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.

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: Objective: Determine the population prevalence and trends of cleft lip and / or palate (CL/P) by department for Colombia in the period 2009 - 2015. Methods: Prevalence study based on Individual Registry of Health Services in general population from 2009 to 2015. All people diagnosed with CL/P were included for all ages, type of diagnosis and any type of health services in the mentioned period. The prevalence rate was calculated by period and point for each year, for each department and according to the type of cleft. Stationarity on time series was evaluated using (Dickey-Fuller) and (Phillips-Perron), the trends and prevalence ratios were calculated using Poisson regression. Results: 15,225 people with CL/P were identified, where 53.3% were men. The national period prevalence of CL/P is 3.37 per 10 000 (IC95%: 3.3-3.4) with upward trend (PR = 1.34 95% CI: 1.0 - 1.8 p = 0.05) and non-stationary behavior. The national period prevalence of CL is 0.93 per 10 000, CP 1.17 per 10 000 and CLP 1.26 per 10 000, where CLP is sub classify into CLPu (0.83 per 10 000), and CLPb (0.43 per 10 000). At the departmental level, the highest CL/P prevalence is Guaviare (11.2 95% CI: 8.6 – 14.2), followed by Guainía (8.4 95% CI:5.4 – 12.2) and the lowest Quindío (0.49 95% CI: 0.3 – 0.7) Conclusions: In Colombia, the national period prevalence of CL/P is 3.37 per 10 000 with upward trend at national level indicates an increase on prevalence from 2009 to 2015.

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.

Abstract: Despite some epidemiological evidence on the protective effects of polyphenol intake on epithelial ovarian cancer (EOC) risk from case-control studies, the evidence is scarce from prospective studies and non-existent for several polyphenol classes. Therefore, we aimed to investigate the associations between the intake of total, classes and subclasses of polyphenols and EOC risk in a large prospective study. The study was conducted in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which included 309,129 adult women recruited mostly from the general population. Polyphenol intake was assessed through validated country-specific dietary questionnaires and the Phenol-Explorer database. During a mean follow-up of 14 years, 1469 first incident EOC cases (including 806 serous, 129 endometrioid, 102 mucinous, and 67 clear cell tumours) were identified. In multivariable-adjusted Cox regression models, the hazard ratio in the highest quartile of total polyphenol intake compared with the lowest quartile (HRQ4vsQ1) was 1.14 (95% CI 0.94–1.39; p-trend = 0.11). Similarly, the intake of most classes and subclasses of polyphenols were not related to either overall EOC risk or any EOC subtype. A borderline statistically significant positive association was observed between phenolic acid intake (HRQ4vsQ1 = 1.20, 95% CI 1.01–1.43; p-trend = 0.02) and EOC risk, especially for the serous subtype and in women with obesity, although these associations did not exceed the Bonferroni correction threshold. The current results do not support any association between polyphenol intake and EOC in our large European prospective study. Results regarding phenolic acid intake need further investigation.

"Las últimas décadas han evidenciado no solamente un creciente interés acerca de todo lo concerniente a la vejez y a los viejos, sino acerca de las diversas perspectivas desde las cuales se ha abordado el envejecimiento, tan diversas como las múltiples facetas que componen este proceso. De ahí que este libro, Envejecer en el siglo xxi, se haya pensado para estimular el “aprender a aprender” sobre estos temas, más allá de las aulas universitarias; para ofrecer soluciones a las problemáticas sociales, y para que los profesionales de la salud se comuniquen de manera efectiva en los diferentes...

Un libro necesario, urgente, en medio del pandemónium de intereses y voces supuestamente expertas.A propósito de la pandemia, el presente texto nos exhorta a reflexionar sobre las repercusiones de esta en la economía, la sociedad y la salud; sobre el papel de las teorías conspiranoicas y negacionistas; sobre cómo se están cuestionando nuestros sistemas sanitarios públicos, qué limitaciones tienen y cómo se ha reaccionado y se está reaccionando a nivel mundial y, por supuesto, en España, así como a pensar los cambios que previsiblemente se producirán o deberían producirse en nuestros modelos sanitarios.

Colección Saberes Cotidianos. Número dedicado al conocimiento de la medicina tradicional china y los meridianos de acupuntura.

La hipertensión arterial es un problema de salud pública en el mundo, constituye un factor importante en el 35% de los eventos cardiovasculares ateroscleróticos y hasta el 49% en los casos de falla cardíaca; además, está involucrada en el incremento de la tasa de eventos cerebrovasculares y, después de la diabetes mellitus, es la causa más frecuente de enfermedad renal crónica. La enfermedad cobra mayor importancia cuando las cifras de presión arterial no solo están relacionadas con aumento de la mortalidad, sino con años de vida perdidos ajustados por discapacidad