Objective To assess the impact of socioeconomic status (SES) on pediatric appendicitis outcomes using the validated Agency for Healthcare Research and Quality (AHRQ) SES Index and incorporating ...block-group data. Study design We reviewed all patients <18 years old who underwent appendectomy for acute appendicitis from 2009-2013 at our institution. Patient addresses were geocoded and linked to 2010 US Census SES block-group data to determine composite AHRQ SES Index scores based on 7 publically reported SES variables. The primary outcome was appendiceal perforation, and the impact of SES scores, age, race, and insurance status on perforation rates were assessed through regression analyses. Results Of 1501 patients, 510 (34%) had perforated appendicitis. On bivariate analysis, components of the SES Index associated with an increased perforation rate included lower household income, lower percentage of adults with college education, and higher percentage of adults with <12th grade education (all P < .05). On multivariate analysis, age ≤10 years (OR 1.7, 95% CI 1.4-2.2) and public insurance (OR 1.5, 95% CI 1.2-2.0) were associated with increased odds of perforation. Conclusions This study used the AHRQ SES scoring system to evaluate SES and its influence on appendiceal perforation. Among our cohort of pediatric patients, the risk of perforation was multifactorial, and younger age and public insurance were stronger predictors of perforation than SES.
Summary Rationale Mounting data suggest that immune cell abnormalities participate in the pathogenesis of pulmonary arterial hypertension (PAH). Objective To determine whether the T lymphocyte subset ...composition in the systemic circulation and peripheral lung is altered in PAH. Methods Flow cytometric analyses were performed to determine the phenotypic profile of peripheral blood lymphocytes in idiopathic PAH (IPAH) patients ( n = 18) and healthy controls ( n = 17). Immunocytochemical analyses of lymphocytes and T cell subsets were used to examine lung tissue from PAH patients ( n = 11) and controls ( n = 11). Measurements and main results IPAH patients have abnormal CD8+ T lymphocyte subsets, with a significant increase in CD45RA+ CCR7− peripheral cytotoxic effector-memory cells ( p = 0.02) and reduction of CD45RA+ CCR7+ naive CD8+ cells versus controls ( p = 0.001). Further, IPAH patients have a higher proportion of circulating regulatory T cells (Treg ) and 4-fold increases in the number of CD3+ and CD8+ cells in the peripheral lung compared with controls ( p < 0.01). Conclusions Alterations in circulating T cell subsets, particularly CD8+ T lymphocytes and CD4+ Treg , in patients with PAH suggest that a dysfunctional immune system contributes to disease pathogenesis. A preponderance of CD3+ and CD8+ T lymphocytes in the peripheral lung of PAH patients supports this concept.
Military Service Members are often exposed to high levels of occupational noise, solvents, and other exposures that can be damaging to the auditory system. Little is known about hearing loss and how ...it progresses in Veterans following military service. This epidemiology study is designed to evaluate and monitor a cohort of Veterans for 20 years or more to determine how hearing loss changes over time and how those changes are related to noise exposure and other ototoxic exposures encountered during military service. Data reported here are from baseline assessments of the first 100 study participants (84 males; 16 females; mean age 33.5 years; SD 8.8; range 21–58). Each participant was asked to complete a comprehensive audiologic examination and self-report questionnaires regarding sociodemographic characteristics, noise and solvent exposures, health conditions common among post-deployment Veterans, and the social and emotional consequences of hearing loss. For this relatively young cohort, 29% exhibited hearing loss, defined as average hearing threshold >20 dB HL in the conventional audiometric range. Forty-two percent exhibited hearing loss in the extended-high-frequency audiometric range using the same criterion (average hearing threshold >20 dB HL). Certain factors were found to be associated with poorer hearing in both conventional and extended-high-frequency ranges, including age, type of military branch, years of military service, number of military deployments, noise exposure, tinnitus, and a positive screen for post-traumatic stress disorder. Although the majority of participants had hearing within normal limits, 27% reported a self-perceived mild/moderate hearing handicap and 14% reported a significant handicap. Further research is needed to identify a cause for this discrepancy in audiologic results versus self-report. The information obtained from this longitudinal study could be used in future resource planning with the goal of preventing, as much as possible, the development of hearing loss during military service, and the exacerbation of prevalent hearing loss after military service and over Veterans' lifetimes.
•In this cohort of 100 recently-separated service members 29% exhibited hearing loss in the conventional audiometric range.•Hearing was poorer as a function of age, service years, # of deployments, noise exposure, tinnitus, and service connection.•Hearing was poorer in extended-high frequencies for those in the Air Force versus those who served in the Marines.•Although most participants had normal hearing, 27% reported mild-moderate hearing handicap and 14% significant handicap.•The Lifetime Exposure to Noise and Solvents Questionnaire revealed higher Index scores for participants with hearing loss.
The transition from lean to obese states involves systemic metabolic remodeling that impacts insulin sensitivity, lipid partitioning, inflammation, and glycemic control. Here, we have taken a ...pharmacological approach to test the role of a nutrient-regulated chromatin modifier, lysine-specific demethylase (LSD1), in obesity-associated metabolic reprogramming. We show that systemic administration of an LSD1 inhibitor (GSK-LSD1) reduces food intake and body weight, ameliorates nonalcoholic fatty liver disease (NAFLD), and improves insulin sensitivity and glycemic control in mouse models of obesity. GSK-LSD1 has little effect on systemic metabolism of lean mice, suggesting that LSD1 has a context-dependent role in promoting maladaptive changes in obesity. In analysis of insulin target tissues we identified white adipose tissue as the major site of insulin sensitization by GSK-LSD1, where it reduces adipocyte inflammation and lipolysis. We demonstrate that GSK-LSD1 reverses NAFLD in a non-hepatocyte-autonomous manner, suggesting an indirect mechanism potentially via inhibition of adipocyte lipolysis and subsequent effects on lipid partitioning. Pair-feeding experiments further revealed that effects of GSK-LSD1 on hyperglycemia and NAFLD are not a consequence of reduced food intake and weight loss. These findings suggest that targeting LSD1 could be a strategy for treatment of obesity and its associated complications including type 2 diabetes and NAFLD.
Highlights • Antibiotic exposure was inversely correlated with intestinal microbiome diversity. • Diversity was lower in patients who received third- or fourth-generation cephalosporins. • Charlson ...Comorbidity Index score was inversely correlated with microbiome diversity. • Directly measuring microbiome disruption might be most predictive of adverse events. • Microbiome disruption indices have the potential to improve infection control efforts.
The objective of this study was to evaluate the survivorship of revision TKA and determine the reasons and predictors for failure. Between January 1999 to December 2005, 499 total knee arthroplasty ...revisions were performed on 474 patients. There were 292 (61.6%) women and 182 (38.4%) men. The average age at the time of index revision was 63.9 years. Revision was defined as surgery in which at least one component (tibial, patellar, femoral, or polyethylene) required exchange. At an average follow-up of 64.8 months (range, 24.1–111.6), and considering reoperation or re-revision as failure, there were 102 failures (18.3%). Infection was the major cause of failure (44.1%) followed by stiffness (22.6%), patellar or extensor mechanism problems (12.8%), periprosthetic fracture (5.9%), loosening (4.9%), haematoma formation (3.9%), malalignment (2.9%), and instability (2.9%). A total of 83% of failures were early (less than two years). Infection was the most common mechanism of failure of revision TKA. The majority of TKA revision failures tend to occur in the first two years after revision. The mode of failure of revision TKA appears to differ from the failure of primary TKA to some extent. Better understanding of current modes by which TKA revisions fail may enable surgeons to prevent these problems and improve outcomes for revision TKA.
Stem cells/progenitors are central to the development of cell therapy approaches for vascular ischemic diseases. The crucial step in rescuing tissues from ischemia is improvement of vascularization ...that can be achieved by promoting neovascularization. Endothelial progenitor cells (EPCs) are the best candidates for developing such an approach due to their ability to self-renew, circulate and differentiate into mature endothelial cells (ECs). Studies showed that intravenously administered progenitors isolated from bone marrow, peripheral or cord blood home to ischemic sites. However, the successful clinical application of such transplantation therapy is limited by low quantities of EPCs that can be generated from patients. Hence, the ability to amplify the numbers of autologous EPCs by long term in vitro expansion while preserving their angiogenic potential is critically important for developing EPC based therapies. Therefore, the objective of this study was to evaluate the capacity of cord blood (CB)-derived AC133+ cells to differentiate, in vitro, towards functional, mature endothelial cells (ECs) after long term in vitro expansion.
We systematically characterized the properties of CB AC133+ cells over the 30 days of in vitro expansion. During 30 days of culturing, CB AC133+ cells exhibited significant growth potential that was manifested as 148-fold increase in cell numbers. Flow cytometry and immunocytochemistry demonstrated that CB AC133+ cells' expression of endothelial progenitor markers was not affected by long term in vitro culturing. After culturing under EC differentiation conditions, cells exhibited high expression of mature ECs markers, such as CD31, VEGFR-2 and von Willebrand factor, as well as the morphological changes indicative of differentiation towards mature ECs. In addition, throughout the 30 day culture cells preserved their functional capacity that was demonstrated by high uptake of DiI fluorescently conjugated-acetylated-low density lipoprotein (DiI-Ac-LDL), in vitro and in vivo migration towards chemotactic stimuli and in vitro tube formation.
These studies demonstrate that primary CB AC133+ culture contained mainly EPCs and that long term in vitro conditions facilitated the maintenance of these cells in the state of commitment towards endothelial lineage.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Prevention of brain injury during congenital heart surgery has focused on intraoperative and perioperative neuroprotection and neuromonitoring. Many strategies have been adopted as “standard of ...care.” However, the strength of evidence for these practices and the relationship to long-term outcomes are unknown. We performed a systematic review (January 1, 1990 to July 30, 2010) of neuromonitoring and neuroprotection strategies during cardiopulmonary bypass (CPB) in infants of age 1 year or less. Papers were graded individually and as thematic groups, assigning evidence-based medicine and American College of Cardiology/American Heart Association (ACC/AHA) level of evidence grades. Consensus scores were determined by adjudication. Literature search identified 527 manuscripts; 162 met inclusion criteria. Study designs were prospective observational cohort (53.7%), case-control (21.6%), randomized clinical trial (13%), and retrospective observational cohort (9.9%). Median sample size was 43 (range 3 to 2,481). Primary outcome was evidence of structural brain injury or functional disability (neuroimaging, electroencephalogram, formal neurologic examination, or neurodevelopmental testing) in 43%. Follow-up information was reported in only 29%. The most frequent level of evidence was evidence-based medicine level 4 (33.3%) or ACC/AHA class IIB: level B (42%). The only intervention with sufficient evidence to recommend “the procedure or treatment should be performed” was avoidance of extreme hemodilution during CPB. Data supporting use of current neuromonitoring and neuroprotective techniques are limited. The level of evidence is insufficient to support effectiveness of most of these strategies. Well-designed studies with correlation to clinical outcomes and long-term follow-up are needed to develop guidelines for neuromonitoring and neuroprotection during CPB in infants.
Ocean warming has been affecting marine ecosystems over the past few decades. The signature of ocean warming in global fisheries catch data has been identified through a variety of methods, one of ...which is the mean temperature of the catch (MTC) index. The MTC is derived from the average temperature preference of fished species weighted by their contribution to annual catches. Here, we used MTC to explore the fisheries catch responses to warming, from 1950 to 2016, along a latitudinal gradient in the western Pacific Ocean, from 37° N, via 2.5° S in the central western Pacific, to 36° S. The tropicalization of catches in a given geographic space, i.e., the increased catch of species with affinity to warmer waters, as a result of increasing sea temperature and the associated poleward migration of species, rather than any large-scale oceanographic variability, was apparent through the increasing MTC at higher latitudes. In particular, MTC in temperate Japan increased by 0.33 °C per decade over the time series. The MTC in subtropical/temperate southeast Australia increased by 0.24 °C per decade over the full time period and by 1.24 °C per decade after 2002. The observed MTC increase was caused by the increasing dominance of thermophilous (preferring warmer waters) over psychrophilous (preferring cooler waters) taxa in the catches in these waters. On the other hand, the MTC in tropical Indonesian waters, as well as the ratio of thermophilous to psychrophilous taxa, showed a gentle yet consistent decrease of 0.05 °C per decade over the full time period. This finding supports the tropicalization hypothesis, given the limited scope for further tropicalization of catches in the already tropical ecosystem of Indonesia. Ocean warming has indeed been altering the distribution of marine organisms, particularly in temperate ecosystems as thermophilous taxa become more abundant, while psychrophilous taxa abundance decreases. Tropicalization impacts fisheries and catch composition and is, therefore, expected to cause conflicts among fishers and challenge fisheries management.
Abstract Background Pulmonary emphysema is divided into 3 major subtypes at autopsy: centrilobular, paraseptal, and panlobular emphysema. These subtypes can be defined by visual assessment on ...computed tomography (CT); however, clinical characteristics of emphysema subtypes on CT are not well defined. We developed a reliable approach to visual assessment of emphysema subtypes on CT and examined if emphysema subtypes have distinct characteristics. Methods The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with chronic obstructive pulmonary disease (COPD) and controls ages 50-79 years with ≥10 pack-years. Participants underwent CT following a standardized protocol. Definitions of centrilobular, paraseptal, and panlobular emphysema were obtained by literature review. Six-minute walk distance and pulmonary function were performed following guidelines. Results Twenty-seven percent of 318 smokers had emphysema on CT. Interrater reliability of emphysema subtype was substantial (K: 0.70). Compared with participants without emphysema, individuals with centrilobular or panlobular emphysema had greater dyspnea, reduced walk distance, greater hyperinflation, and lower diffusing capacity. In contrast, individuals with paraseptal emphysema were similar to controls, except for male predominance. Centrilobular, but not panlobular or paraseptal, emphysema was associated with greater smoking history (+21 pack-years P <.001). Panlobular, but not other types of emphysema, was associated with reduced body mass index (−5 kg/m2 ; P = .01). Other than for dyspnea, these findings were independent of the forced expiratory volume in 1 second. Seventeen percent of smokers without COPD on spirometry had emphysema, which was independently associated with reduced walk distance. Conclusions Emphysema subtypes on CT are common in smokers with and without COPD. Centrilobular and panlobular emphysema, but not paraseptal emphysema, have considerable symptomatic and physiological consequences.
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