A collaborative approach to develop indicators for quality of care for ST segment Elevation Myocardial Infarction in networks without coronary intervention: A position paper.

BACKGROUND: Data about performance measures (PM) in patients with ST segment Elevation Myocardial Infarction (STEMI) in low- and middle-income countries is really scarce. One of the reasons is the lack of appropriate measures for these scenarios where coronary intervention is not the standard treatment. OBJECTIVE: This study aimed to develop a set of PM and quality markers for patients with STEMI in these countries. METHODS: Two investigators systematically reviewed existing guidelines and scientific literature to identify potential PM by referring to documents searched through PubMed from 2010 through 2019, using terms "Myocardial Infarction", "STEMI", "quality indicator", and "performance measure". A modified Delphi technique, involving multidisciplinary panel interview, was used. A 15-member multidisciplinary expert panel individually rated each potential indicator on a scale of 1 (lowest) to 5 (highest) during three rounds. All indicators that received a median score ≥4.5, in final round without significant disagreement were included as PM. RESULTS: Through the consensus-building process, 84 potential indicators were found, of which 10 were proposed as performance measures and 2 as quality metrics, as follows: Pre-Hospital Electrocardiogram; Patients with reperfusion therapy; Pre-hospital Reperfusion; Ischemic time less than 120 minutes; System delay time less than 90 minutes; In-hospital Mortality; Complete in-hospital Treatment; Complete in-hospital Treatment in patients with Heart Failure; 30 day-Re-admissions; 30 day-mortality; Patients with in-hospital stress test performed; and, Patients included in rehabilitation programs. CONCLUSION: This document provides the official set of PM of attention in ST segment Elevation Myocardial Infarction of the Cuban Society of Cardiology and Cuban National Group of Cardiology.

Synthesis of Composites for the Removal of F- Anions.

This work presents the synthesis of amine and ferrihydrite functionalized graphene oxide for the removal of fluoride from water. The synthesis of the graphene oxide and the modified with amine groups is developed by following the modified Hummer's method. Fourier transform infrared spectrometry, X-ray, Raman spectroscopy, thermogravimetric analysis, surface charge distribution, specific surface area and porosity, adsorption isotherms, and the van't Hoff equation are used for the characterization of the synthesized materials. Results show that the addition of amines with ferrihydrite generates wrinkles on the surface layers, suggesting a successful incorporation of nitrogen onto the graphene oxide; and as a consequence, the adsorption capacity per unit area of the materials is increased.

Continuous and Pulsed Ultraviolet-C LED on Germicidal Effect and Energy Consumption in Fresh Products: Applications in Tomatoes as a Model.

Nowadays, lifestyle change is one of the problems of the new world economic order, and the procedures of feeding, purchasing, preparation, and the storage of food products, are forcing authorities to establish more rigorous methods concerning the control of food quality and safety. Owing quality in the agro-food sector is a complex and global issue, due to the distance between production and final consumption, as well as the new demands of society on food. Contributing to the bacteria minimization during their path in the supply chain, the objective of this research is the use of an UV-C LED artificial lighting system with emission in continuous light (CL) and two of pulsed light (Mode 1 and Mode 2) for fresh products' disinfection. A mathematical model is introduced as a reference to establish the equivalence dose of continuous and pulsed UV-C LED irradiation. The doses applied were 5, 15, and 25 mJ cm-². The configured parameters per each technique were the irradiance, time also the frequency (500 Hz), and duty cycle (30, 50, and 80%) for Mode 1 and Mode 2. The germicidal effect (GE), energy consumption, and effective germicidal effect (EGE), were evaluated for the different techniques. According to the results, the technique Mode 1 was the best in the GE with 1.06 ± 0.01 and 1.08 ± 0.01 Log reduction by 25 mJ cm-2 at 30 and 80% duty cycle, correspondingly. The CL and Mode 1 showed an outstanding performance with the EGE. Finally, Mode 1 reduced 11% in energy and the GE is comparable with CL. The pulsed light technique Mode 1 constitutes a powerful method against the microorganism's destruction and a strategy for saving energy during the treatment. The UV-C LEDs proved to be an excellent alternative in the disinfection of fresh products with pulsed light emission in the real process.

Characterization of Mitochondrial Proteome and Function in Luminal A and Basal-like Breast Cancer Subtypes Reveals Alteration in Mitochondrial Dynamics and Bioenergetics Relevant to Their Diagnosis.

Breast cancer (BC) is the most prevalent cancer and the one with the highest mortality among women worldwide. Although the molecular classification of BC has been a helpful tool for diagnosing and predicting the treatment of BC, developments are still being made to improve the diagnosis and find new therapeutic targets. Mitochondrial dysfunction is a crucial feature of cancer, which can be associated with cancer aggressiveness. Although the importance of mitochondrial dynamics in cancer is well recognized, its involvement in the mitochondrial function and bioenergetics context in BC molecular subtypes has been scantly explored. In this study, we combined mitochondrial function and bioenergetics experiments in MCF7 and MDA-MB-231 cell lines with statistical and bioinformatics analyses of the mitochondrial proteome of luminal A and basal-like tumors. We demonstrate that basal-like tumors exhibit a vicious cycle between mitochondrial fusion and fission; impaired but not completely inactive mitochondrial function; and the Warburg effect, associated with decreased oxidative phosphorylation (OXPHOS) complexes I and III. Together with the results obtained in the cell lines and the mitochondrial proteome analysis, two mitochondrial signatures were proposed: one signature reflecting alterations in mitochondrial functions and a second signature exclusively of OXPHOS, which allow us to distinguish between luminal A and basal-like tumors.

Protein degradation-associated mechanisms that are affected in Alzheimer´s disease.

Alzheimer's disease (AD) is the most common type of dementia associated with age-related neurodegeneration. Alteration of several molecular mechanisms has been correlated with the progression of AD. In recent years, dysregulation of proteostasis-associated pathways has emerged as a potential risk factor for neurodegenerative diseases. This review investigated the ubiquitin-proteasome system, lysosome-associated degradation, endoplasmic-reticulum-associated degradation, and the formation of advanced glycation end products. These pathways involved in proteostasis have been reported to be altered in AD, suggesting that their study may be critical for identifying new biomarkers and target molecules for AD.

Diagnóstico y tratamiento de la rinosinusitis crónica en adultos. Consenso de expertos: Asociación Colombiana de Otorrinolaringología-2021. / Diagnosis and treatment of chronic rhinosinusitis in adults. Expert consensus: Asociación Colombiana de Otorrinolaringología -2021.

Introducción: la Rinosinusitis Crónica se define como la inflamación crónica de la nariz y los senos paranasales por más de 12 semanas. La prevalencia varía entre el 5% - 30% de acuerdo con la zona geográfica según un estudio de carga de enfermedad (2012-2014), la prevalencia de las enfermedades respiratorias crónicas (rinitis y sinusitis crónica) varió entre el 10% y el 25%. Objetivo: establecer un conjunto de consideraciones basadas en consenso de expertos, para el diagnóstico y el tratamiento de la rinosinusitis crónica en pacientes adultos, en el contexto colombiano. Métodos: se llevó a cabo un consenso formal (Delphi y nominal). Se conformó un grupo de expertos, se definieron el alcance y las preguntas. Se realizaron dos rondas de calificación anónimas, y una discusión para las preguntas sin consenso. En las preguntas con opciones de uno a nueve, se consideró consenso con una mediana de uno a tres o de siete a nueve. En las preguntas tipo Likert, se consideró consenso un porcentaje igual o superior al 80% en acuerdos o desacuerdos. Resultados: se definieron y calificaron 18 preguntas, con la participación de 17 otorrinolaringólogos, de 8 ciudades colombianas, todos miembros de la Asociación Colombiana de Otorrinolaringología y con un promedio de experticia de 19.2 años (Desviación estándar [DE]: 10,2). Se obtuvieron 18 recomendaciones para el diagnóstico y el tratamiento de esta patología. Conclusiones: las recomendaciones emitidas por los expertos permiten orientar y estandarizar el diagnóstico y el tratamiento de la rinosinusitis crónica en adultos, en el contexto de los servicios de salud en Colombia.

Introduction: Chronic Rhinosinusitis is defined as chronic inflammation of the nose and paranasal sinuses for more than 12 weeks. The prevalence varies between 5% - 30% depending on the geographical area according to a disease burden study (2012-2014), the prevalence of chronic respiratory diseases (rhinitis and chronic sinusitis) varied between 10% - 25%. Objective: To establish a set of considerations based on expert consensus, for the diagnosis and treatment of chronic rhinosinusitis in adult patients, in the Colombian context. Methods: A formal consensus (Delphi and nominal) was carried out. A group of experts was formed, the scope and questions were defined. Two anonymous grading rounds were conducted, and a discussion for questions without consensus. In the Questions with options from one to nine were considered consensus with a median of one to three or seven to nine. In the Likert-type questions, a percentage equal to or greater than 80% in agreements or disagreements was considered consensus. Results: 18 questions were defined and scored, with the participation of 17 otorhinolaryngologists, from eight Colombian cities, all members of the Colombian Association of Otorhinolaryngology and with an average experience of 19.2 years (Standard desviation [SD]: 10.2). 18 recommendations were obtained for the diagnosis and treatment of this pathology. Conclusions: The recommendations issued by the experts allow to guide and standardize the diagnosis and treatment of chronic rhinosinusitis in adults, in the context of health services in Colombia.

Cellular Senescence and ApoE4: Their Repercussions in Alzheimer's Disease.

Alzheimer's Disease (AD) is characterized by progressive memory loss due to neurodegeneration that occurs mainly during aging. The accumulation of senescent cells has been related to aging. Furthermore, the expression of the variant ApoE ε4 is a critical risk factor for AD. Some events that occur in senescence, such as the secretion of pro-inflammatory molecules, and metabolic and epigenetic changes, in addition to the detection of ApoE4, may accelerate the progression of AD. Here, we discuss the implications of cellular senescence and the ApoE variants in AD. Molecular studies of these risk factors for AD may hence be pivotal to define new biomarkers and novel therapeutic strategies for this neurodegenerative pathology.

Regulation of autophagy by high- and low-risk human papillomaviruses.

While high-risk human papillomavirus (HR-HPV) infection is related to the development of cervical, vulvar, anal, penile and oropharyngeal cancer, low-risk human papillomavirus (LR-HPV) infection is implicated in about 90% of genital warts, which rarely progress to cancer. The carcinogenic role of HR-HPV is due to the overexpression of HPV E5, E6 and E7 oncoproteins which target and modify cellular proteins implicated in cell proliferation, apoptosis and immortalization. LR-HPV proteins also target and modify some of these processes; however, their oncogenic potential is lower than that of HR-HPV. HR-HPVs have substantial differences with LR-HPVs such as viral integration into the cell genome, induction of p53 and retinoblastoma protein degradation, alternative splicing in HR-HPV E6-E7 open reading frames, among others. In addition, LR-HPV can activate the autophagy process in infected cells while HR-HPV infection deactivates it. However, in cancer HR-HPV might reactivate autophagy in advance stages. Autophagy is a catabolic process that maintains cell homoeostasis by lysosomal degradation and recycling of damaged macromolecules and organelles; nevertheless, depending upon cellular context autophagy may also induce cell death. Therefore, autophagy can contribute either as a promotor or as a suppressor of tumours. In this review, we focus on the role of HR-HPV and LR-HPV in autophagy during viral infection and cancer development. Additionally, we review key regulatory molecules such as microRNAs in HPV present during autophagy, and we emphasize the potential use of cancer treatments associated with autophagy in HPV-related cancers.

Alterations in mitochondrial homeostasis in a potassium dichromate model of acute kidney injury and their mitigation by curcumin.

Curcumin has protective effects in several acute kidney injury models, including that induced by potassium dichromate (K2Cr2O7). The protective effect of curcumin in this experimental model has been associated to the preservation of mitochondrial bioenergetics. This study is aimed at evaluating whether or not curcumin's protective effect in mitochondrial bioenergetics is related to the modulation of mitochondrial dynamics and biogenesis. Wistar rats were treated with a single subcutaneous dose of K2Cr2O7 (12.5 mg/kg) or received curcumin (400 mg/kg/day) by oral gavage 10 days before and one day after the K2Cr2O7 injection. K2Cr2O7 induced kidney dysfunction and increased mitochondrial hydrogen peroxide production, while decreasing the respiration directly attributable to oxidative phosphorylation and mitochondrial membrane potential. In mitochondria, K2Cr2O7 increased fission and reduced fusion. Structural analysis of mitochondria in the proximal tubular cells corroborated their fragmentation and loss of crests' integrity. Regarding mitochondrial biogenesis, K2Cr2O7 decreased peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) levels. Conversely, curcumin treatment mitigated the aforementioned alterations and increased the expression of the mitochondrial transcription factor A (TFAM). Taken together, our results suggest that curcumin can protect against renal injury by modulating mitochondrial homeostasis, mitigating alterations in bioenergetics and dynamics, possibly by stimulating mitochondrial biogenesis.

Association of childhood smoking and adult mortality: prospective study of 120 000 Cuban adults.

BACKGROUND: The average age at which people start smoking has been decreasing in many countries, but insufficient evidence exists on the adult hazards of having started smoking in childhood and, especially, in early childhood. We aimed to investigate the association between smoking habits (focusing on the age when smokers started) and cause-specific premature mortality in a cohort of adults in Cuba. METHODS: For this prospective study, adults were recruited from five provinces in Cuba. Participants were interviewed (data collected included socioeconomic status, medical history, alcohol consumption, and smoking habits) and had their height, weight, and blood pressure measured. Participants were followed up until Jan 1, 2017 for cause-specific mortality; a subset was resurveyed in 2006-08. We used Cox regression to calculate adjusted rate ratios (RRs) for mortality at ages 30-69 years, comparing never-smokers with current smokers by age they started smoking and number of cigarettes smoked per day and with ex-smokers by the age at which they had quit. FINDINGS: Between Jan 1, 1996, and Nov 24, 2002, 146 556 adults were recruited into the study, of whom 118 840 participants aged 30-69 years at recruitment contributed to the main analyses. 27 264 (52%) of 52 524 men and 19 313 (29%) of 66 316 women were current smokers. Most participants reported smoking cigarettes; few smoked only cigars. About a third of current cigarette smokers had started before age 15 years. Compared with never-smokers, the all-cause mortality RR was highest in participants who had started smoking at ages 5-9 years (RR 2·51, 95% CI 2·21-2·85), followed by ages 10-14 years (1·83, 1·72-1·95), 15-19 years (1·56, 1·46-1·65), and ages 20 years or older (1·50, 1·39-1·62). Smoking accounted for a quarter of all premature deaths in this population, but quitting before about age 40 years avoided almost all of the excess mortality due to smoking. INTERPRETATION: In this cohort of adults in Cuba, starting to smoke in childhood was common and quitting was not. Starting in childhood approximately doubled the rate of premature death (ie, before age 70 years). If this 2-fold mortality RR continues into old age, about half of participants who start smoking before age 15 years and do not stop will eventually die of complications from their habit. The greatest risks were found among adults who began smoking before age 10 years. FUNDING: UK Medical Research Council, Cancer Research UK, British Heart Foundation, US Centers for Disease Control and Prevention (CDC) Foundation (with support from Amgen).

Altered proximal tubule fatty acid utilization, mitophagy, fission and supercomplexes arrangement in experimental Fanconi syndrome are ameliorated by sulforaphane-induced mitochondrial biogenesis.

The kidney proximal tubule function relies on oxidative phosphorylation (OXPHOS), thus mitochondrial dysfunction is characteristic of acute kidney injury (AKI). Maleic acid (MA) can induce an experimental model of Fanconi syndrome that is associated to oxidative stress and decreased oxygen consumption. Sulforaphane (SF) is an antioxidant known to protect against MA-induced AKI. The molecular basis by which SF maintains the bioenergetics in MA-induced AKI is not fully understood. To achieve it, rats were submitted to a protective scheme: SF (1 mg/kg/day i.p.) for four days and, at the fourth day, they received a single dose of MA (400 mg/kg i.p.), getting four main experimental groups: (1) control (CT), (2) MA-nephropathy (MA), (3) SF-protected and (4) SF-control (SF). Additionally, a similar protective schema was tested in cultured NRK-52E cells with different concentrations of SF and MA. In the animal model, SF prevented the MA-induced alterations: decrease in fatty acid-related oxygen consumption rate, OXPHOS capacity, mitochondrial membrane potential (Ψmt), and the activity of complex I (CI) as its monomeric and supercomplexes forms; the antioxidant also increased the activity of cytochrome c oxidase as well as mitochondrial biogenesis markers. Thus, SF prevented the MA-induced increase in fission, mitophagy and autophagy markers. In NRK-52E cells, we found that SF prevented the MA-induced cell death, increased mitochondrial mass and ameliorated the loss of Ψmt. We concluded that SF-induced biogenesis protects against mitochondrial dysfunction maintaining Ψmt, activities of mitochondrial complexes and supercomplexes, and prevents the extensive fission and mitophagy.

"Funny" channels in cardiac mitochondria modulate membrane potential and oxygen consumption.

The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are encoded by a family of four genes (HCN1-4). All isoforms are expressed in the heart, HCN4 being the most abundant in the sinoatrial node (SAN). HCN channels are responsible for the "funny" current (If) associated with the generation and autonomic control of the diastolic depolarization phase of cardiac action potential. In this work we performed a proteomic analysis of HCN4 transfected in HEK293 cells. Most of the identified proteins in the HCN4 network belonged to mitochondria. The subcellular localization of HCN channels was predicted in plasma membrane, mitochondria and nucleus. Experimentally, HCN2 (full-length, truncated), HCN3 (full-length, truncated) and HCN4 (truncated) were detected in rat heart mitochondria by immunoblotting. If sensitive to ZD7288, was recorded by patch-clamp in mitoplasts from cardiomyocytes. Mitochondrial membrane potential (ΔΨm) assessment in H9c2 cells revealed that ZD7288 induced almost 50% higher hyperpolarization respect to control at 30 min. Furthermore, ZD7288 reduced oxygen consumption attributed to ATP synthesis in H9c2 cells. In conclusion, we identify for the first time functional HCN channels in mammalian cardiac mitochondria and demonstrate their impact on ΔΨm and respiration.

Congenital meningocele associated with corpus callosum agenesis and midline superior labial cleft due to Tessier 0-14 facial fissure: A case report.

A case of a 31-day-old infant patient with a Tessier 0-14 deformity related to multiple midline deformities is presented. Although Transnasal endoscopic surgery is the mainstay for the treatment of anterior and middle skull base meningoceles, there are complex cases in which a combined and multidisciplinary approach is necessary. The surgical decisions and techniques are described. To date, this is the first patient reported with Tessier 0-14 deformity treated with a combined endoscopic and external surgical approach.

Lista de chequeo preoperatorio para la cirugía endoscópica de hipófisis / Preoperative checklist for endoscopic pituitary surgery

Introducción: las listas de chequeo son herramientas que buscan evitar errores y complicaciones al momento de realizar un procedimiento. El adenoma hipofisiario es la primera causa de cirugía endoscópica transnasal de la región selar, y se estima que ocurren hasta un 20 % de complicaciones derivadas de esta cirugía. Objetivo: desarrollar una lista de chequeo preoperatoria que sirva como una guía para la evaluación prequirúrgica de los pacientes a quienes se les realicen cirugías de la región selar. Metodología: se realizó una revisión de la literatura para desarrollar una lista de chequeo preliminar y una serie de declaraciones que resumían los puntos importantes de la lista. Se construyó un comité de expertos en cirugía endoscópica de la base de cráneo conformado por neurocirujanos y otorrinolaringólogos de hospitales de Bogotá. Utilizando la metodología Delphi modificada, se llegó a un consenso para la realización de la lista de chequeo final. Resultados: se describieron 15 declaraciones; de estas, hubo una discrepancia en 6 declaraciones. Por esta razón, se realizaron modificaciones en 5 declaraciones, y se llegó a un consenso entre los expertos participantes. La lista de chequeo final aprobada está compuesta por 4 ítems. Discusión/conclusiones: la cirugía para el manejo de la patología de la región selar es compleja y requiere de un equipo quirúrgico entrenado y disciplinado para lograr los mejores desenlaces posibles. Consideramos que nuestra lista de chequeo es una herramienta que permitirá a los equipos que realizan estas cirugías en Colombia tener una visión más completa del paciente y, eventualmente, ayudar a evitar errores y posibles complicaciones.

Introduction: checklists that seek to avoid errors are very useful tools for any surgical practice. Pituitary adenomas are the leading indication to perform a transnasal endoscopic surgery in the sellar region and up to 20 % complications have been reported related to this procedure. Objetive: develop a preoperative checklist, based on an expert consensus, to serve as a guide for the skull base teams to consistently evaluate preoperatively all patients with pathologies in the sellar region. Methods: a literature review was conducted to develop a preliminary checklist and a series of statements summarizing the most important items on the list. A committee of experts in endoscopic skull base surgery was summoned, made up of neurosurgeons and otolaryngologists from hospitals in Bogotá. Using the modified Delphi methodology, a consensus was reached for the completion of the final checklist. Results: fifteen statements were developed. A discrepancy was seen in six statements. Modifications were made for five statements, thus reaching a consensus among the participating experts. The final approved checklist is made up of 4 items. Conclusion: surgery for treating different pathologies in the sellar region is complex and requires a welltrained and disciplined surgical team to achieve the best possible outcomes. We consider that our preoperative checklist is a valuable resource for skull base surgical teams performing transnasal endoscopic surgery of the sellar region. This tool will allow skull base surgical teams in Colombia to have a more comprehensive view of the patient and eventually help to avoid errors and possible complications.

Novel Potassium Channels in Kidney Mitochondria: The Hyperpolarization-Activated and Cyclic Nucleotide-Gated HCN Channels.

Hyperpolarization-activated cationic HCN channels comprise four members (HCN1-4) that control dendritic integration, synaptic transmission and action potential firing. In the kidney, HCN1, HCN2 and HCN3 are differentially expressed and contribute to the transport of sodium, potassium (K+) and ammonium into the nephrons. HCN3 is regulated by K+ diets in the kidney. In this work we performed a proteomic analysis of HCN3 expressed in human embryonic kidney cells (HEK293 cells). More than 50% of the interacting proteins belonged to mitochondria. Therefore, we explored the presence of HCN channels in kidney mitochondria. By immunoblotting and immunogold electron microscopy HCN3 protein expression was found in rat kidney mitochondria; it was also confirmed in human kidney. Patch-clamp recordings of renal mitochondria and mitochondria from HEK293 cells overexpressing HCN1, HCN2 and HCN3 channels, stained with MitoTracker Green FM, indicated that only HCN3 could produce inwardly K+ currents that were inhibited by ZD7288, a specific blocker of HCN channels. Furthermore, ZD7288 caused inhibition of the oxygen consumption coupled to ATP synthesis and hyperpolarization of the inner mitochondrial membrane. In conclusion, we show for the first time that pacemaker HCN channels contribute to K+ transport in mitochondria facilitating the activity of the respiratory chain and ATP synthesis by controlling the inner mitochondrial membrane potential.

Divide et Impera: Drp1-mediated Mitochondrial Fission in Glioma Malignancy.

Mitochondria are pivotal organelles involved in vital cellular functions, including energy generation, reactive oxygen species and calcium signaling, as well as intermediate biosynthesis. They are dynamic organelles that adapt their shape, size, and distribution to changes in intracellular conditions, being able to divide, fuse, or move along the cell, processes known as mitochondrial dynamics. Mitochondrial dynamics are involved in cell division and migration, as well as maintenance of pluripotency in stem (non-differentiated) cells. Thus, its central role in carcinogenesis is not surprising. Particularly, mitochondrial dynamics have been found to be pivotal to the development of gliomas, a lethal group of tumors developed from glial cells, which are nervous system cells that provide support to neurons. Unfortunately, prognosis of glioma patients is poor, most of them do not survive more than five years after diagnosis. In this context, it is fundamental to understand the cellular mechanisms involved in this pathology, in order to develop an appropriate clinical approach. As previously mentioned, mitochondrial dynamics is central to glioma development, particularly, mitochondrial division (fission) and one of its central effectors, dynamin-related protein 1 (Drp1), have been observed to be enhanced in gliomas and involved in the maintenance of stem cells (which initiate and maintain the tumor), as well as in migration and invasiveness, being central to gliomagenesis. In this review, we discuss the findings on mitochondrial fission role in these processes, further, we analyze the potential use of Drp1 as a novel prognostic biomarker in glioma patients.

Burden of hypertension and associated risks for cardiovascular mortality in Cuba: a prospective cohort study.

BACKGROUND: In Cuba, hypertension control in primary care has been prioritised as a cost-effective means of addressing premature death from cardiovascular disease. However, there is little evidence from large-scale studies on the prevalence and management of hypertension in Cuba, and no direct evidence of the expected benefit of such efforts on cardiovascular mortality. METHODS: In a prospective cohort study, adults in the general population identified via local family medical practices were interviewed between Jan 1, 1996, and Nov 24, 2002, in five areas of Cuba, and a subset of participants were resurveyed between July 14, 2006, and Oct 19, 2008, in one area. During household visits, blood pressure was measured and information obtained on diagnosis and treatment of hypertension. We calculated the prevalence of hypertension (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg, or receiving treatment for hypertension) and the proportion of people with hypertension in whom it was diagnosed, treated, and controlled (systolic blood pressure <140 mm Hg, diastolic blood pressure <90 mm Hg). Deaths were identified through linkage by national identification numbers to the Cuban Public Health Ministry records, to Dec 31, 2016. We used Cox regression analysis to compare cardiovascular mortality between participants with versus without uncontrolled hypertension. Rate ratios (RRs) were used to estimate the fraction of cardiovascular deaths attributable to hypertension. FINDINGS: 146 556 participants were interviewed in the baseline survey in 1996-2002 and 24 345 were interviewed in the resurvey in 2006-08. After exclusion for incomplete data and age outside the range of interest, 136 111 respondents aged 35-79 years (mean age 54 [SD 12] years; 75 947 [56%] women, 60 164 [44%] men) were eligible for inclusion in the analyses. 34% of participants had hypertension. Among these, 67% had a diagnosis of hypertension. 76% of participants with diagnosed hypertension were receiving treatment and blood pressure was controlled in 36% of those people. During 1·7 million person-years of follow-up there were 5707 cardiovascular deaths. In the age groups 35-59, 60-69, and 70-79 years, uncontrolled hypertension at baseline was associated with RRs of 2·15 (95% CI 1·88-2·46), 1·86 (1·69-2·05), and 1·41 (1·32-1·52), respectively, and accounted for around 20% of premature cardiovascular deaths. INTERPRETATION: In this Cuban population, a third of people had hypertension. Although levels of hypertension diagnosis and treatment were commensurate with those in some high-income countries, the proportion of participants whose blood pressure was controlled was low. As well as reducing hypertension prevalence, improvement in blood pressure control among people with diagnosed hypertension is required to prevent premature cardiovascular deaths in Cuba. FUNDING: Medical Research Council, British Heart Foundation, Cancer Research UK.

Protective effects of N-acetyl-cysteine in mitochondria bioenergetics, oxidative stress, dynamics and S-glutathionylation alterations in acute kidney damage induced by folic acid.

Folic acid (FA)-induced acute kidney injury (AKI) is a widely used model for studies of the renal damage and its progression to chronic state. However, the molecular mechanisms by which FA induces AKI remain poorly understood. Since renal function depends on mitochondrial homeostasis, it has been suggested that mitochondrial alterations contribute to AKI development. Additionally, N-acetyl-cysteine (NAC) can be a protective agent to prevent mitochondrial and renal dysfunction in this model, given its ability to increase mitochondrial glutathione (GSH) and to control the S-glutathionylation levels, a reversible post-translational modification that has emerged as a mechanism able to link mitochondrial energy metabolism and redox homeostasis. However, this hypothesis has not been explored. The present study demonstrates for the first time that, at 24 h, FA induced mitochondrial bioenergetics, redox state, dynamics and mitophagy alterations, which are involved in the mechanisms responsible for the AKI development. On the other hand, NAC preadministration was able to prevent mitochondrial bioenergetics, redox state and dynamics alterations as well as renal damage. The protective effects of NAC on mitochondria and renal function could be related to its observed capacity to preserve the S-glutathionylation process and GSH levels in mitochondria. Taken together, our results support the idea that these mitochondrial processes can be targets for the prevention of the renal damage and its progression in FA-induced AKI model.

Curcumin prevents potassium dichromate (K2Cr2O7)-induced renal hypoxia.

Curcumin exhibits several therapeutic properties. Potassium dichromate (K2Cr2O7)-induced nephropathy is associated with oxidative stress. Reactive oxygen species production affects renal oxygenation that may participate in the progression of renal damage. The aim of the present work was to elucidate whether K2Cr2O7-induced nephropathy is associated to partial O2 pressure (pO2) impairment and if curcumin is able to prevent it. Four groups of rats were studied: control group; K2Cr2O7 group (12.5 mg/kg, s.c.); curcumin + K2Cr2O7 group, in which animals were treated with curcumin (400 mg/kg/day, p.o.) for 10 days before K2Cr2O7 injection; and curcumin group. All animals were sacrificed 48 h after the end of the treatments. K2Cr2O7 administration increased renal function markers and decreased glomerular filtration rate, pO2 and renal perfusion. Concerning hemodynamic parameters, K2Cr2O7 increased mean arterial pressure and renal vascular resistance and reduced renal blood flow. The hemodynamic changes were attributed to decreased availability of nitric oxide and increased 3-nitrotyrosine levels. Moreover, increased superoxide anion production and vascular endothelial growth factor levels were observed after K2Cr2O7 administration. Curcumin attenuated all the above-described alterations. Our results suggest that the protective effects of curcumin in K2Cr2O7-induced nephropathy are associated with its ability to prevent O2 supply reduction.