Engineering bacterial biocatalysts for the degradation of phthalic acid esters.

Phthalic acid esters (PAEs) are synthetic diesters derived from o-phthalic acid, commonly used as plasticizers. These compounds pose significant environmental and health risks due to their ability to leach into the environment and act as endocrine disruptors, carcinogens, and mutagens. Consequently, PAEs are now considered major emerging contaminants and priority pollutants. Microbial degradation, primarily by bacteria and fungi, offers a promising method for PAEs bioremediation. This article highlights the current state of microbial PAEs degradation, focusing on the major bottlenecks and associated challenges. These include the identification of novel and more efficient PAE hydrolases to address the complexity of PAE mixtures in the environment, understanding PAEs uptake mechanisms, characterizing novel o-phthalate degradation pathways, and studying the regulatory network that controls the expression of PAE degradation genes. Future research directions include mitigating the impact of PAEs on health and ecosystems, developing biosensors for monitoring and measuring bioavailable PAEs concentrations, and valorizing these residues into other products of industrial interest, among others.

Parahydrogen-enhanced pH measurements using [1-13C]bicarbonate derived from non-enzymatic decarboxylation of [1-13C]pyruvate-d3.

Alterations in pH are a hallmark in several pathologies including cancer, ischemia, and inflammation. Non-invasive magnetic resonance methods to measure pH offer a new approach for early diagnosis of diseases characterized by acid-base imbalances. The hyperpolarization with parahydrogen-induced polarization (PHIP) enhances inherently low signals in magnetic resonance experiments by several orders of magnitude and offers a suitable platform to obtain biocompatible markers in less than one minute. Here, we present an optimized preparation of an hyperpolarized H13CO3-/13CO2 pH sensor via non-enzymatic decarboxylation with H2O2 of [1-13C]pyruvate-d3 obtained by PHIP at 7 T. An improved 13C polarization of purified [1-13C]pyruvate-d3 in water with 36.65 ± 0.06% polarization was obtained starting from 50 mM precursor. Subsequent decarboxylation, H13CO3-/13CO2 exhibited 12.46 ± 0.01% of polarization at physiological pH, 45 seconds after the reaction start. Considering the dilution factor that [1-13C]pyruvate-d3 exhibits in vivo, we optimized our methodology to test the accuracy of the pH sensor at single digit millimolar concentration. In vitro pH estimations on phantoms and cell culture media demonstrated accurate pH calculations with uncertainties of less than 0.08 units. These promising results highlight the efficiency of a pH sensor generated via PHIP in less than one minute, with remarkable polarization, and biocompatibility suitable for future in vivo studies.

Tissue explants as tools for studying the epigenetic modulation of the GH-IGF-I axis in farmed fish.

Somatic growth in vertebrates is mainly controlled by the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis. The role of epigenetic mechanisms in regulating this axis in fish is far from being understood. This work aimed to optimize and evaluate the use of short-term culture of pituitary and liver explants from a farmed fish, the gilthead seabream Sparus aurata, for studying epigenetic mechanisms involved in GH/IGF-I axis regulation. Our results on viability, structure, proliferation, and functionality of explants support their use in short-term assays. Pituitary explants showed no variation in gh expression after exposure to the DNA methylation inhibitor decitabine (5-Aza-2'-deoxycytidine; DAC), despite responding to DAC by changing dnmt3bb and tet1 expression, and TET activity, producing an increase in overall DNA hydroxymethylation. Conversely, in liver explants, DAC had no effects on dnmt s and tet s expression or activity, but modified the expression of genes from the GH-IGF-I axis. In particular, the expression of igfbp2a was increased and that of igfbp4, ghri and ghrii was decreased by DAC as well as by genistein, which is suggestive of impaired growth. While incubation of liver explants with S-adenosylmethionine (SAM) produced no clear effects, it is proposed that nutrients must ensure the methylation milieu within the liver in the fish to sustain proper growth, which need further in vivo verification. Pituitary and liver explants from S. aurata can be further used as described herein for the screening of inhibitors or activators of epigenetic regulators, as well as for assessing epigenetic mechanisms behind GH-IGF-I variation in farmed fish.

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.

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.

Safety and Outcomes in Multiplane Facial Rejuvenation with Tranexamic Acid: A Cohort Study.

Background: Tranexamic acid (TXA) has demonstrated promising outcomes in plastic surgery. Our aim was to assess the effect of TXA in intraoperative bleeding, operative time, and complications among patients undergoing facial surgical procedures. Methods: A retrospective cohort study of patients who underwent multiplane facial rhytidectomy from January 2018 to September 2022 at the Clinica Ziegler, Lima, Peru. Patients were divided into two groups according to the use of intravenous plus local infiltration of TXA. We performed the chi square test to assess associations among categorical variables, the Student t test and Mann-Whitney U test for categorical with continuous variables, and Pearson correlation for quantitative variables. Results: A total of 100 patients were included with 50 patients in each group. The median age was 59.5 years and the majority were women (88%). The median operative time was 288.5 minutes. The TXA group presented less intraoperative bleeding (40 versus 90 mL, P < 0.05) and shorter operative time (237 versus 353 minutes, P < 0.05); no differences in the development of hematoma (2% versus 12%, P = 0.11), less ecchymosis (2% versus 36%, P < 0.05), edema (2% versus 100%, P < 0.05), and time to drain removal (3 versus 6 days, P < 0.05). Conclusions: TXA improves the short- and long-term outcomes of patients who undergo multiplane facial rhytidectomy. It also decreases intraoperative bleeding by more than half and reduces the operative time by one third. Moreover, patients receiving TXA presented significantly less ecchymosis, edema, and time to drain removal.

Prepectoral and Retropectoral Breast-implant-Associated Anaplastic Large-cell Lymphoma.

Breast-implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a non-Hodgkin lymphoma that arises in the space between the surface of a breast implant and the fibrous capsule that grows around the implant. Since its first description 20 years ago, almost 1000 cases of BIA-ALCL have been diagnosed worldwide. Nowadays, guidelines describe the diagnosis, staging, and treatment of this disease. We present the first two cases diagnosed and treated in Peru, demonstrating a wide range of aggressiveness of BIA-ALCL.

Caracterización de neonatos con asfixia perinatal. Hospital Provincial Docente Ginecobstétrico José Ramón López Tabrane. 2016-2021

Introducción: La asfixia perinatal es un síndrome caracterizado por la suspensión o grave disminución del intercambio gaseoso a nivel de la placenta o de los pulmones. Objetivo: Caracterizar los neonatos con asfixia perinatal durante el trabajo de parto con la introducción de la gasometría de la arteria umbilical. Materiales y métodos: Se realizó un estudio descriptivo, transversal, de octubre de 2016 a diciembre de 2021. Se trabajó con la totalidad del universo: 75 neonatos asfícticos. Las variables fueron: edad materna, edad gestacional al nacimiento, enfermedades asociadas y dependientes del embarazo, tipo y tiempo de trabajo de parto, características del líquido amniótico, anomalías de la placenta y cordón umbilical, pH de la gasometría de la arteria del cordón, evolución clínica del recién nacido. Los datos se almacenaron y procesaron en una hoja de cálculo de Microsoft Excel, utilizando la estadística descriptiva. Resultados: Predominaron pacientes con edad materna menor de 20 años (56 %), y edad gestacional al nacimiento de 28 a 33,6 semanas (77,3 %). La hipertensión arterial fue la comorbilidad más común, así como la preeclampsia, entre las enfermedades dependiente del embarazo (30,7 %); 61,3 % tuvieron parto eutócico, con líquido amniótico claro (65,3 %), placenta previa (38,7 %) y circulares en cordón umbilical (30,7 %). En el 86,7 % el pH de la gasometría fue menor que 7, y el 92 % presentó evolución clínica favorable. Conclusiones: La asfixia perinatal estuvo predominantemente asociada a madres adolescentes, con tiempo gestacional entre 28 y 36 semanas, preeclampsia, placenta previa, circulares del cordón umbilical y predominio de gasometría con pH menor que 7.

Introduction: Perinatal asphyxia is a syndrome characterized by the suspension or severe decrease in gas exchange at the level of the placenta or lungs. Objective: To characterize neonates with perinatal asphyxia during labor with the introduction of umbilical arterial blood gas test. Materials and methods: A descriptive, cross-sectional study was carried out from October 2016 to December 2021. It dealt with the entire universe, 75 asphyxiated neonates. The variables were: maternal age, gestational age at birth, associated and pregnancy-dependent diseases, type and time of labor, characteristics of the amniotic fluid, anomalies of the placenta and umbilical cord, pH of the cord arterial blood gas test, clinical evolution of the newborn. The data were stored and processed in a Microsoft Excel spreadsheet, using descriptive statistics. Results: Patients with maternal age below 20 years (56%), and gestational age at birth from 28 to 33.6 weeks (77.3%) predominated. Arterial hypertension was the most common comorbidity, as well as preeclampsia, among pregnancy-dependent diseases (30.7%); 61.3% had eutocic delivery, with clear amniotic fluid (65.3%), previous placenta (38.7%) and umbilical cord circulars (30.7%). In 86.7%, the blood gas pH was less than 7 and 92% had a favorable clinical evolution. Conclusions: Perinatal asphyxia was predominantly associated with adolescent mothers, with gestational time between 28-36 weeks; preeclampsia, placenta previa, umbilical cord circulars, and blood gases pH lower than 7.

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.

Risk of Intraocular Lens Opacification After Endothelial Keratoplasty for Different Intraocular Lens Models: A Retrospective Single-Center Cohort Study.

PURPOSE: The aims of this study were to calculate the specific risk of opacification for different intraocular lens (IOL) models and to determine whether differences exist, even between lenses made of similar acrylic materials. METHODS: This is a retrospective cohort study of all patients who underwent endothelial keratoplasty (EK), either after or in conjunction with cataract surgery, from June 2009 to October 2020 at Fundación Jiménez Díaz Hospital. RESULTS: Three hundred seventy-two eyes of 308 patients with a median follow-up of 856 days [interquartile range (IQR): 384-1570] were included, of which 128 IOLs were hydrophobic, 120 hydrophilic, and 124 unknown. 12.9% of IOLs opacified after a median of 466 days (IQR: 255-743). Visual acuity (VA) was significantly lower in the opacified IOL group [0.51 (IQR: 0.36-1.13)] compared with the nonopacified group [0.22 (IQR: 0.11-0.65)] ( P < 0.001). IOL explantation and exchange was performed in 10 eyes, in which VA improved markedly, from 1.75 (IQR: 0.99-3.00) to 0.60 (IQR: 0.36-0.86) ( P = 0.004). IOL material and opacification events were not independent ( P < 0.001). Significant differences were found between the Akreos ADAPT AO and MI60P models and the Asphina 409M model ( P = 0.022). No significant differences were found in the opacification ratio for hydrophilic IOLs in the clinical diagnosis ( P = 0.11), the type of EK ( P = 0.25), the rebubbling rate ( P = 0.44), or the tamponade used ( P = 0.36). CONCLUSIONS: Hydrophilic lenses should be avoided in patients at risk of requiring EK. It is important to know the probability of opacification of each IOL model to balance risk and benefits when planning an EK procedure because not all lenses opacify equally. Opacification is an unwanted event with a negative impact on VA, making IOL explantation and exchange the only viable treatment, although one that is not without risks.

Caracterización clínica de las gestantes hipertensas crónicas. Hospital Provincial Ginecobstétrico Docente José Ramón López Tabrane

RESUMEN Introducción: la hipertensión arterial crónica durante el embarazo se asocia al incremento de complicaciones obstétricas y perinatales. Objetivo: caracterizar a las gestantes hipertensas crónicas en el Hospital Provincial Ginecobstétrico Docente José Ramón López Tabrane. Materiales y métodos: estudio descriptivo prospectivo efectuado mediante la revisión de las historias clínicas, interrogatorios y el examen de gestantes que ingresaron al Hospital Provincial Ginecobstétrico Docente José Ramón López Tabrane, entre septiembre de 2020 y septiembre de 2021, con diagnóstico de hipertensión arterial crónica. Se identificaron ocho variables y se estimó la prevalencia de estas mediante frecuencias absolutas y relativas. Resultados: se estudiaron 126 gestantes, de las cuales 86 tenían 35 años o más, la mayoría clasificadas como hipertensas leves. En el 70,6 % de los casos se presentó alguna enfermedad asociada; 25,4 % presentó una ganancia de peso normal; en el 81 % de las pacientes se utilizó la cesárea como vía para concluir la gestación. Las principales complicaciones fueron: parto pretérmino (27,1 %), preeclampsia (16,7 %), oligoamnios (16,7 %) y restricción del crecimiento intrauterino (13,5 %). Ocurrieron cuatro muertes neonatales. La evolución posparto fue insatisfactoria en 24 casos. Conclusiones: la gestante hipertensa fue generalmente mayor de 35 años, con anemia como entidad asociada. Predominó la hipertensión arterial crónica leve, con ganancia de peso excesiva. La vía de terminación del embarazo de elección fue la cesárea, la que predominó en gestaciones a término. Las principales complicaciones fueron el parto pretérmino y la preeclampsia sobreañadida, el oligoamnios y la restricción del crecimiento intrauterino.

ABSTRACT Introduction: chronic arterial hypertension during pregnancy is associated with an increase in obstetric and perinatal complications. Objective: to characterize chronic hypertensive pregnant women at Provincial Teaching Gynecobstetric Hospital José Ramón Lopez Tabrane. Materials and methods: descriptive-prospective study carried out by reviewing the medical records, interviews and examination of pregnant women who were admitted to the Provincial teaching Gynecobstetric Hospital José Ramón López Tabrane, between September 2020 and September 2021, with a diagnosis of chronic arterial hypertension. Eight variables were identified and their prevalence was estimated using absolute and relative frequencies. Results: 126 pregnant women were studied, 86 of whom were 35 years old or older, most classified as mild hypertensive. In 89 cases, some associated disease was present. 25.4 % presented normal weight gain. In 81 % of patients, cesarean section was used as a way to end the pregnancy. The main complications were: preterm delivery (27.1 %), preeclampsia (16.7 %), oligohydramnios (16.7 %) and intrauterine growth restriction (13.5 %). Four neonatal deaths occurred. Postpartum evolution was unsatisfactory in 24 cases. Conclusions: the hypertensive pregnant woman was generally older than 35 years, with anemia as an associated entity. Chronic mild arterial hypertension prevailed, with excessive weight gain. The way of ending pregnancy of choice was cesarean section, which prevailed in full-term pregnancies. The main complications were pre-term deliveries and overadded preeclampsia, oligohydramnios and intrauterine growth restriction.

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.

Sinopsis de la Situación de Salud Oral en Chile - Parte IV: Traumatismo Dentoalveolar / Synopsis of the Oral Health Situation in Chile - Part IV: Traumatic Dental Injuries

RESUMEN: Objetivo: Sintetizar los resultados de estudios epidemiológicos sobre Traumatismo Dentoalveolar (TDA) en la población chilena. Material y métodos: Se realizó una revisión sistemática de la literatura para identificar estudios poblacionales a nivel nacional, regional, provincial y comunal, además de datos de servicios dentales de atención primaria y secundaria sobre TDA en Chile. Resultados: Se incluyeron 2 estudios con representatividad nacional y 8 realizados en centros de atención en salud. A nivel nacional, la prevalencia de TDA a los 6 años fue de un 2.57%, y a los 12 años, 4.97%. En los estudios realizados en centros de salud, el diagnóstico más prevalente en dentición primaria fueron las lesiones de tejidos de soporte y en dentición permanente, la fractura coronaria. Fue más frecuente la afectación de un solo diente, y los incisivos centrales superiores fueron los dientes más afectados. Conclusiones: Los estudios representativos de la población en Chile son escasos, realizados hace más de una década y representativos sólo de la población de 6 y 12 años, lo cual pone de manifiesto la necesidad de mayor información epidemiológica sobre el TDA en la población chilena.

ABSTRACT: Aim: To summarize the evidence on epidemiological studies about traumatic dental injuries (TDI) in Chile. Methods: A systematic literature review was carried out in two databases to identify population studies at national, regional, provincial and community levels, as well as reports from primary and secondary dental care services, regarding TDI in Chile. Results: Two studies with national representation and eight studies from primary and secondary healthcare centers were included in the analysis. National prevalence for 6-year-old children was 2.57%, and 4.97% for 12-year-old children. While the most frequent diagnosis in primary dentition was traumatic injury involving tooth-supporting tissues, the most commonly reported diagnosis in permanent dentition was crown fracture. Single tooth affection was more frequent, and the upper central incisors were the most affected teeth. Conclusions: Data on representative studies about TDIs in Chile are scarce. Few studies, carried out more than a decade ago and only on 6- and 12-year-old children are available. There is a need for further epidemiological information about TDIs in Chile.

Double heterozygous mutation in RAD50 and ATM genes in a Peruvian family with five cancer types: a case report.

INTRODUCTION: Cancer is the second leading cause of death worldwide, with 70% of cancer deaths occurring in low- or middle- income countries. To mitigate the mortality of this disease, it is recommended the evaluation of multiple high-penetrance genes. METHODS: We used a multi-gene panel testing to identify germline variants in a unique case of a breast cancer patient with a family history of five different neoplasm types. The patient, at the age of 50 years, was diagnosed with a high-grade cribriform ductal carcinoma in situ in her left breast. RESULTS: We identified two heterozygous mutations, one classified as pathogenic/likely pathogenic in RAD50 and the other classified as a variant of uncertain significance (VUS) in ATM. CONCLUSION: In conclusion, the use of the multi-gene panel leads to the identification of a double heterozygous mutation in RAD50 and ATM in a breast cancer patient from a Peruvian family with several cancer types. This data helps our physician team and the patient to choose a treatment following the post-test genetic counseling.

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.

HEARTS in the Americas appraisal checklist and clinical pathway for comprehensive hypertension management in primary care / Lista de verificación para la evaluación de HEARTS en las Américas y vía clínica para el manejo integral de la hipertensión en la atención primaria de salud / Lista de verificação para a avaliação HEARTS nas Américas e caminho clínico para o manejo integral da hipertensão arterial na atenção primária à saúde

ABSTRACT 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.

RESUMEN 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.

RESUMO 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.

Fatores impulsionadores e scorecards para melhorar o controle da hipertensão arterial na atenção primária: recomendações do Grupo de Inovação da Iniciativa HEARTS nas Américas / Drivers and scorecards to improve hypertension control in primary care practice: Recommendations from the HEARTS in the Americas Innovation Group / 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

RESUMO 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 fatores 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, a nível populacional, dos centros de saúde participantes nos países que estão implementando a iniciativa HEARTS.

ABSTRACT 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.

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