Goblet cell LRRC26 regulates BK channel activation and protects against colitis in mice.

Goblet cells (GCs) are specialized cells of the intestinal epithelium contributing critically to mucosal homeostasis. One of the functions of GCs is to produce and secrete MUC2, the mucin that forms the scaffold of the intestinal mucus layer coating the epithelium and separates the luminal pathogens and commensal microbiota from the host tissues. Although a variety of ion channels and transporters are thought to impact on MUC2 secretion, the specific cellular mechanisms that regulate GC function remain incompletely understood. Previously, we demonstrated that leucine-rich repeat-containing protein 26 (LRRC26), a known regulatory subunit of the Ca2+-and voltage-activated K+ channel (BK channel), localizes specifically to secretory cells within the intestinal tract. Here, utilizing a mouse model in which MUC2 is fluorescently tagged, thereby allowing visualization of single GCs in intact colonic crypts, we show that murine colonic GCs have functional LRRC26-associated BK channels. In the absence of LRRC26, BK channels are present in GCs, but are not activated at physiological conditions. In contrast, all tested MUC2- cells completely lacked BK channels. Moreover, LRRC26-associated BK channels underlie the BK channel contribution to the resting transepithelial current across mouse distal colonic mucosa. Genetic ablation of either LRRC26 or BK pore-forming α-subunit in mice results in a dramatically enhanced susceptibility to colitis induced by dextran sodium sulfate. These results demonstrate that normal potassium flux through LRRC26-associated BK channels in GCs has protective effects against colitis in mice.

Strengthening public health policies for childhood cancer: Peru's achievements through the WHO Global Initiative for Childhood Cancer.

Objective: To report the progress in Peru, since June 2019, in the implementation of the World Health Organization Global Initiative for Childhood Cancer using the CureAll framework, which can be replicated in low- and middle-income countries. Methods: A mixed method was used of participatory and documentary evaluation. The participatory evaluation included stakeholders from various government institutions, nonprofit organizations, and international partners. The documentary aspect consisted of a review of data on the regulatory environment, national projects, and interventions implemented. The Ministry of Health engaged more than 150 participants to form working committees, which have developed policy and regulatory documents to strengthen care services. Results: Achievements include a decrease in the national treatment abandonment rate from 18.6% to 8.5%, the approval of the Childhood Cancer Law, improvements in the management of patients with febrile neutropenia, and a reduction in rates of events of clinical deterioration and mortality of hospitalized patients. The Cure All implementation framework allows local teams to implement specific strategies and monitor early outcomes in pediatric oncology. Conclusions: The results obtained reflect the teamwork, the leadership of the authorities, the technical support of professionals, and the support of involved organizations. Further actions will be needed to guarantee sustainability, and monitoring tools are needed to assure success in the planned activities.

Regulation of BK Channels by Beta and Gamma Subunits.

Ca2+- and voltage-gated K+ channels of large conductance (BK channels) are expressed in a diverse variety of both excitable and inexcitable cells, with functional properties presumably uniquely calibrated for the cells in which they are found. Although some diversity in BK channel function, localization, and regulation apparently arises from cell-specific alternative splice variants of the single pore-forming α subunit ( KCa1.1, Kcnma1, Slo1) gene, two families of regulatory subunits, ß and γ, define BK channels that span a diverse range of functional properties. We are just beginning to unravel the cell-specific, physiological roles served by BK channels of different subunit composition.

The LRRC family of BK channel regulatory subunits: potential roles in health and disease.

Large conductance K+ channels, termed BK channels, regulate a variety of cellular and physiological functions. Although universally activated by changes in voltage or [Ca2+ ]i , the threshold for BK channel activation varies among loci of expression, often arising from cell-specific regulatory subunits including a family of leucine rich repeat-containing (LRRC) γ subunits (LRRC26, LRRC52, LRRC55 and LRRC38). The 'founding' member of this family, LRRC26, was originally identified as a tumour suppressor in various cancers. An LRRC26 knockout (KO) mouse model recently revealed that LRRC26 is also highly expressed in secretory epithelial cells and partners with BK channels in the salivary gland and colonic goblet cells to promote sustained K+ fluxes likely essential for normal secretory function. To accomplish this, LRRC26 negatively shifts the range of BK channel activation such that channels contribute to K+ flux near typical epithelial cell resting conditions. In colon, the absence of LRRC26 increases vulnerability to colitis. LRRC26-containing BK channels are also likely important regulators of epithelial function in other loci, including airways, female reproductive tract and mammary gland. Based on an LRRC52 KO mouse model, LRRC52 regulation of large conductance K+ channels plays a role both in sperm function and in cochlear inner hair cells. Although our understanding of LRRC-containing BK channels remains rudimentary, KO mouse models may help define other organs in which LRRC-containing channels support normal function. A key topic for future work concerns identification of endogenous mechanisms, whether post-translational or via gene regulation, that may impact LRRC-dependent pathologies.

[Drivers and scorecards to improve hypertension control in primary care practice: Recommendations from the HEARTS in the Americas Innovation GroupFactores impulsores y métodos de puntuación para mejorar el control de la hipertensión en la práctica clínica de la atención primaria: recomendaciones del grupo de innovación de HEARTS en las Américas]. / Fatores impulsionadores e scorecards para melhorar o controle da hipertensão arterial na atenção primária: recomendações do Grupo de Inovação da Iniciativa HEARTS nas Américas.

Background: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Americas, and hypertension is the most significant modifiable risk factor. However, hypertension control rates remain low, and CVD mortality is stagnant or rising after decades of continuing reduction. In 2016, the World Health Organization (WHO) launched the HEARTS technical package to improve hypertension control. The Pan American Health Organization (PAHO) designed the HEARTS in the Americas Initiative to improve CVD risk management, emphasizing hypertension control, to date implemented in 21 countries. Methods: To advance implementation, an interdisciplinary group of practitioners was engaged to select the key evidence-based drivers of hypertension control and to design a comprehensive scorecard to monitor their implementation at primary care health facilities (PHC). The group studied high-performing health systems that achieve high hypertension control through quality improvement programs focusing on specific process measures, with regular feedback to providers at health facilities. Findings: The final selected eight drivers were categorized into five main domains: (1) diagnosis (blood pressure measurement accuracy and CVD risk evaluation); (2) treatment (standardized treatment protocol and treatment intensification); (3) continuity of care and follow-up; (4) delivery system (team-based care, medication refill), and (5) system for performance evaluation. The drivers and recommendations were then translated into process measures, resulting in two interconnected scorecards integrated into the HEARTS in the Americas monitoring and evaluation system. Interpretation: Focus on these key hypertension drivers and resulting scorecards, will guide the quality improvement process to achieve population control goals at the participating health centers in HEARTS implementing countries.

Antecedentes: Las enfermedades cardiovasculares (ECV) son la principal causa de morbilidad y mortalidad en la Región de las Américas y la hipertensión es el factor de riesgo modificable asociado más importante. Sin embargo, las tasas de control de la hipertensión siguen siendo bajas y la mortalidad por ECV está estancada o en aumento después de décadas de reducción continua. En el 2016, la Organización Mundial de la Salud (OMS) presentó el paquete técnico HEARTS para mejorar el control de la hipertensión. La Organización Panamericana de la Salud (OPS) diseñó la iniciativa HEARTS en las Américas para mejorar el control del riesgo de ECV, que hace hincapié en el control de la hipertensión y que, hasta la fecha, se ha implementado en 21 países. Métodos: Para avanzar en la implementación, se creó un grupo interdisciplinario de profesionales de la salud con el objetivo de seleccionar los factores impulsores claves del control de la hipertensión basados en la evidencia y diseñar un método de puntuación integral para dar seguimiento a su implementación en los centros de atención de salud primaria (APS). El grupo estudió los sistemas de salud de alto desempeño que logran un control elevado de la hipertensión mediante programas de mejora de la calidad que se centran en medidas específicas con respecto a los procesos, con retroalimentación regular a los prestadores en los centros de salud. Resultados: Los ocho factores impulsores finales seleccionados se clasificaron en cinco dominios principales: 1) diagnóstico (exactitud de la medición de la presión arterial y evaluación del riesgo de ECV); 2) tratamiento (protocolo de tratamiento e intensificación del tratamiento estandarizados); 3) continuidad de la atención y seguimiento; 4) sistema de prestación del tratamiento (atención basada en un trabajo en equipo, reposición de la medicación) y 5) sistema para la evaluación del desempeño. Los factores impulsores y las recomendaciones se tradujeron en medidas con respecto a los procesos, lo que llevó a dos métodos de puntuación integrados e interconectados en el sistema de seguimiento y evaluación del programa HEARTS en las Américas. Conclusiones: El enfoque que se centra en estos factores impulsores clave de la hipertensión y los métodos de puntuación resultantes servirá de guía para el proceso de mejora de la calidad con objeto de alcanzar los objetivos de control a nivel poblacional en los centros de salud participantes de los países que implementan el programa HEARTS.

[Drivers and scorecards to improve hypertension control in primary care practice: Recommendations from the HEARTS in the Americas Innovation GroupFatores impulsionadores e scorecards para melhorar o controle da hipertensão arterial na atenção primária: recomendações do Grupo de Inovação da Iniciativa HEARTS nas Américas]. / Factores impulsores y métodos de puntuación para mejorar el control de la hipertensión en la práctica clínica de la atención primaria: recomendaciones del grupo de innovación de HEARTS en las Américas.

Background: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Americas, and hypertension is the most significant modifiable risk factor. However, hypertension control rates remain low, and CVD mortality is stagnant or rising after decades of continuing reduction. In 2016, the World Health Organization (WHO) launched the HEARTS technical package to improve hypertension control. The Pan American Health Organization (PAHO) designed the HEARTS in the Americas Initiative to improve CVD risk management, emphasizing hypertension control, to date implemented in 21 countries. Methods: To advance implementation, an interdisciplinary group of practitioners was engaged to select the key evidence-based drivers of hypertension control and to design a comprehensive scorecard to monitor their implementation at primary care health facilities (PHC). The group studied high-performing health systems that achieve high hypertension control through quality improvement programs focusing on specific process measures, with regular feedback to providers at health facilities. Findings: The final selected eight drivers were categorized into five main domains: (1) diagnosis (blood pressure measurement accuracy and CVD risk evaluation); (2) treatment (standardized treatment protocol and treatment intensification); (3) continuity of care and follow-up; (4) delivery system (team-based care, medication refill), and (5) system for performance evaluation. The drivers and recommendations were then translated into process measures, resulting in two interconnected scorecards integrated into the HEARTS in the Americas monitoring and evaluation system. Interpretation: Focus on these key hypertension drivers and resulting scorecards, will guide the quality improvement process to achieve population control goals at the participating health centers in HEARTS implementing countries.

Fundamentos: As doenças cardiovasculares (DCV) são as principais causas de morbimortalidade nas Américas, e a hipertensão arterial (HÁ) é o fator de risco modificável mais importante. Porém, as taxas de controle da HA continuam baixas, e a mortalidade por DCV está estagnada ou aumentando após décadas de redução contínua. Em 2016, a Organização Mundial da Saúde (OMS) lançou o pacote de medidas técnicas HEARTS para melhorar o controle da HA. A Organização Pan-Americana da Saúde (OPAS) criou a iniciativa HEARTS nas Américas para melhorar a gestão do risco cardiovascular (RCV), com ênfase no controle da HA. Até agora, essa iniciativa foi implementada em 21 países. Métodos: Para impulsionar a implementação, recrutou-se um grupo multidisciplinar de profissionais para selecionar impulsionadores-chave do controle da HA com base em evidências e elaborar um scorecard completo para monitorar sua implementação em unidades de atenção primária à saúde (APS). O grupo estudou sistemas de saúde com alto desempenho que haviam conseguido atingir um alto nível de controle da HA por meio de programas de melhoria da qualidade focados em medidas específicas de processo, com feedback regular para os profissionais das unidades de saúde. Resultados: Os oito fatores impulsionadores incluídos na seleção final foram categorizados em cinco domínios principais: (1) diagnóstico (exatidão da medição da pressão arterial e avaliação do RCV); (2) tratamento (protocolo padronizado de tratamento e intensificação do tratamento); (3) continuidade do cuidado e acompanhamento; (4) modelo de atenção (atendimento baseado em equipe, renovação da prescrição); e (5) sistema de avaliação do desempenho. Em seguida, os impulsionadores e as recomendações foram transformados em medidas de processo, gerando dois scorecards inter-relacionados integrados ao sistema de monitoramento e avaliação da Iniciativa HEARTS nas Américas. Interpretação: O foco nesses impulsionadores-chave da HA e nos scorecards resultantes orientará o processo de melhoria da qualidade para atingir as metas de controle, em nível populacional, dos centros de saúde participantes nos países que estão implementando a iniciativa HEARTS.

Regulatory γ1 subunits defy symmetry in functional modulation of BK channels.

Structural symmetry is a hallmark of homomeric ion channels. Nonobligatory regulatory proteins can also critically define the precise functional role of such channels. For instance, the pore-forming subunit of the large conductance voltage and calcium-activated potassium (BK, Slo1, or KCa1.1) channels encoded by a single KCa1.1 gene assembles in a fourfold symmetric fashion. Functional diversity arises from two families of regulatory subunits, ß and γ, which help define the range of voltages over which BK channels in a given cell are activated, thereby defining physiological roles. A BK channel can contain zero to four ß subunits per channel, with each ß subunit incrementally influencing channel gating behavior, consistent with symmetry expectations. In contrast, a γ1 subunit (or single type of γ1 subunit complex) produces a functionally all-or-none effect, but the underlying stoichiometry of γ1 assembly and function remains unknown. Here we utilize two distinct and independent methods, a Forster resonance energy transfer-based optical approach and a functional reporter in single-channel recordings, to reveal that a BK channel can contain up to four γ1 subunits, but a single γ1 subunit suffices to induce the full gating shift. This requires that the asymmetric association of a single regulatory protein can act in a highly concerted fashion to allosterically influence conformational equilibria in an otherwise symmetric K+ channel.

Gating-induced large aqueous volumetric remodeling and aspartate tolerance in the voltage sensor domain of Shaker K+ channels.

Neurons encode electrical signals with critically tuned voltage-gated ion channels and enzymes. Dedicated voltage sensor domains (VSDs) in these membrane proteins activate coordinately with an unresolved structural change. Such change conveys the transmembrane translocation of four positively charged arginine side chains, the voltage-sensing residues (VSRs; R1-R4). Countercharges and lipid phosphohead groups likely stabilize these VSRs within the low-dielectric core of the protein. However, the role of hydration, a sign-independent charge stabilizer, remains unclear. We replaced all VSRs and their neighboring residues with negatively charged aspartates in a voltage-gated potassium channel. The ensuing mild functional effects indicate that hydration is also important in VSR stabilization. The voltage dependency of the VSR aspartate variants approached the expected arithmetic summation of charges at VSR positions, as if negative and positive side chains faced similar pathways. In contrast, aspartates introduced between R2 and R3 did not affect voltage dependence as if the side chains moved outside the electric field or together with it, undergoing a large displacement and volumetric remodeling. Accordingly, VSR performed osmotic work at both internal and external aqueous interfaces. Individual VSR contributions to volumetric works approached arithmetical additivity but were largely dissimilar. While R1 and R4 displaced small volumes, R2 and R3 volumetric works were massive and vectorially opposed, favoring large aqueous remodeling during VSD activation. These diverse volumetric works are, at least for R2 and R3, not compatible with VSR translocation across a unique stationary charge transfer center. Instead, VSRs may follow separated pathways across a fluctuating low-dielectric septum.

Knockout of the LRRC26 subunit reveals a primary role of LRRC26-containing BK channels in secretory epithelial cells.

Leucine-rich-repeat-containing protein 26 (LRRC26) is the regulatory γ1 subunit of Ca2+- and voltage-dependent BK-type K+ channels. BK channels that contain LRRC26 subunits are active near normal resting potentials even without Ca2+, suggesting they play unique physiological roles, likely limited to very specific cell types and cellular functions. By using Lrrc26 KO mice with a ß-gal reporter, Lrrc26 promoter activity is found in secretory epithelial cells, especially acinar epithelial cells in lacrimal and salivary glands, and also goblet and Paneth cells in intestine and colon, although absent from neurons. We establish the presence of LRRC26 protein in eight secretory tissues or tissues with significant secretory epithelium and show that LRRC26 protein coassembles with the pore-forming BK α-subunit in at least three tissues: lacrimal gland, parotid gland, and colon. In lacrimal, parotid, and submandibular gland acinar cells, LRRC26 KO shifts BK gating to be like α-subunit-only BK channels. Finally, LRRC26 KO mimics the effect of SLO1/BK KO in reducing [K+] in saliva. LRRC26-containing BK channels are competent to contribute to resting K+ efflux at normal cell membrane potentials with resting cytosolic Ca2+ concentrations and likely play a critical physiological role in supporting normal secretory function in all secretory epithelial cells.

Stereospecific binding of a disordered peptide segment mediates BK channel inactivation.

A number of functionally important actions of proteins are mediated by short, intrinsically disordered peptide segments, but the molecular interactions that allow disordered domains to mediate their effects remain a topic of active investigation. Many K+ channel proteins, after initial channel opening, show a time-dependent reduction in current flux, termed 'inactivation', which involves movement of mobile cytosolic peptide segments (approximately 20-30 residues) into a position that physically occludes ion permeation. Peptide segments that produce inactivation show little amino-acid identity and tolerate appreciable mutational substitutions without disrupting the inactivation process. Solution nuclear magnetic resonance of several isolated inactivation domains reveals substantial conformational heterogeneity with only minimal tendency to ordered structures. Channel inactivation mechanisms may therefore help us to decipher how intrinsically disordered regions mediate functional effects. Whereas many aspects of inactivation of voltage-dependent K+ channels (Kv) can be described by a simple one-step occlusion mechanism, inactivation of the voltage-dependent large-conductance Ca2+-gated K+ (BK) channel mediated by peptide segments of auxiliary ß-subunits involves two distinguishable kinetic steps. Here we show that two-step inactivation mediated by an intrinsically disordered BK ß-subunit peptide involves a stereospecific binding interaction that precedes blockade. In contrast, blocking mediated by a Shaker Kv inactivation peptide is consistent with direct, simple occlusion by a hydrophobic segment without substantial steric requirement. The results indicate that two distinct types of molecular interaction between disordered peptide segments and their binding sites produce qualitatively similar functions.

Functional regulation of BK potassium channels by γ1 auxiliary subunits.

Many K(+) channels are oligomeric complexes with intrinsic structural symmetry arising from the homo-tetrameric core of their pore-forming subunits. Allosteric regulation of tetramerically symmetric proteins, whether by intrinsic sensing domains or associated auxiliary subunits, often mirrors the fourfold structural symmetry. Here, through patch-clamp recordings of channel population ensembles and also single channels, we examine regulation of the Ca(2+)- and voltage-activated large conductance Ca(2+)-activated K(+) (BK) channel by associated γ1-subunits. Through expression of differing ratios of γ1:α-subunits, the results reveal an all-or-none functional regulation of BK channels by γ-subunits: channels either exhibit a full gating shift or no shift at all. Furthermore, the γ1-induced shift exhibits a state-dependent labile behavior that recapitulates the fully shifted or unshifted behavior. The γ1-induced shift contrasts markedly to the incremental shifts in BK gating produced by 1-4 ß-subunits and adds a new layer of complexity to the mechanisms by which BK channel functional diversity is generated.

Reduced voltage sensitivity in a K+-channel voltage sensor by electric field remodeling.

Propagation of the nerve impulse relies on the extreme voltage sensitivity of Na(+) and K(+) channels. The transmembrane movement of four arginine residues, located at the fourth transmembrane segment (S4), in each of their four voltage-sensing domains is mostly responsible for the translocation of 12 to 13 e(o) across the transmembrane electric field. Inserting additional positively charged residues between the voltage-sensing arginines in S4 would, in principle, increase voltage sensitivity. Here we show that either positively or negatively charged residues added between the two most external sensing arginines of S4 decreased voltage sensitivity of a Shaker voltage-gated K(+)-channel by up to approximately 50%. The replacement of Val363 with a charged residue displaced inwardly the external boundaries of the electric field by at least 6 A, leaving the most external arginine of S4 constitutively exposed to the extracellular space and permanently excluded from the electric field. Both the physical trajectory of S4 and its electromechanical coupling to open the pore gate seemed unchanged. We propose that the separation between the first two sensing charges at resting is comparable to the thickness of the low dielectric transmembrane barrier they must cross. Thus, at most a single sensing arginine side chain could be found within the field. The conserved hydrophobic nature of the residues located between the voltage-sensing arginines in S4 may shape the electric field geometry for optimal voltage sensitivity in voltage-gated ion channels.

A phase 3, randomised, double-blind, placebo-controlled clinical trial evaluation of the efficacy and safety of a SARS-CoV-2 recombinant spike RBD protein vaccine in adults (ABDALA-3 study).

Background: The pandemic of COVID-19 raised the urgent need for safe and efficacious vaccines against SARS-CoV-2. We evaluated the efficacy and safety of a new SARS-CoV-2 virus receptor-binding domain (RBD) vaccine. Methods: A phase 3, multicentre, randomised, double-blind, placebo-controlled trial was carried out at 18 clinical sites in three provinces of the south-eastern region of Cuba. Subjects (healthy or those with controlled chronic diseases) aged between 19 and 80 years, who gave written informed consent were eligible. Subjects were randomly assigned (1:1, in blocks) to two groups: placebo, and 50 µg RBD vaccine (Abdala). The product was administered intramuscularly, 0.5 mL in the deltoid region, in a three-dose immunization schedule at 0-14-28 days. The organoleptic characteristics and presentations of the vaccine and placebo were identical. All participants (subjects, clinical researchers, statisticians, laboratory technicians, and monitors) remained blinded during the study period. The main endpoint was to evaluate the efficacy of the Abdala vaccine in the prevention of symptomatic COVID-19. The trial is registered with the Cuban Public Registry of Clinical Trials, RPCEC00000359. Findings: Between March 22 to April 03, 2021, 48,290 subjects were included (24,144 and 24,146 in the placebo and Abdala groups, respectively) in the context of predominant D614G variant circulation. The evaluation of the main efficacy outcomes occurred during May-June 2021, starting at May 3rd, in the context of high circulation of mutant viruses, predominantly VOC Beta. The incidence of adverse reactions for individuals in the placebo and Abdala vaccine groups were 1227/24,144 (5.1%) and 1621/24,146 (6.7%), respectively. Adverse reactions were mostly mild, and from the injection site, which resolved in the first 24-48 h. No severe adverse events with demonstrated cause-effect relationship attributable to the vaccine were reported. Symptomatic COVID-19 disease was confirmed in 142 participants in the placebo group (78.44 incidence per 1000 person-years, 95% confidence interval [CI], 66.07-92.46) and in 11 participants in Abdala vaccine group (6.05 incidence per 1000 person years; 95% CI 3.02-10.82). The Abdala vaccine efficacy against symptomatic COVID-19 was 92.28% (95% CI 85.74-95.82). Moderate/serious forms of COVID-19 occurred in 30 participants (28 in the placebo group and only 2 in the Abdala vaccine group) for a vaccine efficacy of 92.88% (95% CI 70.12-98.31). There were five critical patients (of which four died), all in the placebo group. Interpretation: The Abdala vaccine was safe, well tolerated, and highly effective, fulfilling the WHO target product profile for COVID-19 vaccines. Those results, along with its immunization schedule and the advantage of easy storage and handling conditions at 2-8 °C, make this vaccine an option for the use in immunization strategies as a key tool for the control of the pandemic. Funding: Centre for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba.

Drivers and scorecards to improve hypertension control in primary care practice: Recommendations from the HEARTS in the Americas Innovation Group.

Background: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Americas, and hypertension is the most significant modifiable risk factor. However, hypertension control rates remain low, and CVD mortality is stagnant or rising after decades of continuing reduction. In 2016, the World Health Organization (WHO) launched the HEARTS technical package to improve hypertension control. The Pan American Health Organization (PAHO) designed the HEARTS in the Americas Initiative to improve CVD risk management, emphasizing hypertension control, to date implemented in 21 countries. Methods: To advance implementation, an interdisciplinary group of practitioners was engaged to select the key evidence-based drivers of hypertension control and to design a comprehensive scorecard to monitor their implementation at primary care health facilities (PHC). The group studied high-performing health systems that achieve high hypertension control through quality improvement programs focusing on specific process measures, with regular feedback to providers at health facilities. Findings: The final selected eight drivers were categorized into five main domains: (1) diagnosis (blood pressure measurement accuracy and CVD risk evaluation); (2) treatment (standardized treatment protocol and treatment intensification); (3) continuity of care and follow-up; (4) delivery system (team-based care, medication refill), and (5) system for performance evaluation. The drivers and recommendations were then translated into process measures, resulting in two interconnected scorecards integrated into the HEARTS in the Americas monitoring and evaluation system. Interpretation: Focus on these key hypertension drivers and resulting scorecards, will guide the quality improvement process to achieve population control goals at the participating health centers in HEARTS implementing countries. Funding: No funding to declare.

Weak and fragmented regulatory frameworks on the accuracy of blood pressure-measuring devices pose a major impediment for the implementation of HEARTS in the Americas.

Global HEARTS is a WHO initiative for cardiovascular disease prevention and control. Accurate blood pressure (BP) measurement is an essential component of the initiative. This study aimed to determine the regulatory frameworks governing the accuracy of BPMDs in countries of the Americas participating in the HEARTS initiative. Quantitative and qualitative analysis of the laws and regulations relevant to ensuring the accuracy of BPMDs were determined from the Ministries of Health/Regulatory Agencies among 13 countries in Latin America and the Caribbean. Analysis included characterizing the scope of regulations (ie, pre-market approval, sales and promotion, labeling, cuff sizes, and procurement), information systems for monitoring the models of BPMDs used in primary health care (PHC), and systems to enforce compliance with regulations. Ten of the 13 countries had medical device laws, but regulations that specifically address BPMDs only existed in three countries. Only one country (Brazil) had regulations for mandatory accuracy validation testing and only two countries regulated internet sales of BPMDs. Labeling and cuff size regulations existed in four and two countries, respectively. Less than half the countries reported having a data repository on the BPMD models being used in PHC facilities (four countries) or sold (five countries). Weak and fragmented regulatory frameworks on the accuracy of BPMDs exist among countries of the Americas. This will adversely affect the accuracy of blood pressure assessment and hence poses a major impediment for successful implementation of HEARTS initiative.

Beneficios que reciben los pacientes asmáticos tras la aplicación de un tratamiento fisioterapéutico y rehabilitador

El asma bronquial sigue siendo la enfermedad crónica más frecuente en la infancia. Su prevalencia continúa aumentando a pesar de que en la actualidad se disponen de eficaces manuales terapéuticos para el correcto manejo de los principales síntomas de la enfermedad. El tratamiento no farmacológico de este padecimiento se fundamenta en tres pilares esenciales: la educación sobre la enfermedad, las guías para profesionales y pacientes y la fisioterapia respiratoria. Los pacientes que tienen un tratamiento fisioterapéutico y rehabilitador de manera habitual, tienen una mejoría significativa en el control del asma, especialmente si estos se practican bajo la supervisión de un fisioterapeuta. Los beneficios que los pacientes asmáticos logran con la fisioterapia y la rehabilitación son numerosos y uno de los efectos más importante es el impacto positivo sobre la calidad de vida.

Bronchial asthma continues to be the most common chronic disease in childhood. Its prevalence continues to increase despite the fact that effective therapeutic manuals are currently available for the correct management of the main symptoms of the disease. The non-pharmacological treatment of this condition is based on three pillars: education about the disease, guides for professionals and patients, and respiratory physiotherapy. Patients who have regular physiotherapy and rehabilitation treatment have a significant improvement in asthma control, especially if these are practiced under the supervision of a physiotherapist. The benefits that asthmatic patients achieve with physiotherapy and rehabilitation are numerous and one of the most important effects is the positive impact on quality of life.

Organización del enfrentamiento a la COVID-19 en una institución hospitalaria. Provincia Cienfuegos, 2020-2021

Fundamento: las epidemias ponen a prueba la capacidad técnica y humana de los profesionales de la salud. Objetivo: describir la organización de los servicios de atención médica en el enfrentamiento a la COVID-19 en el Centro Especializado Ambulatorio Héroes de Paya Girón, en Cienfuegos. Métodos: se realizó una investigación en sistemas y servicios de salud que describe las etapas de reconversión hospitalaria para la atención de sospechosos y confirmados de COVID-19, el número de pacientes ingresados, la extensión a un centro escolar aledaño y el mantenimiento de otros servicios vitales, disponibilidad de recursos humanos y de camas. Se aplicó el método After Action Review (reflexión después de la acción) para el estudio de lecciones aprendidas. La información se obtuvo de las entrevistas a diez informantes clave y de los informes de los departamentos de estadística y de recursos humanos. Resultados: la organización de la atención médica estuvo relacionada con la evolución de la pandemia en la provincia. Se ingresaron 569 adultos y 91 niños sospechosos en la primera etapa. En la segunda se transformó la misión del centro hacia la atención de casos positivos, se incrementó el número de camas para cuidados intensivos, sobre todo a partir de finales del mes de junio, julio y agosto del 2021. Conclusiones: el centro demostró la capacidad de reordenarse para asumir la atención a enfermedades infecciosas emergentes con expresión epidémica. Las lecciones aprendidas mostraron la necesidad de incrementar la formación en Enfermería Intensiva, y de crear un Manual de Organización y Procedimientos en cada servicio.

ASTRACT Background: epidemics of unknown emerging diseases test not only the technical and human capacity of health professionals, but also of all those who make up the scientific community in society. Objective: to describe the organization of health care services in the fight against COVID-19 at the Héroes de Paya Girón Specialized Outpatient Center, in Cienfuegos. Methods a research was carried out on health systems and services that describe the stages of hospital reconversion for the care of suspected and confirmed patients, the number of admitted patients, the extension to a nearby school center and the maintenance of other vital services. Human resources and availability of beds for patient care were also taken into account. The After Action Review method was applied to study lessons learned. The information was obtained from interviews with ten key informants and from the statistics and human resources departments' reports. Results: the organization of medical care during the year 2020 was related to the evolution of the pandemic in the province. 569 adults and 91 pediatric patients were admitted. On January the 5th, 2021, the second stage of confronting the disease began and the mission of the center was transformed towards the care of positive cases of COVID-19, the number of intensive care beds was increased, a sign of the progressive worsening of patients especially from the end of June, July and August 2021. Conclusions: it can be affirmed that there is a center in the Cienfuegos Province with the capacity to rearrange itself in less than 24 hours to take care of patients with emerging infectious diseases. This shows the need to increase the training of Graduates in Intensive Nursing, as well as to create an Organization and Procedures Manual in each service, adjusted to the care protocols and asepsis, antisepsis and biosafety measures.

Vasculitis del sistema nervioso central

La vasculitis primaria del Sistema Nervioso Central (VPSNC) se refiere a un grupo de enfermedades que resultan de la inflamación y destrucción de los vasos sanguíneos de la médula espinal, encéfalo y meninges, tanto en el sector venoso como arterial, esto puede conducir a la oclusión o formación de aneurismas, con las consiguientes alteraciones isquémico-hemorrágicas.1 La presentación es heterogénea y poco sistematizable. El diagnóstico se establece con un cuadro clínico compatible, una angiografía o biopsia del parénquima encefálico y/o meninges que evidencien vasculitis. Presentamos el caso de un paciente portador de retrovirus con probable VPSNC con clínica compatible, hallazgos imagenológicos sugestivos, con escasa alteración de LCR y EEG.2

Primary vasculitis of the Central Nervous System (VPSNC) refers to a group of diseases that result from inflammation and destruction of the blood vessels of the spinal cord, brain and meninges, both in the venous and arterial sector, this can lead to the occlusion or formation of aneurysms, with the consequent ischemic-hemorrhagic alterations.1 The presentation is heterogeneous and little systematizable. The diagnosis is established with a compatible clinical picture, an angiography or biopsy of the brain parenchyma and/or meninges that show vasculitis. We present the case of a patient with a retrovirus with probable NCPSV with compatible symptoms, suggestive imaging findings, with little CSF and EEG alteration.2

Infección por el VIH/sida en personas de 50 años y más. Cienfuegos 1986-2021

Fundamento: la infección por el virus de la inmunodeficiencia humana es una de las infecciones de trasmisión sexual más importantes para la salud a nivel mundial y una de las más temibles del presente siglo. Objetivo: caracterizar la infección por el virus de la inmunodeficiencia humana en personas de 50 años y más. Métodos: se realizó una investigación observacional descriptiva de corte transversal, que incluyó todas las personas diagnosticadas con el virus de la inmunodeficiencia humana, en Cienfuegos, en el período comprendido de 1986 a 2021. Las variables analizadas fueron: edad, sexo, orientación sexual, grupo de pesquisa, diagnósticos por año y municipio de residencia. Resultados: las personas en el grupo de edad de 50 a 59 años aportaron la mayor incidencia con un 75, 21 %; la orientación sexual predominante fue la homosexual (58,9 %); según los grupos de pesquisa, en los tres grupos de edades sobresale el grupo captado con un 41,88 %. En la provincia se observó un incremento mantenido, fundamentalmente en el sexo masculino, en ascenso en los últimos años. Conclusiones: el aumento de los pacientes con 50 años y más, diagnosticados con virus de la inmunodeficiencia humana, indica que es preciso abordar la problemática con un enfoque clínico epidemiológico diferente. Estas características incrementan el riesgo de infección por VIH por lo que deben ser monitorizadas con la aplicación de la Línea de Trabajo 50 y +, del MINSAP. Es necesario realizar actividades dirigidas a disminuir el riesgo.

Background: infection by the human immunodeficiency virus is one of the most important sexually transmitted infections for health worldwide and one of the most frightening of this century. Objective: to characterize the infection by the human immunodeficiency virus in people aged 50 years and older. Methods: a cross-sectional descriptive observational research was carried out, which included all the people diagnosed with the human immunodeficiency virus, in Cienfuegos, from 1986 to 2021. The analyzed variables were: age, sex, sexual orientation, research group, diagnoses by year and residence municipality. Results: people in the age group of 50 to 59 years contributed the highest incidence with 75.21%; the predominant sexual orientation was homosexual (58,9 %). According to the research groups, in the three age groups the captured group stands out with 41.88%. A sustained increase was observed in the province, mainly in the male sex, rising in recent years. Conclusions: the increase in patients aged 50 and older diagnosed with human immunodeficiency virus indicates that it is necessary to address the problem with a different clinical-epidemiological approach. These characteristics increase the risk of HIV infection, they must be monitored with the application of the MINSAP 50 and + Work Line. It is necessary to carry out activities aimed at reducing the risk.

Strengthening public health policies for childhood cancer: Peru's achievements through the WHO Global Initiative for Childhood Cancer / Fortalecimiento de las políticas de salud pública contra el cáncer infantil: logros de Perú en el marco de la Iniciativa Mundial de la OMS contra el Cáncer Infantil / Fortalecimento das políticas públicas de saúde para o câncer infantil: As conquistas do Peru por meio da Iniciativa Global da OMS para o Câncer Infantil

ABSTRACT Objective. To report the progress in Peru, since June 2019, in the implementation of the World Health Organization Global Initiative for Childhood Cancer using the CureAll framework, which can be replicated in low- and middle-income countries. Methods. A mixed method was used of participatory and documentary evaluation. The participatory evaluation included stakeholders from various government institutions, nonprofit organizations, and international partners. The documentary aspect consisted of a review of data on the regulatory environment, national projects, and interventions implemented. The Ministry of Health engaged more than 150 participants to form working committees, which have developed policy and regulatory documents to strengthen care services. Results. Achievements include a decrease in the national treatment abandonment rate from 18.6% to 8.5%, the approval of the Childhood Cancer Law, improvements in the management of patients with febrile neutropenia, and a reduction in rates of events of clinical deterioration and mortality of hospitalized patients. The Cure All implementation framework allows local teams to implement specific strategies and monitor early outcomes in pediatric oncology. Conclusions. The results obtained reflect the teamwork, the leadership of the authorities, the technical support of professionals, and the support of involved organizations. Further actions will be needed to guarantee sustainability, and monitoring tools are needed to assure success in the planned activities.

RESUMEN Objetivo. Informar sobre los avances de Perú en el periodo transcurrido a partir de junio del 2019, en relación con la puesta en práctica de la Iniciativa Global de la Organización Mundial de la Salud contra el Cáncer Infantil utilizando el marco CureAll, que es posible replicar en los países de ingresos bajos y medianos. Métodos. Se utilizó un método mixto de evaluación participativa y documental. En la evaluación participativa intervinieron las partes interesadas de diversas instituciones gubernamentales, organizaciones sin fines de lucro y asociados internacionales. El aspecto documental consistió en un examen de los datos sobre el entorno regulatorio, los proyectos nacionales y las intervenciones llevadas a cabo. El Ministerio de Salud involucró a más de 150 participantes que formaron los comités de trabajo que han elaborado documentos normativos y regulatorios a fin de reforzar los servicios de asistencia. Resultados. Entre los logros cabe citar la disminución del 18,6% al 8,5% de la tasa nacional de abandono del tratamiento, la aprobación de la Ley de Cáncer Infantil, las mejoras en el tratamiento de los pacientes con neutropenia febril y la reducción de las tasas de episodios de deterioro clínico y de mortalidad en los pacientes hospitalizados. El marco de aplicación de CureAll permite que los equipos locales pongan en práctica estrategias específicas y realicen un seguimiento de los resultados iniciales en el ámbito de la oncología pediátrica. Conclusiones. Los resultados obtenidos reflejan el trabajo en equipo, el liderazgo de las autoridades, el respaldo técnico de los profesionales y el apoyo de las organizaciones implicadas. En el futuro, será necesario adoptar nuevas medidas para asegurar su viabilidad, y será preciso contar con herramientas de seguimiento para garantizar el éxito de las actividades planificadas.

RESUMO Objetivo. Relatar o progresso, desde junho de 2019, da implementação da Iniciativa Global da Organização Mundial da Saúde para o Câncer Infantil no Peru, no âmbito do marco CureAll, que pode ser replicado em países de baixa e média renda. Método. Foi utilizado um método misto de avaliação participativa e documental. A avaliação participativa incluiu interessados diretos de diferentes instituições governamentais, organizações sem fins lucrativos e parceiros internacionais. O aspecto documental consistiu em uma revisão de dados sobre o ambiente regulatório, projetos nacionais e intervenções implementadas. O Ministério da Saúde do Peru contou com mais de 150 participantes para a formação de comitês de trabalho, que elaboraram políticas e documentos normativos para fortalecer os serviços de atenção primária à saúde. Resultados. Entre os resultados alcançados estão a redução da taxa nacional de abandono do tratamento, de 18,6% para 8,5%, a aprovação da Lei do Câncer Infantil, melhorias no manejo de pacientes com neutropenia febril e redução nas taxas de deterioração clínica e mortalidade de pacientes hospitalizados. A implementação do CureAll permite que as equipes locais adotem estratégias específicas e monitorem os resultados iniciais em oncologia pediátrica. Conclusões. Os resultados obtidos refletem o trabalho em equipe, a liderança das autoridades, o suporte técnico dos profissionais e o apoio das organizações envolvidas. Serão necessárias mais ações para garantir a sustentabilidade, além de ferramentas de monitoramento para assegurar o sucesso das atividades planejadas.