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Background: Minorities constitute groups with higher risk of stroke and stroke severity. Disparities in stroke care may result from greater prevalence of risk factors, barriers to medical care, and lower utilization of preventive therapies. Insurance status may be one limiting factor in access to care and preventive measures. Purpose: We hypothesize that vascular risk factors differ between racial groups and that insurance status may affect stroke treatment, secondary prevention measures, stroke severity, and outcomes. Methods: We included 1061 consecutive patients with ischemic stroke (2005-2008) in our local Get-With-The-Guidelines (GWTG) database. Multivariate logistic regression analysis was used to evaluate the relation of race and insurance status to risk factors, intravenous thrombolytic therapy (IV-tPA) use, stroke severity (National Institute of Health Stroke Scale [NIHSS]), hospital complications, and ambulatory status at discharge. Results: Whites were older than Non-Whites (mean age 65 vs 62 years, p

Background and objectives Traditionally, the health-related quality of life (HRQoL) of patients with systemic lupus erythematosus (SLE) has been assessed using instruments that neglect the specific characteristics of the disease. This study determines the validity of the Lupus Quality of Life (LupusQoL) questionnaire as a psychometrically stable instrument to measure the HRQoL of patients with SLE in Venezuela and establishes the cutoff points of the questionnaire for the Venezuelan population. Patients and methods A cross-sectional study was conducted that included patients with SLE from April to July 2018. Patients completed the LupusQoL and the “Generalitat de Catalunya” (GENCAT) scale; sociodemographic data, activity index (SLEDAI) and accumulated damage (SLICC), were obtained. Reliability was evaluated by internal consistency and the convergent validity of the LupusQoL was determined with the GENCAT scale. Results Of the 100 patients, 93% were women, the mean age was 42 years old (SD: 13) and the mean duration of the disease was 11 years (SD: 9); the mean of SLEDAI and SLICC was 3 and 1, respectively. The cutoff point that defined a “better” or “worse” HRQoL for LupusQoL was 64.55 points. A moderate convergence was found after grouping, according to the cutoff points, of the LupusQoL with the GENCAT scale (Cohen’s kappa coefficient = .556; p = .000). Conclusions The LupusQoL is a valid psychometrically stable instrument to measure the HRQoL of patients with SLE in Venezuela. Cutoff points were established to stratify the HRQoL in the Venezuelan population with LES, being useful to complement a comprehensive evaluation.

Resumen Introduccion El hipoparatiroidismo (HP) es la complicacion mas frecuente de la tiroidectomia total y puede suponer una urgencia. Objetivos Describir la prevalencia de HP tras tiroidectomia total en menores de 14 anos, las variables relacionadas con su aparicion y su expresion clinica. Pacientes y metodos Estudio retrospectivo en un hospital infantil en los ultimos 20 anos. El HP se definio por la necesidad de suplementar calcio tras la intervencion y se considero permanente si no pudo suspenderse en 12 meses. Metodo estadistico de Fisher de comparacion de proporciones. Resultados Treinta y nueve ninos y adolescentes (26 mujeres) de un rango de edad de 3,67 a 14,00 anos. En 25 pacientes la intervencion fue profilactica y en 14 terapeutica. Catorce sufrieron exeresis accidental de alguna glandula paratiroides, pero ninguno de mas de 2 de ellas. Doce presentaron HP, de los cuales 3 fueron permanentes, 5 presentaron sintomatologia clinica y uno de ellos supuso una urgencia. La frecuencia de HP fue de 4/4 cuando se disecaron 2 paratiroides, de 2/10 cuando se diseco una y de 6/25 cuando no se diseco ninguna (p = 0,02). En la intervencion profilactica fue de 6/25 frente a 6/14 en la terapeutica (p = 0,29). Los 3 casos de HP permanente fueron ninos menores de 6 anos, no ocurriendo este tipo de HP en ningun nino mayor (p = 0,09). Conclusiones El HP es una complicacion frecuente y en ocasiones grave en el nino tras la tiroidectomia total. Puede ocurrir, e incluso ser permanente, aunque la intervencion sea profilactica y queden glandulas paratiroides in situ. La menor edad podria ser un factor de riesgo.

Inconsistencies have been reported on the effect of sex on aldosterone (ALDO) levels leading to clinical confusion. The reasons for these inconsistencies are uncertain but include estrogen and/or its receptor modulating target gene responses to mineralocorticoid receptor activation and ALDO secretagogues’ levels. This study’s goal was to determine whether ALDO’s biosynthesis also differed by sex. Two approaches were used. First, plasma renin activity and aldosterone were measured in rats. Both were significantly higher in males. Secondly, using rat zona glomerulosa (ZG) cells, we assessed three ex vivo areas: (1) activity/levels of early steps in ALDO’s biosynthesis (StAR and CYP11A1); (2) activity/levels of a late step (CYP11B2); and (3) the status of the mineralocorticoid receptor (MR)-mediated, ultrashort feedback loop. Females had higher expression of CYP11A1 and StAR and increased CYP11A1 activity (increased pregnenolone/corticosterone levels) but did not differ in CYP11B2 expression or activity (ALDO levels). Activating the ZG’s MR (thereby activating the ultrashort feedback loop) reduced CYP11B2’s activity similarly in both sexes. Exvivo, these molecular effects were accompanied, in females, by lower ALDO basally but higher ALDO with angiotensin II stimulation. In conclusion, we documented that not only was there a sex-mediated difference in the activity of ALDO’s biosynthesis but also these differences at the molecular level help explain the variable reports on ALDO’s circulating levels. Basally, both in vivo and ex vivo, males had higher ALDO levels, likely secondary to higher ALDO secretagogue levels. However, in response to acute stimulation, ALDO levels are higher in females because of the greater levels and/or activity of their StAR/CYP11A1.

Background We have here assessed the impact of demographic, clinical, and treatment compliance characteristics on health-related quality of life (HRQoL) of Venezuelan patients with systemic lupus erythematosus (SLE). We have used a disease-specific questionnaire, the Lupus Quality of Life (LupusQoL), validated in our patient population, to measure HRQoL. Methods A cross-sectional study was conducted among 100 patients with SLE from outpatient clinics. Patients completed a form with demographic, clinical, and treatment compliance data, and the LupusQoL questionnaire. HRQoL was classified as better or worse according to previously established cut-off points for this patient population. Spearman’s r test was used to determine the correlations between age, years of education, disease duration, SLEDAI, and SLICC-DI with the eight domains of the LupusQoL. Mann–Whitney U test was used to compare the HRQoL between the two groups of patients according to treatment compliance. Binomial logistic regression using the backward stepwise selection method was performed to identify the risk factors associated with each of the eight domains of the LupusQoL among patients with inactive (SLEDAI Results HRQoL of our patients was classified as better in all domains of the LupusQoL. Age correlated negatively with all domains of the LupusQoL, except with “burden to others”, and disease activity correlated negatively with all domains of the LupusQoL, except with “intimate relationships” and “burden to others” (p p worse “planning” and “intimate relationships” was advanced age, while having had SLE flare-ups in the previous six months was a risk factor associated with worse “physical health” (p Conclusion Age and disease activity were negatively correlated with almost all domains of the LupusQoL, and treatment compliance was associated with higher score in the “physical health” domain. Disease control and treatment compliance should be the main goals for a better HRQoL in our patients with SLE.

Objective: Stroke is the most common cause of epilepsy in older age. Subclinical cerebrovascular disease is believed to underlie some of the 30%–50% of late-onset epilepsy without a known cause (Li et al. Epilepsia. 1997;38:1216; Cleary et al. Lancet. 2004;363:1184). We studied the role of modifiable vascular risk factors in predicting subsequent epilepsy among participants ages 45 or older in the Framingham Heart Study (FHS), a longitudinal, community-based study. Methods: Participants of the Offspring Cohort who attended FHS exam 5 (1991–1995) were included who were at least 45-years-old at that time, had available vascular risk factor data, and epilepsy follow-up (n = 2986, mean age 58, 48% male). Adjudication of epilepsy cases included review of medical charts to exclude seizure mimics and acute symptomatic seizures. The vascular risk factors studied included hypertension, diabetes mellitus, smoking, and hyperlipidemia. The role of the Framingham Stroke Risk Profile score was also investigated. Cox proportional hazards regression models were used for the analyses. Results: Fifty-five incident epilepsy cases were identified during a mean of 19 years of follow-up. Hypertension was associated with a near 2-fold risk (hazard ratio [HR]: 1.93, 95% confidence interval [CI]: 1.10–3.37, p =.022) of developing epilepsy, even after adjustment for prevalent and interim stroke. In secondary analysis, excluding patients with normal blood pressure who were receiving anti-HTN (anti-hypertensive) treatment (n = 2613, 50 incident epilepsy cases) the association was (HR: 2.44, 95% CI: 1.36–4.35, p =.003). Significance: Our results offer further evidence that hypertension, a potentially modifiable and highly prevalent vascular risk factor in the general population, increases 2- to 2.5-fold the risk of developing late-onset epilepsy.

The studies on knowledge, attitudes, and practices (KAP) regarding COVID-19 help to identify erroneous concepts and inadequate practices related to the disease. This baseline information is essential to design effective strategies and improve adherence to prevention measures.To identify the COVID-19-related KAP in Venezuelan patients screened at the Hospital Universitario de Caracas triage tent.We conducted a cross-sectional study among 215 patients between April 25th and May 25th, 2020, with in-person interviews using a KAP survey.Most surveyed patients (53.5%) were asymptomatic. Most of them, both from the symptomatic and the asymptomatic groups, had adequate knowledge about the symptoms and transmission of the disease and the majority said they were practicing quarantine, frequent handwashing, and the use of face masks in public areas. However, the daily replacement of cloth face masks was more frequent in the asymptomatic group whereas replacement every three days was more frequent in the symptomatic group. Finally, more than half of the participants admitted having been in crowded places, a common practice among the symptomatic compared to the asymptomatic patients.This is the first KAP study in Venezuela about COVID-19. Knowledge and practices among Venezuelans could be improved by strengthening education and training programs. This information from the early phase of the pandemic in Venezuela may contribute to the design of COVID-19 promotion and prevention strategies.Introducción: Los estudios sobre conocimientos, actitudes y prácticas (CAP) sobre COVID-19 ayudan a identificar conceptos erróneos y prácticas inadecuadas relacionadas con la enfermedad. Esta información de referencia es fundamental para diseñar estrategias efectivas y mejorar la adherencia a las medidas de prevención. Objetivo: Identificar la CAP relacionada con COVID-19 en pacientes venezolanos cribados en la carpa de triaje del Hospital Universitario de Caracas. Materiales y métodos: Realizamos un estudio transversal entre 215 pacientes entre el 25 de abril y el 25 de mayo de 2020, con entrevistas en persona utilizando una encuesta KAP. Resultados: La mayoría de los pacientes encuestados (53,5%) se encontraban asintomáticos. La mayoría de ellos, tanto del grupo sintomático como asintomático, tenían un conocimiento adecuado sobre los síntomas y la transmisión de la enfermedad y la mayoría dijo que practicaban la cuarentena, el lavado frecuente de manos y el uso de mascarillas en las áreas públicas. Sin embargo, el reemplazo diario de mascarillas de tela fue más frecuente en el grupo asintomático, mientras que el reemplazo cada tres días fue más frecuente en el grupo sintomático. Finalmente, más de la mitad de los participantes admitieron haber estado en lugares concurridos, una práctica común entre los sintomáticos en comparación con los asintomáticos. Conclusiones: Este es el primer estudio CAP en Venezuela sobre COVID-19. El conocimiento y las prácticas entre los venezolanos podrían mejorarse fortaleciendo los programas de educación y capacitación. Esta información de la fase inicial de la pandemia en Venezuela puede contribuir al diseño de estrategias de promoción y prevención del COVID-19.

Background and Purpose: Novel noninvasive measures of vascular function are emerging as subclinical markers for cardiovascular disease (CVD) and may be useful to predict CVD events. The purpose of our prospective study was to assess associations between digital peripheral arterial tonometry (PAT) measures and first-onset major CVD events in a sample of FHS (Framingham Heart Study) participants. Methods: Using a fingertip PAT device, we assessed pulse amplitude in Framingham Offspring and Third Generation participants (n=3865; mean age, 55±14 years; 52% women) at baseline and in 30-second intervals for 4 minutes during reactive hyperemia. The PAT ratio (relative hyperemia index) was calculated as the post-to-pre occlusion pulse signal ratio in the occluded arm, relative to the same ratio in the control (nonoccluded) arm, and corrected for baseline vascular tone. Baseline pulse amplitude and PAT ratio during hyperemia are measures of pressure pulsatility and microvascular function in the finger, respectively. We used Cox proportional hazards regression to relate PAT measures in the fingertip to incident CVD events. Results: During follow-up (median, 9.2 years; range, 0.04–10.0 years), 270 participants (7%) experienced new-onset CVD events (n=270). In multivariable models adjusted for cardiovascular risk factors, baseline pulse amplitude (hazard ratio [HR] per 1 SD, 1.04 [95% CI, 0.90–1.21]; P =0.57) and PAT ratio (HR, 0.95 [95% CI, 0.84–1.08]; P =0.43) were not significantly related to incident composite CVD events, including myocardial infarction or heart failure. However, higher PAT ratio (HR, 0.76 [95% CI, 0.61–0.94]; P =0.013), but not baseline pulse amplitude (HR, 1.15 [95% CI, 0.89–1.49]; P =0.29), was related to lower risk for incident stroke. In a sensitivity analysis by stroke subtype, higher PAT ratio was related to lower risk of incident ischemic stroke events (HR, 0.68 [95% CI, 0.53–0.86]; P =0.001). Conclusions: Novel digital PAT measures may represent a marker of stroke risk in the community.

In December 2020, the Food and Drug Administration (FDA) issued Emergency Use Authorizations (EUAs) for Pfizer-BioNTech and Moderna COVID-19 vaccines, and in February 2021, FDA issued an EUA for the Janssen (Johnson & Johnson) COVID-19 vaccine. After each EUA, the Advisory Committee on Immunization Practices (ACIP) issued interim recommendations for vaccine use; currently Pfizer-BioNTech is authorized and recommended for persons aged ≥12 years and Moderna and Janssen for persons aged ≥18 years (1-3). Both Pfizer-BioNTech and Moderna vaccines, administered as 2-dose series, are mRNA-based COVID-19 vaccines, whereas the Janssen COVID-19 vaccine, administered as a single dose, is a recombinant replication-incompetent adenovirus-vector vaccine. As of July 22, 2021, 187 million persons in the United States had received at least 1 dose of COVID-19 vaccine (4); close monitoring of safety surveillance has demonstrated that serious adverse events after COVID-19 vaccination are rare (5,6). Three medical conditions have been reported in temporal association with receipt of COVID-19 vaccines. Two of these (thrombosis with thrombocytopenia syndrome [TTS], a rare syndrome characterized by venous or arterial thrombosis and thrombocytopenia, and Guillain-Barre syndrome [GBS], a rare autoimmune neurologic disorder characterized by ascending weakness and paralysis) have been reported after Janssen COVID-19 vaccination. One (myocarditis, cardiac inflammation) has been reported after Pfizer-BioNTech COVID-19 vaccination or Moderna COVID-19 vaccination, particularly after the second dose; these were reviewed together and will hereafter be referred to as mRNA COVID-19 vaccination. ACIP has met three times to review the data associated with these reports of serious adverse events and has comprehensively assessed the benefits and risks associated with receipt of these vaccines. During the most recent meeting in July 2021, ACIP determined that, overall, the benefits of COVID-19 vaccination in preventing COVID-19 morbidity and mortality outweigh the risks for these rare serious adverse events in adults aged ≥18 years; this balance of benefits and risks varied by age and sex. ACIP continues to recommend COVID-19 vaccination in all persons aged ≥12 years. CDC and FDA continue to closely monitor reports of serious adverse events and will present any additional data to ACIP for consideration. Information regarding risks and how they vary by age and sex and type of vaccine should be disseminated to providers, vaccine recipients, and the public.

In December 2020, the Food and Drug Administration (FDA) issued Emergency Use Authorizations (EUAs) for the Pfizer-BioNTech COVID-19 (BNT162b2) vaccine and the Moderna COVID-19 (mRNA-1273) vaccine,† and the Advisory Committee on Immunization Practices (ACIP) issued interim recommendations for their use in persons aged ≥16 years and ≥18 years, respectively.§ In May 2021, FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12-15 years; ACIP recommends that all persons aged ≥12 years receive a COVID-19 vaccine. Both Pfizer-BioNTech and Moderna vaccines are mRNA vaccines encoding the stabilized prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19. Both mRNA vaccines were authorized and recommended as a 2-dose schedule, with second doses administered 21 days (Pfizer-BioNTech) or 28 days (Moderna) after the first dose. After reports of myocarditis and pericarditis in mRNA vaccine recipients,¶ which predominantly occurred in young males after the second dose, an ACIP meeting was rapidly convened to review reported cases of myocarditis and pericarditis and discuss the benefits and risks of mRNA COVID-19 vaccination in the United States. Myocarditis is an inflammation of the heart muscle; if it is accompanied by pericarditis, an inflammation of the thin tissue surrounding the heart (the pericardium), it is referred to as myopericarditis. Hereafter, myocarditis is used to refer to myocarditis, pericarditis, or myopericarditis. On June 23, 2021, after reviewing available evidence including that for risks of myocarditis, ACIP determined that the benefits of using mRNA COVID-19 vaccines under the FDA's EUA clearly outweigh the risks in all populations, including adolescents and young adults. The EUA has been modified to include information on myocarditis after receipt of mRNA COVID-19 vaccines. The EUA fact sheets should be provided before vaccination; in addition, CDC has developed patient and provider education materials about the possibility of myocarditis and symptoms of concern, to ensure prompt recognition and management of myocarditis.

We aimed to study the predictive factors for recovery of parathyroid function in hypoparathyroid patients after total thyroidectomy for thyroid cancer.We designed a retrospective, multicentre and nation-wide analysis of patients with total thyroidectomy who were seen in twenty endocrinology departments from January to March 2018. We selected patients with histologically proven thyroid cancer and retrieved information related to surgical procedure and thyroid cancer features. Survival analysis and Cox regression analysis were used to study the relationship between these variables and the recovery of parathyroid function.From 685 patients with hypoparathyroidism at discharge of surgery, 495 (72.3%) recovered parathyroid function over time. Kaplan-Meier analysis showed that this recovery was significantly related to the presence of specialized surgical team (P0.001), identification of parathyroid glands at surgery (P0.001), papillary histopathology (P=0.040), and higher levels of postoperative calcium (Ca) (P0.001) and parathyroid hormone (PTH) (P0.001). Subjects with gross extrathyroidal extension (P=0.040), lymph node metastases (P=0.004), and surgical re-intervention after initial surgery (P=0.024) exhibited a significant risk of persistence of hypoparathyroidism. Multivariate Cox regression analysis showed that the significant and independent factors for recovery of parathyroid function were postoperative concentrations of Ca (P=0.038) and PTH (P=0.049). The presence of lymph node metastases was a negative predictor of recuperation of parathyroid function (P=0.042) in this analysis.In patients with thyroid cancer, recovery of parathyroid function after total thyroidectomy was directly related to postoperative Ca and PTH concentrations, and inversely related to lymph node metastases.

Introduction Immune checkpoint inhibitors (ICPI) have improved progression-free survival in several solid tumors. Side effects are related to overstimulation of the immune system. Thyroid dysfunction (TD) is the most common endocrine immune-related adverse event of ICPI. Objective To describe the clinical presentation and the course of TD in cancer patients treated with ICPI referred to an endocrinology outpatient clinic. Material and methods This was a descriptive, retrospective and multicenter study of patients with TD associated with ICPI in six Spanish hospitals. Results 120 patients (50.8% women), mean age 60 ± 12 years were included. The initial TD was hypothyroidism in 49% of patients and hyperthyroidism in 51%, with an average of 76 (41–140) and 43 (26–82) days respectively between the onset of ICPI and the analytical alteration. Significantly, the earlier the first analytical determination was, the greater the prevalence of hyperthyroidism. A turnover was observed in 80% of subjects during follow-up, mostly from hyperthyroidism to hypothyroidism. Twenty-one percent received double ICPI therapy. The most frequent form of presentation in monotherapy was hypothyroidism (57%), and in double therapy it was hyperthyroidism (77%) (p = 0.002). Patients under double therapy showed thyroid alterations earlier than those in the monotherapy group (p = 0.001). After a follow-up of 205 (112–360) days, half of the patients continued under levothyroxine treatment. Conclusions Hypothyroidism and hyperthyroidism present in a similar proportion in cancer patients undergoing ICPI therapy. Our results suggest that transitory hyperthyroidism may not be detected in a relevant number of cases. In addition, TD in double therapy presents earlier. This should be taken into account in the follow-up protocols of these patients.

On February 27, 2021, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the Janssen COVID-19 (Ad.26.COV2.S) vaccine (Janssen Biotech, Inc., a Janssen Pharmaceutical company, Johnson & Johnson; New Brunswick, New Jersey), and on February 28, 2021, the Advisory Committee on Immunization Practices (ACIP) issued interim recommendations for its use in persons aged ≥18 years (1,2). On April 13, 2021, CDC and FDA recommended a pause in the use of the Janssen COVID-19 vaccine after reports of six U.S. cases of cerebral venous sinus thrombosis (CVST) with thrombocytopenia, a rare thromboembolic syndrome, among Janssen COVID-19 vaccine recipients (3). Two emergency ACIP meetings were rapidly convened to review reported cases of thrombosis with thrombocytopenia syndrome (TTS) and to consider updated recommendations for use of the Janssen COVID-19 vaccine in the United States. On April 23, 2021, after a discussion of the benefits and risks of resuming vaccination, ACIP reaffirmed its interim recommendation for use of the Janssen COVID-19 vaccine in all persons aged ≥18 years under the FDA's EUA, which now includes a warning that rare clotting events might occur after vaccination, primarily among women aged 18-49 years. Patient and provider education about the risk for TTS with the Janssen COVID-19 vaccine, especially among women aged

Patients with type 2 diabetes (T2D) and Latin American subjects in particular are at an increased risk of developing severe COVID-19 and mortality. Altered renal function and lower magnesium levels have been reported to play important roles in the pathophysiology of T2D. The aim of the study was to investigate the relationship between renal function, serum magnesium levels and mortality in T2D patients with COVID-19. In this retrospective study, we characterized 118 T2D and non-diabetic subjects hospitalized with COVID-19. Patients were clinically characterized and electrolyte, renal function and inflammatory markers were evaluated. Patients were grouped according to their estimated glomerular filtration rate (eGFR

Objective We aimed to characterize cortical superficial siderosis, its determinants and sequel, in community-dwelling older adults. Methods The sample consisted of Framingham ( n = 1724; 2000–2009) and Rotterdam ( n = 4325; 2005–2013) study participants who underwent brain MRI. In pooled individual-level analysis, we compared baseline characteristics in patients with cortical superficial siderosis to two reference groups: (i) persons without hemorrhagic MRI markers of cerebral amyloid angiopathy (no cortical superficial siderosis and no microbleeds) and (ii) those with presumed cerebral amyloid angiopathy based on the presence of strictly lobar microbleeds but without cortical superficial siderosis. Results Among a total of 6049 participants, 4846 did not have any microbleeds or cortical superficial siderosis (80%), 401 had deep/mixed microbleeds (6.6%), 776 had strictly lobar microbleeds without cortical superficial siderosis (12.8%) and 26 had cortical superficial siderosis with/without microbleeds (0.43%). In comparison to participants without microbleeds or cortical superficial siderosis and to those with strictly lobar microbleeds but without cortical superficial siderosis, participants with cortical superficial siderosis were older (OR 1.09 per year, 95% CI 1.05, 1.14; p 999.99; p = 0.006). During a mean follow-up of 5.6 years, 42.4% participants with cortical superficial siderosis had a stroke (five intracerebral hemorrhage, two ischemic strokes and four undetermined strokes), 19.2% had transient neurological deficits and 3.8% developed incident dementia. Conclusion Our study adds supporting evidence to the association between cortical superficial siderosis and cerebral amyloid angiopathy within the general population. Community-dwelling persons with cortical superficial siderosis may be at high risk for intracerebral hemorrhage and future neurological events.

The first vaccines for prevention of coronavirus disease 2019 (COVID-19) in the United States were authorized for emergency use by the Food and Drug Administration (FDA) (1) and recommended by the Advisory Committee on Immunization Practices (ACIP) in December 2020.* However, demand for COVID-19 vaccines is expected to exceed supply during the first months of the national COVID-19 vaccination program. ACIP advises CDC on population groups and circumstances for vaccine use.† On December 1, ACIP recommended that 1) health care personnel§ and 2) residents of long-term care facilities¶ be offered COVID-19 vaccination first, in Phase 1a of the vaccination program (2). On December 20, 2020, ACIP recommended that in Phase 1b, vaccine should be offered to persons aged ≥75 years and frontline essential workers (non-health care workers), and that in Phase 1c, persons aged 65-74 years, persons aged 16-64 years with high-risk medical conditions, and essential workers not recommended for vaccination in Phase 1b should be offered vaccine.** These recommendations for phased allocation provide guidance for federal, state, and local jurisdictions while vaccine supply is limited. In its deliberations, ACIP considered scientific evidence regarding COVID-19 epidemiology, ethical principles, and vaccination program implementation considerations. ACIP's recommendations for COVID-19 vaccine allocation are interim and might be updated based on changes in conditions of FDA Emergency Use Authorization, FDA authorization for new COVID-19 vaccines, changes in vaccine supply, or changes in COVID-19 epidemiology.

To reduce the spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) and its associated impacts on health and society, COVID-19 vaccines are essential. The U.S. government is working to produce and deliver safe and effective COVID-19 vaccines for the entire U.S. population. The Advisory Committee on Immunization Practices (ACIP)* has broadly outlined its approach for developing recommendations for the use of each COVID-19 vaccine authorized or approved by the Food and Drug Administration (FDA) for Emergency Use Authorization or licensure (1). ACIP's recommendation process includes an explicit and transparent evidence-based method for assessing a vaccine's safety and efficacy as well as consideration of other factors, including implementation (2). Because the initial supply of vaccine will likely be limited, ACIP will also recommend which groups should receive the earliest allocations of vaccine. The ACIP COVID-19 Vaccines Work Group and consultants with expertise in ethics and health equity considered external expert committee reports and published literature and deliberated the ethical issues associated with COVID-19 vaccine allocation decisions. The purpose of this report is to describe the four ethical principles that will assist ACIP in formulating recommendations for the allocation of COVID-19 vaccine while supply is limited, in addition to scientific data and implementation feasibility: 1) maximize benefits and minimize harms; 2) promote justice; 3) mitigate health inequities; and 4) promote transparency. These principles can also aid state, tribal, local, and territorial public health authorities as they develop vaccine implementation strategies within their own communities based on ACIP recommendations.

ObjectiveTo test the hypothesis that reduced slow-wave sleep, or N3 sleep, which is thought to underlie the restorative functions of sleep, is associated with MRI markers of brain aging, we evaluated this relationship in the community-based Framingham Heart Study Offspring cohort using polysomnography and brain MRI.MethodsWe studied 492 participants (age 58.8 ± 8.8 years, 49.4% male) free of neurological diseases who completed a brain MRI scan and in-home overnight polysomnography to assess slow-wave sleep (absolute duration and percentage of total sleep). Volumes of total brain, total cortical, frontal cortical, subcortical gray matter, hippocampus, and white matter hyperintensities were investigated as a percentage of intracranial volume, and the presence of covert brain infarcts was evaluated. Linear and logistic regression models were adjusted for age, age squared, sex, time interval between polysomnography and MRI (3.3 ± 1.0 years), APOE ε4 carrier status, stroke risk factors, sleeping pill use, body mass index, and depression.ResultsLess slow-wave sleep was associated with lower cortical brain volume (absolute duration, β [standard error] = 0.20 [0.08], p = 0.015; percentage, 0.16 [0.08], p = 0.044), lower subcortical brain volume (percentage, 0.03 [0.02], p = 0.034), and higher white matter hyperintensities volume (absolute duration, −0.12 [0.05], p = 0.010; percentage, −0.10 [0.04], p = 0.033). Slow-wave sleep duration was not associated with hippocampal volume or the presence of covert brain infarcts.ConclusionLoss of slow-wave sleep might facilitate accelerated brain aging, as evidence by its association with MRI markers suggestive of brain atrophy and injury. Alternatively, subtle injuries and accelerated aging might reduce the ability of the brain to produce slow-wave sleep.

To reduce the spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) and its associated impacts on health and society, COVID-19 vaccines are essential. The U.S. government is working to produce and deliver safe and effective COVID-19 vaccines for the entire U.S. population. The Advisory Committee on Immunization Practices (ACIP)* has broadly outlined its approach for developing recommendations for the use of each COVID-19 vaccine authorized or approved by the Food and Drug Administration (FDA) for Emergency Use Authorization or licensure (1). ACIP's recommendation process includes an explicit and transparent evidence-based method for assessing a vaccine's safety and efficacy as well as consideration of other factors, including implementation (2). Because the initial supply of vaccine will likely be limited, ACIP will also recommend which groups should receive the earliest allocations of vaccine. The ACIP COVID-19 Vaccines Work Group and consultants with expertise in ethics and health equity considered external expert committee reports and published literature and deliberated the ethical issues associated with COVID-19 vaccine allocation decisions. The purpose of this report is to describe the four ethical principles that will assist ACIP in formulating recommendations for the allocation of COVID-19 vaccine while supply is limited, in addition to scientific data and implementation feasibility: 1) maximize benefits and minimize harms; 2) promote justice; 3) mitigate health inequities; and 4) promote transparency. These principles can also aid state, tribal, local, and territorial public health authorities as they develop vaccine implementation strategies within their own communities based on ACIP recommendations.

Background and Purpose: Enlarged perivascular spaces (EPVS) are considered subclinical markers of small vessel disease, associated with increased risk of stroke and dementia. Increasing evidence links chronic kidney disease (CKD) to small vessel disease. We explored the relationship between CKD and EPVS burden and the influence of racial group in this relation. Methods: Consecutive patients with stroke who underwent brain magnetic resonance imaging were included (n=894). Racial group was categorized as White, Black, or other (other racial groups). CKD was defined by glomerular filtration rate 2 for >3 months. EPVS were rated following a standardized method, dichotomized for analyses (mild [ Results: In multivariable-adjusted analysis, the association of CKD with severe EPVS varied across racial groups. Comparing patients with and without CKD within racial groups, we found that Whites with CKD had higher odds of severe centrum semiovale EPVS (odds ratio [OR], 2.41 [95% CI, 0.98–5.88]). Among patients with CKD, Black patients had higher odds of severe EPVS in the basal ganglia and centrum semiovale compared with Whites (OR, 1.93 [95% CI, 1.18–3.16] and OR, 1.90 [95% CI, 1.16–3.11], respectively) and other racial groups (OR, 2.03 [95% CI, 1.23–3.36] and OR, 2.02 [95% CI, 1.22–3.34], respectively). Conclusions: CKD was more prevalent in our sample of patients with stroke with severe EPVS in the centrum semiovale. The relation differed when stratified by racial group and brain topography. Further studies are needed to confirm that CKD may relate differently to subclinical measures of small vessel disease according to race.

Stress is a physiological response that promotes maintenance of balance against harmful stimuli. Unfortunately, chronic activation of stress systems facilitates the development of psychiatric disorders. A stress-mediated hypercholinergic state could underlie this facilitation, as cholinergic mechanisms have been suggested to play a role in anxiety, depression, and substance use disorder (SUD). Stimulation by stress hormones, urocortin (Ucn1) or corticotropin-releasing factor (CRF), of the CRF receptor type 1 (CRFR1) of acetylcholine-containing neurons of the laterodorsal tegmental nucleus (LDT) could be involved in modulation of cholinergic transmission during periods of stress hormone activation, which could play a role in psychiatric disorders as cholinergic LDT neurons project to, and control activity in, mood-, arousal- and SUD-controlling regions. The present study investigated for the first time the membrane effects and intracellular outcomes of CRFR1 activation by endogenous stress hormones on LDT neurons. Patch clamp recordings of immunohistochemically-identified cholinergic and non-cholinergic LDT neurons with concurrent calcium imaging were used to monitor cellular responses to CRFR1 stimulation with Ucn1 and CRF. Postsynaptically-mediated excitatory currents were elicited in LDT cholinergic neurons, accompanied by an enhancement in synaptic events. In addition, CRFR1 activation resulted in rises in intracellular calcium levels. CRFR1 stimulation recruited MAPK/ERK and SERCA-ATPase involved pathways. The data presented here provide the first evidence that Ucn1 and CRF exert pre and postsynaptic excitatory membrane actions on LDT cholinergic neurons that could underlie the hypercholinergic state associated with stress which could play a role in the heightened risk of psychiatric disorders associated with a chronic stress state.

Objective Cerebral microbleeds (CMBs) are associated with higher risk of stroke and dementia, predating clinical diagnosis by several years. CMB are considered markers of cerebral small vessel disease (CSVD): hypertensive (deep CMB) and cerebral amyloid angiopathy (lobar CMB). We related plasma β‐Amyloid (40, 42 and their ratio), clusterin, and tau levels to CMB to elucidate their role as biomarkers for the angiopathies represented by CMB. Methods Dementia, stroke, and other neurological disease‐free Framingham Heart Study participants with available CMB and biomarker measurements were included. We related biomarker levels (standardized for analyses) to CMB presence overall and stratified by brain topography (any, lobar, deep), using multivariable logistic regression analyses. Results CMB were observed in 208 (5.7%) participants (mean age 57 years, 54% women). After multivariable adjustment, Aβ1‐40 was associated with any CMB (OR (95%CI) 1.20 (0.99, 1.45) P = 0.062)) and lobar CMB (OR (95%CI) 1.33 (1.05, 1.68) P = 0.019), but not with deep CMB. Log‐Aβ1‐42 levels were not associated with CMB overall. Clusterin was related to mixed CMB (1.70 [1.05, 2.74], P = 0.031). Tau levels were associated with any CMB (OR (95%CI) 1.26 (1.07, 1.49) P = 0.006), lobar CMB (OR (95%CI) 1.26 (1.05, 1.52) P = 0.013), and with deep CMB (OR (95% CI) 1.46 (1.13, 1.89) P = 0.004). Interpretation We found that plasma Aβ1‐40 and Tau are associated with CMB but further studies are needed to confirm their role in hemorrhage prone CSVD represented by CMB and as indicators of ongoing subclinical neuronal injury.

Aldosterone modulates the activity of both epithelial (specifically renal) and non-epithelial cells. Binding to the mineralocorticoid receptor (MR), activates two pathways: the classical genomic and the rapidly activated non-genomic that is substantially modulated by the level of striatin. We hypothesized that disruption of MR’s non-genomic pathway would alter aldosterone-induced cardiovascular/renal damage. To test this hypothesis, wild type (WT) and striatin heterozygous knockout (Strn+/−) littermate male mice were fed a liberal sodium (1.6% Na+) diet and randomized to either protocol one: 3 weeks of treatment with either vehicle or aldosterone plus/minus MR antagonists, eplerenone or esaxerenone or protocol two: 2 weeks of treatment with either vehicle or L-NAME/AngII plus/minus MR antagonists, spironolactone or esaxerenone. Compared to the WT mice, basally, the Strn+/− mice had greater (~26%) estimated renal glomeruli volume and reduced non-genomic second messenger signaling (pAkt/Akt ratio) in kidney tissue. In response to active treatment, the striatin-associated-cardiovascular/renal damage was limited to volume effects induced by aldosterone infusion: significantly increased blood pressure (BP) and albuminuria. In contrast, with aldosterone or L-NAME/AngII treatment, striatin deficiency did not modify aldosterone-mediated damage: in the heart and kidney, macrophage infiltration, and increases in aldosterone-induced biomarkers of injury. All changes were near-normalized following MR blockade with spironolactone or esaxerenone, except increased BP in the L-NAME/AngII model. In conclusion, the loss of striatin amplified aldosterone-induced damage suggesting that aldosterone’s non-genomic pathway is protective but only related to effects likely mediated via epithelial, but not non-epithelial cells.

Although only 10–15% of liver cancers are cholangiocarcinomas (CCAs), which derive from the epithelial cells of the biliary tree, these cancers constitute a serious and growing health problem worldwide.

The continuous flow of new research articles on MDR-TB diagnosis, treatment, prevention and rehabilitation requires frequent update of existing guidelines. This review is aimed at providing clinicians and public health staff with an updated and easy-to-consult document arising from consensus of Global Tuberculosis Network (GTN) experts. The core published documents and guidelines have been reviewed including the recently published MDR-TB WHO rapid advice and ATS/CDC/ERS/IDSA guidelines. After a rapid review of epidemiology and risk factors, the clinical priorities on MDR-TB diagnosis (including whole genome sequencing and drug-susceptibility testing interpretations) and treatment (treatment design and management, TB in children) are discussed. Furthermore, the review comprehensively describes the latest information on contact tracing and LTBI management in MDR-TB contacts, while providing guidance on post-treatment functional evaluation and rehabilitation of TB sequelae, infection control and other public health priorities.

A new series of tetrahydroquinoline-isoxazoline hybrid derivatives (3a–p) were efficiently synthesized involving 1,3-dipolar cycloaddition reaction according to click chemistry approach, from the corresponding N-allyl-4-(2-oxopyrrolinidyl-1)-tetrahydroquinolines preformed, with moderate to good yields (63–77%). To establish new candidates with anticancer activity, the antiproliferative effect of these compounds was measured by the MTT assay on different cancer cell lines such as human breast adenocarcinoma (MCF-7), human liver carcinoma (HepG2), human lung adenocarcinoma (A549), cervical cancer (HeLa), and murine melanoma (B16F10). Compounds 3a (CC50 = 11.37 μM, SI = 5.1) and 3i (CC50 = 25.59 μM, SI > 4.6) showed the best anticancer activities against murine melanoma cells with considerable selectivity compared with VERO cells. Compound 3h showed the best anticancer activity on cervical cancer (HeLa) cells (CC50 = 10.21 μM, SI = 4.1), and it was also slightly more active than the reference drug oxaliplatin. In addition, the compounds 3a and 3m decrease the mitochondrial membrane potential and induce apoptosis, suggesting that their cytotoxic effects may be based on mitochondrial parameter modulation.

Hepatocellular carcinoma (HCC) is a malignancy with poor prognosis when diagnosed at advanced stages in which curative treatments are no longer applicable. A small group of these patients may still benefit from transarterial chemoembolization. The only therapeutic option for most patients with advanced HCC is systemic pharmacological treatments based on tyrosine kinase inhibitors (TKIs) and immunotherapy. Available drugs only slightly increase survival, as tumor cells possess additive and synergistic mechanisms of pharmacoresistance (MPRs) prior to or enhanced during treatment. Understanding the molecular basis of MPRs is crucial to elucidate the genetic signature underlying HCC resistome. This will permit the selection of biomarkers to predict drug treatment response and identify tumor weaknesses in a personalized and dynamic way. In this article, we have reviewed the role of MPRs in current first-line drugs and the combinations of immunotherapeutic agents with novel TKIs being tested in the treatment of advanced HCC.

Smoking topography (ST) is a set of measures profiling the behavioral characteristics of smoking in various settings. The CReSS portable device can measure ST in the natural environment. No standard protocol exists for measuring ST longitudinally with the CReSS. This study examined the utilization of the CReSS to measure ST and highlights challenges and opportunities in a naturalistic setting. This study is part of a randomized cross-over clinical trial of smoking filtered or unfiltered cigarettes. Participants (n = 43) smoked in each study condition for two weeks using the CReSS device for five days in their naturalistic smoking setting. The devices were calibrated and cleaned during the washout period, and data were downloaded every visit. Five test puffs were administered to calibrate each device. Moderate compliance rates (74.1%) were found with device usage, and the issues encountered were overheating/clogging, incorrectly registered date/time-stamped data, and device repair/replacement. Routine inspection/cleaning and training in device usage were instrumental in mitigating device malfunctioning. The CReSS device proved to be a feasible tool to examine naturalistic smoking topography and the potential impact of changes in tobacco product design on smoking unfiltered cigarettes. This is the first study to examine ST variables longitudinally, measured at multiple time points, and using unfiltered cigarettes.