Reduced dengue incidence following city-wide wMel Wolbachia mosquito releases throughout three Colombian cities: Interrupted time series analysis and a prospective case-control study.

BACKGROUND: The introduction of Wolbachia (wMel strain) into Aedes aegypti mosquitoes reduces their capacity to transmit dengue and other arboviruses. Randomised and non-randomised studies in multiple countries have shown significant reductions in dengue incidence following field releases of wMel-infected Ae. aegypti. We report the public health outcomes from phased, large-scale releases of wMel-Ae. aegypti mosquitoes throughout three contiguous cities in the Aburrá Valley, Colombia. METHODOLOGY/PRINCIPAL FINDINGS: Following pilot releases in 2015-2016, staged city-wide wMel-Ae. aegypti deployments were undertaken in the cities of Bello, Medellín and Itagüí (3.3 million people) between October 2016 and April 2022. The impact of the Wolbachia intervention on dengue incidence was evaluated in two parallel studies. A quasi-experimental study using interrupted time series analysis showed notified dengue case incidence was reduced by 95% in Bello and Medellín and 97% in Itagüí, following establishment of wMel at ≥60% prevalence, compared to the pre-intervention period and after adjusting for seasonal trends. A concurrent clinic-based case-control study with a test-negative design was unable to attain the target sample size of 63 enrolled virologically-confirmed dengue (VCD) cases between May 2019 and December 2021, consistent with low dengue incidence throughout the Aburrá Valley following wMel deployments. Nevertheless, VCD incidence was 45% lower (OR 0.55 [95% CI 0.25, 1.17]) and combined VCD/presumptive dengue incidence was 47% lower (OR 0.53 [95% CI 0.30, 0.93]) among participants resident in wMel-treated versus untreated neighbourhoods. CONCLUSIONS/SIGNIFICANCE: Stable introduction of wMel into local Ae. aegypti populations was associated with a significant and sustained reduction in dengue incidence across three Colombian cities. These results from the largest contiguous Wolbachia releases to-date demonstrate the real-world effectiveness of the method across large urban populations and, alongside previously published results, support the reproducibility of this effectiveness across different ecological settings. TRIAL REGISTRATION: NCT03631719.

Spatiotemporal dynamics of dengue in Colombia in relation to the combined effects of local climate and ENSO.

Dengue virus (DENV) is an endemic disease in the hot and humid low-lands of Colombia. We characterize the association of monthly series of dengue cases with indices of El Niño/Southern Oscillation (ENSO) at the tropical Pacific and local climatic variables in Colombia during the period 2007-2017 at different temporal and spatial scales. For estimation purposes, we use lagged cross-correlations (Pearson test), cross-wavelet analysis (wavelet cross spectrum, and wavelet coherence), as well as a novel nonlinear causality method, PCMCI, that allows identifying common causal drivers and links among high dimensional simultaneous and time-lagged variables. Our results evidence the strong association of DENV cases in Colombia with ENSO indices and with local temperature and rainfall. El Niño (La Niña) phenomenon is related to an increase (decrease) of dengue cases nationally and in most regions and departments, with maximum correlations occurring at shorter time lags in the Pacific and Andes regions, closer to the Pacific Ocean. This association is mainly explained by the ENSO-driven increase in temperature and decrease in rainfall, especially in the Andes and Pacific regions. The influence of ENSO is not stationary, given the reduction of DENV cases since 2005, and that local climate variables vary in space and time, which prevents to extrapolate results from one region to another. The association between DENV and ENSO varies at national and regional scales when data are disaggregated by seasons, being stronger in DJF and weaker in SON. Overall, the Pacific and Andes regions control the relationship between dengue dynamics and ENSO at national scale. Cross-wavelet analysis indicates that the ENSO-DENV relation in Colombia exhibits a strong coherence in the 12 to 16-months frequency band, which implies the frequency locking between the annual cycle and the interannual (ENSO) timescales. Results of nonlinear causality metrics reveal the complex concomitant effects of ENSO and local climate variables, while offering new insights to develop early warning systems for DENV in Colombia.

Dímeros D e hiperglucemia y mortalidad en COVID-19 en un centro hospitalario de México / D-dimers, hyperglycemia and mortality in COVID-19 in a hospital in Mexico

Resumen Objetivo: Evaluar la asociación entre la concentración de glucosa al ingreso y los niveles circulantes de dímeros D en pacientes hospitalizados por enfermedad por coronavirus 2019 (COVID-19). Pacientes y métodos: Se estudiaron 187 pacientes hospitalizados por COVID-19. Se evaluaron las características bioquímicas, la concentración de glucosa y dímeros D, la gravedad de la enfermedad definida por la presencia de neumonía y/o insuficiencia respiratoria que ameritó ventilación mecánica invasiva (VMI) y la causa del egreso hospitalario. Resultados: La edad promedio de los pacientes fue 52 años, el 68% eran hombres, un 40.8% con obesidad y un 23.5% con hipertensión. Del total de pacientes hospitalizados, el 45.5% presentaba diabetes o hiperglucemia a la admisión. La concentración de proteína C reactiva y de dímeros D (1,134 [646.5-4,135.0] vs. 755 [548.7-1,780.0] ng/ml; p = 0.04] fue superior en pacientes con diabetes e hiperglucemia, en comparación con los pacientes con glucosa normal. Los pacientes que requirieron VMI presentaron también mayor concentración de dímeros D. Se observó una correlación directa entre las concentraciones de glucosa inicial y dímeros D (r: 0.239; p = 0.003). Conclusión: En los pacientes con COVID-19 el estado hiperglucémico se asocia directamente con un incremento de la concentración de dímeros D. Los resultados de este estudio deben conducir a insistir en el control glucémico como estrategia fundamental en los pacientes con COVID-19.

Abstract Objective: To evaluate the association between glucose level at admission and circulating levels of D-dimers in patients hospitalized for coronavirus disease 2019 (COVID-19). Methods: 187 patients hospitalized for COVID-19 were studied. Biochemical characteristics, glucose and D-dimers levels, severity of disease, defined by the presence of pneumonia and/or respiratory failure that required invasive mechanical ventilation (IVM) and the cause of hospital discharge were evaluated. Results: Age was 52 years, 68% were male, 40.8% with obesity and 23.5% with hypertension. Of the total of hospitalized patients, 45.5% had diabetes or hyperglycemia upon admission. Patients with diabetes and/or admission hyperglycemia had higher levels of protein C-reactive and D-dimers [(1134 (646.5-4135.0) vs. 755 (548.7-1780.0) ng/ml, p = 0.04], compared to patients with normal glucose level. Patients who required IMV also had a higher concentration of D-dimers. A correlation between glucose and D-dimers levels was evidenced (r=0.239, p=0.003). Conclusions: In patients with COVID-19, the hyperglycemic state is directly associated with an increase in the concentration of D-dimers and severity of disease. The results of this study should lead to insisting on glycemic control as a fundamental strategy in patients with COVID-19.

Epicatechin Reduces Spatial Memory Deficit Caused by Amyloid-ß25⁻35 Toxicity Modifying the Heat Shock Proteins in the CA1 Region in the Hippocampus of Rats.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by dementia and the aggregation of the amyloid beta peptide (Aß). Aß25-35 is the most neurotoxic sequence, whose mechanism is associated with the neuronal death in the Cornu Ammonis 1 (CA1) region of the hippocampus (Hp) and cognitive damage. Likewise, there are mechanisms of neuronal survival regulated by heat shock proteins (HSPs). Studies indicate that pharmacological treatment with flavonoids reduces the prevalence of AD, particularly epicatechin (EC), which shows better antioxidant activity. The aim of this work was to evaluate the effect of EC on neurotoxicity that causes Aß25-35 at the level of spatial memory as well as the relationship with immunoreactivity of HSPs in the CA1 region of the Hp of rats. Our results show that EC treatment reduces the deterioration of spatial memory induced by the Aß25-35, in addition to reducing oxidative stress and inflammation in the Hp of the animals treated with EC + Aß25-35. Likewise, the immunoreactivity to HSP-60, -70, and -90 is lower in the EC + Aß25-35 group compared to the Aß25-35 group, which coincides with a decrease of dead neurons in the CA1 region of the Hp. Our results suggest that EC reduces the neurotoxicity induced by Aß25-35, as well as the HSP-60, -70, and -90 immunoreactivity and neuronal death in the CA1 region of the Hp of rats injected with Aß25-35, which favors an improvement in the function of spatial memory.

The Combination of RET, BRAF and Demographic Data Identifies Subsets of Patients with Aggressive Papillary Thyroid Cancer.

The use of BRAFV600E and RET/PTC1 as biomarkers to guide the extent of surgery in patients with papillary thyroid cancer (PTC) remains controversial. We assessed the combined use of demographic data (sex and age) with mRNA expression levels and/or mutational status (BRAFV600E and RET/PTC1) to identify potential subsets of patients with aggressive histopathological features (lymph node metastases and extrathyroidal extension). In a cohort of 126 consecutive patients, BRAFV600E and RET/PTC1 mutations were found in 52 and 18%, respectively. By conditional bivariate analysis (CBVA), a 'high activity' profile of BRAF (BRAFV600E positive or high expression) and 'low activity' profile of RET (RET/PTC1 negative or low expression) was associated with extrathyroidal extension (ETE) (OR 4.48). Alternatively, a 'high activity' profile of RET (RET/PTC1 positive or high expression) and 'low activity' profile of BRAF (BRAFV600E negative or low expression) were associated with lymph node metastasis (LNM) (OR 12.80). Furthermore, in patients younger than 55 years, a low expression of BRAF was associated with LNM (OR 17.65) and the presence of BRAFV600E mutation was associated with ETE (OR 2.76). Our results suggest that the analysis of demographic and molecular variables by CBVA could contribute to identify subsets of patients with aggressive histopathologic features, providing a potential guide to personalised surgical management of PTC.

The impact of city-wide deployment of Wolbachia-carrying mosquitoes on arboviral disease incidence in Medellín and Bello, Colombia: study protocol for an interrupted time-series analysis and a test-negative design study.

Background: Dengue, chikungunya and Zika are viral infections transmitted by Aedes aegypti mosquitoes, and present major public health challenges in tropical regions. Traditional vector control methods have been ineffective at halting disease transmission. The World Mosquito Program has developed a novel approach to arbovirus control using Ae. aegypti stably transfected with the Wolbachia bacterium, which have significantly reduced ability to transmit dengue, Zika and chikungunya in laboratory experiments. Field releases in eight countries have demonstrated Wolbachia establishment in local Ae. aegypti populations. Methods: We describe a pragmatic approach to measuring the epidemiological impact of city-wide Wolbachia deployments in Bello and Medellín, Colombia. First, an interrupted time-series analysis will compare the incidence of dengue, chikungunya and Zika case notifications before and after Wolbachia releases, across the two municipalities. Second, a prospective case-control study using a test-negative design will be conducted in one quadrant of Medellín. Three of the six contiguous release zones in the case-control area were allocated to receive the first Wolbachia deployments in the city and three to be treated last, approximating a parallel two-arm trial for the >12-month period during which Wolbachia exposure remains discordant. Allocation, although non-random, aimed to maximise balance between arms in historical dengue incidence and demographics. Arboviral disease cases and arbovirus-negative controls will be enrolled concurrently from febrile patients presenting to primary care, with case/control status classified retrospectively following laboratory diagnostic testing. Intervention effect is estimated from an aggregate odds ratio comparing Wolbachia-exposure odds among test-positive cases versus test-negative controls. Discussion: The study findings will add to an accumulating body of evidence from global field sites on the efficacy of the Wolbachia method in reducing arboviral disease incidence, and can inform decisions on wider public health implementation of this intervention in the Americas and beyond. Trial registration: ClinicalTrials.gov: NCT03631719. Registered on 15 August 2018.

Adherencia a la ingesta de los productos del Programa de Alimentación Complementaria del Adulto Mayor (PACAM) desde la subjetividad de los adultos mayores de la comuna de Hualpén, Chile / Understanding older adults' adherence to the consumption of products provided by the Supplementary Food Program for Older Adults (PACAM ) by exploring the point of view of users from the municipality of Hualpén, Chile

INTRODUCCIÓN. El Programa de Alimentación Complementaria del Adulto Mayor (PACAM) es un programa chileno destinado a prevenir y recuperar el daño nutricional en los adultos mayores. La escasa adherencia de los últimos años motiva este estudio. OBJETIVO. Comprender cuáles son los motivos de la baja adherencia de las personas mayores a la ingesta de los productos del PACAM (bebida láctea y crema en polvo fortificada llamada 'Años Dorados'), con el fin de proponer alternativas de mejora del programa desde los propios intereses y valoraciones de los usuarios adultos mayores. MÉTODO. Es un estudio cualitativo de carácter fenomenológico y hermenéutico enfocado en la interpretación del significado de las experiencias individuales subjetivas. El estudio realizado el primer semestre del 2017, conllevó 20 entrevistas semiestructuradas realizadas a los adultos de ambos sexos beneficiarios del PACAM de la comuna de Hualpén, Chile. RESULTADOS Y CONCLUSIÓN. Olor, sabor, consistencia, formas de preparación y cantidad de los formatos son algunos de los elementos organolépticos definidos por las personas mayores, mientras los elementos externos incluyen calidad de vida, red social, influencia de otros usuarios, relación con los profesionales en los servicios de salud, cotidianidad y hábitos.

INTRODUCTION. The Supplementary Food Program for Older Adults (known by the acronym PACAM) is a Chilean program aimed at preventing and/or supporting elderly individuals' recovery from malnutrition. Poor adherence to PACAM in recent years motivates this study. OBJECTIVES. To understand the reasons for the low adherence of older adults to the consumption of PACAM products (milk drink and a fortified powdered soup known as "Golden Years Cream"), in order to propose alternatives for improving the program based on the interests and preferences of elderly users. METHODS. A qualitative study, with a phenomenological and hermeneutical approach, was conducted, focused on interpreting the meaning of the users' subjective experiences. The study, which was carried out during the first semester of 2017, consisted of 20 semi-structured interviews conducted with older adults of both sexes, who were beneficiaries of PACAM in the Chilean municipality of Hualpén. RESULTS AND CONCLUSIONS: Food odor, taste, consistency, preparation, and quantity were some of the organoleptic properties identified by the subjects, while the external factors included quality of life, social networks, the influence of other users, relationships with professionals in the health centers, daily life, and habits.

LGA-newborn from patients with pregestational obesity present reduced adiponectin-mediated vascular relaxation and endothelial dysfunction in fetoplacental arteries.

Maternal obesity is associated with large-for-gestational-age (LGA) neonates and programming of obesity-related cardiovascular disease in the offspring, however, the mechanisms that lead to the later are unclear. Presently, interpretations of NO-dependent changes in vascular function in LGA newborn from obese mothers are conflicting. Adiponectin improves endothelial function by increasing eNOS activity and NO production. We propose that LGAs from obese mothers present a diminished vascular response to adiponectin; thus, affecting eNOS and AMPK activation. Chorionic arteries, umbilical cord and primary cultures of umbilical artery endothelial cells (HUAEC) were collected at term (>38 weeks) from uncomplicated singleton pregnancies of LGA and adequate-for-gestational (AGA) newborn. Vascular reactivity of chorionic plate arteries was assessed by wire myography. mRNA expression of adiponectin receptors 1 (AdipoR1) and AdipoR2 in HUAEC was determined by qPCR. Protein expression of AdipoR1, AdipoR2, AMPK, phospho-AMPKαThr172 , eNOS, and phospho-eNOSSer1177 after stimulation with AdipoRon was determined by Western Blot. Maximal adiponectin-induced chorionic artery relaxation in LGAs was diminished compared to control. In vitro studies showed no differences in expression of AdipoRs, total AMPK and, eNOS activation between groups; however, higher expression of total eNOS and AMPK activation in HUAEC of LGA relative to AGAs were observed. LGA HUAEC showed diminished NO production and eNOS activity compared to AGA in response to AdipoRon but no changes in AMPK activation. Placental endothelium of LGAs shows a diminished vascular response to adiponectin. Moreover, eNOS activation and adiponectin-dependent NO production is lower in HUAEC of LGA from obese mothers, indicating they present dysfuncional placental-endothelial responses.

Intususcepción íleo-ileal secundaria a un pólipo fibrinoide inflamatorio / Ileoileal intussusception secondary to inflammatory fibrinoid polyp

Introducción. El pólipo fibrinoide inflamatorio es una lesión inflamatoria no neoplásica que se presenta especialmente en el estómago, aunque puede ocurrir en cualquier parte del tubo digestivo, en donde puede ocasionar episodios de intususcepción y obstrucción intestinal. Presentación del caso. Se presenta el caso de una mujer de 49 años de edad, con un cuadro clínico de una semana de evolución consistente en episodios intermitentes de dolor abdominal, distensión abdominal y emesis. Ingresó a urgencias de la Clínica CES de Medellín, donde se le practicó una tomografía de abdomen que mostró una invaginación intestinal en el íleon, por lo que se programó para una laparotomía exploratoria. Se encontró una intususcepción secundaria a una lesión polipoide que ocupaba la luz del íleon, se resecó el segmento comprometido y se hizo una anastomosis látero-lateral, sin complicaciones. El estudio anatomo-patológico y la inmunohistoquímica confirmaron el diagnóstico de pólipo fibrinoide inflamatorio. Conclusión. El pólipo fibrinoide inflamatorio es una entidad poco frecuente, benigna, que al presentarse en el íleon puede causar intususcepción y obstrucción intestinal. Los estudios imaginológicos proporcionan hallazgos indirectos. Sin embargo, su diagnóstico definitivo se logra con los estudios anatomo-patológico y de inmunohistoquímica después la resección quirúrgica completa, la cual es curativa en la inmensa mayoría de los casos.Palabras clave: enfermedades intestinales; pólipos intestinales; neoplasias intestinales; obstrucción intestinal.

Introduction: Inflammatory fibrinoid polyp is a non-neoplastic inflammatory lesion, which occurs especially at gastric level, but may also occur anywhere in the gastrointestinal tract, where it can cause episodes of intussusceptions and intestinal obstruction. Case report: We report the case of a 49 year old woman with clinical presentation of one week of evolution consisting in episodes of intermittent abdominal pain, abdominal distension and emesis. She presented at the emergency department of Clinica CES (Medellín, Colombia), where a CT scan of the abdomen reported ileal intussusception. At exploratory laparotomy an intussusception secondary to a polypoid lesion that occupied the ileal lumen was found, and resection of the involved segment and anastomosis were performed without complications. Pathology and immunohistochemistry study confirmed the diagnosis of Inflammatory fibrinoid polyp. Conclusion: The inflammatory fibrinoid polyp is a rare, benign entity that when located in the ileum may cause intussusception and intestinal obstruction. Imagening studies exhibit indirect findings. However, definitive diagnosis is made with pathology and immunohistochemistry studies followimg complete surgical resection, which is curative in the majority of cases.

Natural killer cell cytotoxicity is not regulated by folic acid in vitro.

OBJECTIVES: Folate supplementation may be associated with an increased risk of developing several types of cancer and a derangement of immune function. Among the latter, Natural killer (NK) cells are involved in non-MHC-restricted natural immunity against malignant target cells. Abnormalities in NK cell number or function have been associated with a higher cancer risk. The aim of this study was to study in vitro the possible effect of different concentrations of 5-methyltetrahydrofolic acid (5-MTHF) or folic acid on NK cell cytotoxic function, and expression of the stimulatory and inhibitory receptors KIRDL4, KIRDL3, and NKG2D. METHODS: Volunteer-derived peripheral mononuclear cells (PBMC) and highly enriched NK cells (95% CD56+ CD16+) were grown in folic acid free-RPMI 1640, supplemented either with folic acid or 5-MTHF (15-100 nM) during 72 h to 96 h. RESULTS: No differences in the cytolytic activity of PBMC and enriched NK cells were observed. After 96 h of in vitro culture without folate or supplemented with FA or 5-MTHF (30 or 100 nM), there were no changes in the percentage of HPNK receptor-positive cells. CONCLUSIONS: Our data indicate that a high dose of 5-MTHF or folic acid does not influence NK cell function in vitro.