Chronic infection with the hepatitis C virus (HCV) is associated with failures of T-cell–mediated immune clearance and with abnormal B-cell growth and activation. We examined the levels of chemokines ...that bind to CXC chemokine receptor 3 (CXCR3) to determine whether such chemokines might play a role in the failure of the immune system to clear HCV infection. Elevations in CXC ligand 9 (CXCL9), CXCL10, and CXCL11 were observed in all patients with HCV. CXCR3 expression was increased significantly on peripheral blood B lymphocytes, but not T lymphocytes, from individuals with HCV infection. Chemokine levels were measured in samples collected before, during, and after antiviral therapy from a group of 29 patients infected with HCV genotypes 1a (24 patients) and 1b (5 patients). Levels of CXCL10 and CXCL9 decreased following successful antiviral therapy; CXCL11 did not decline significantly during or in the first 6 months after therapy. The baseline level of CXCL10 (measured before the start of antiviral treatment) was greatest in patients with HCV who subsequently became nonresponders to therapy. These results suggest that plasma concentrations of immunoreactive CXCL10 may be a predictor of responsiveness or nonresponsiveness to antiviral therapy with pegylated interferon (IFN) with or without ribavirin. This observation has implications for understanding the pathogenesis of HCV infection.
Informed energy decision making requires effective software, high-quality input data, and a suitably trained user community. Developing these resources can be expensive and time consuming. Even when ...data and tools are intended for public re-use they often come with technical, legal, economic and social barriers that make them difficult to adopt, adapt and combine for use in new contexts. We focus on the promise of open, publically accessible software and data as well as crowdsourcing techniques to develop robust energy analysis tools that can deliver crucial, policy-relevant insight, particularly in developing countries, where planning resources are highly constrained—and the need to adapt these resources and methods to the local context is high. We survey existing research, which argues that these techniques can produce high-quality results, and also explore the potential role that linked, open data can play in both supporting the modelling process and in enhancing public engagement with energy issues.
► We focus on the promise of open, publicly accessible software and data. ► These emerging techniques can produce high-quality results for energy analysis. ► Developing economies require new techniques for energy planning.
Background The present study aimed to describe and compare the operative experience of cardiothoracic surgical residents for basic and advanced cardiac surgical procedures. Methods Data were obtained ...from the 2015 Thoracic Surgery Directors Association Survey administered to all thoracic surgical residents taking the yearly In-Service Training Examination (n = 356). Residents were asked whether they routinely served as the operative surgeon on various cardiac operations and operative tasks. Results were stratified by postgraduate year (PGY), residency type, and primary career interest. Results The survey response rate was 100%. Considering all training pathways, only 2 of 13 cardiac operations surveyed were routinely performed by graduating chief residents as the operative surgeon: coronary artery bypass grafting (CABG; 92%) and aortic valve replacement (AVR; 88%). Off-pump CABG, minimally invasive mitral valve operation, and transcatheter aortic interventions were infrequently (<30% of the time) performed by graduating residents as the operative surgeon. These results were similar when residents with a career interest in general thoracic surgery were excluded from the analysis. For the operative progression of integrated 6-year (I-6) residents, most began to routinely cannulate for cardiopulmonary bypass, perform proximal coronary anastomoses, and harvest the mammary artery during PGY3. The majority (>50%) of I-6 residents performed CABG as the operative surgeon by PGY4. Conclusions There is pronounced heterogeneity in the cardiac operative experience of cardiothoracic surgical residents in the United States, with only CABG and AVR routinely performed by graduating residents as the operative surgeon. This heterogeneity may lead to insufficient training in certain procedures for many graduates.
The current epidemic of inactivity and the associated epidemic of obesity are being driven by multiple factors (societal, technologic, industrial, commercial, financial) and must be addressed ...likewise on several fronts. Foremost among these are the expansion of school physical education, dissuading children from pursuing sedentary activities, providing suitable role models for physical activity, and making activity-promoting changes in the environment. This statement outlines ways that pediatric health care providers and public health officials can encourage, monitor, and advocate for increased physical activity for children and teenagers.
Sports and energy drinks are being marketed to children and adolescents for a wide variety of inappropriate uses. Sports drinks and energy drinks are significantly different products, and the terms ...should not be used interchangeably. The primary objectives of this clinical report are to define the ingredients of sports and energy drinks, categorize the similarities and differences between the products, and discuss misuses and abuses. Secondary objectives are to encourage screening during annual physical examinations for sports and energy drink use, to understand the reasons why youth consumption is widespread, and to improve education aimed at decreasing or eliminating the inappropriate use of these beverages by children and adolescents. Rigorous review and analysis of the literature reveal that caffeine and other stimulant substances contained in energy drinks have no place in the diet of children and adolescents. Furthermore, frequent or excessive intake of caloric sports drinks can substantially increase the risk for overweight or obesity in children and adolescents. Discussion regarding the appropriate use of sports drinks in the youth athlete who participates regularly in endurance or high-intensity sports and vigorous physical activity is beyond the scope of this report.
Mental and behavioral health (MBH) emergencies in children and youth continue to increasingly affect not only the emergency department (ED), but the entire spectrum of emergency medical services for ...children, from prehospital services to the community. Inadequate community and institutional infrastructure to care for children and youth with MBH conditions makes the ED an essential part of the health care safety net for these patients. As a result, an increasing number of children and youth are referred to the ED for evaluation of a broad spectrum of MBH emergencies, from depression and suicidality to disruptive and aggressive behavior. However, challenges in providing optimal care to these patients include lack of personnel, capacity, and infrastructure; challenges with timely access to a mental health professional; the nature of a busy ED environment; and paucity of outpatient post-ED discharge resources. These factors contribute to prolonged ED stays and boarding, which negatively affect patient care and ED operations. Strategies to improve care for MBH emergencies, including systems-level coordination of care, are therefore essential. The goal of this policy statement and its companion technical report is to highlight strategies, resources, and recommendations for improving emergency care delivery for pediatric MBH.
Real-world evaluations have demonstrated high effectiveness of vaccines against COVID-19-associated hospitalizations (1-4) measured shortly after vaccination; longer follow-up is needed to assess ...durability of protection. In an evaluation at 21 hospitals in 18 states, the duration of mRNA vaccine (Pfizer-BioNTech or Moderna) effectiveness (VE) against COVID-19-associated hospitalizations was assessed among adults aged ≥18 years. Among 3,089 hospitalized adults (including 1,194 COVID-19 case-patients and 1,895 non-COVID-19 control-patients), the median age was 59 years, 48.7% were female, and 21.1% had an immunocompromising condition. Overall, 141 (11.8%) case-patients and 988 (52.1%) controls were fully vaccinated (defined as receipt of the second dose of Pfizer-BioNTech or Moderna mRNA COVID-19 vaccines ≥14 days before illness onset), with a median interval of 65 days (range = 14-166 days) after receipt of second dose. VE against COVID-19-associated hospitalization during the full surveillance period was 86% (95% confidence interval CI = 82%-88%) overall and 90% (95% CI = 87%-92%) among adults without immunocompromising conditions. VE against COVID-19- associated hospitalization was 86% (95% CI = 82%-90%) 2-12 weeks and 84% (95% CI = 77%-90%) 13-24 weeks from receipt of the second vaccine dose, with no significant change between these periods (p = 0.854). Whole genome sequencing of 454 case-patient specimens found that 242 (53.3%) belonged to the B.1.1.7 (Alpha) lineage and 74 (16.3%) to the B.1.617.2 (Delta) lineage. Effectiveness of mRNA vaccines against COVID-19-associated hospitalization was sustained over a 24-week period, including among groups at higher risk for severe COVID-19; ongoing monitoring is needed as new SARS-CoV-2 variants emerge. To reduce their risk for hospitalization, all eligible persons should be offered COVID-19 vaccination.
species,
, and
are opportunistic pathogens that cause a range of brain, skin, eye, and disseminated diseases in humans and animals. These pathogenic free-living amoebae (pFLA) are commonly ...misdiagnosed and have sub-optimal treatment regimens which contribute to the extremely high mortality rates (>90%) when they infect the central nervous system. To address the unmet medical need for effective therapeutics, we screened kinase inhibitor chemotypes against three pFLA using phenotypic drug assays involving CellTiter-Glo 2.0. Herein, we report the activity of the compounds against the trophozoite stage of each of the three amoebae, ranging from nanomolar to low micromolar potency. The most potent compounds that were identified from this screening effort were:
(
EC
: 0.92 ± 0.3 μM; and
EC
: 0.43 ± 0.13 μM),
and
(
EC
s: <0.63 μM, and 0.3 ± 0.21 μM), and
and
(
EC
s: 1.0 ± 0.12 μM, and 1.4 ± 0.17 μM, respectively). With several of these pharmacophores already possessing blood-brain barrier (BBB) permeability properties, or are predicted to penetrate the BBB, these hits present novel starting points for optimization as future treatments for pFLA-caused diseases.
Longer lives and fertility far below the replacement level of 2.1 births per woman are leading to rapid population aging in many countries. Many observers are concerned that aging will adversely ...affect public finances and standards of living. Analysis of newly available National Transfer Accounts data for 40 countries shows that fertility well above replacement would typically be most beneficial for government budgets. However, fertility near replacement would be most beneficial for standards of living when the analysis includes the effects of age structure on families as well as governments. And fertility below replacement would maximize per capita consumption when the cost of providing capital for a growing labor force is taken into account. Although low fertility will indeed challenge government programs and very low fertility undermines living standards, we find that moderately low fertility and population decline favor the broader material standard of living.
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