Insights and strategies for improving equity in graduate school admissions.

Applying to graduate school can be particularly challenging for students from historically minoritized backgrounds due to a hidden curriculum in the graduate admissions process. To address this issue, a team of volunteer STEM trainees established the Científico Latino Graduate Student Mentorship Initiative (CL-GSMI) in 2019 to support applicants from historically minoritized backgrounds. CL-GSMI is designed to improve access to critical resources, including information, mentorship, and financial support, and has assisted 443 students in applying and matriculating to graduate school. Using program evaluation data from 2020 to 2021, we highlight areas in graduate school admissions that can be improved to promote equity and inclusion.

Characterization of a MHYT domain-coupled transcriptional regulator that responds to carbon monoxide.

The MHYT domain, identified over two decades ago for its potential to detect diatomic gases like CO, O2 or NO, has awaited experimental validation as a protein sensory domain. Here, we characterize the MHYT domain-containing transcriptional regulator CoxC, which governs the expression of the cox genes responsible for aerobic CO oxidation in the carboxidotrophic bacterium Afipia carboxidovorans OM5. The C-terminal LytTR-type DNA-binding domain of CoxC binds to an operator region consisting of three direct repeats sequences overlapping the -35 box at the target PcoxB promoter, which is consistent with the role of CoxC as a specific transcriptional repressor of the cox genes. Notably, the N-terminal transmembrane MHYT domain endows CoxC with the ability to sense CO as an effector molecule, as demonstrated by the relief of CoxC-mediated repression and binding to the PcoxB promoter upon CO exposure. Furthermore, copper serves as the essential divalent cation for the interaction of CO with CoxC, thereby confirming previous hypothesis regarding the role of copper in the gas-sensing mechanism of MHYT domains. CoxC represents the prototype of a novel subfamily of single-component LytTR transcriptional regulators, characterized by the fusion of a DNA-binding domain with a membrane-bound MHYT sensor domain.

Maf/ham1-like pyrophosphatases of non-canonical nucleotides are host-specific partners of viral RNA-dependent RNA polymerases.

Cassava brown streak disease (CBSD), dubbed the "Ebola of plants", is a serious threat to food security in Africa caused by two viruses of the family Potyviridae: cassava brown streak virus (CBSV) and Ugandan (U)CBSV. Intriguingly, U/CBSV, along with another member of this family and one secoviridae, are the only known RNA viruses encoding a protein of the Maf/ham1-like family, a group of widespread pyrophosphatase of non-canonical nucleotides (ITPase) expressed by all living organisms. Despite the socio-economic impact of CDSD, the relevance and role of this atypical viral factor has not been yet established. Here, using an infectious cDNA clone and reverse genetics, we demonstrate that UCBSV requires the ITPase activity for infectivity in cassava, but not in the model plant Nicotiana benthamiana. HPLC-MS/MS experiments showed that, quite likely, this host-specific constraint is due to an unexpected high concentration of non-canonical nucleotides in cassava. Finally, protein analyses and experimental evolution of mutant viruses indicated that keeping a fraction of the yielded UCBSV ITPase covalently bound to the viral RNA-dependent RNA polymerase (RdRP) optimizes viral fitness, and this seems to be a feature shared by the other members of the Potyviridae family expressing Maf/ham1-like proteins. All in all, our work (i) reveals that the over-accumulation of non-canonical nucleotides in the host might have a key role in antiviral defense, and (ii) provides the first example of an RdRP-ITPase partnership, reinforcing the idea that RNA viruses are incredibly versatile at adaptation to different host setups.

Unveiling Melanoma: A Deep Dive into Disparities at a Latin-American Cancer Institute.

INTRODUCTION: The worldwide incidence of melanoma has increased in the last 40 years. Our aim was to describe the clinic-pathological characteristics and outcomes of three cohorts of patients diagnosed with melanoma in a Latin-American cancer institute during the last 20 years. METHODS: We evaluated three retrospective patient cohorts diagnosed with melanoma at Instituto Nacional de Enfermedades Neoplasicas (INEN), a public hospital in Lima, Peru, for the years 2005-2006, 2010-2011, and 2017-2018. Survival rate differences were assessed using the Log-rank test. RESULTS: Overall, 584 patients were included (only trunk and extremities); 51% were male, the mean age was 61 (3-97) years, and 48% of patients resided in rural areas. The mean time to diagnosis was 22.6 months, and the mean Breslow thickness was 7.4 mm (T4). Lower extremity was the most common location (72%). A majority of the patients (55%) had metastases at the time of presentation, with 36% in stage III and 19% in stage IV. Cohorts were distributed as 2005-2006 (n = 171), 2010-2011 (n = 223), and 2017-2018 (n = 190). No immunotherapy was used. Cohort C exhibited the most significant increase in stage IV diagnoses (12.3%, 15.7%, 28.4%, respectively; p < 0.01). The median overall survival rates at the three-year follow-up demonstrated a decline over the years for stages II (97%, 98%, 57%, respectively; p < 0.05) and III (66%, 77%, 37%; p < 0.01). CONCLUSIONS: There has been a worsening in the incidence of late-stage metastatic melanoma in Peru throughout the years, coupled with a significant decline in overall survival rates. This is underscored by the fact that half of the population lives in regions devoid of oncological access.

Simultaneous determination of favipiravir and surrogates of its metabolites by means of heart-cutting bidimensional liquid chromatography (2D-LC).

Therapeutic monitoring of drugs, particularly those with multiple metabolites, can be time-consuming and labor-intensive due to the need for different analytical methods depending on the specific metabolite or matrix of interest. In this study, we employed a heart-cutting 2D-LC separation method based on the coupling of reversed-phase and mixed-mode mechanisms to determine Favipiravir and surrogates of five main metabolites. This approach was applied to serum, plasma, urine, and human peripheral blood mononuclear cells. The method underwent validation to ensure its reliability. The findings highlight the potential of 2D-LC as a practical and efficient approach for therapeutic drug monitoring.

Comparison of the predictive power of two models of cortico-cortical connections in primates: the distance rule model and the structural model.

Synaptic tract-tracing studies in macaques have provided a wealth of data about cortico-cortical connections that have been used to identify regularities and propose models and theories to explain cortical connectivity. The two most relevant of these models are the distance rule model (DRM) and the structural model (SM). They relate the strength and laminar pattern of cortico-cortical connections to two different factors: Euclidean distance (according to the DRM) and cortical type distance (according to the SM). If both predictive factors were correlated, the DRM and the SM would be compatible, but quite often, two cortical areas of similar cortical type are far apart from each other. In the present article, we have performed a conceptual analysis of the DRM and the SM to obtain predictions from each of the two models about strength and laminar pattern of cortico-cortical connections. We then tested the predictive power of each model with analyses of several cortico-cortical connectivity databases to check which of them provide the most accurate predictions. We conclude that the DRM and the SM capture the decrease in connection strength with increasing Euclidean and cortical type distances, respectively; but, for laminar pattern, type distance is a better predictor than Euclidean distance.

Determination of Aminoglycosides by Ion-Pair Liquid Chromatography with UV Detection: Application to Pharmaceutical Formulations and Human Serum Samples.

Aminoglycosides (AGs) represent a prominent class of antibiotics widely employed for the treatment of various bacterial infections. Their widespread use has led to the emergence of antibiotic-resistant strains of bacteria, highlighting the need for analytical methods that allow the simple and reliable determination of these drugs in pharmaceutical formulations and biological samples. In this study, a simple, robust and easy-to-use analytical method for the simultaneous determination of five common aminoglycosides was developed with the aim to be widely applicable in routine laboratories. With this purpose, different approaches based on liquid chromatography with direct UV spectrophotometric detection methods were investigated: on the one hand, the use of stationary phases based on hydrophilic interactions (HILIC); on the other hand, the use of reversed-phases in the presence of an ion-pairing reagent (IP-LC). The results obtained by HILIC did not allow for an effective separation of aminoglycosides suitable for subsequent spectrophotometric UV detection. However, the use of IP-LC with a C18 stationary phase and a mobile phase based on tetraborate buffer at pH 9.0 in the presence of octanesulfonate, as an ion-pair reagent, provided adequate separation for all five aminoglycosides while facilitating the use of UV spectrophotometric detection. The method thus developed, IP-LC-UV, was optimized and applied to the quality control of pharmaceutical formulations with two or more aminoglycosides. Furthermore, it is demonstrated here that this methodology is also suitable for more complex matrices, such as serum, which expands its field of application to therapeutic drug monitoring, which is crucial for aminoglycosides, with a therapeutic index ca. 50%.

Protium heptaphyllum essential oil from the fruit as a sedative and anesthetic in Rhamdia quelen: influence in cardiac frequency, biochemical, and oxidative parameters.

This study aimed to evaluate the effects of Protium heptaphyllum fruit essential oil (PHEO) on the physiology of silver catfish (Rhamdia quelen) during anesthesia and recovery, through studying echocardiograms, oxidative status, and metabolic parameters. Three experiments were performed: (1) 50 silver catfish juveniles were submitted to anesthesia and recovery tests with 300, 400, 500, 600, and 700 mg L-1 of PHEO. (2) Echocardiogram analysis was performed in anesthetized and non-anesthetized fish. (3) Biochemical parameters were evaluated at 0, 30, 60, and 120 min of recovery after being anesthetized for 3 min with 600 mg L-1 PHEO. Times to sedation and deep anesthesia were reduced with PHEO increasing concentrations. The echocardiogram showed a higher cardiac rate in anesthetized fish. Plasma glucose levels increased in control fish through recovery time, but anesthetized fish showed lower levels than controls at 120 min of recovery. Metabolic parameters such as plasma and hepatic glucose did not show changes considering the recovery time of up to 120 min. Hepatic glycogen, lactate, and triglycerides reduced their levels over recovery times. Fish anesthetized enhanced superoxide dismutase activity and thiobarbituric acid reactive substances levels but decreased reduced glutathione (GSH) levels at 30 min compared to controls. After 60 min, GSH values were significantly higher in anesthetized fish than in controls. These results suggest that PHEO at 600 mg L-1 is an effective anesthetic for the rapid handling of silver catfish, providing stable metabolic parameters and enhanced antioxidant responses during recovery. Echocardiogram analysis confirms the anesthetic effect, supporting PHEO as a viable and efficient option for fish anesthesia in aquaculture. The use of PHEO in aquaculture can enhance fish welfare by reducing stress during handling and transportation, potentially leading to improved growth, health, and survival rates.

Hyperpolarization of 15N-Pyridinium by Using Parahydrogen Enables Access to Reactive Oxygen Sensors and Pilot In Vivo Studies.

Magnetic resonance with hyperpolarized contrast agents is one of the most powerful and noninvasive imaging platforms capable for investigating in vivo metabolism. While most of the utilized hyperpolarized agents are based on 13C nuclei, a milestone advance in this area is the emergence of 15N hyperpolarized contrast agents. Currently, the reported 15N hyperpolarized agents mainly utilize the dissolution dynamic nuclear polarization (d-DNP) protocol. The parahydrogen enhanced 15N probes have proven to be elusive and have been tested almost exclusively in organic solvents. Herein, we designed a reaction based reactive oxygen sensor 15N-boronobenzyl-2-styrylpyridinium (15N-BBSP) which can be hyperpolarized with para-hydrogen. Reactive oxygen species plays a vital role as one of the essential intracellular signalling molecules. Disturbance of the H2O2 level usually represents a hallmark of pathophysiological conditions. This H2O2 probe exhibited rapid responsiveness toward H2O2 and offered spectrally resolvable chemical shifts. We also provide strategies to bring the newly developed probe from the organic reaction solution into a biocompatible injection buffer and demonstrate the feasibility of in vivo 15N signal detection. The present work manifests its great potential not only for reaction based reactive sensing probes but also promises to serve as a platform to develop other contrast agents.

Novel approaches to energize microbial biocatalysts.

An efficient and cheap energization of microbial biocatalysts is essential in current biotechnological processes. A promising alternative to the use of common organic or inorganic electron donors is the semiconductor nanoparticles (SNs) that absorb light and transfer electrons (photoelectrons) behaving as artificial photosynthetic systems (biohybrid systems). Excited photoelectrons generated by illuminated SNs are highly reductive and readily accepted by membrane-bound proteins and electron shuttles to drive specific cell reduction processes and energy generation in microbes. However, the operational mechanisms of these hybrid systems are still poorly understood, especially at the material-microbe interface, and therefore the design and production of efficient biohybrids are challenging. Some major limitations/challenges and future prospects of SNs as microbial energization systems are discussed.

Super-resolution of sodium images from simultaneous 1 H MRF/23 Na MRI acquisition.

In this work, we introduce a super-resolution method that generates a high-resolution (HR) sodium (23 Na) image from simultaneously acquired low-resolution (LR) 23 Na density-weighted MRI and HR proton density, T1 , and T2 maps from proton (1 H) MR fingerprinting in the brain at 7 T. The core of our method is a partial least squares regression between the HR (1 H) images and the LR (23 Na) image. An iterative loop and deconvolution with the point spread function of each acquired image were included in the algorithm to generate a final HR 23 Na image without losing features from the LR 23 Na image. The method was applied to simultaneously acquired HR proton and LR sodium data with in-plane resolution ratios between sodium and proton data of 3.8 and 1.9 and the same slice thickness. Four volunteers were scanned to evaluate the method's performance. For the data with a resolution ratio of 3.8, the mean absolute difference between the generated and ground truth HR 23 Na images was in the range of 1.5%-7.2% of the ground truth with a multiscale structural similarity index (M-SSIM) of 0.93 ± 0.03. For the data with a resolution ratio of 1.9, the mean absolute difference was in the range of 4.8%-6.3% with an M-SSIM of 0.95 ± 0.01.

CPEB4-CLOCK crosstalk during temporal lobe epilepsy.

OBJECTIVE: Posttranscriptional mechanisms are increasingly recognized as important contributors to the formation of hyperexcitable networks in epilepsy. Messenger RNA (mRNA) polyadenylation is a key regulatory mechanism governing protein expression by enhancing mRNA stability and translation. Previous studies have shown large-scale changes in mRNA polyadenylation in the hippocampus of mice during epilepsy development. The cytoplasmic polyadenylation element-binding protein CPEB4 was found to drive epilepsy-induced poly(A) tail changes, and mice lacking CPEB4 develop a more severe seizure and epilepsy phenotype. The mechanisms controlling CPEB4 function and the downstream pathways that influence the recurrence of spontaneous seizures in epilepsy remain poorly understood. METHODS: Status epilepticus was induced in wild-type and CPEB4-deficient male mice via an intra-amygdala microinjection of kainic acid. CLOCK binding to the CPEB4 promoter was analyzed via chromatin immunoprecipitation assay and melatonin levels via high-performance liquid chromatography in plasma. RESULTS: Here, we show increased binding of CLOCK to recognition sites in the CPEB4 promoter region during status epilepticus in mice and increased Cpeb4 mRNA levels in N2A cells overexpressing CLOCK. Bioinformatic analysis of CPEB4-dependent genes undergoing changes in their poly(A) tail during epilepsy found that genes involved in the regulation of circadian rhythms are particularly enriched. Clock transcripts displayed a longer poly(A) tail length in the hippocampus of mice post-status epilepticus and during epilepsy. Moreover, CLOCK expression was increased in the hippocampus in mice post-status epilepticus and during epilepsy, and in resected hippocampus and cortex of patients with drug-resistant temporal lobe epilepsy. Furthermore, CPEB4 is required for CLOCK expression after status epilepticus, with lower levels in CPEB4-deficient compared to wild-type mice. Last, CPEB4-deficient mice showed altered circadian function, including altered melatonin blood levels and altered clustering of spontaneous seizures during the day. SIGNIFICANCE: Our results reveal a new positive transcriptional-translational feedback loop involving CPEB4 and CLOCK, which may contribute to the regulation of the sleep-wake cycle during epilepsy.

Stress response of Rhamdia quelen to the interaction stocking density - Feeding regimen.

This study aimed to verify the effect of different feeding and stocking conditions during 14 days on the gene expression of several hormones and enzymes related to the stress cascade and metabolic parameters in silver catfish Rhamdia quelen under the following experimental conditions: 1) fed at low stocking density (2.5 kg m-3, LSD-F); 2) fed at high stocking density (32 kg m-3, HSD-F); 3) food-deprived at LSD (LSD-FD); and 4) food-deprived at HSD (HSD-FD). Fish from LSD-F and HSD-F groups were fed daily (1 % of their body mass), while fish from food-deprived groups (LSD-FD and HSD-FD) were not fed during the experimental time. Plasma metabolic parameters (glucose, lactate, triglycerides, and proteins) and hepatosomatic index (HSI) were evaluated. In addition, mRNA expression of genes related to the stress axis (crh, pomca, pomcb, nr3c2, star, hsd11b2 and hsd20b), heat shock protein family (hsp90 and hspa12a), sodium-dependent noradrenaline transporter (slc6a2), and growth axis (gh and igf1) were also assessed. Specific growth rate and HSI decreased in food-deprived fish regardless of stocking density. The HSD-FD group showed weight loss compared to the HSD-F, LSD-F, and LSD-FD groups. Plasma glucose and triglycerides were reduced in food-deprived groups, while lactate and protein levels did not change. The expression of key players of the stress response (crh, pomca, pomcb, hsd11b2, nr3c2, and hsp90b) and growth (gh and igf1) pathways were differently regulated depending on the experimental condition, whereas no statistical difference between treatments was found for hsd20b, scl6a2, hspa12a, and star mRNAs expression. This study suggests that LSD acts as a stressor affecting negatively the physiological status of fed fish, as demonstrated by the reduction in growth rates, altered metabolic orchestration, and a higher crh mRNA expression. In addition, food deprivation also increased mRNA expression of other assessed genes (nr3c2, hsp90b, pomca, and pomcb) in fish from the HSD group, indicating higher responsiveness to stress in this stocking density when combined with food deprivation.

Melanocytic Matricoma With Atypical Histopathological Features: A Case Report of an Extremely Rare Entity and Review of the Literature.

ABSTRACT: Melanocytic matricoma with atypical features is a rare, biphasic adnexal neoplasm displaying hair matrix differentiation, with only 3 reported cases worldwide. Generally, the lesion comprised a solid matrical and supramatrical cell proliferation, admixed with intermediate cell aggregates with sparse anucleated "shadow cells" and a prominent pigmented melanocytic hyperplasia. We report the case of a 78-year-old man with a slow-growing crusted lesion on the frontal left scalp, which in a matter of 1-2 months became a 0.6 cm well-defined, black purplish exophytic nodule. Histopathologically, the lesion presented a well-circumscribed border with a nodular dermal growth pattern, presenting different architectural features varying from benign pilomatricoma-like changes to atypical features such as moderate-to-high nuclear pleomorphism in both basaloid (matrical/supramatrical) and epidermal (keratinous) components. Strong nuclear and cytoplasmic positivity for ß-catenin was observed in matrical cells, whereas prominent cytoplasmic membrane positivity for Melan-A in dendritic melanocytes. Owing to the evidence of atypical cytological features, we propose the "atypical/borderline" category of melanocytic matricoma as part of a possible spectrum among matrical neoplasms. Pathologists should be aware of any atypical histopathological features while reporting cases due to their potential malignant transformation.

Protective Role of Tacrolimus, Deleterious Role of Age and Comorbidities in Liver Transplant Recipients With Covid-19: Results From the ELITA/ELTR Multi-center European Study.

BACKGROUND AND AIMS: Despite concerns that liver transplant (LT) recipients may be at increased risk of unfavorable outcomes from COVID-19 due the high prevalence of co-morbidities, immunosuppression and ageing, a detailed analysis of their effects in large studies is lacking. METHODS: Data from adult LT recipients with laboratory confirmed SARS-CoV2 infection were collected across Europe. All consecutive patients with symptoms were included in the analysis. RESULTS: Between March 1 and June 27, 2020, data from 243 adult symptomatic cases from 36 centers and 9 countries were collected. Thirty-nine (16%) were managed as outpatients while 204 (84%) required hospitalization including admission to the ICU (39 of 204, 19.1%). Forty-nine (20.2%) patients died after a median of 13.5 (10-23) days, respiratory failure was the major cause. After multivariable Cox regression analysis, age >70 (HR, 4.16; 95% CI, 1.78-9.73) had a negative effect and tacrolimus (TAC) use (HR, 0.55; 95% CI, 0.31-0.99) had a positive independent effect on survival. The role of co-morbidities was strongly influenced by the dominant effect of age where comorbidities increased with the increasing age of the recipients. In a second model excluding age, both diabetes (HR, 1.95; 95% CI, 1.06-3.58) and chronic kidney disease (HR, 1.97; 95% CI, 1.05-3.67) emerged as associated with death CONCLUSIONS: Twenty-five percent of patients requiring hospitalization for COVID-19 died, the risk being higher in patients older than 70 and with medical co-morbidities, such as impaired renal function and diabetes. Conversely, the use of TAC was associated with a better survival thus encouraging clinicians to keep TAC at the usual dose.

Are short-term complications associated with poor allograft and patient survival after liver transplantation? A systematic review of the literature and expert panel recommendations.

BACKGROUND: Maximizing patient and allograft survival after liver transplant (LT) is important from both a patient care and organ utilization perspective. Although individual studies have addressed the effects of short-term post-LT complications on a limited scale, there has not been a systematic review of the literature formally assessing the potential effects of early complications on long-term outcomes. OBJECTIVES: To identify whether short-term complications after LT affect allograft and overall survival, to identify short-term complications of particular clinical interest and significance, and to provide recommendations to improve post-LT graft and patient survival. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: A systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. RESULTS: The literature review and analysis provided show that short-term complications have a large impact on allograft and patient survival after LT. The complications with the strongest effect on survival are acute kidney injury (AKI), biliary complications, and early allograft dysfunction (EAD). CONCLUSION: This panel recommends taking measures to reduce the risk and incidence of short-term complications post-LT. Clinicians should pay particular attention to preventing or ameliorating AKI, biliary complications, and EAD (Quality of evidence; Moderate | Grade of Recommendation; Strong).

Perioperative management of adult living donor liver transplantation: Part 1 - recipients.

Living donor liver transplantation was first developed to mitigate the limited access to deceased donor organs in Asia in the 1990s. This alternative liver transplantation option has become an established and widely practiced transplantation method for adult patients suffering from end-stage liver disease. It has successfully addressed the shortage of deceased donors. The Society for the Advancement of Transplant Anesthesia and the Korean Society of Transplant Anesthesia jointly reviewed published studies on the perioperative management of live donor liver transplant recipients. The review aims to offer transplant anesthesiologists and critical care physicians a comprehensive overview of the perioperative management of adult live liver transplantation recipients. We feature the status, outcomes, surgical procedure, portal venous decompression, anesthetic management, prevention of acute kidney injury, avoidance of blood transfusion, monitoring and therapeutic strategies of hemodynamic derangements, and Enhanced Recovery After Surgery protocols for liver transplant recipients.

HEARTS in the Americas appraisal checklist and clinical pathway for comprehensive hypertension management in primary care.

Cardiovascular diseases are the leading cause of mortality and morbidity in the Region of the Americas, and hypertension represents its main risk factor. However, population hypertension control rates in the Region are poor. Global Hearts is the World Health Organization's flagship initiative to reduce the burden of cardiovascular diseases. HEARTS in the Americas Initiative is its regional adaptation that seeks to be the cardiovascular disease risk management model, including hypertension and diabetes, in primary health care throughout the Americas by 2025. HEARTS in the Americas is being implemented in 22 countries and over 2 095 primary care centers. All implementing countries have defined their treatment protocols, and HEARTS in the Americas has supported continuous improvement. Because WHO recently released the 2021 Guideline for the Pharmacological Treatment of Hypertension in Adults and HEARTS in the Americas introduced the key drivers for hypertension control, the initiative generated a methodology to help countries update and strengthen their treatment protocols. This article describes the process of developing the treatment protocol appraisal checklist and defines the resulting clinical pathway. This tool can help countries and primary care centers to improve their protocols by identifying the improvement points and upgrading clinical pathways.

Las enfermedades cardiovasculares son la principal causa de mortalidad y morbilidad en la Región de las Américas, y la hipertensión representa su principal factor de riesgo. Sin embargo, las tasas de control de la hipertensión arterial en la Región son desalentadoras. Global Hearts es la iniciativa insignia de la Organización Mundial de la Salud para reducir la carga de las enfermedades cardiovasculares. La iniciativa HEARTS en las Américas es su adaptación regional, y tiene como objetivo ser el modelo de manejo del riesgo de enfermedades cardiovasculares, incluida la hipertensión y la diabetes, en la atención primaria de salud en la Región para el año 2025.HEARTS en las Américas se está aplicando en 22 países y más de 2 095 centros de atención primaria. Todos los países que están aplicando esta iniciativa han definido sus protocolos de tratamiento, y HEARTS en las Américas ha brindado apoyo para la mejora continua. Debido a que la OMS publicó recientemente la guía para el tratamiento farmacológico de la hipertensión en adultos (2021) y HEARTS en las Américas determinó cuáles son los impulsores clave para el control de la hipertensión, la iniciativa elaboró una metodología para ayudar a los países a actualizar y fortalecer sus protocolos de tratamiento.En este artículo se describe el proceso de elaboración de la lista de verificación para la evaluación del protocolo de tratamiento y se define la vía clínica resultante. Esta herramienta puede ayudar a los países y los centros de atención primaria a mejorar sus protocolos para que determinen cuáles son los puntos que se deben mejorar y elaboren las vías clínicas.

A iniciativa HEARTS nas Américas está sendo implementada em 22 países e mais de 2 095 centros de atenção primária à saúde. Todos os países que estão implementando a iniciativa definiram seus protocolos de tratamento, e a HEARTS nas Américas contribuiu para a melhoria contínua. Como a OMS lançou recentemente as Diretrizes de 2021 para o tratamento medicamentoso da hipertensão arterial em adultos e a HEARTS nas Américas desenvolveu os elementos essenciais para o controle da hipertensão, a iniciativa criou uma metodologia para auxiliar os países na atualização e no fortalecimento de seus protocolos de tratamento.Este artigo descreve o processo de elaboração da lista de verificação para avaliação do protocolo de tratamento e define o caminho clínico resultante. Esta ferramenta pode ajudar os países e os centros de atenção primária à saúde a aprimorarem seus protocolos mediante a identificação dos pontos para melhoria e o desenvolvimento de caminhos clínicos.As doenças cardiovasculares são a principal causa de morbimortalidade na Região das Américas, e a hipertensão é seu principal fator de risco. Entretanto, as taxas de controle da hipertensão na população da Região são baixas. Global Hearts é a principal iniciativa da Organização Mundial da Saúde para reduzir a carga de doenças cardiovasculares. A iniciativa HEARTS nas Américas é sua adaptação regional, que almeja ser o modelo para o gerenciamento de risco de doenças cardiovasculares, incluindo a hipertensão e o diabetes, na atenção primária à saúde em toda a Região das Américas até 2025.

[Implementation of the HEARTS Initiative in Argentina: initial resultsImplementação da Iniciativa HEARTS na Argentina: primeiros resultados]. / Implementación de la Iniciativa HEARTS en Argentina: primeros resultados.

Cardiovascular diseases are the leading cause of mortality and morbidity in the Region of the Americas, and hypertension is one of the main risk factors. In 2018, Argentina began implementing the HEARTS Initiative in five primary health care centers, through the National Plan for the Prevention and Control of Arterial Hypertension. This study presents the impact its implementation has had on the indicators of effective coverage, treatment, combination therapy, and control. The HEARTS Initiative has multiple components; these include training health teams, reassigning tasks based on the transfer of clinical competencies, providing automatic and clinically validated blood pressure measurement devices, and using a single standardized treatment protocol. A longitudinal data model (generalized estimating equation analysis) was used, and the information from the five health centers was grouped using weighted averages according to the size of the population under coverage. Analysis of the results was stratified into two time periods delimited by the imposition of restrictions due to COVID-19. During the first period of 18 months, significant improvement was observed in treatment (5.9%; p<0.01) and combination therapy (13.4%; p<0.01), with no significant change in coverage (8.4%; p=0.87) and with a paradoxical decrease in control (-3.3%; p=0.02). When the period of restrictions was compared to the previous period, a generalized reduction was observed in all indicators, particularly coverage (-23.6%; p<0.01) and control (-12.5%; p<0.01). However, treatment and combination therapy levels remained above baseline values (1.7%; p<0.01 and 5.4%; p<0.01, respectively).

As doenças cardiovasculares são a principal causa de morbimortalidade, e a hipertensão, seu principal fator de risco. Em 2018, a Argentina começou a implementar a Iniciativa HEARTS em 5 centros de atenção primária à saúde por meio do Plano Nacional de Prevenção e Controle da Hipertensão Arterial. Este estudo apresenta o impacto de sua implementação nos indicadores de cobertura efetiva, tratamento, tratamento combinado e controle. A Iniciativa HEARTS inclui vários componentes. Entre eles, se destacam a capacitação das equipes de saúde, a reorganização das tarefas com base na transferência de competências clínicas, a disponibilização de aparelhos automáticos e clinicamente validados para aferição da pressão arterial e a utilização de um único protocolo padronizado de tratamento. Foi utilizado um modelo de equações de estimativas generalizadas para a análise de dados longitudinais, e as informações dos 5 centros de saúde foram agrupadas por meio de médias ponderadas de acordo com o tamanho da população coberta. A análise dos resultados foi estratificada em dois períodos de tempo delimitados pela irrupção das restrições em virtude da COVID-19. Durante os primeiros 18 meses, houve melhora significativa no tratamento (5,9%; p<0,01) e no tratamento combinado (13,4%; p<0,01), sem mudança significativa na cobertura (8,4%; p=0,87) e com uma diminuição paradoxal no controle (−3,3%; p=0,02). Durante as restrições e em relação ao período anterior, verificou-se redução generalizada em todos os indicadores, principalmente na cobertura (−23,6%; p<0,01) e no controle (−12,5%; p<0,01). No entanto, os níveis de tratamento e tratamento combinado persistiram acima dos valores basais (1,7%; p<0,01 e 5,4%; p<0,01, respectivamente).

[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.