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We sought to prospectively characterize the nutritional status of adults ≥ 19 years (n=22, 27% males) and children (n=38, 61% male) with genetically-confirmed primary mitochondrial disease (PMD) to guide development of precision nutritional support strategies to be tested in future clinical trials. We excluded subjects who were exclusively tube-fed. Daily caloric requirements were estimated using World Health Organization (WHO) equations to predict resting energy expenditure (REE) multiplied by an activity factor (AF) based on individual activity levels. We developed a Mitochondrial Disease Activity Factors (MOTIVATOR) score to encompass fatigue typical of PMD. PMD cohort daily diet intake was estimated to be 1,143 ± 104.1 Kcal in adults (mean ± SEM, 76.2% of WHO-MOTIVATOR predicted requirement), and 1,114 ± 62.3 Kcal in children (86.4% predicted). A total of 11/22 (54.5%) adults and 18/38 (47.4%) children with PMD consumed ≤75% predicted daily Kcal needs. Malnutrition was identified in 16/60 (26.7%) PMD subjects. Increased protein and fat intake correlated with improved muscle strength in those with insufficient daily Kcal intake (£75% predicted); higher protein and fat intake correlated with decreased muscle fatigue; and higher protein, fat and CHO intake correlated with improved quality of life (QoL). These data demonstrate the frequent occurrence of malnutrition in PMD and emphasize the critical need to devise nutritional interventions to optimize clinical outcomes.

Sponsors often rely on multi-regional clinical trials (MRCTs) to introduce new treatments more rapidly into the global market. Many commonly used statistical methods do not account for regional differences, and small regional sample sizes frequently result in lower estimation quality of region-specific treatment effects. The International Council for Harmonisation E17 guidelines suggest consideration of methods that allow for information borrowing across regions to improve estimation. In response to these guidelines, we develop a novel methodology to estimate global and region-specific treatment effects from MRCTs with time-to-event endpoints using Bayesian model averaging (BMA). This approach accounts for the possibility of heterogeneous treatment effects between regions, and we discuss how to assess the consistency of these effects using posterior model probabilities. We obtain posterior samples of the treatment effects using a Laplace approximation, and we show through simulation studies that the proposed modeling approach estimates region-specific treatment effects with lower MSE than a Cox proportional hazards model while resulting in a similar rejection rate of the global treatment effect. We then apply the BMA approach to data from the LEADER trial, an MRCT designed to evaluate the cardiovascular safety of an anti-diabetic treatment. This article is protected by copyright. All rights reserved.

Hematopoietic stem and progenitor cells (HSPC) are responsible for the reconstitution of blood cells and thought to contribute to peripheral tissue repair. Following acute exercise in young adults, HSPC are mobilized from their niche in bone marrow into circulation, however the kinetics of mobilization following exercise is not well understood in older adults. In the present study, we aimed to investigate how exercise intensity influences mobilization of specific subpopulations of HSPC, and how mobilization is affected by aging. Healthy older men (OM; 69.9 ± 2.0 years) and young men (YM; 21.5 ± 0.8 years) performed three separate bouts of exercise on a cycle ergometer: 70% of their peak work rate (WRpeak) until volitional fatigue, 30% of their WRpeak work matched to the 70% WRpeak trial, and a high intensity interval training (HIIT) trial. Blood samples were collected before, immediately post, and 10, 30, and 60 min post-exercise. Total blood cells, hematocrit, and mononuclear cells isolated by density gradient centrifugation were quantified using flow cytometry. Mononuclear cells, CD34+, CD34+/CD38+, CD34+/CD110+, CD3+/CD(16 + 56)+, CD11c+/CD123−, and CD11c−/CD123+ cells per millilitre of blood increased immediately post-exercise, but predominately in the 70% WRpeak trial in both OM and YM. Taken together, our evidence suggests that higher intensity exercise but also volume is necessary for the mobilization of HSPC. Furthermore, the pattern of mobilization was nearly identical in OM as compared to YM though to a lesser extent than their younger counterparts.

OBJECTIVES: Assessing the effects of diabetes mellitus (DM), non-insulin-dependent diabetes mellitus (NIDDM), and insulin-dependent diabetes mellitus (IDDM) on revision TKA (rTKA) has become increasingly imperative due to the increased rates of revisions associated with DM. This study sought to identify complications in rTKA that were independently associated with NIDDM/IDDM compared to non-diabetic (Non-DM) patients and whether IDDM was associated with specific postoperative complications compared to NIDDM. METHODS AND MATERIALS: 16,428 rTKA patients were identified from the ACS-NSQIP database from 2005 to 2016 and stratified into three separate cohorts. 12,922 (78.66%) were Non-DM, 2335 (14.21%) had NIDDM, and 1171 (7.13%) had IDDM. Univariate analyses were utilized to assess for differences in demographics, preoperative comorbidities, and postoperative complication rates. Multivariate logistic regression analyses were then employed to control for significant differences in patients characteristics to assess NIDDM and IDDM as independent risk factors for complications in comparison to Non-DM. IDDM was further analyzed as a risk factor in comparison to NIDDM for the purpose of elucidating the impact of insulin dependence on risk for postoperative complications. RESULTS: NIDDM was an independent risk factor for deep incisional surgical site infections (Odds Ratio (OR): 2.477) and urinary tract infections (UTI) (OR 1.862) (p

Background Previous work has validated consumer-grade electroencephalography (EEG) systems for use in research. Systems in this class are cost-effective and easy to set up and can facilitate neuroscience outside of the laboratory. The aim of the current study was to determine if a new consumer-grade system, the Emotiv EPOC Saline Flex, was capable of capturing research-quality data. Method The Emotiv system was used simultaneously with a research-grade EEG system, Neuroscan Synamps2, to collect EEG data across 16 channels during five well-established paradigms: (1) a mismatch negativity (MMN) paradigm that involved a passive listening task in which rare deviant (1,500 Hz) tones were interspersed amongst frequent standard tones (1,000 Hz), with instructions to ignore the tones while watching a silent movie; (2) a P300 paradigm that involved an active listening task in which participants were asked to count rare deviant tones presented amongst frequent standard tones; (3) an N170 paradigm in which participants were shown images of faces and watches and asked to indicate whether the images were upright or inverted; (4) a steady-state visual evoked potential (SSVEP) paradigm in which participants passively viewed a flickering screen (15 Hz) for 2 min; and (5) a resting state paradigm in which participants sat quietly with their eyes open and then closed for 3 min each. Results The MMN components and P300 peaks were equivalent between the two systems (BF10 = 0.25 and BF10 = 0.26, respectively), with high intraclass correlations (ICCs) between the ERP waveforms (>0.81). Although the N170 peak values recorded by the two systems were different (BF10 = 35.88), ICCs demonstrated that the N170 ERP waveforms were strongly correlated over the right hemisphere (P8; 0.87–0.97), and moderately-to-strongly correlated over the left hemisphere (P7; 0.52–0.84). For the SSVEP, the signal-to-noise ratio (SNR) was larger for Neuroscan than Emotiv EPOC Flex (19.94 vs. 8.98, BF10 = 51,764), but SNR z-scores indicated a significant brain response at the stimulus frequency for both Neuroscan (z = 12.47) and Flex (z = 11.22). In the resting state task, both systems measured similar alpha power (BF10 = 0.28) and higher alpha power when the eyes were closed than open (BF10 = 32.27). Conclusions The saline version of the Emotiv EPOC Flex captures data similar to that of a research-grade EEG system. It can be used to measure reliable auditory and visual research-quality ERPs. In addition, it can index SSVEP signatures and is sensitive to changes in alpha oscillations.

The percutaneous muscle biopsy procedure is an invaluable tool for characterizing skeletal muscle and capillarization. Little is known about methodological or biological variation stemming from the technique in heterogeneous muscle. Five muscle biopsies were taken from the vastus lateralis of a group of young men (n = 29, 22 ± 1 years) over a 96-h period. We investigated the repeatability of fibre distribution, indices of muscle capillarization and perfusion, and myofibre characteristics. No differences between the biopsies were reported in myofibre type distribution, cross-sectional area (CSA), and perimeter. Capillary-to-fibre perimeter exchange index and individual capillary-fibre contacts were unchanged with respect to the location of the muscle biopsy and index of capillarization. The variability in the sampling distribution of fibre type specific muscle CSA increased when fewer than 150 muscle fibres were quantified. Variability in fibre type distribution increased when fewer than 150 muscle fibres were quantified. Myofibre characteristics and indices of capillarization are largely consistent throughout the vastus lateralis when assessed via the skeletal muscle biopsy technique. Novelty Markers of muscle capillarization and perfusion were unchanged across multiple sites of the human vastus lateralis. Myofibre characteristics such as muscle cross-sectional area, perimeter, and fibre type distribution were also unchanged. Variation of muscle CSA was higher when fewer than 150 muscle fibres were quantified.

Aging gradually renders bone marrow hematopoietically inactive. Endurance exercise reverses this phenotype in young mice. Here, we determine the effects in aged mice. Twenty-two month old mice (n = 6) underwent a progressive exercise training protocol. In appendicular bones, marrow cellularity increased by 51% (p < 0.05) and marrow CFU, CFU-GM, and CAFC increased by 12%, 71%, and 86%, respectively (p < 0.05). Vertebral cellularity remained unchanged. The mechanical forces associated with treadmill exercise training may be responsible for these observations.

Although there are reports of the impact of congestive heart failure (CHF) on total knee arthroplasty and total hip arthroplasty, there is a lack of literature analyzing CHF in hip hemiarthroplasty (HHA) procedures. The main objective of this study was to evaluate the effect of CHF on risks for complications following HHA for the treatment of FNF. The ACS-NSQIP database was queried for all patients who had undergone HHA from 2005 to 2016. Patients were propensity-matched without replacement in a 1:1 manner based on age and gender. Pearson’s Chi squared tests and Fischer’s exact tests were utilized to compare differences in demographics, comorbidities, and complication rates. Multivariate logistic regression analyses were used to assess the impact of CHF as an independent risk factor for postoperative complications. A propensity-matched cohort of 537 (4.24%) non-CHF patients was generated in order to analyze differences between the two cohorts. CHF was found to be a significant independent risk factor for pneumonia (p = 0.003), progressive renal insufficiency (p = 0.040), myocardial infarctions (p = 0.050), extended length of stay (≥ 5 days) (p

Background Isolated internal iliac artery aneurysms (IIIAA) are a rare form of aneurysm. The incidence increases with age, and the prevalence is higher in men. The clinical presentation can vary, and standard treatment protocols are not established. The first case of an IIIAA was described more than 100 years ago. The purpose of the study is to summarize the various clinical presentations and treatment options that have been reported in the literature in the past 100 years. Methods Literature about IIIAA was reviewed using the electronic databank PubMed. All case reports and case series were analyzed, and we included our own data with 2 case reports. Results Over time, IIIAA diagnosis increasingly resulted from asymptomatic incidental findings on radiologic studies. Various clinical presentations included abdominal pain, back pain, rectal bleeding, hydronephrosis with renal failure, hematuria, and free rupture with shock. Rupture has a mortality rate of 53%. IIIAAs were more common on the left (61.8% left, 27.3% right, 10.9% bilateral). Treatments include open surgical repair and endovascular repair using a variety of methods. One article reported a hybrid method using both endovascular and open surgical technique. Conclusions Since its first description 100 years ago, we have gained knowledge about the natural history of IIIAA. Multiple treatment options have been described, but long-term outcome needs further investigation.

La presente tesi ha per oggetto l\' azione di diritto sostanziale, così considerata il potere giuridico (di diritto sostanziale) nato da un illecito e rivolto contro il loro causante (o un terzo responsabile), avente per contenuto la previsione degli effetti giuridici di diritto materiale que il titolare dallazione può imporre il trasgressore, anche se non direttamente, ma attraverso lo Stato-giudice, o un\'altro ente di applicazione della legge. La tesi analisa, quindi: (i) l\'esistenza (o la sussistenza) dell azione di diritto sostanziale in un ordinamento giuridico moderno, già caratterizzato dal monopolio statale della giustizia; (ii) la sua natura giuridica; (iii) il rispettivo soggetto passivo; (iv) il suo contenuto; (v) la sua efficacia; e (vi) la dinamica tra l\'azione di diritto sostanziale e le altre posizioni giuridiche predisposti, dall\' ordinamento giuridico, per lesercizio e la realizzazione di quella azione, in particolare il diritto fondamentale alla giurisdizione, di natura astratta, e la pretesa alla tutela giurisdizionale dellazione, di natura concreta. A presente tese tem por tema a ação de direito material, assim considerada o poder jurídico, de direito material, surgido a partir de um ilícito e voltado contra o respectivo causador (ou um terceiro responsável), tendo por conteúdo a previsão dos efeitos de direito material que seu titular pode impor ao violador, ainda que não diretamente, mas por meio do Estado-juiz, ou de outro órgão de aplicação do direito. A tese analisa, portanto: (i) a existência (ou subsistência) da ação de direito material num ordenamento moderno, já caracterizado pelo monopólio estatal da justiça; (ii) sua natureza jurídica; (iii) seu respectivo sujeito passivo; (iv) seu conteúdo; (v) sua eficácia; e (vi) a dinâmica entre a ação de direito material e as demais posições jurídicas predispostas, pelo ordenamento, para o exercício e a realização daquela ação, notadamente o direito fundamental à jurisdição, de natureza abstrata, e a pretensão à tutela jurisdicional da ação, de natureza concreta.

Mirizzi syndrome has been defined in the literature as common bile duct obstruction resulting from calculi within Hartmann’s pouch or cystic duct. We present a case of a 78-year-old female, who developed postcholecystectomy Mirizzi syndrome from a remnant cystic duct stone. Diagnosis of postcholecystectomy Mirizzi syndrome was made on endoscopic retrograde cholangiography (ERCP) performed postoperatively. The patient was treated with a novel strategy by combining advanced endoscopic and laparoscopic techniques in three stages as follows: Stage 1 (initial presentation): endoscopic sphincterotomy with common bile duct stent placement; Stage 2 (6 weeks after Stage 1): laparoscopic ultrasonography to locate the remnant cystic duct calculi followed by laparoscopic retrieval of the calculi and intracorporeal closure of cystic duct stump; Stage 3 (6 weeks after Stage 2): endoscopic removal of common bile duct stent along with performance of completion endoscopic retrograde cholangiogram. In addition, we have performed an extensive review of the various endoscopic and laparoscopic management techniques described in the literature for the treatment of postcholecystectomy syndrome occurring from retained cystic duct stones.

In recent years, with the explosive adoption of smart phone devices, mobile health and fitness applications have been increasingly used by healthcare practitioners and the general public to manage electronic health records, chronic medical conditions, dietary references etc. Despite the rapid growth in the number of mobile and fitness applications on various platforms, very little work has been done to quantitatively and qualitatively assess these applications to guide users in the selection process. Automatic categorization of mobile health and fitness applications is the first step in this direction. In this paper, we report results from crawling 1,430 Android and 62,286 iOS apps in Nov. 2013. Among them, 1,399 apps were manually classified to one or multiple categories out of a total of 11 categories. Text mining tools were applied to the description section of the apps for keyword extraction, feature selection and automatic categorization. The classifiers we experimented with have comparable performance with Linear SVC achieving the highest precision, recall and f1 scores of 0.89, 0.79 and 0.88, respectively.

Serum prostate-specific antigen complexed to alpha2-macroglobulin is occult and is not detected by conventional immunoassays. Conditions affecting alpha2-macroglobulin levels may alter the specificity of prostate-specific antigen free/total ratio in predicting prostate cancer. A group of patients (n=24) undergoing surgical stress due to a coronary artery bypass grafting was followed pre- and postoperatively up to 6 days. Total and free prostate-specific antigen, alpha2-macroglobulin, and C-reactive protein were measured by electrochemiluminescence, immunonephelometry, and immunoturbidimetry, respectively. Total prostate-specific antigen and C-reactive protein increased significantly postsurgery and remained elevated. Free/total ratio correlated negatively with C-reactive protein only (p = 0.000) using xtgee panel data analysis, after correction for plasma volume changes using albumin. Increased C-reactive protein may reflect falsely decreased free/total ratio. Therefore, prostate-specific antigen free/total ratio would be more reliable if interpreted in combination with information about CRP. However, it is recommended to defer the measurement of free/total ratio if CRP is highly elevated.

Like most pharmaceutical agents, vitamin D analogs are subject to hepatic metabolism by a variety of cytochrome P450 (CYP)-based systems. Metabolism can involve activation as well as inactivation of the vitamin D analog and one of the more successful families includes the 1alpha-hydroxyvitamin D prodrugs (1alpha-OH-D2, 1alpha-OH-D3, 1alpha-OH-D4, 1alpha-OH-D5), that all require a step of activation. Some of these prodrugs are in use or clinical trial because they have a therapeutic advantage over calcitriol. However, the nature of the activation of these molecules is poorly understood, particularly with regard to the CYP isoform involved. Various transfected CYPs and hepatic cell lines combined with tandem LC-MS analysis were used to investigate the metabolism of a spectrum of vitamin D analogs, including 1alpha-OH-Ds and the topical analog, calcipotriol. In the case of the 1alpha-OH-Ds, evidence was found of multiple sites of side-chain hydroxylation consistent with the generation of more than one active form. The potential involvement of CYP27A and other putative 25-hydroxylases in 1alpha-OH-D activation was also shown, as well as the potential for CYP24 activation and inactivation. In the case of calcipotriol, the respective roles of non-vitamin D-related CYPs and CYP24 in the catabolism of this anti-psoriatic drug were dissected out using cell lines with or without CYP24 expression, allowing us to demonstrate the potential contribution of CYP24 to "vitamin D resistance". The implications of hepatic metabolism in the context of other facets thought to play a role in the mechanism of action of anticancer and antiproliferative vitamin D analogs are discussed.