Red light mediates the exocytosis of vasodilatory vesicles from cultured endothelial cells: a cellular, and ex vivo murine model.

We have previously established that 670 nm energy induces relaxation of blood vessels via an endothelium derived S-nitrosothiol (RSNO) suggested to be embedded in vesicles. Here, we confirm that red light facilitates the exocytosis of this vasodilator from cultured endothelial cells and increases ex vivo blood vessel diameter. Ex vivo pressurized and pre-constricted facial arteries from C57Bl6/J mice relaxed 14.7% of maximum diameter when immersed in the medium removed from red-light exposed Bovine Aortic Endothelial Cells. In parallel experiments, 0.49 nM RSNO equivalent species was measured in the medium over the irradiated cells vs dark control. Electron microscopy of light exposed endothelium revealed significant increases in the size of the Multi Vesicular Body (MVB), a regulator of exosome trafficking, while RSNO accumulated in the MVBs as detected with immunogold labeling electron microscopy (1.8-fold of control). Moreover, red light enhanced the presence of F-actin related stress fibers (necessary for exocytosis), and the endothelial specific marker VE-cadherin levels suggesting an endothelial origin of the extracellular vesicles. Flow cytometry coupled with DAF staining, an indirect sensor of nitric oxide (NO), indicated significant amounts of NO within the extracellular vesicles (1.4-fold increase relative to dark control). Therefore, we further define the mechanism on the 670 nm light mediated traffic of endothelial vasodilatory vesicles and plan to leverage this insight into the delivery of red-light therapies.

HIV treatment cascade in regions of Peru with the highest HIV prevalence.

OBJECTIVES: To describe the HIV treatment cascade and care continuum in regions of highest HIV prevalence in Peru. METHODS: An observational longitudinal study was carried out in 14 tertiary hospitals in Peru. These are the main hospitals that administer antiretroviral treatment (ART) in the regions that represent approximately 95% of reports of HIV/AIDS cases in Peru in 2013. We included individuals older than 18 years newly diagnosed with HIV from 1 January 2011 to 31 December 2012. Medical records were reviewed until 2015. RESULTS: A total of 2119 people living with HIV (PLHIV) were identified in the selected health facilities (mean age = 35.26 years, 78% male). 97.25% [1845/1897; 95% confidence interval (CI): 96.4-97.9%] of the patients attended the consultation at least once during the follow-up, but only 64.84% (885/1365; 95% CI: 62.2-67.4%) attended within a month after the diagnosis. After starting ART, 74.63% (95% CI: 71.9-77.2%) of PLHIV remained in healthcare. Regardless of the time after diagnosis, 88.40% (1837/2078; 95% CI: 86.9-89.7%) of PLHIV started ART during the observation time. However, 78.68% (95% CI: 76.8-80.4%) did so during the first post-treatment year and only 28.88% (95% CI: 27.9-31.9%) after 1 month. After starting treatment, it was observed that 51.60% (95% CI: 49.2-54%) of PLHIV reached viral suppression during the follow-up period. CONCLUSIONS: Further analysis and improvements in the definition of indicators are required to achieve conclusive results; however, these data will give us a general understanding of the progress of Peruvian health policies in achieving the goal established by the WHO.

Excellent hemostatic control during cardiac surgery in a patient with hemophilia B treated with albutrepenonacog alfa (rIX-FP): A case report.

Key Clinical Message: In hemophilia patients undergoing cardiac surgery, ROTEM® and Quantra® viscoelastic tests are useful to monitor perioperative hemostatic status and a single dose of rIX-FP is safe and avoids any hemorrhagic or thrombotic complication. Abstract: Cardiac surgery poses a high hemostatic risk in patients with hemophilia. We present the first case of an adult patient with hemophilia B on treatment with albutrepenonacog alfa (rIX-FP) who underwent surgery for acute coronary syndrome. Treatment with rIX-FP made it possible to perform the surgery safely.

Epidemiological characteristics of mortality from infectious intestinal diseases (diarrhea) Paraguay (2015-2019)

Introduction: Infectious intestinal diseases (diarrhea) are a major cause of morbidity and mortality worldwide. In 2015, it constituted the ninth leading cause of death for all ages. Objective: To describe the epidemiological characteristics of mortality due to infectious intestinal diseases (diarrhea) in Paraguay from 2015 to 2019. Methods: Descriptive, ecological, cross-sectional, retrospective, and non-probabilistic sampling of consecutive cases was performed. ICD-10 deaths included cholera (A01), typhoid and paratyphoid fever (A01), shigellosis (A03), other bacterial intestinal infections (A04), other bacterial food poisoning (A05), amebiasis (A06), other intestinal diseases due to protozoa (A07), intestinal infections due to viruses (A08), and diarrhea and gastroenteritis of presumed infectious origin (A09). Open access data were obtained from the WEB page of the General Directorate of Strategic Information in Health of the MSP and BS of all the Departments of the country. Crude and adjusted rates (per 100,000 inhabitants) were calculated. Excel and EPI INFO 7.0 were used. Results: 495 deaths were registered; the highest prevalence was in 2019 (adjusted rate of 1.83) and the lowest in 2017 (1.36). The months with the highest mortality rates were January and July (9.9%). 51.72% were women (256), 30.91% were over 80 years old and 28.28% (140) were under 5 years old, average age 50.8, single 56.77% (281) and without any type of education 41.82% (207). A total of 80.61% (399) of the respondents resided in urban areas. The highest rates were registered in Boquerón (33.3) and Amambay (15.2). Diarrhea and gastroenteritis of infectious origin accounted for 95.56% of the cases (473). Discussion: There was a high percentage of mortality from infectious diarrhea. Extremes of life were the most vulnerable populations.

Introducción: Las enfermedades infecciosas intestinales (diarrea) son una causa importante de morbilidad y mortalidad a nivel mundial. En 2015, constituyeron la novena causa principal de muerte para todas las edades. Objetivo: describir las características epidemiológicas de la mortalidad por enfermedades infecciosas intestinales (diarreas) en Paraguay durante los años 2015 al 2019. Metodología: Estudio descriptivo, ecológico, transversal, retrospectivo, muestreo no probabilístico de casos consecutivos. Se consideraron los óbitos del CIE - 10, que incluyen al cólera (A01), fiebres tifoidea y paratifoidea (A01), shigelosis (A03), otras infecciones intestinales bacterianas (A04), otras intoxicaciones alimentarias bacterianas (A05), amebiasis (A06), otras enfermedades intestinales debidas a protozoarios (A07), infecciones intestinales debidas a virus (A08) y diarrea y gastroenteritis de presunto origen infeccioso (A09). Se utilizaron datos de acceso abierto de la página WEB de la Dirección General de Información Estratégica en Salud del MSP y BS de todos los Departamentos del país. Se calcularon tasas crudas y ajustadas (por 100.000 habitantes). Se utilizaron Excel y EPI INFO 7.0. Resultados: Se registraron 495 muertes, la mayor prevalencia fue en 2019 (tasa ajustada de 1,83) y menor en 2017 (1,36). Los meses con mayor mortalidad fueron enero y julio (9,9%). El 51,72% fueron mujeres (256), 30,91% mayores de 80 años y 28,28% (140) menores de 5 años, edad promedio 50,8, solteros 56,77% (281) y sin ningún tipo de educación 41,82% (207). El 80,61% (399) residía en área urbana. Las mayores tasas se registraron en Boquerón (33,3) y Amambay (15,2). El 95,56% (473) fueron diarreas y gastroenteritis de origen infeccioso. Discusión: Se registra alto porcentaje de mortalidad de diarreas de origen infeccioso. Los extremos de la vida constituyen la población más vulnerable.

Post-hypoxia Invasion of the fetal brain by multidrug resistant Staphylococcus.

Herein we describe an association between activation of inflammatory pathways following transient hypoxia and the appearance of the multidrug resistant bacteria Staphylococcus simulans in the fetal brain. Reduction of maternal arterial oxygen tension by 50% over 30 min resulted in a subseiuent significant over-expression of genes associated with immune responses 24 h later in the fetal brain. The activated genes were consistent with stimulation by bacterial lipopolysaccharide; an influx of macrophages and appearance of live bacteria were found in these fetal brains. S. simulans was the predominant bacterial species in fetal brain after hypoxia, but was found in placenta of all animals. Strains of S. simulans from the placenta and fetal brain were equally highly resistant to multiple antibiotics including methicillin and had identical genome sequences. These results suggest that bacteria from the placenta invade the fetal brain after maternal hypoxia.