Abstract: Seasonal influenza is an infectious disease of multi-causal etiology and a major cause of mortality worldwide that has been associated with environmental factors. In the attempt to model and predict future outbreaks of seasonal influenza with multiple environmental factors, we face the challenge of increased dimensionality that makes the models more complex and unstable. In this paper, we propose a nowcasting and forecasting framework that compares the theoretical approaches of Single Environmental Factor and Multiple Environmental Factors. We introduce seven solutions to minimize the weaknesses associated with the increased dimensionality when predicting seasonal influenza activity levels using multiple environmental factors as external proxies. Our work provides evidence that using dimensionality reduction techniques as a strategy to combine multiple datasets improves seasonal influenza forecasting without the penalization of increased dimensionality.

Abstract: Cornelia de Lange Syndrome (CdLS) is a congenital autosomal dominant (NIPBL, SMC3 and RAD21) or Xlinked (SMC1A and HDAC8) disorder characterized by facial dysmorphism, pre and postnatal growth retardation, developmental delay and/or intellectual disability, and multiorgan involvement. Musculoskeletal malformations are usually bilateral and affect mainly the upper limbs; the range goes from brachyclinodactyly to severe reduction defects. Instead lower extremities are usually less and mildly involved. Here, we report on a 3-year-old Senegalese boy with typical craniofacial CdLS features, pre and postnatal growth retardation, atrial septal defect, developmental delay and right ipsilateral limb malformations, consistent with oligodactyly of the 3rd and 4th fingers, tibial agenesis and fibula hypoplasia. Exome sequencing and Sanger sequencing showed a novel missense mutation in NIPBL gene (c.6647A>G; p.(Tyr2216Cys)), which affects a conserved residue located within NIPBL HEAT repeat elements. Pyrosequencing analysis of NIPBL gene, disclosed similar levels of wild-type and mutated alleles in DNA and RNA samples from all tissues analyzed (oral mucosa epithelial cells, peripheral blood leukocytes and fibroblasts). These findings indicated the absence of somatic mosaicism, despite of the segmental asymmetry of the limbs, and confirmed biallelic expression for NIPBL transcripts, respectively. Additionally, conditions like Split-hand/foot malformation with long-bone deficiency secondary to duplication of BHLHA9 gene have been ruled out by the array-CGH and MLPA analysis. To our knowledge, this is the first CdLS patient described with major ipsilateral malformations of both the upper and lower extremities, that even though this finding could be due to a random event, expands the spectrum of limb reduction defects in CdLS.

Bogotá. Art News Service. 1952-08

Abstract: Botulism is caused by a potent neurotoxin that blocks neuromuscular transmission, resulting in death by asphyxiation. Currently, the therapeutic options are limited and there is no antidote. Here, we harness the structural and trafficking properties of an atoxic derivative of botulinum neurotoxin (BoNT) to transport a function-blocking single-domain antibody into the neuronal cytosol where it can inhibit BoNT serotype A (BoNT/A1) molecular toxicity. Post-symptomatic treatment relieved toxic signs of botulism and rescued mice, guinea pigs, and nonhuman primates after lethal BoNT/A1 challenge. This platform might enable delivery of antibodies and other protein-based therapeutics to previously inaccessible intraneuronal targets. Resumen: El botulismo es causado por una potente neurotoxina que bloquea la transmisión neuromuscular, provocando la muerte por asfixiamiento. Actualmente, las opciones de tratamiento son limitadas y no existe un antídoto. En este artículo aprovechamos las propiedades estructurales y de tráfico neuronal de un derivado atóxico de la neurotoxina botulínica (BoNT) para transportar un anticuerpo que bloquea la función al citosol neuronal, donde puede inhibir la toxicidad molecular del serotipo A de la BoNT (BoNT /A1). El tratamiento post-sintomático alivió los signos tóxicos del botulismo y rescató de la muerte a ratones, conejillos de indias y primates no humanos después de la exposición letal a BoNT / A1. Esta plataforma podría permitir la administración de anticuerpos y otros terapéuticos basados en proteínas a blancos intraneuronales que previamente eran inaccesibles.

Abstract: Mixed microbial cultures have become a preferred choice of biocatalyst for chain elongation systems due to their ability to convert complex substrates into medium chain carboxylates. However, the complexity of the effects of process parameters on the microbial metabolic networks is a drawback that makes the task of optimizing product selectivity challenging. Here, we studied the effects of small air contaminations on the microbial community dynamics and the product formation in anaerobic bioreactors fed with lactate, acetate and H2/CO2. Two stirred tank reactors and two bubble column reactors were operated with H2/CO2 gas recirculation for 139 and 116 days, respectively, at pH 6.0 and 32°C with a hydraulic retention time of 14 days. One reactor of each type had periods with air contamination (between 97 ± 28 and 474 ± 33 mL O2 L−1 d−1, lasting from 4 to 32 days), while the control reactors were kept anoxic. During air contamination, production of n-caproate and CH4 was strongly inhibited, whereas no clear effect on nbutyrate production was observed. In a period with detectable O2 concentrations that went up to 18%, facultative anaerobes of the genus Rummeliibacillus became predominant and only n-butyrate was produced. However, at low air contamination rates and with O2 below the detection level, Coriobacteriia and Actinobacteria gained a competitive advantage over Clostridia and Methanobacteria, and propionate production rates increased to 0.8–1.8 mmol L−1 d−1 depending on the reactor (control reactors 0.1–0.8 mmol L−1 d−1). Moreover, i-butyrate production was observed, but only when Methanobacteria abundances were low and, consequently, H2 availability was high. After air contamination stopped completely, production of n-caproate and CH4 recovered, with n-caproate production rates of 1.4–1.8 mmol L−1 d−1 (control 0.7–2.1 mmol L−1 d−1). The results underline the importance of keeping strictly anaerobic conditions in fermenters when consistent n-caproate production is the goal. Beyond that, micro-aeration should be further tested as a controllable process parameter to shape the reactor microbiome. When odd-chain carboxylates are desired, further studies can develop strategies for their targeted production by applying micro-aerobic conditions.

In 2007, Mexico City legalized abortion in the first 12 weeks of pregnancy. By doing so, it became the first and only state in Mexico where abortion on demand is legal. In this paper, I use this natural experiment to estimate the effects of abortion legalization on child and maternal health. I perform Difference-In-Differences estimates using information from all births and deaths occurred between 2002 and 2012. My findings suggest that the change in the abortion legislation in Mexico City reduced the Infant Mortality Rate and the Under 5 Mortality Rate by approximately 2.3 and 2.4 deaths per 1,000 live births, respectively. Moreover, for the Maternal Mortality Rate I find that the estimations range from -5.49 to -6 deaths per 100,000 live births. These results are validated by the use of a more accurate control group generated by the Synthetic Control Method. To the best of my knowledge, this if the first paper that attempts to examine the effects of abortion legalization in Mexico City on child health. En el 2007, Ciudad de México legalizó el aborto en las 12 primeras semanas de gestación. Al hacerlo, se convirtió en el primero y único estado del país en donde el aborto voluntario es legal. En este artículo utilizo este experimento natural para estimar los efectos de la legalización del aborto en la salud materno infantil. Realizo estimaciones de Diferencias en Diferencias utilizando información de todos los nacimientos y muertes ocurridos entre 2002 y 2012. Mis hallazgos sugieren que el cambio en la legislación relativa el aborto en la Ciudad de México redujo la tasa de mortalidad Infantil y la tasa de mortalidad en menores de 5 años en aproximadamente 2.3 y 2.4 muertes por cada 1.000 nacidos vivos, respectivamente. Además, para la tasa de mortalidad materna, encuentro que las estimaciones oscilan entre -5,49 y -6 muertes por 100.000 nacidos vivos. Estos resultados se validan mediante el uso de un grupo de control más preciso, utilizando la metodología de control sintético. Según mi conocimiento, este es el primer artículo que intenta examinar los efectos de la legalización del aborto en la Ciudad de México sobre la salud infantil.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and its incidence is rising. The introduction of new systemic therapies, including immune-based therapies and biomarker driven therapies, has improved survival in patients at advanced stages. However, overall survival is still poor, and recent advances in understanding of the molecular alterations of HCC have not translated yet into novel biomarkers. Over the past decade, major advancements in 'omic' technologies have enabled monitoring of a variety of molecular and organismal processes. A comprehensive analysis of single gene mutations in HCC might lead to detect biomarkers that improve our prognosis and treatment. We developed a bioinformatics pipeline capable of analyzing genomic data to identify key regulatory molecular changes in HCC development and their influence in patient’s prognosis. By looking at genetically determined subgroups of HCC in the TCGA Liver Cancer dataset, we managed to obtain 15 genes frequently affected by oncogenic mutations and analyzed their influence in patient’s survival, identifying CSMD1 as a prognostic biomarker candidate. Nevertheless, the validation in the ICGC HCC database showed that it did not have any statistically significant influence in overall survival. This work reveals that the most frequent single gene mutations are not enough for significant survival changes in HCC and that we should focus our efforts in integrative analysis of clinical information and multi-omics to maximize our clinical benefits in this devastating disease. Resumen: El carcinoma hepatocelular (CHC) es el tipo más común de cáncer de hígado y su incidencia está aumentando. La introducción de nuevas terapias sistémicas, incluidas las inmunoterapias y las terapias impulsadas por biomarcadores, ha mejorado la supervivencia de los pacientes en etapas avanzadas. Sin embargo, la supervivencia general sigue siendo escasa y los avances recientes en la comprensión de las alteraciones moleculares del CHC aún no se han traducido en nuevos biomarcadores. Durante la última década, los principales avances en las tecnologías "ómicas" han permitido el seguimiento de una variedad de procesos moleculares y orgánicos. Un análisis completo de las mutaciones de un solo gen en el CHC podría conducir a detectar biomarcadores que mejoren nuestro pronóstico y tratamiento. Desarrollamos un protocolo de bioinformática capaz de analizar datos genómicos para identificar cambios moleculares reguladores clave en el desarrollo del CHC y su influencia en el pronóstico del paciente. Al observar subgrupos genéticamente determinados de CHC en la base de datos TCGA-Liver Cancer, logramos obtener 15 genes frecuentemente afectados por mutaciones oncogénicas y analizamos su influencia en la supervivencia del paciente, identificando CSMD1 como un candidato a biomarcador pronóstico. Sin embargo, la validación en la base de datos ICGC-CHC mostró que no tuvo ninguna influencia estadísticamente significativa en la supervivencia global. Este trabajo revela que las mutaciones de un solo gen más frecuentes no son suficientes para cambios significativos en la supervivencia del CHC y que debemos centrar nuestros esfuerzos en el análisis integrador de la información clínica y la multi-ómica para maximizar nuestros beneficios clínicos en esta devastadora enfermedad.

Abstract: One of the great challenges for students of any discipline is to be able to put into practice the knowledge learned in theory. Public health does not escape this challenge. Research Methods for Public Health is a book that seeks to help students understand in a simple way how to enter into the practice of public health research. This book stands out for its easy reading, but especially because it emphasizes the existence of quantitative and qualitative methods, as well as the combination of both methods. On the other hand, the authors show between the lines, and sometimes more clearly, the importance of teamwork in research groups, a key element to avoid errors, validate procedures or instruments and increase the reliability of the results, as well as the importance of criteria of validity, reliability, precision, relevance, transparency and credibility, among others. Resumen: Uno de los grandes retos para los estudiantes de cualquier disciplina es poder poner en práctica los conocimientos aprendidos en la teoría. La salud pública no se escapa de este desafío. Research Methods for Public Health es un libro que busca ayudar a comprender de manera sencilla cómo introducirse en la práctica de la investigación en salud pública. Este libro se destaca por su fácil lectura, pero especialmente porque pone el énfasis en la existencia de los métodos cuantitativos y cualitativos, así como en la combinación de ambos métodos. Por otro lado, los autores dejan ver entrelíneas, y a veces más claramente, la importancia del trabajo en equipo en los grupos de investigación, elemento clave para evitar errores, validar procedimientos o instrumentos y aumentar la confiabilidad de los resultados, así como la importancia de criterios de validez, confiabilidad, precisión, relevancia, transparencia y credibilidad, entre otros.

Resumen: ¿Se puede lograr un buen libro académico cuando se percibe que la rabia es lo que ha llevado al autor a escribirlo? Esta es una pregunta que surge al leer Repensar la salud global. Marcos de poder,* pues la autora habla explícitamente de cómo comenzó su rabia hacia la inequidad (p. 72) y cómo de alguna manera todavía sigue teniendo esta rabia (p. 93). La respuesta a dicha pregunta la podrá tener el lector al finalizar el libro, des- pués de leer diferentes tipos de relatos. La autora menciona, entre otros casos, la epidemia del cólera en Haití, durante la cual se vivió una situación muy difícil, como se puede leer a continuación: “Se hicieron agujeros en la base de los colcho- nes para que el signo revelador del cólera, la diarrea constante e implacable, pudiera manejarse más fácilmente sin tener que trasladar a los pacientes” (p. 79). Lo cierto es que la doctora Rochelle Burgess dice que escribió este libro con la esperanza de llevar al lector en un viaje para iluminar la complejidad de cómo funcionan las di- námicas de poder en el ámbito de la salud global desde la posición de una psicóloga de salud comunitaria, en cuyo ejercicio profesional encontró su insatisfacción con la salud global. Abstract: Can a good academic book be achieved when it is perceived that anger is what drove the author to write it? This is a question that arises when reading Rethinking Global Health. Frames of Power,* as the author explicitly talks about how she began her rage at inequity (p. 72) and how in some ways she still has this rage (p. 93). The answer to this question can be found at the end of the book, after reading different types of stories. The author mentions, among other cases, the cholera epidemic in Haiti, during which a very difficult situation was experienced, as can be read as follows: "Holes were drilled in the base of the colchages so that the telltale sign of cholera, the constant and relentless diarrhea, could be handled more easily without having to move the patients" (p. 79). The truth is that Dr. Rochelle Burgess says she wrote this book in the hope of taking the reader on a journey to illuminate the complexity of how power dynamics work in global health from the position of a community health psychologist, in whose practice she encountered her dissatisfaction with global health.

Abstract: Changes in demographics and epidemiology have made non-communicable diseases (NCDs) a global and highly relevant problem. Globally, oral diseases cause serious health and economic burdens, leading to a substantial reduction in quality of life for those affected. Oral diseases and other NCDs share modifiable risk factors, including tobacco use, harmful use of alcohol and unhealthy diets, as well as the same socioeconomic determinants. The oral cavity provides valuable insights into overall health, as systemic diseases such as diabetes, HIV/AIDS, and autoimmune disorders often presents oral manifestations. However, in prison settings, where access to healthcare is limited and challenging as a human right, individuals experience exacerbated oral health outcomes and complications. Oral health status serves as a mirror of overall health, highlighting the interconnectedness between oral health and general well-being. The involvement of health authorities in prison settings plays a significant role in promoting and maintaining optimal oral health, which in turn has a profound impact on the physical and mental health of PLP. The World Health Organization's Oral Health Report of 2022 emphasizes the importance of addressing oral health inequalities as a crucial step in achieving fairness and implementing preventive interventions. Therefore, coherent and comprehensive regulation and legislation in oral health are needed to achieve social justice, ethical public health policies and professional practice. This study used a combination of methods with a focus on qualitative research. The first phase involved following the guidelines set out in “Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA)” to conduct a comprehensive and systematic scoping review addressing the primary and secondary objectives of the study. The third objective was covered by semi structured interviews involving purposive sampling, identified by three target groups: dentist personnel working in prisons; prison health experts; harm reduction policymakers, to gain insight from global prison health experts on potential areas of improvement for oral health in prison. In the first phase of this study, scientific articles published between January and August 2022 were gathered and reviewed. Subsequently, in 2023, a series of interviews were conducted involving fifteen participants. Ethical approval for the study was obtained from the Ethics Committee of the Ruprecht Karls Faculty of Medicine in Heidelberg (S 288/2023). The data collection instrument was carefully designed to accommodate the specific profiles of the participants, all owing for necessary adjustments to ensure the relevance and effectiveness of the study. Online in depth semi structured interviews were conducted via Zoom with relevant health prison experts. The combination of inductive and deductive approaches was used to design the study, collect and analyze data, and answer the research questions. The major findings of this study shed light on the persistent neglection of oral health into the health systems across different settings. Challenges and limitations in addressing oral health in prison, remains with a focus on the provision of emergency treatments and dental mutilations as services provided instead of conservatives approaches. Comprehensive and specialized dental care is necessary to avoid burdens on the health system, mostly from preventable oral disorders. Oral care and basic dental hygiene are still on the list of necessities in prison settings, as well as lack of resources, committed staff, and infrastructure to support the delivery of comprehensive dental services in prisons. In order to increase access to quality dental care, address oral health disparities, and promote the overall well-being of PLP, policy reforms, capacity building, and collaboration are necessary.