da gravidez em adolescentes grávidas na cidade de Bucaramanga / Conceptions on pregnancy in pregnant adolescents from the city of Bucaramanga

Introducción: el embarazo adolescente es una problemática que tiene consecuencias en la vida de las adolescentes y sus familias. Conocer las concepciones y representaciones que tienen las adolescentes gestantes es una herramienta fundamental para fortalecer la toma de decisiones y las redes de apoyo social. Objetivo: Identificar las concepciones sobre el embarazo, las características sociales, económicas y de redes de apoyo en un grupo de adolescentes gestantes de Bucaramanga. Materiales y Métodos: Se realizó un estudio cualitativo (estudio de caso) mediante las técnicas de grupo focal, observación participante y elaboración de diario de campo. Se incluyeron 15 participantes de las 100 adolescentes beneficiadas por el Programa Plan Padrino de la Secretaría de Salud y Ambiente de Bucaramanga durante el año 2014. Resultados: La mayoría de las participantes refirieron que, aunque el embarazo fue no deseado lo han aceptado y asumido con grandes cambios en sus vidas, especialmente la relación con sus amigos y con su familia. Identificaron como red de apoyo fundamental la familia. Discusión: Las concepciones sobre embarazo en las adolescentes coinciden con los estudios reportados en Colombia en el sentido que lo asumieron con responsabilidad, pero les representó un doble reto en especial para continuar con sus estudios. Conclusiones: Fortalecer la red de apoyo de las adolescentes en especial la relacionada con procesos educativos y de familia.

Introduction: pregnancy in adolescents is a problem that brings consequences to the lives of adolescent girls and their families. Knowing the conceptions and representations the pregnant adolescents have is a fundamental tool to enhance decision-making and social support networks. Objective: The work sought to identify conceptions about pregnancy, along with social, economic, and support network characteristics in a group of pregnant adolescents from Bucaramanga. Materials and Methods: A qualitative study (case study) was conducted through focal group techniques, participant observation, and elaboration of a field diary. The study included 15 participants of the 100 adolescent girls benefiting from the Plan Padrino program by the Health and Environment Secretary in Bucaramanga during 2014. Results: Most of the participants stated that, although the pregnancy was not desired, they have accepted and assumed it with big changes in their lives, especially the relationship with their friends and family. They identified the family as the fundamental support network. Discussion: The conceptions on pregnancy in adolescents coincide with studies reported in Colombia in the sense that they assumed it with responsibility, but posed a double challenge specifically related to continuing their studies. Conclusions: It is necessary to strengthen the support network of the adolescent girls, especially that related to educational processes and family.

Introdução: a gravidez na adolescência é um problema que tem consequências na vida dos adolescentes e suas famílias. Conhecer as concepções e representações que têm as adolescentes grávidas é uma ferramenta fundamental para fortalecer a tomada de decisões e as redes de apoio social. Objetivo: Identificar as concepções sobre a gravidez, características sociais, econômicas e redes de apoio por um grupo de adolescentes grávidas em Bucaramanga. Materiais e Métodos: Foi realizado um estudo qualitativo (estudo de caso) por meio da técnica de grupo focal, observação participante e elaboração de diário de campo. Foram incluídos 15 participantes das 100 adolescentes beneficiadas pelo Programa Plano Padrinho da Secretaria de Saúde e Ambiente de Bucaramanga durante o ano 2014. Resultados: A maioria dos participantes relataram que, embora a gravidez não fosse desejada, aceitaram e assumiram com grandes mudanças em suas vidas, especialmente a relação com seus amigos e com sua família. Identificaram como rede de apoio fundamental a família. Discussão: As concepções sobre gravidez nas adolescentes coincidem com os estudos relatados na Colômbia no sentido de que é assumido com responsabilidade, mas representou um duplo desafio especialmente para continuar seus estudos. Conclusões: Fortalecer a rede de apoio das adolescentes, especialmente a relacionada aos processos educativos e de família.

Validación técnica de una PCR: Reacción en cadena de la polimerasa para la detección de Chlamydia trachomatis / Technical validation of a polymerase chain reaction for Chlamydia trachomatis detection

Resumen Objetivo: Estandarizar una técnica de PCR para la detección de Chlamydia trachomatis. Materiales y método: Estudio experimental en el que se optimizaron las condiciones de PCR para la detección in vitro de C. trachomatis. Se utilizó ADN de C. trachomatis VR885D y los cebadores CtP15'-TAGTAACTGCCACTTCATCA-3'y CtP2 5'- TTCCCCTTGTAATTCGTTGC-3, que amplificaron un segmento de 201 pb del plásmido clamidial. Se realizaron diluciones logarítmicas de ADN clamidial y fueron empleados para determinar la sensibilidad analítica expresada como copias de plásmidos y/o de cuerpos elementales. La especificidad analítica de la prueba se evaluó usando los cebadores CtP1 y CtP2 y ADN de microorganismos colonizadores y/o patógenos urogenitales. La variabilidad intraensayo fue evaluada sobre muestras por triplicado, mientras que la variabilidad interensayo se determinó mediante comparación de los resultados obtenidos por tres técnicos en diferentes días. Resultados: Las condiciones de PCR para la amplificación del gen de interés fueron establecidas (94°C/4 min; 40 ciclos de 94°C/1 min, 56°C/1 min. y 72°C/1.5 min; 72°C/4 min); 1.5 mM MgCl2 y 1 U/pL Taq polimerasa. La sensibilidad analítica de la PCR fue de 10-17 g de ADN, equivalentes a una copia del plásmido o menos de un cuerpo elemental de C. trachomatis. Los cebadores CtP1 y CtP2 amplificaron específicamente el ADN de C. trachomatis bajo las condiciones experimentales evaluadas. La repetitibilidad y reproducibilidad de la PCR se determinó con experimentos de variabilidad intra e interensayo respectivamente. Conclusiones: La estandarización de esta PCR es el primer paso para su utilización en el diagnóstico de infecciones por C. trachomatis. Se requieren estudios adicionales de validación clínica de ésta prueba.

Abstract Objective: To standardize a PCR for Chlamydia trachomatis detection. Materials and methods: An experimental study was designed to standardize a C. trachomatis PCR test. Genomic DNA from C. trachomatis serovar D ATCC VR885D was used for the PCR standardization. An amplicon of 201 bp from clamidial plasmid was obtained using primers CtP15'-TAGTAACTGCCACTTCATCA-3' and CtP2 5'- TTCCCCTTGTAATTCGTT-GC-3'. Serial dilutions of clamidial DNA were used to determine the analytical sensitivity. Analytical specificity was tested using DNA from several urogenital microorganisms. Intra assay variability was assessed on triplicate DNA samples, while inter assay variability was assessed comparing the results by three technicians on different days. Results: Established (94°C/4 min; 40 cycles at 94 °C/1 min, 56°C/1 min and 72°C/1.5 min; 72°C/4 min; 1.5 mM of MgCl2 and 1U/pL of Taq polymerase. The analytical sensitivity was 10-17 g of DNA equivalent to one plasmid or less than one elementary body from C. trachomatis. Primers CtP1 and CtP2 amplified specifically C. trachomatis in the experimental conditions evaluated. Intra and inter assay variability demonstrated the repeatability and reproducibility of the PCR respectively. Conclusions: We standardized the experimental conditions for a C. trachomatis PCR that can be used for diagnostic purposes. Other studies are required for further clinical evaluation of this test.

Rare breast tumors: Review of the literature.

Breast cancer tumors have different morphological phenotypes and specific histopathological types with particular prognostic and clinical characteristics. The treatment of rare malignant lesions is frequently controversial due to the absence of trials to determine the optimal managements. This review describes the spectrum of rare breast tumors indicating the clinical, epidemiological and treatment characteristics.

Community-based health care for indigenous women in Mexico: a qualitative evaluation.

INTRODUCTION: Indigenous women in Mexico represent a vulnerable population in which three kinds of discrimination converge (ethnicity, gender and class), having direct repercussions on health status. The discrimination and inequity in health care settings brought this population to the fore as a priority group for institutional action. The objective of this study was to evaluate the processes and performance of the "Casa de la Mujer Indígena", a community based project for culturally and linguistically appropriate service delivery for indigenous women. The evaluation summarizes perspectives from diverse stakeholders involved in the implementation of the model, including users, local authorities, and institutional representatives. METHODS: The study covered five Casas implementation sites located in four Mexican states. A qualitative process evaluation focused on systematically analyzing the Casas project processes and performance was conducted using archival information and semi-structured interviews. Sixty-two interviews were conducted, and grounded theory approach was applied for data analysis. RESULTS: Few similarities were observed between the proposed model of service delivery and its implementation in diverse locations, signaling discordant operating processes. Evidence gathered from Casas personnel highlighted their ability to detect obstetric emergencies and domestic violence cases, as well as contribute to the empowerment of women in the indigenous communities served by the project. These themes directly translated to increases in the reporting of abuse and referrals for obstetric emergencies. CONCLUSIONS: The model's cultural and linguistic competency, and contributions to increased referrals for obstetric emergencies and abuse are notable successes. The flexibility and community-based nature of the model has allowed it to be adapted to the particularities of diverse indigenous contexts. Local, culturally appropriate implementation has been facilitated by the fact that the Casas have been implemented with local leadership and local women have taken ownership. Users express overall satisfaction with service delivery, while providing constructive feedback for the improvement of existing Casas, as well as more cost-effective implementation of the model in new sites. Integration of user's input obtained from this process evaluation into future planning will undoubtedly increase buy-in. The Casas model is pertinent and viable to other contexts where indigenous women experience disparities in care.