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High glucose/High Lipids impair vascular adiponectin function via inhibition of caveolin-1/AdipoR1 signalsome formation. - Free radical biology & medicine
Reduced levels of adiponectin (APN) contribute to cardiovascular injury in the diabetic population. Recent studies demonstrate elevated circulating APN levels are associated with endothelial dysfunction during pre-diabetes, suggesting the development of APN resistance. However, mechanisms leading to, and the role of, vascular APN resistance in endothelial dysfunction remain unidentified. The current study determined whether diabetes cause endothelial APN resistance, and by what mechanisms. Under high glucose/high lipids (HG/HL), APN-stimulated nitric oxide production by HUVEC was decreased, phosphorylation of eNOS, AMPK, and Akt was attenuated (P<0.01), and APN's anti-TNFÎ± effect was blunted (P<0.01). APN receptor expression remained normal, whereas Cav1 expression was reduced in HG/HL cells (P<0.01). The AdipoR1/Cav1 signaling complex was dissociated in HG/HL cells. Knock-down of Cav1 inhibited APN's anti-oxidative and anti-inflammatory actions. Conversely, preventing HG/HL-induced Cav1 downregulation by Cav1 overexpression preserved APN signaling in HG/HL cells. Knock-in of a wild type Cav1 in Cav1 knock-down cells restored caveolae structure and rescued APN signaling. In contrast, knock-in of a mutated Cav1 scaffolding domain restored caveolae structure, but failed to rescue APN signaling in Cav1 knock-down cells. Finally, AdipoR1/Cav1 interaction was significantly reduced in diabetic vascular tissue, and the vasorelaxative response to APN was impaired in diabetic animals. The current study demonstrates for the first time the interaction between AdipoR1 and Cav1 is critical for adiponectin-mediated vascular signaling. The AdipoR1/Cav1 interaction is adversely affected by HG/HL, due largely to reduced Cav1 expression, supporting a potential mechanism for the development of APN resistance, contributing to diabetic endothelial dysfunction.Copyright Â© 2015 Elsevier Inc. All rights reserved.
Nature and Utilization of Civil Commitment for Substance Abuse in the United States. - The journal of the American Academy of Psychiatry and the Law
Substance abuse is a leading cause of morbidity and mortality in the United States. Although civil commitment has been used to address substance abuse for more than a century, little is known today about the nature and use of substance-related commitment laws in the United States. We examined statutes between July 2010 and October 2012 from all 50 states and the District of Columbia for provisions authorizing civil commitment of adults for substance abuse and recorded the criteria and evidentiary standard for commitment and the location and the maximum duration of commitment orders. High-level state representatives evaluated these data and provided information on the use of commitment. Thirty-three states have statutory provisions for the civil commitment of persons because of substance abuse. The application of these statutes ranged from a few commitment cases to thousands annually. Although dangerousness was the most common basis for commitment, many states permitted it in other contexts. The maximum duration of treatment ranged from less than 1 month to more than 1 year for both initial and subsequent civil commitment orders. These findings show wide variability in the nature and application of civil commitment statutes for substance abuse in the United States. Such diversity reflects a lack of consensus on the role that civil commitment should play in managing substance abuse and the problems associated with it.Â© 2015 American Academy of Psychiatry and the Law.
Culture revisited: A reply to comments. - The American psychologist
Replies to comments by Winston & Maher (see record 2015-45553-005), Abi-Hashem (see record 2015-45553-006), and Hook & Watkins (see record 2015-45553-007), on the original article by Christopher et al. (see record 2014-20055-001). In this brief response, the authors clarify some elements of their thinking and address some misconceptions put forward by the commentators. (PsycINFO Database Record(c) 2015 APA, all rights reserved).
Nutritional Status and Mortality in the Critically Ill. - Critical care medicine
The association between nutritional status and mortality in critically ill patients is unclear based on the current literature. To clarify this relation, we analyzed the association between nutrition and mortality in a large population of critically ill patients and hypothesized that mortality would be impacted by nutritional status.Retrospective observational study.Single academic medical center.Six thousand five hundred eighteen adults treated in medical and surgical ICUs between 2004 and 2011.None.All cohort patients received a formal, in-person, standardized evaluation by a registered dietitian. The exposure of interest, malnutrition, was categorized as nonspecific malnutrition, protein-energy malnutrition, or well nourished and determined by data related to anthropometric measurements, biochemical indicators, clinical signs of malnutrition, malnutrition risk factors, and metabolic stress. The primary outcome was all-cause 30-day mortality determined by the Social Security Death Master File. Associations between nutrition groups and mortality were estimated by bivariable and multivariable logistic regression models. Adjusted odds ratios were estimated with inclusion of covariate terms thought to plausibly interact with both nutrition status and mortality. We used propensity score matching on baseline characteristics to reduce residual confounding of the nutrition status category assignment. In the cohort, nonspecific malnutrition was present in 56%, protein-energy malnutrition was present in 12%, and 32% were well nourished. The 30-day and 90-day mortality rates for the cohort were 19.1% and 26.6%, respectively. Nutritional status is a significant predictor of 30-day mortality following adjustment for age, gender, race, medical versus surgical patient type, Deyo-Charlson index, acute organ failure, vasopressor use, and sepsis: nonspecific malnutrition 30-day mortality odds ratio, 1.17 (95% CI, 1.01-1.37); protein-energy malnutrition 30-day mortality odds ratio, 2.10 (95% CI, 1.70-2.59), all relative to patients without malnutrition. In the matched cohort, the adjusted odds of 30-day mortality in the group of propensity score-matched patients with protein-energy malnutrition was two-fold greater than that of patients without malnutrition.In a large population of critically ill adults, an association exists between nutrition status and mortality.
Association of Model for End-Stage Liver Disease Score and Mortality in Trauma Patients With Chronic Liver Disease. - JAMA surgery
The Model for End-Stage Liver Disease (MELD) score is predictive of trauma outcomes.To determine whether a decrease in MELD score is associated with improved mortality in critically ill trauma patients.We performed a retrospective registry study of critically ill trauma patients 18 years or older with chronic liver disease treated between August 3, 1998, and January 5, 2012, at 2 level I trauma centers in Boston, Massachusetts. The consecutive sample included 525 patients (male, 373 [71.0%]; white, 399 [76.0%]; mean [SD] age, 55.0 [12.4] years).Change in MELD score from intensive care unit (ICU) admission to 48 to 72 hours later.Thirty-day all-cause mortality.The mean (SD) MELD score at ICU admission was 19.3 (9.7). The 30-day mortality was 21.9%. The odds of 30-day mortality with a change in MELD score of less than -2, -2 to -1, +1 to +4, and greater than +4 were 0.23 (95% CI, 0.10-0.51), 0.30 (95% CI, 0.10-0.85), 0.57 (95% CI, 0.27-1.20), and 1.31 (95% CI, 0.58-2.96), respectively, relative to a change in MELD score of 0 and adjusted for age, sex, race, Charlson/Deyo Index, sepsis, number of acute organ failures, International Classification of Diseases, Ninth Revision-based injury severity score, and ICU admission MELD score.A decrease in MELD score within 72 hours of ICU admission is associated with improved mortality.
Orexin Receptor Antagonists: Historical Perspectives and Future Opportunities. - Current topics in medicinal chemistry
The orexin receptors OX1 and OX2 play important roles in the regulation of sleep-wake cycles, feeding, reward and energy homeostasis. Since these G protein-coupled receptors were deorphanised in 1998, more than 200 patents containing orexin receptor antagonists have been filed and, in 2014, suvorexant (BelsomraÂ®) became the first of these compounds to receive approval from the FDA. Suvorexant is a dual orexin receptor antagonist (DORA) which is available for the treatment of insomnia. This review provides a historical perspective on the discovery and development of DORAs as well as selective OX1 receptor antagonists (1-SORAs) and selective OX2 receptor antagonists (2-SORAs). 2-SORAs are under clinical evaluation for their ability to modulate sleep, and 1-SORAs have shown promise for the treatment of addiction in pre-clinical animal models. Detailed medicinal chemistry case studies are presented and future opportunities for orexin receptor antagonists are considered.
Disseminated Salmonella Infection Coexisting with Thymoma. - The Indian journal of chest diseases & allied sciences
A 21-year-old boy presented with high grade fever, diffuse chest pain and exertional breathlessness of one month duration. Radiologically he had a large lobulated anterior mediastinal mass with necrotic thick enhancing septaes. Histopathology of the mass was suggestive of thymoma and culture from the necrotic aspirate yielded Salmonella typhi. The same pathogen was isolated in subsequent blood and sputum cultures. This current report describes the rare association of salmonella infection with thymoma.
RePORT International: Advancing Tuberculosis Biomarker Research Through Global Collaboration. - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Progress in tuberculosis clinical research is hampered by a lack of reliable biomarkers that predict progression from latent to active tuberculosis, and subsequent cure, relapse, or failure. Regional Prospective Observational Research in Tuberculosis (RePORT) International represents a consortium of regional cohorts (RePORT India, RePORT Brazil, and RePORT Indonesia) that are linked through the implementation of a Common Protocol for data and specimen collection, and are poised to address this critical research need. Each RePORT network is designed to support local, in-country tuberculosis-specific data and specimen biorepositories, and associated research. Taken together, the expected results include greater global clinical research capacity in high-burden settings, and increased local access to quality data and specimens for members of each network and their domestic and international collaborators. Additional networks are expected to be added, helping to spur tuberculosis treatment and prevention research around the world.Â© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: firstname.lastname@example.org.
Ending neglect: providing effective childhood tuberculosis training for health care workers in Tanzania. - Public health action
Health care facilities in Dar es Salaam, Pwani, and Arusha, Tanzania.To assess health care worker (HCW) knowledge and practices 1 year after specialized training in childhood tuberculosis (TB).Using a standardized survey, we interviewed a convenience sample of HCWs providing both general and specialized care to children.We interviewed 117 HCWs in TB clinics, maternal and child health clinics, human immunodeficiency virus (HIV) clinics, out-patient departments, and pediatric in-patient wards at 12 facilities. A total of 81 HCWs (62% of nurses, 74% of clinicians) reported having attended the national childhood TB training course. Most HCWs responded correctly to questions on childhood TB diagnosis, treatment, and TB-HIV co-management, regardless of training history. Most HCWs reported that they routinely obtain chest radiographs, HIV testing, and a TB contact history when evaluating children for TB. Less than half of HCWs reported routinely obtaining sputum for mycobacterial culture or performing a tuberculin skin test. Three times as many trained as untrained HCWs reported having ever prescribed isoniazid preventive therapy (IPT) to a child (P < 0.05).In general, levels of childhood TB knowledge were high and practices were in accordance with national guidance. Specific gaps in diagnosis, treatment and use of IPT were identified for future focused training.
Radiation Pneumonitis After Conventional Radiotherapy For Breast Cancer: A Prospective Study. - Journal of clinical and diagnostic research : JCDR
Loco-regional radiotherapy is an important treatment modality in breast cancer and radiation pneumonitis (RP) is one of the early toxicities.To study the occurrence, correlation of RP with patient and radiotherapy related factors and the effects on pulmonary function following conventional radiotherapy in breast cancer.Prospective study, from a tertiary hospital in a developing country.Prospective analysis of clinical symptoms, pulmonary function and radiologic changes was done prior to and 12 weeks after adjuvant radiotherapy (n=46). Statistical analysis was done using SPSS version 10 software.Radiological and clinical RP was seen in 45.65% (n=21) and 19.56% (n=9) respectively. RP was significantly higher with age >50 years (OR 4.4), chest wall irradiation with electrons, (electrons 83.3% vs cobalt60 32.4%, p=0.02) and supraclavicular field treatment with 6 MV photons (p= 0.011). There was significant relationship between Inferior Lung Distance (ILD) and RP (p=0.013). The fall in Total Lung Capacity (TLC) was significantly more in those with RP (p=0.02).Clinical RP occurs in almost one-fifth of breast cancer patients treated with conventional radiotherapy. Chest wall irradiation with electrons, supraclavicular field irradiation with 6 MV photons, higher ILD and age >50 years was associated with increased RP. The pulmonary function parameter most affected was TLC. The factors associated with increased RP should be considered when adjuvant radiotherapy is planned to minimize its likelihood and intervene appropriately.
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