Purinergic regulation of pulmonary vascular tone.

Purinergic signaling is a crucial determinant in the regulation of pulmonary vascular physiology and presents a promising avenue for addressing lung diseases. This intricate signaling system encompasses two primary receptor classes: P1 and P2 receptors. P1 receptors selectively bind adenosine, while P2 receptors exhibit an affinity for ATP, ADP, UTP, and UDP. Functionally, P1 receptors are associated with vasodilation, while P2 receptors mediate vasoconstriction, particularly in basally relaxed vessels, through modulation of intracellular Ca2+ levels. The P2X subtype receptors facilitate extracellular Ca2+ influx, while the P2Y subtype receptors are linked to endoplasmic reticulum Ca2+ release. Notably, the primary receptor responsible for ATP-induced vasoconstriction is P2X1, with α,ß-meATP and UDP being identified as potent vasoconstrictor agonists. Interestingly, ATP has been shown to induce endothelium-dependent vasodilation in pre-constricted vessels, associated with nitric oxide (NO) release. In the context of P1 receptors, adenosine stimulation of pulmonary vessels has been unequivocally demonstrated to induce vasodilation, with a clear dependency on the A2B receptor, as evidenced in studies involving guinea pigs and rats. Importantly, evidence strongly suggests that this vasodilation occurs independently of endothelium-mediated mechanisms. Furthermore, studies have revealed variations in the expression of purinergic receptors across different vessel sizes, with reports indicating notably higher expression of P2Y1, P2Y2, and P2Y4 receptors in small pulmonary arteries. While the existing evidence in this area is still emerging, it underscores the urgent need for a comprehensive examination of the specific characteristics of purinergic signaling in the regulation of pulmonary vascular tone, particularly focusing on the disparities observed across different intrapulmonary vessel sizes. Consequently, this review aims to meticulously explore the current evidence regarding the role of purinergic signaling in pulmonary vascular tone regulation, with a specific emphasis on the variations observed in intrapulmonary vessel sizes. This endeavor is critical, as purinergic signaling holds substantial promise in the modulation of vascular tone and in the proactive prevention and treatment of pulmonary vascular diseases.

Heparin-induced DRESS syndrome in a paediatric patient and successful anaesthetic management in cardiovascular bypass surgery: case report.

BACKGROUND: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome is a severe adverse drug reaction marked by delayed hypersensitivity reactions causing skin and systemic complications. DRESS diagnosis is challenging due to the variety of clinical presentations and symptom overlap with other conditions. The perioperative period in these patients requires precise pharmacological strategies to prevent complications associated with this syndrome. The treatment of DRESS induced by unfractionated heparin during cardiopulmonary bypass (CPB) surgery presents some challenges that must be considered when selecting an anticoagulant to avoid side effects. In this case, bivalirudin, a direct thrombin inhibitor, is indicated as an alternative to heparin in patients undergoing CPB. However, in contrast to heparin/protamine, there is no direct reversal agent for bivalirudin. CASE PRESENTATION: We report the case of an 11-year-old male diagnosed with native aortic valve endocarditis and thrombosis in his left lower extremity. During valvular replacement surgery, systemic unfractionated heparin was administered. Postoperatively, the patient developed fever, eosinophilia and pruritic rash. Warm shock and elevated alanine transaminase (ALT) and aspartate transaminase (AST) levels followed, leading to the diagnosis of DRESS syndrome. Treatment with methylprednisolone resulted in complete resolution of symptoms. Seven years later, the patient was readmitted due to insufficient anticoagulation and a thrombus in the prosthetic aortic valve, presenting a recurrent DRESS episode due to the administration of unfractionated heparin, which was later replaced with low-molecular-weight heparin during hospitalization. Treatment with corticosteroids and antihistamines was initiated, resulting in the resolution of this episode. Ultimately, the patient required the Ross procedure. During this intervention the anticoagulation strategy was modified, unfractionated heparin was replaced with bivalirudin during the procedure and fondaparinux was administered during the postoperative period. This resulted in stable transaminases levels and no eosinophilia. CONCLUSION: The severity of DRESS Syndrome underscores the importance of early recognition, heightened monitoring, and a comprehensive approach tailored to each patient's needs. This particular case highlights the significance of this approach and may have a substantial clinical impact since it provides alternatives to heparin, such as bivalirudin and fondaparinux, in the anticoagulation strategy of CPB for patients who have a hypersensibility reaction to this medication; thus, enhancing clinical outcomes by minimizing risks linked to adverse drug reactions.

Scs system links copper and redox homeostasis in bacterial pathogens.

The bacterial envelope is an essential compartment involved in metabolism and metabolites transport, virulence, and stress defense. Its roles become more evident when homeostasis is challenged during host-pathogen interactions. In particular, the presence of free radical groups and excess copper in the periplasm causes noxious reactions, such as sulfhydryl group oxidation leading to enzymatic inactivation and protein denaturation. In response to this, canonical and accessory oxidoreductase systems are induced, performing quality control of thiol groups, and therefore contributing to restoring homeostasis and preserving survival under these conditions. Here, we examine recent advances in the characterization of the Dsb-like, Salmonella-specific Scs system. This system includes the ScsC/ScsB pair of Cu+-binding proteins with thiol-oxidoreductase activity, an alternative ScsB-partner, the membrane-linked ScsD, and a likely associated protein, ScsA, with a role in peroxide resistance. We discuss the acquisition of the scsABCD locus and its integration into a global regulatory pathway directing envelope response to Cu stress during the evolution of pathogens that also harbor the canonical Dsb systems. The evidence suggests that the canonical Dsb systems cannot satisfy the extra demands that the host-pathogen interface imposes to preserve functional thiol groups. This resulted in the acquisition of the Scs system by Salmonella. We propose that the ScsABCD complex evolved to connect Cu and redox stress responses in this pathogen as well as in other bacterial pathogens.

Enfermedad de Caffey: reporte de un caso clínico / Caffey's disease: report of a clinical case / Doença de Caffey: relato de um caso clínico

Introducción: La enfermedad de Caffey es una patología ósea inflamatoria, rara, autolimitada, casi exclusiva de lactantes. Objetivos: Jerarquizar el abordaje diagnóstico de una patología poco frecuente. Caso clínico: 4 meses 22 días, varón, consulta por irritabilidad y edema de miembro inferior izquierdo de 4 días de evolución. Sin traumatismos ni fiebre. Examen físico: edema indurado en tercio medio e inferior de pierna izquierda, no rubor ni calor local. Dolor a la palpación de cara anterior y lateral de tibia y peroné. Limitación funcional, no resaltos óseos. Radiografía: engrosamiento del periostio en tibia y peroné a nivel diafisario. Hemograma: Glóbulos blancos 15.380 KU/L, Hemoglobina 10,8 g/dL, Plaquetas 816.400 10/ul, proteína C reactiva 13,90 mg/dl. Con planteo de probable infección osteoarticular se inicia clindamicina ( gentamicina e ingresa a cuidados moderados. Dada la persistencia de edema e irritabilidad, al quinto día se solicita resonancia magnética: hallazgos sugerentes de un probable proceso inflamatorio- infeccioso de partes blandas con compromiso óseo. Completa 14 días de clindamicina y 7 días de gentamicina intravenosa, hemocultivo negativo. Persiste con edema, irritabilidad y dolor. A los 21 días, se revalora la presentación clínica-imagenológica, se plantea enfermedad de Caffey. Se inicia anti-inflamatorio con buena evolución. Conclusiones: La enfermedad de Caffey es una colagenopatía rara, que afecta lactantes. El diagnóstico es clínico - radiológico (irritabilidad, tumefacción de partes blandas y alteraciones radiológicas). El pronóstico a largo plazo suele ser favorable. Es importante considerar el diagnóstico en lactantes que se presentan con esta sintomatología para evitar retrasos diagnósticos e instauración de tratamientos innecesarios.

Introduction: Caffey's disease is a rare disease that is reported almost exclusively in infants. Objective: Describe the case of a rare pathology, prioritizing the diagnostic approach. Clinical case: 4 month -old, healthy male. Consultation due to irritability and edema of the left lower limb for 4 days. No trauma or fever. Physical examination: indurated edema in the left leg, no redness or local heat. Pain on palpation of the anterior and lateral aspect of the tibia and fibula. Functional limitation, no bony protusions. Leg x-ray: thickening of the periosteum in the tibia and fibula at the diaphyseal level. Hemogram: White Blood Cells 15,380 KU/L Hemoglobin: 10.8 g/dL. Platelets: 816,400 10/ul, C-reactive protein: 13.90 mg/dl. He was admitted with a suggestion of probable osteoarticular infection. Clindamycin ( gentamicin is started. Given the persistence of edema and irritability despite treatment, on the fifth day an MRI was requested: findings suggestive of a probable inflammatory-infectious process of soft tissues with bone involvement. Completed 14 days of clindamycin and 7 days of intravenous gentamicin, blood culture negative. It persists with edema, irritability and pain. After 21 days, the clinical-imaging presentation was reassessed and Caffey's disease was considered. Anti-inflammatory begins with good evolution. Conclusions: Caffey's disease is a rare collagenopathy, that affects infants. The diagnosis is clinical - radiological (irritability, soft tissue swelling and radiological alterations). The long-term prognosis is usually favorable. It is important to consider the diagnosis in infants who present with these symptoms to avoid diagnostic delays and initiation of unnecessary treatments.

Introdução: A doença de Caffey é uma patologia óssea inflamatória rara, autolimitada, quase exclusiva de lactentes. Objetivos: Priorizar a abordagem diagnóstica de uma patologia rara. Caso clínico: 4 meses 22 dias, sexo masculino, consulta por irritabilidade e edema do membro inferior esquerdo de 4 dias de evolução. Sem trauma ou febre. Exame físico: edema endurecido em terço médio e inferior da perna esquerda, sem vermelhidão ou calor local. Dor à palpação das faces anterior e lateral da tíbia e fíbula. Limitação funcional, sem saliências ósseas. Radiografia: espessamento do periósteo na tíbia e fíbula ao nível diafisário. Hemograma: Glóbulos brancos 15.380 KU/L, Hemoglobina 10,8 g/dL, Plaquetas 816.400 10/ul, Proteína C reativa 13,90 mg/dl. Com sugestão de provável infecção osteoarticular, foi iniciada clindamicina + gentamicina e internado em cuidados moderados. Dada a persistência do edema e da irritabilidade, no quinto dia foi solicitada ressonância magnética: achados sugestivos de provável processo inflamatório-infeccioso de partes moles com envolvimento ósseo. Completou 14 dias de clindamicina e 7 dias de gentamicina intravenosa, hemocultura negativa. Persiste com edema, irritabilidade e dor. Após 21 dias, o quadro clínico-imagem foi reavaliado e considerada doença de Caffey. O antiinflamatório começa com uma boa evolução. Conclusões: A doença de Caffey é uma colagenopatia rara que afeta lactentes. O diagnóstico é clínico-radiológico (irritabilidade, edema de partes moles e alterações radiológicas). O prognóstico a longo prazo é geralmente favorável. É importante considerar o diagnóstico em lactentes que apresentam esses sintomas para evitar atrasos no diagnóstico e início de tratamentos desnecessários.

Availability and characteristics of pulmonary rehabilitation programs in family health centers and hospitals from Chile: Descriptive, retrospective and multicentric study.

OBJECTIVE: To determine availability and characteristics of pulmonary rehabilitation programs performed in 2019 in family health centers and hospitals from Chile. METHODOLOGY: A descriptive and retrospective study was designed, considering PR programs operated in 2019. A non-probability and convenience sample was obtained. Availability and characteristics of centers and PR were measured using a questionnaire translated, modified, validated, and sent by email. RESULTS: Out of 80 responses (22.8%), 60% of centers offered PR program, where the lack of time was the greatest barrier. The programs were mainly outpatient, non-personalized, with 10(IQR 4-11) participants, 12 (IQR 12-16) weeks of length, with 2.4 ± 0.6 session/week, and 1 (IQR 1-2) hours/session. Chronic Obstructive Pulmonary Disease (COPD) was the most frequent diagnostic. The programs were mainly comprised of strength training exercises of lower extremity, upper extremity, walking and education. Team was constituted of physiotherapist and physician, with completed training, and directed by a physiotherapist. Modified Borg, MRC dyspnea scale, six-minute walking test and oximetry were used in the assessments. Between 40-80% of patients completed PR, and the major barrier was patient relocated. CONCLUSION: Increasing PR availability, homogenization of exercises and education, prioritization of assessments supported by scientific evidence, and inclusion of follow-up could be useful to improve the access, quality and results of the treatment, considering new models of PR that allow greater access and acceptability.

Impact of pulmonary rehabilitation pre- and post-lung transplantation in a child with cystic fibrosis: a case report / Impacto da reabilitação pulmonar pré e pós-transplante de pulmão em paciente pediátrico com fibrose cística: relato de caso / Impacto de la rehabilitación pulmonar en el pretrasplante y en el postrasplante pulmonar en paciente pediátrico con fibrosis quística: un reporte de caso

ABSTRACT Cystic Fibrosis (CF) is a genetic disease that reduces quality of life. Lung transplantation (LTx) is a strategy for end-stage lung disease treatment in CF. Pulmonary rehabilitation (PR) in LTx is effective, however, only one study has determined its effectiveness in children, and most studies have not included CF exclusively. Thus, reports showing components for PR protocols and outcomes not considered in previous studies of PR in LTx due to CF in children are still needed. To report this case, written informed assent and consent of patient and parent were obtained. Ethical Requirement was formally waived by the institution. A 12-year-old patient with CF was referred to PR due to LTx. A general and respiratory training was conducted daily for six months (pre) and two years (post) the transplantation, with the parents' full support. General training included treadmill and cycle ergometer use and upper limbs exercises. Respiratory protocol included inspiratory training and respiratory physical therapy. We observed improvements in pulmonary function, exercise capacity, inspiratory muscle strength, and quality of life, including school functioning, with progress maintenance after 2.5 years of continuous intervention. This case presents a PR protocol pre- and post-LTx with good long-term results. These components for treatment protocols and outcomes may be useful to consider in clinical interventions or future investigations.

RESUMO Fibrose cística (FC) é uma doença genética que reduz a qualidade de vida. O transplante pulmonar (LTx) é uma estratégia para o tratamento de doenças pulmonares em fase terminal na FC. A reabilitação pulmonar (PR) no LTx é eficaz, porém apenas um estudo determinou sua eficácia em crianças, e outros estudos não incluíram a FC exclusivamente. Portanto, relatórios que mostram componentes para protocolos e resultados de RP, não considerados em estudos anteriores de RP em LTx devido à FC em crianças, ainda são necessários. Assim, descreve-se o caso de um paciente de 12 anos com FC encaminhado para RP devido à LTx. Foi obtido o consentimento informado e por escrito do paciente e dos pais. O requisito ético foi formalmente renunciado pela instituição. Um treinamento geral e respiratório foi realizado por seis meses antes e dois anos após a LTx, diariamente, com total apoio dos pais. O treinamento geral incluiu esteira, cicloergômetro e exercícios para os membros superiores. O protocolo respiratório incorporou treinamento inspiratório e fisioterapia respiratória. Foram observadas melhorias na função pulmonar, capacidade de exercício, força muscular inspiratória e qualidade de vida, incluindo o funcionamento escolar, com manutenção dos avanços após 2,5 anos de intervenção contínua. O caso apresenta um protocolo de RP pré e pós-LTx com bons resultados a longo prazo. Os componentes para protocolos de tratamento e resultados encontrados podem ser úteis para intervenções clínicas ou investigações futuras.

RESUMEN La fibrosis quística (FQ) es una enfermedad genética que reduce la calidad de vida de los afectados. El trasplante de pulmón (LTx) es una estrategia para el tratamiento de enfermedades pulmonares en fase terminal en FQ. La rehabilitación pulmonar (RP) en el LTx es eficaz, aunque solo un estudio evaluó su eficacia en niños, y otros estudios no han tratado exclusivamente de FQ. Por lo tanto, se necesitan informes que contengan elementos de los protocolos y de los resultados de RP y que no habían sido considerados en los estudios anteriores sobre RP en LTx por FQ pediátrica. Así se describe el caso del paciente de 12 años de edad con FQ que fue remitido a RP debido a LTx. Para ello, se obtuvieron el consentimiento informado y el consentimiento por escrito del paciente y sus padres. La institución renunció formalmente a los requisitos éticos. Se realizó entrenamiento general y respiratorio durante seis meses antes de LTx y dos años después de LTx, diariamente, con apoyo de los padres. El entrenamiento general incluyó cinta de correr, cicloergómetro y ejercicios para extremidades superiores. El protocolo respiratorio incluía entrenamiento inspiratorio y fisioterapia respiratoria. Se observaron mejorías en la función pulmonar, capacidad de ejercicio, fuerza muscular inspiratoria y calidad de vida del participante, incluida en la limitación de actividades, con mantenimiento de los logros tras 2,5 años de la intervención continua. El caso del estudio presentó un protocolo de RP pre- y post-LTx con buenos resultados a largo plazo. Estos elementos de los protocolos de tratamiento y los resultados encontrados pueden ser útiles en las intervenciones clínicas o en futuras investigaciones.

Barreras en acceso a control preventivo en padres migrantes de infantes en Santiago, Chile, 2018

Objetivo Identificar barreras en el acceso a control preventivo de la Atención Primaria en padres migrantes de lactantes y preescolares en Santiago, Chile, en el año 2018. Métodos Estudio observacional, descriptivo, transversal, en una muestra no probabilística de 108 padres migrantes de lactantes y preescolares entre 0-4 años, 11 meses, 29 días, que asisten a jardines infantiles de la comuna de Santiago, en quienes se autoaplicó un cuestionario en español y creole, diseñado y validado en contenido y traducción de forma piloto, previa autorización de Comité de Ética, entre julio y octubre de 2018. Se midieron variables de caracterización sociodemográfica, asistencia a control preventivo y barreras. Resultados Un 7,8% de padres manifestó que su hijo no asistía a control, y 48,5% de los padres indicó que tenía dificultades para asistir. Las barreras para asistir a control fueron en un 63% horario y tiempos de espera, en un 39,8% desconocimiento del funcionamiento del sistema y en un 11,1% transporte. Conclusiones Son necesarias estrategias para mejorar el acceso a salud con una mirada desde los determinantes sociales de la salud.

Objective To identify barriers to preventive healthcare access in migrant parents of Infants and young children in Santiago, Chile, 2018. Methods An observational, descriptive, cross-sectional study, in a non-probability sample from 108 migrant parents of 0-4 years old children, attending at pre-primary schools in Santiago was designed. A self-administered questionnaire was used to determine variables, which was designed and validated through pilot tested after approval by an Ethics Committee. Sociodemographic characterization, preventive healthcare attendance, and barriers were measured. Results 7.8% of parents said their child was not attendant to healthcare and 48.5% of parents had difficulties to attend. The barriers were appointment and waiting time (63%), unknowledge (39.8%), and transport (11.1%). Conclusions The design of strategies to improve access to preventive healthcare in children considering determinants of health is needed.

Household and social characteristics associated with COVID-19 vaccine intent among Latino families in the San Francisco Bay Area.

BACKGROUND: Latinos have had higher case counts, hospitalization rates and deaths during the COVID-19 pandemic nationally and in the state of California. Meanwhile, Latino vaccination rates remain lower than those of non-Hispanic Whites. COVID-19 vaccine nonintent, defined as intent to not vaccinate against COVID-19, among Latino individuals continues to be an issue in the state of California. METHODS: Families from three Latino longitudinal mother-child cohorts previously recruited in the San Francisco Bay Area were surveyed telephonically from February to June 2021 to assess attitudes towards vaccination against COVID-19 and prior vaccination, in general, for themselves and their children. Risk for vaccine nonintent was assessed using the Mann-Whitney rank sum non-parametric test for continuous predictors and chi-squared tests for categorical ones. RESULTS: Three hundred and nineteen families were surveyed from the Telomere at Birth (TAB), Hispanic Eating and Nutrition (HEN) and Latino Eating and Diabetes Cohort (LEAD). Approximately 36% from TAB and 28% from HEN/LEAD indicated COVID-19 vaccine nonintent for themselves and/or their children. Risk factors for vaccine nonintent included lower maternal age (p = 0.01), concern about vaccine side effects (p < 0.01) and prior history of a household members being infected with SARS-CoV-2 (p < 0.01) and indexes of household crowding including number of people sharing a bathroom (p = 0.048). Vaccine intent was also associated with receiving vaccine input from friends (p = 0.03), family (p < 0.01) and/or coworkers (p = 0.02) compared with those who were not planning on getting vaccinated against COVID-19. CONCLUSIONS: Latino families living in crowded living situations who may not have received any COVID-19 advice from family, coworkers or friends are at particular risk for nonintent for vaccinatation against COVID-19. Community-based grassroots or promotor/a based interventions centered on trusted individuals with close community ties and counseling concerning vaccination against COVID-19 could help boost vaccination rates in this population group.

Evolution of Copper Homeostasis and Virulence in Salmonella.

Salmonella enterica sv. Typhimurium modulates the expression of factors essential for virulence, contributing to its survival against the surge of copper (Cu) in the Salmonella-containing vacuole. This bactericidal host innate immune component primarily targets the bacterial envelope, where most cuproproteins are localized. While in most enteric species periplasmic Cu homeostasis is maintained by the CusR/CusS-controlled CusCFBA efflux system encoded in the cus locus, we noticed that these genes were lost from the Salmonella-core genome. At the same time, Salmonella acquired cueP, coding for a periplasmic Cu chaperone. As cus, cueP was shown to be essential for bacterial survival in a copper-rich environment under anaerobiosis, suggesting that it can functionally substitute the CusCFBA system. In the present study, the whole Escherichia coli cus locus was reintroduced to the chromosome of the Salmonella wild-type or the ΔcueP strain. While the integrated cus locus did not affect Cu resistance under aerobic conditions, it increases Cu tolerance under anaerobiosis, irrespective of the presence or absence of cueP. In contrast to the Cus system, CueP expression is higher at high copper concentrations and persisted over time, suggesting separate functions. Finally, we observed that, regardless of the presence or absence of cus, a mutant deleted of cueP shows a deficiency in replication inside macrophages compared to the wild-type strain. Our results demonstrate that CueP and CusCFBA exert redundant functions for metal resistance, but not for intracellular survival, and therefore for the virulence of this pathogen.

The heterogeneity of Human Papilloma Virus genotypes in the oropharyngeal cavity, anus, and urogenital sites.

The distribution of Human Papilloma Virus (HPV) genotypes is not homogeneous among the infectedcells in a specific anatomical site. Thus, we conducted a prospective cross-sectional studywith 2,130 Mexican men and women aged 16 to 80 years. We described the prevalence of HPVgenotypes at the oropharyngeal cavity, anus, and urogenital sites. The most prevalent genotypes inwomen were HR-HPV 66 (5.6%), 16 (4.2%), 59 (4.3%) and LR-HPV 6 (10.1%); for men, HR-HPV16 (4.2%), 53 (3.8%), 66 (3.5%) and LR-HPV 6 (14.1%). In the cervix the most frequent genotypeswere: 6 (7.7%) and 66 (4.6%); vagina 6 (0.4%) and 16 (0.4%); genital wart 6 (5.9%) and 11 (2.7%);external genitalia 6 (0.5%) and 66 (0.5%); oropharyngeal cavity 6 (0.06%) and 66 (0.05%). In bothgenders, the most frequent genotype was HPV 6. The prevalence of HPV genotypes 31 (p=0.016),52 (p=0.049), 56 (0.036), 6 (p<0.0001) and 11 (p<0.0001) showed significant differences when comparinggenders. The kappa analysis demonstrated that in males, the HPV genotypes in the urethra/balanopreputial sulcus and urethral/genital warts had moderate concordance. In conclusion, HPVgenotyping screening tests among anatomical sites should be performed simultaneously to reinforcecurrent strategies, as well as for the development of vaccines and the discovery of oncogenic potentialfor genotypes that are not commonly analyzed.

Overcrowding and exposure to secondhand smoke increase risk for COVID-19 infection among Latinx families in the greater San Francisco Bay Area.

INTRODUCTION: Environmental risk factors, including community level pollution burden and exposure to smoking and secondhand smoke, have not been evaluated in relation to risk for infection with COVID-19 in high risk, urban Latinx families. METHODS: We evaluated risk factors for COVID-19 infection in three, preexisting, longitudinal, Latinx family cohorts in the San Francisco Bay Area from May through September 2020 (N=383 households, 1875 people). All households were previously recruited before the pandemic. For the COVID-19 sub-study, participants responded to a telephone interview where we assessed food consumption patterns, housing and employment status, and history of COVID-19 infection. Secondhand smoke exposure was based on previously collected selfreported data, and environmental pollution exposure was determined from census tract residence. Non-parametric tests and multiple logistic regression were used to assess independent predictors of COVID-19 infection. RESULTS: Larger household size increased risk for infection (OR=1.58; 95% CI: 1.12-2.23, p<0.01) as did increasing number of children in household (OR=3.79; 95% CI: 1.51-9.56). Any exposure to secondhand smoke was also associated with increased risk for COVID infection (OR 4.69; 95% CI: 1.01-21.85) and having a greater number of family members eating at home was protective against infection (OR=0.10; 95% CI: 0.02-0.52, p<0.01). CONCLUSIONS: Crowding, as indicated by larger household size, increases risk for COVID-19 infection in Latinx families, as does exposure to secondhand smoke. Public policy and health interventions need to ensure that multiunit residential complexes do not allow exposure to secondhand smoke between units, that individuals eat in the home environment, and that large households can safely separate individuals exposed to COVID-19.

Exploring Functional Differences between the Right and Left Ventricles to Better Understand Right Ventricular Dysfunction.

The right and left ventricles have traditionally been studied as individual entities. Furthermore, modifications found in diseased left ventricles are assumed to influence on right ventricle alterations, but the connection is poorly understood. In this review, we describe the differences between ventricles under physiological and pathological conditions. Understanding the mechanisms that differentiate both ventricles would facilitate a more effective use of therapeutics and broaden our knowledge of right ventricle (RV) dysfunction. RV failure is the strongest predictor of mortality in pulmonary arterial hypertension, but at present, there are no definitive therapies directly targeting RV failure. We further explore the current state of drugs and molecules that improve RV failure in experimental therapeutics and clinical trials to treat pulmonary arterial hypertension and provide evidence of their potential benefits in heart failure.

A Rare Case of Traumatic Thyroid Gland Hypoperfusion/Devascularization After a Gunshot Wound Through the Neck: Computed Tomography Findings.

BACKGROUND The thyroid gland is rarely injured in cases of penetrating neck trauma. Computed tomography (CT) plays a central role in prompt evaluation of the extent of penetrating neck trauma and can demonstrate thyroid gland injury. The current literature on thyroid gland injury is limited mostly to blunt trauma, with little emphasis on findings seen on CT imaging. In the present case report, we focus on CT imaging findings of thyroid gland hypoperfusion/devascularization in a patient who had a gunshot wound injury through the base of his neck. CASE REPORT A 26-year-old man was transferred to our trauma center after experiencing multiple gunshot wounds, including one through the base of the neck. The bullet path through his neck was associated with enlargement/edema involving the right thyroid lobe, with an asymmetric decrease in enhancement involving the mid and superior aspects of the right thyroid lobe. Maximum-intensity-projection angiographic images of the vascular supply of the thyroid gland suggested an abrupt decrease in caliber close to the origin of the posterior glandular branch of the right superior thyroid artery. The findings favored vasospasm rather than an arterial injury, which led to hypoperfusion/devascularization of the upper pole of the right thyroid lobe. CONCLUSIONS Thyroid gland hypoperfusion/devascularization after a penetrating neck injury is rare. Recognition of CT imaging findings that favor post-traumatic organ hypoperfusion/devascularization is crucial for prompt management and to decrease morbidity in such cases.

Tlr2 Gene Deletion Delays Retinal Degeneration in Two Genetically Distinct Mouse Models of Retinitis Pigmentosa.

Although considered a rare retinal dystrophy, retinitis pigmentosa (RP) is the primary cause of hereditary blindness. Given its diverse genetic etiology (>3000 mutations in >60 genes), there is an urgent need for novel treatments that target common features of the disease. TLR2 is a key activator of innate immune response. To examine its role in RP progression we characterized the expression profile of Tlr2 and its adaptor molecules and the consequences of Tlr2 deletion in two genetically distinct models of RP: Pde6brd10/rd10 (rd10) and RhoP23H/+ (P23H/+) mice. In both models, expression levels of Tlr2 and its adaptor molecules increased in parallel with those of the proinflammatory cytokine Il1b. In rd10 mice, deletion of a single Tlr2 allele had no effect on visual function, as evaluated by electroretinography. However, in both RP models, complete elimination of Tlr2 attenuated the loss of visual function and mitigated the loss of photoreceptor cell numbers. In Tlr2 null rd10 mice, we observed decreases in the total number of microglial cells, assessed by flow cytometry, and in the number of microglia infiltrating the photoreceptor layers. Together, these results point to TLR2 as a mutation-independent therapeutic target for RP.

Conceptual validation of an innovative remote pulmonary rehabilitation solution for Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) is the third leading cause of death in the world. Pulmonary rehabilitation (PR) reduces COPD hospitalisations, although its use is low. Telerehabilitation is effective; however, in Chile the development of remote PR technology is incipient. Therefore, the aim of the study was to validate conceptual aspects of an innovative remote PR solution for COPD. METHODS: This mixed study used a nonprobabilistic sample of PR professionals and people with COPD (PwCOPD) from Santiago. The perception of a conceptual solution for PR through a semi-structured interview was determined. Professionals were also asked about willingness to use technology using a questionnaire designed and validated in 75 professionals in this study. The study was approved by the Ethics Committee and data were collected after informed consent. RESULTS: Twenty-two participants were recruited, of which 14 were professionals and eight were PwCOPD. Among professionals and patients, the willingness to use the solution is positive because it would reduce visits and improve self-management, although it should include a remote/in-person combination, training, and user-friendly interface. Most of the professionals were willing to use technology for pulmonary rehabilitation. CONCLUSIONS: The development of telehealth technologies should consider the expectations of patients and professionals and may incorporate elements of persuasive technologies in the design. The results could contribute to the development of digital solutions for remote PR in PwCOPD.

High food insecurity in Latinx families and associated COVID-19 infection in the Greater Bay Area, California.

BACKGROUND: Food insecurity impacts nearly one-in-four Latinx households in the United States and has been exacerbated by the novel coronavirus or COVID-19 pandemic. METHODS: We examined the impact of COVID-19 on household and child food security in three preexisting, longitudinal, Latinx urban cohorts in the San Francisco Bay Area (N = 375 households, 1875 individuals). Households were initially recruited during pregnancy and postpartum at Zuckerberg San Francisco General Hospital (ZSFG) and UCSF Benioff prior to the COVID-19 pandemic. For this COVID-19 sub-study, participants responded to a 15-min telephonic interview. Participants answered 18 questions from the US Food Security Food Module (US HFSSM) and questions on types of food consumption, housing and employment status, and history of COVID-19 infection as per community or hospital-based testing. Food security and insecurity levels were compared with prior year metrics. RESULTS: We found low levels of household food security in Latinx families (by cohort: 29.2%; 34.2%; 60.0%) and child food security (56.9%, 54.1%, 78.0%) with differences between cohorts explained by self-reported levels of education and employment status. Food security levels were much lower than those reported previously in two cohorts where data had been recorded from prior years. Reported history of COVID-19 infection in households was 4.8% (95% Confidence Interval (CI); 1.5-14.3%); 7.2% (95%CI, 3.6-13.9%) and 3.5% (95%CI, 1.7-7.2%) by cohort and was associated with food insecurity in the two larger cohorts (p = 0.03; p = 0.01 respectively). CONCLUSIONS: Latinx families in the Bay Area with children are experiencing a sharp rise in food insecurity levels during the COVID-19 epidemic. Food insecurity, similar to other indices of poverty, is associated with increased risk for COVID-19 infection. Comprehensive interventions are needed to address food insecurity in Latinx populations and further studies are needed to better assess independent associations between household food insecurity, poor nutritional health and risk of COVID-19 infection.

Metabolic rearrangements in imbibed maize (Zea mays L) embryos in the presence of oxidative stressors.

Cadmium (Cd) is a metal known to generate oxidative stress in plants and may be particularly harmful during germination. Herein, the growth and metabolic rearrangements of maize embryo axes subjected during the imbibition stage to Cd ions and other two well-known oxidative stressors, methyl viologen (MV) and hydrogen peroxide (H2O2), were assessed for 48 h. Similar decreases in embryo's length were detected for all stressed axes up to 48 h of imbibition. By this time, treated embryos revealed greater accumulation of reactive oxygen species (ROS) and increased levels of carbonylated and ubiquitinated proteins. The proteolytic activities were intensely enhanced in the treated axes, particularly at 48 h of imbibition, and several antioxidant enzymes were induced in most cases. NMR spectroscopy followed by principal component analysis (PCA) and hierarchical cluster analysis (HCA) showed that a large proportion of polar metabolites, mainly amino acids and organic acids, were decreased under stress conditions, while carbohydrates were increased at 48 h of imbibition, with significant increases in glucose and raffinose for treated embryos relatively to controls. We demonstrated that maize embryo axes were capable of shifting their metabolism to improve their antioxidant defense system, at the expense of their growth. Under these adverse conditions, proteolysis seems to play a key role by providing free amino acids needed for the de novo synthesis of defense-related proteins.

Tyr-nitration in maize CDKA;1 results in lower affinity for ATP binding.

Cyclin-dependent kinase A (CDKA) is a key component for cell cycle progression. The catalytic kinase activity depends on the protein's ability to form an active complex with cyclins and on phosphoregulatory mechanisms. Cell cycle arrest and plant growth impairment under abiotic stress have been linked to different molecular processes triggered by increased levels of reactive oxygen and nitrogen species (ROS and RNS). Among these, posttranslational modifications (PTMs) of key proteins such as CDKA;1 may be of significance. Herein, isolated maize embryo axes were subjected to sodium nitroprusside (SNP) as an inductor of nitrosative conditions to evaluate if CDKA;1 protein was a target for RNS. A high degree of protein nitration was detected; this included the specific Tyr-nitration of CDKA;1. Tyr15 and Tyr19, located at the ATP-binding site, were the selective targets for nitration according to both in silico analysis using the predictive software GPS-YNO2, and in vitro mass spectrometry studies of recombinant nitrated ZmCDKA;1. Spectrofluorometric measurements demonstrated a reduction of ZmCDKA;1-NO2 affinity for ATP. From these results, we conclude that Tyr nitration in CDKA;1 could act as an active modulator of cell cycle progression during redox stress.

Optimization of recombinant maize CDKA;1 and CycD6;1 production in Escherichia coli by response surface methodology.

The complex formed by the cyclin-dependent kinase A (CDKA) and cyclin D is responsible for the G1-S transition in the plant cell cycle. Maize (Zea mays L) CDKA; 1 and CycD6; 1 were cloned and expressed in E. coli. The present study describes the optimization of both proteins production using a statistical approach known as response surface methodology (RSM). The experimental design took into account the effects of four variables: optical density of the culture (OD600) before induction, isopropyl ß-d-1-thiogalactopyranoside (IPTG) concentration, post-induction temperature, and post-induction time. For each protein, a 24 full factorial central composite rotary design for these four independent variables (at five levels each) was employed to fit a polynomial model; which indicated that 30 experiments were required for this procedure. An optimization of CDKA; 1 and CycD6; 1 production levels in the soluble fraction was achieved. Protein conformation and stability were studied by circular dichroism and fluorescence spectroscopy. Finally, in vitro Cyc-CDK complex formation and its kinase activity were confirmed.

Oxidation of proline from the cyclin-binding motif in maize CDKA;1 results in lower affinity with its cyclin regulatory subunit.

Cyclin dependent kinase A; 1 (CDKA; 1) is essential in G1/S transition of cell cycle and its oxidation has been implicated in cell cycle arrest during plant abiotic stress. In the present study, an evaluation at the molecular level was performed to find possible sites of protein oxidative modifications. In vivo studies demonstrated that carbonylation of maize CDKA,1 is associated with a decrease in complex formation with maize cyclin D (CycD). Control and in vitro oxidized recombinant CDKA; 1 were sequenced by mass spectrometry. Proline at the PSTAIRE cyclin-binding motif was identified as the most susceptible oxidation site by comparative analysis of the resulted peptides. The specific interaction between CDKA; 1 and CycD6; 1, measured by surface plasmon resonance (SPR), demonstrated that the affinity and the kinetic of the interaction depended on the reduced-oxidized state of the CDKA; 1. CDKA; 1 protein oxidative modification would be in part responsible for affecting cell cycle progression, and thus producing plant growth inhibition under oxidative stress.