Nuestra vida depende de la alimentación sana, y por lo tanto tenemos derecho a ella según lo promulga la constitución colombiana de 1.991: los niños, las niñas y los jóvenes son sujetos de derecho en materia de alimentación. La normatividad internacional también reconoce el derecho humano a una alimentación adecuada, el cual incluye el derecho a no pasar hambre, a un acceso seguro de agua potable, a un acceso a recursos, incluyendo recursos eléctricos o gas para cocinar y reducir el consumo de leña con su efecto sobre la deforestación, también incluye el derecho a un alto estándar de salud mental y física. El mundo ha reconocido que los derechos humanos son universales, indivisibles, interconectados, e interdependientes. Para que el derecho a la alimentación sea completamente realizado, son indispensables los derechos humanos a trabajar y recibir salarios que contribuyan a un estándar de vida adecuado, a un ambiente sano y seguro, a no ser discriminados por motivos de sexo, raza, o cualquier otra condición, a la igualdad entre hombre y mujer. Incluye así mismo los derechos de los niños a un ambiente apropiado para un desarrollo físico y mental, a una educación y acceso a la información, a un seguro social, al desarrollo, a la paz, y a disfrutar de los beneficios del progreso científico.

As inundações podem ter um grande impacto na saúde das populações. Doenças produzidas pela exposição direta ou indireta às águas, podem resultar em surtos de doenças gastrointestinais, infecções respiratórias, leptospirose entre outras. Já que os cenários de mudança climática predizem o aumento na frequência e severidade das inundações devido ao aquecimento global, é necessário ter claridade nos impactos gerados sobre a saúde humana como reflexo dos efeitos combinados das mudanças climáticas sobre os ecossistemas, o sistema econômico e o sistema social. A pesquisa visa analisar a vulnerabilidade da população do município de São Paulo às doenças infecciosas relacionadas com inundações. O processo tem como fio condutor o modelo de avaliação da vulnerabilidade conhecido como modelo de vulnerabilidade expandida. Dez variáveis consideradas como representativas para o município de São Paulo, foram escolhidas para a análise da vulnerabilidade social, correlacionadas e analisadas dentro da unidade espacial bacia hidrográfica para o ano 2010, mediante a análise de componentes principais. Bases de dados de precipitação da Rede Telemétrica de Pluviômetros de Superfície do Departamento de Águas e Energia Elétrica (DAAE), foram os dados usados para a avaliação dos níveis de precipitação. Adicionalmente, as estatísticas das bases de dados de Autorização de Internação Hospitalar do Sistema Universal de Saúde (AIH/SUS) foram usadas para a avaliação das variáveis epidemiológicas. Os resultados mostram que a vulnerabilidade social aumenta na direção centro-periferia e que as aglomerações de valores altos, evidentemente mais abundantes do que as aglomerações de valores baixos, aparecem nas bacias de vulnerabilidades sociais significativamente altas. Las inundaciones pueden tener un gran impacto sobre la salud de las poblaciones humanas. Las enfermedades producidas por la exposición directa o indirecta a agua contaminada, puede resultar en brotes de enfermedades gastrointestinales, infecciones respiratorias y Leptospirosis entre otras. Debido a que los escenarios de cambio climático predicen el aumento en la frecuencia y severidad de las inundaciones resultado del calentamiento global, es necesario tener claridad de los impactos generados sobre la salud humana que reflejan los efectos combinados de estos cambios ambientales sobre los ecosistemas, el sistema económico y el sistema social. Esta investigación tuvo como objetivo analizar la vulnerabilidad de la población del municipio de Sao Paulo a enfermedades infecciosas relacionadas con inundaciones. El proceso tuvo como hilo conductor el modelo de evaluación de la vulnerabilidad conocido como modelo de vulnerabilidad expandida. Diez variables consideradas como representativas para el municipio, fueron escogidas para el análisis de la vulnerabilidad social por cuenca hidrográfica para el año 2010. El análisis final de la vulnerabilidad consistió en la correlación y análisis de componentes principales. Fueron utilizados datos de la red telemétrica de pluviómetros de superficie del departamento de aguas y energía eléctrica (DAAE), para analizar los niveles de precipitación. Adicionalmente, las estadísticas de las bases de datos de Autorizaciones de Hospitalización del Sistema Universal de Salud (AIH/SUS) fueron usadas para la evaluación de las variables epidemiológicas. Los resultados muestran que la vulnerabilidad social dentro del municipio aumenta en la dirección centro-periferia y que las aglomeraciones de valores altos, evidentemente más abundantes que las aglomeraciones de valores bajos, aparecen en las cuencas hidrográficas con vulnerabilidades sociales altamente significativas.

Abstract: Background: Seasonal Influenza is considered to be a cyclic and ordered sequence of values, influenced by external factors that can be predicted and used to detect disease outbreaks and monitoring. In machine learning, the key challenges that limit these analyses are in model explainability and limitations associated with ecological bias. Aim: Determine the best environmental variable selection method to predict Seasonal Influenza in Norway, using an environmental medicine approach combined with machine learning techniques. Methods: This is a quasi-experimental study that compares three approaches (non-variable selection, isolate component, and multipollutant mixture), represented in five methods (univariable, bivariable, multivariable AME, multivariable PCA, multivariable LDA). Per method, the best co-variable combination will be performed, following the internal rules of each method. The best covariable combination is the result of three components: variable selection, validation data set and lag. The first one involves 13 environmental variables (temperature, relative humidity, specific humidity, air pressure, wind speed, precipitation, CO, NO, NO2, O3, PM10, PM2,5 and SO2); second one compares a test dataset compiled from the data from 2019, last year (2018) and a synthetic environmental (avg. 2013-2018) data set in the validation process; and the third one compares a combination of lag from 0 to 12. All the predictions are made using ARIMA algorithm. The evaluation is given in terms of MAE, MSE, RMSE, OR. The training set is from 2 Jun 2013 (week 22/2013) to 28 May 2018 (week 21/2018), and test set is from (week 22/2018) to (week 21/2019) with a window of predictions of 52 weeks. Results: The increment of dimensionality in the environmental variable selection introduce different noise levels and optimize the prediction. Considerations that impact the explainability, usability, ecological bias and performance will be described. Conclusion: The increment of dimensionality in the variable selection has a better impact on performance than using complex algorithms.

Abstract: Biological and physiological changes in response to stress are crucial to achieving adaption to environmental constraints. Typical stress responses activate the sympathetic nervous system and the hypothalamic-pituitary-adrenal cortical axis, which aim to maintain homeostasis in response to demands and influence various biological responses at neuroendocrine, cellular, and immune levels. In particular, there is compelling evidence showing the devastating effects of high-stress levels on immune responses and brain functionality. In that sense, data suggest that a sustained stress-physiological response predicts decreases in immunity and leads to allostatic load, the wear, and tear of biological systems. Similarly, in cancer research, chronic stress levels have been reported to impair the bodysurveillance systems and be related to cancer incidence, progression, and mortality. Despite the evidence demonstrating the associations between stress and cancer, there are limited data on whether lifetime stress exposure relates to clinical indicators of cancer aggressiveness. Considering the evidence showing the adverse effects of prolonged stress exposure on cancer disease, this thesis aimed to explore the relationship between lifetime stress exposure and the clinical characteristics of tumor-aggressiveness in a cohort of patients affected with triple-negative breast cancer (TNBC). Likewise, as research has shown that coping responses moderate the stress-physiological response, we aimed to investigate the role of coping responses in moderating the association between tumor aggressiveness and lifetime stress exposure. According to the scientific literature, high-stress levels would increase physiological arousal and allostatic load favoring a debilitated immune system. Thus, we hypothesized finding positive associations between lifetime stress exposure and tumor-aggressiveness. In the same line, we suspected that adaptative coping styles would be negatively related to tumoraggressiveness. The participants of this study were 29 women diagnosed with TNBC who were treated in the University Hospital for Gynecology Pius-Hospital (Oldenburg, Germany). Correlation and moderation regression analyses with the use of composite scores were conducted. Overall, we could not demonstrate significant associations between lifetime stress exposure and coping responses on the clinical indicators of tumor aggressiveness in this cohort of patients. Possible explanations for these results are discussed, and suggestions for future research are provided. This study was the first to investigate the effect of lifetime stress exposure and coping response on the aggressive tumor characteristics of TNBC. We provided a deep theoretical framework to understand the interplay between biological and psychological aspects of cancer disease, and we hope that our recommendations may serve as a base for upcoming studies.

Background: Post-stroke fatigue (PSF) is one of the most challenging clinical consequences to manage after stroke as no effective treatment has been developed. However, the mechanisms of PSF remain unclear. Aims: This study aimed to replicate Vecchio et al (2017) using resting-state EEG in stroke patients suffering from varying degrees of fatigue to describe the functional organisation within sensory and motor networks. Methods: Resting-state eyes-open EEG was recorded in 22 strokesurvivors. Upper limb functional tests (grip strength, Nine Hole Peg Test), symbol digit modalities test (SDTM), anxiety and depression scale (HADS), Fatigue Severity Scale (FSS-7), state fatigue, and Neurological Fatigue Index (NFI-stroke) were measured. Graph theory was used to calculate the small-world (SW) index. SW was calculated in four separate networks, motor and sensory within the left and right hemispheres. Exact low-resolution brain electromagnetic tomography (eLORETA) was applied using seven frequency bands (delta, theta, alpha1, alpha2, beta1, beta2, and gamma). Results: Correlation analysis demonstrated a positive association between SW in the right motor network in beta2 band and higher FSS-7 score and a negative correlation between SW in the left sensory network in alpha1 and higher state fatigue. Conclusion: Beta oscillations have been associated with top-down processes which are crucial for perceptual inference and alpha oscillations are involved in sensorimotor information processing. The interaction between the top-down and bottom-up processes, and perceived error explains the sensory attenuation model of fatigue. Our results were consistent this model of fatigue as stroke survivors had difficulty in attenuating the sensory input leading to higher perceived effort.

This thesis examines the concept of medical futility and its importance for the practice of medicine nowadays. It presents an overview of the development of the concept throughout history and it discusses the main arguments in favor and against a determination of futile treatment in the clinical setting. The notion of futility, in broad terms, describes the situation in which certain medical interventions no longer benefit the patient and therefore, it follows that there must be a derived moral obligation to stop said intervention. Such an idea brings forward numerous problematic pitfalls that are discussed in this thesis, among which are the debate about the limits of medicine, the tension between the notions of patient autonomy and physician authority and the practice of medical rationing in hospitals. This thesis aims to provide a new perspective on the subject in hopes that it will help to keep the ongoing debate running so in the near future, more experts will decide to contribute themselves with their expertise. Situations where a medical intervention ceases to benefit the patient will continue to occur at the bedside; what is more, these ethical conundrums will become more and more problematic as the technological imperative intensifies and the possibilities of biotechnology increase. The leading question that directed the development of the thesis was “when enough it’s enough?” in other words, what are the ethical considerations on the limits of medicine? The paper concludes that the concept of medical futility has a heuristic value, and thus it has helped yield more clarity about relevant matters such as the differentiation between futility and rationing, the fact that more research is needed to test what works and what does not and it has brought to the spotlight the importance of more robust standards of practice that, for example, prevent physicians from practicing defensive medicine. Resumen: Esta tesis examina el concepto de futilidad médica y su importancia para la práctica de la medicina en la actualidad. Presenta una visión general del desarrollo del concepto a lo largo de la historia y discute los principales argumentos a favor y en contra de la determinación de un tratamiento fútil en el ámbito clínico. La noción de futilidad, en términos generales, describe la situación en la que ciertas intervenciones médicas ya no benefician al paciente y, por lo tanto, se deduce que debe existir una obligación moral derivada de detener dicha intervención. Esta idea plantea numerosos asuntos problemáticos que se discuten en esta tesis, entre los que se encuentran el debate sobre los límites de la medicina, la tensión entre las nociones de autonomía del paciente y autoridad del médico, y la práctica del racionamiento médico en los hospitales. Esta tesis pretende aportar una nueva perspectiva sobre el tema con la esperanza de que esta ayude a mantener el debate vigente, de manera que, en un futuro próximo, más expertos decidan aportar su experiencia. Las situaciones en las que una intervención médica deja de beneficiar al paciente seguirán; más aún, estos debates éticos se volverán cada vez más problemáticos a medida que se intensifique el imperativo tecnológico y aumenten las posibilidades de la biotecnología. La pregunta principal que dirigió el desarrollo de la tesis fue ""¿cuándo es momento de parar?"", es decir, ¿cuáles son las consideraciones éticas sobre los límites de la medicina? El documento concluye que el concepto de futilidad médica tiene un valor heurístico y, por lo tanto, ha contribuido a aclarar cuestiones pertinentes como la diferenciación entre futilidad y racionamiento, el hecho de que se necesita más investigación para probar lo que funciona y lo que no, y ha puesto de relieve la importancia de contar con normas de práctica más sólidas que, por ejemplo, impidan a los médicos practicar la medicina defensiva.

Mutations in PCDH19 gene are associated with Early Infantile Epileptic Encephalopathy type 9 (EIEE-9), a very rare disorder characterized by early onset of seizures, intellectual disability and psychiatric comorbidities with an unusual form of X-linked inheritance in which only females and mosaic male patients are affected. Materials and Methods: We report three patients, one male and two females carrying PCDH19 variants (D233G, V589Cfs*8 and N1103K) found by Whole exome sequencing (WES). One is a novel missense mutation (N1103K) while the others had been previously reported in female affected patients. Although, there is the first time that variant V589Cfs*8 is reported in a male patient. We performed a complete phenotype evaluation of our cases and establish the pathogenicity of each variant by in silico and functional analysis accessing many aspects of Protocadherin-19 including subcellular localization and protein expression. Results: Two of the three variants are predicted to be deleterious to protein function. The variant D233G is predicted to affect the calcium binding site and avoids cadherin strands swapping compromising the cell adhesion activity and the structural stability of the protein. While, the variant V589Cfs*8 introduced a premature stop codon which led to the loss of the transmembrane domain of the protein as well as to the cytoplasmic domain, including all predicted nuclear localization signals, suggesting the variant might affect the subcellular localization of Pcdh-19. The last findings were corroborated by western blotting and immunolabelling comparing the protein localization in patient and control fibroblasts. Conclusions: Our findings enhance understanding of molecular functions of Protocadherin-19, as well as highlighting the importance of functional testing of variants that emerge from NGS studies. Resumen: Las mutaciones en el gen PCDH19 están asociadas con la encefalopatía epiléptica infantil temprana tipo 9 (EIEE-9), un trastorno muy raro caracterizado por la aparición temprana de convulsiones, discapacidad intelectual y comorbilidades psiquiátricas con una forma inusual de herencia ligada al cromosoma X en la que solo las mujeres y mosaico pacientes masculinos se ven afectados. Materiales y métodos: Reportamos tres pacientes, un hombre y dos mujeres con variantes en el gen PCDH19 (D233G, V589Cfs*8 y N1103K) encontrados por secuenciación de exoma completo (WES). Una es una nueva mutación sin sentido (N1103K) mientras que las otras habían sido reportadas previamente en pacientes femeninas afectadas. Aunque, es la primera vez que se informa la variante V589Cfs*8 en un paciente masculino. Realizamos una evaluación completa del fenotipo de nuestros casos y establecimos la patogenicidad de cada variante mediante análisis in silico y funcional accediendo a muchos aspectos de la Protocadherin-19, incluida la localización subcelular y la expresión de proteínas. Resultados: se predice que dos de las tres variantes son perjudiciales para la función de la proteína. La variante D233G afecta el sitio de unión al calcio y evita el intercambio de hebras de caderina que comprometen la actividad de adhesión celular y la estabilidad estructural de la proteína. Mientras que la variante V589Cfs*8 introdujo un codón de parada prematuro que condujo a la pérdida del dominio transmembrana de la proteína, así como al dominio citoplasmático, incluidas todas las señales de localización nuclear esperadas, lo que sugiere que la variante podría afectar la localización subcelular de la proteína. Los últimos hallazgos fueron corroborados por Western blot e inmunomarcaje comparando la localización de la proteína en fibroblastos de pacientes y controles. Conclusiones: Nuestros hallazgos mejoran la comprensión de las funciones moleculares de Protocadherin-19, así como resaltan la importancia de las pruebas funcionales de las variantes que surgen de los estudios de secuenciación de siguiente generación (NGS).

Abstract: SEPSIS-3 IN PREGNANT WOMEN IN LABOUR Abstract Introduction: Maternal sepsis represents 10.7% of maternal deaths worldwide, ranking as the third cause of mortality after haemorrhage and hypertensive disorders. Despite its high incidence, it still lacks a gold standard diagnosis. The latest update that proposed new sepsis criteria and scores, Sepsis-3, did not mention pregnancy as part of the study population. This study aims to evaluate the inclusion or exclusion of Sepsis- 3 pregnancy. Methods: This is a literature review of the Sepsis-3 database looking for the inclusion or exclusion of pregnancy from the latest update in sepsis and the basis of current definitions and guidelines. In addition, I reported the retrospective measurement of qSOFA and SOFA scores in 100 pregnant patients in labour from the EPIFEVER-2 cohort at the Royal London Hospital compared to their infection status. Results: Sepsis-3 investigators evaluated the predictive validity of the SOFA and qSOFA score for mortality in sepsis among nearly 1 million patients, however, pregnant women were not included. The SOFA and qSOFA score overlap with the normal physiological changes of pregnancy and labour, in the EPIFEVER-2 cohort 16% of uninfected pregnant patients during labour scored 1 point on qSOFA and 17% 1 point on SOFA score. The highest SOFA score of 3 points was obtained in a patient with bleeding rather than infection. Conclusion: Pregnant patients were not included in the Sepsis-3 databases. Therefore, qSOFA and SOFA score have not been validated for use in this population. Furthermore, as they are not modified for the normal physiological changes of pregnancy, detection of patients without infection has been reported. Further validation of qSOFA or modified SOFA scores as sepsis-specific maternal warning scores is expected in future research.

Abstract: Las lesiones cerebrales agudas (LCA) se asocian con altas tasas de mortalidad y malos resultados funcionales a largo plazo. La medición de biomarcadores del líquido cefalorraquídeo ventricular (vLCR) en pacientes con LCA puede ayudar a dilucidar algunas de las vías fisiopatológicas implicadas en el pronóstico de estos pacientes. Primero realizamos una búsqueda sistemática y una revisión descriptiva (Crit Care. 5 de agosto de 2021; 25 (1): 278; DOI: 10.1186/s13054-021-03698-z) donde concluimos que en pacientes con LCA, las concentraciones alteradas de biomarcadores proteicos en el vLCR relacionados con el daño citoesquelético, la inflamación, la apoptosis y el estrés oxidativo pueden predecir peores resultados neurológicos. Debido a estos resultados, realizamos un estudio de observación prospectivo (Neurocrit Care. 2022 Oct;37(2):463-470.doi:10.1007/s12028-022-01507-1.) donde concluimos que la expresión desregulada de la proteína en el vLCR diferenciaba entre LCA y no LCA. Luego realizamos otro estudio (J Neurosurg Anesthesiol. 27 de abril de 2023. doi:10.1097/ANA.0000000000000916.) donde concluimos que la expresión de patrones moleculares asociados al peligro (DAMP) específicos del vLCR se asociaba con un aumento de episodios de hipertensión intracraneal severa y muerte. Por último, en otro estudio observacional (Crit Care. 2023 Jun 24;27(1):249. doi: 10.1186/s13054-023-04538-y.), concluimos que las concentraciones de proteínas del vLCR después de una LCA eran un factor de riesgo para el desarrollo de enfermedades neurodegenerativas crónicas después de una LCA no traumática. Los hallazgos más importantes de esta tesis fueron que la respuesta proteómica después de una LCA es homogénea entre la LCA traumática y no traumática, involucra múltiples proteínas (DAMP) y puede estar asociada con enfermedades neurodegenerativas a largo plazo también en la LCA no traumática.

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.