The Development and Validation of a Disordered Eating Screening Tool for Current and Former Athletes: The Athletic Disordered Eating (ADE) Screening Tool.

BACKGROUND: Current and former athletes are one of the most at-risk population groups for disordered eating (DE), impacting their dietary practices, body composition, performance and health during and following their athletic careers. Few comprehensive DE screening tools exist for this group. To help address this, the current study utilised a mixed-methods approach of Classic Test Theory (CTT) and Item Response Theory (IRT) to develop and validate a DE screening tool suitable for current and former athletes. METHODS: Novel scale development methodologies were used to develop and assess the validity (content, face, cross-cultural, construct), test-retest reliability, internal consistency reliability, factor analysis and Rasch analysis of a new DE scale. RESULTS: A new validated Athletic Disordered Eating (ADE) screening tool was created, with 17 items and four subscales (food control, bingeing, body control, body discontent), with an internal consistency reliability of 0.91, excellent content and construct validity, an Intraclass Correlation Coefficient of 0.97 and excellent Rasch model fit. CONCLUSIONS: The ADE screening tool has been dually developed for research purposes and as a clinically applicable screening tool to detect DE in current and former athletes and is suitable for a global use across sporting categories, diverse genders and levels of competition.

The Genomics of Young Lung Cancer: Comprehensive Tissue Genomic Analysis in Patients Under 40 With Lung Cancer.

INTRODUCTION: Lung adenocarcinomas in young patients (<40 y) are more likely to harbor targetable genomic alterations. This study aimed to determine whether the prevalence of targetable alterations is greater in young adults with lung carcinoma than in the overall lung cancer population. To reach this rare patient population, a web-based platform was used to recruit and enroll patients remotely. METHODS: In this prospective study, patients less than 40 years old at the time of primary lung cancer diagnosis with confirmed lung carcinoma were recruited from four global sites and remotely by means of a website. Genotyping data were collected, if available, or obtained by means of next-generation sequencing using the FoundationOne platform. The prevalence of targetable alterations was quantified across patients with advanced adenocarcinoma. RESULTS: Overall, 133 patients across five continents were included, 41% of whom enrolled online. The mean (SD) age at diagnosis was 34 (5.2) years; 79% had stage IV disease at diagnosis. Among patients with adenocarcinoma (n = 115), 112 entered the study with previous genomic testing results and 86 (77%) had targetable alterations in EGFR, ALK, ROS1, MET, ERBB2, or RET. Among those without targetable alterations, 14 received further testing and a targetable alteration was identified in eight (57%). CONCLUSIONS: This study revealed the feasibility of using a web-based platform to recruit young patients with lung cancer and revealed that 94 of 112 (84%) with adenocarcinoma at any stage had targetable genomic alterations. Among patients with stage IV adenocarcinoma, 85% had a targetable alteration, which is higher than historical expectations for the general population.

Higher habitual dietary flavonoid intake associates with lower central blood pressure and arterial stiffness in healthy older adults.

Flavonoids have shown anti-hypertensive and anti-atherosclerotic properties: the impact of habitual flavonoid intake on vascular function, central haemodynamics and arterial stiffness may be important. We investigated the relationship between habitual flavonoid consumption and measures of central blood pressure and arterial stiffness. We performed cross-sectional analysis of 381 non-smoking healthy older adults (mean age 66·0 (sd 4·1) years; BMI, 26·4 (sd 4·41) kg/m2; 41 % male) recruited as part of the Australian Research Council Longevity Intervention study. Flavonoid intake (i.e. flavonols, flavones, flavanones, anthocyanins, isoflavones, flavan-3-ol monomers, proanthocyanidins, theaflavins/thearubigins and total consumption) was estimated from FFQ using the US Department of Agriculture food composition databases. Measures of central haemodynamics and arterial stiffness included systolic blood pressure (cSBP), diastolic blood pressure (cDBP), mean arterial pressure (cMAP) and augmentation index (cAIx). After adjusting for demographic and lifestyle confounders, each sd/d higher intake of anthocyanins ((sd 44·3) mg/d) was associated with significantly lower cDBP (-1·56 mmHg, 95 % CI -2·65, -0·48) and cMAP (-1·62 mmHg, 95 % CI -2·82, -0·41). Similarly, each sd/d higher intake of flavanones ((sd 19·5) mg/d) was associated with ~1 % lower cAIx (-0·93 %, 95 % CI -1·77, -0·09). These associations remained significant after additional adjustment for (1) a dietary quality score and (2) other major nutrients that may affect blood pressure or arterial stiffness (i.e. Na, K, Ca, Mg, n-3, total protein and fibre). This study suggests a possible benefit of dietary anthocyanin and flavanone intake on central haemodynamics and arterial stiffness; these findings require corroboration in further research.

Comprehensive Genomic Profiling of Adult Renal Sarcomas Provides Insight into Disease Biology and Opportunities for Targeted Therapies.

BACKGROUND: Primary adult renal sarcomas (RSs) are rare aggressive neoplasms. Clinical outcomes are extremely poor, and optimal treatment remains challenging. OBJECTIVE: To identify genomic alterations (GAs) in patients with RSs. DESIGN, SETTING, AND PARTICIPANTS: Comprehensive genomic profiling (CGP) was conducted on DNA/RNA extracted from formalin-fixed paraffin-embedded tissue using the FoundationOne Heme/Sarcoma assay in 13 adult, locally advanced or metastatic RSs of various histologic types. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: All classes of GAs, including base substitutions, small indels, rearrangements, copy number alterations, tumor mutational burden (TMB), and microsatellite instability (MSI), were analyzed. RESULTS AND LIMITATIONS: CGP revealed 55 GAs (4.2 per tumor), 29 of which were clinically relevant genomic alterations (CRGAs; 2.2 per tumor). At least one CRGA was detected in nine (69%) cases. High-level amplifications (more than six copies) involving 4q12 amplicon of the KIT and PDGFRA genes were identified in four (31%) cases (two undifferentiated pleomorphic sarcomas [UPSs], one sarcomatoid renal cell carcinoma, and one myxofibrosarcoma). Both UPSs also had KDR gene amplification in addition to KIT and PDGFRA. Additional CRGAs were found in CDKN2A/B (23%), NF1 (23%), and MET (8%). All RSs were MSI stable, the mean TMB was 3.5 mutations/megabase (Mb), and none (0%) featured TMB >10 mutations/Mb. Limitations include the small sample size. CONCLUSIONS: RSs are characterized by diverse histology and genomic profiles including 31% of cases with 4q12 amplification harboring the KIT/PDGFRA/KDR genes. Of the tumors, 69% carry CRGAs, which could lead to potential benefit from targeted therapies; however, a low TMB also suggests that these cases are unlikely to respond to checkpoint inhibitors. PATIENT SUMMARY: This study provides insights into molecular biology of renal sarcoma, a rare aggressive subtype of kidney tumors. We demonstrated that renal sarcomas harbor unique, recurrent, clinically relevant molecular abnormalities that provide new opportunities for targeted therapies.

Genomic profiling reveals high frequency of DNA repair genetic aberrations in gallbladder cancer.

DNA repair gene aberrations (GAs) occur in several cancers, may be prognostic and are actionable. We investigated the frequency of DNA repair GAs in gallbladder cancer (GBC), association with tumor mutational burden (TMB), microsatellite instability (MSI), programmed cell death protein 1 (PD-1), and its ligand (PD-L1) expression. Comprehensive genomic profiling (CGP) of 760 GBC was performed. We investigated GAs in 19 DNA repair genes including direct DNA repair genes (ATM, ATR, BRCA1, BRCA2, FANCA, FANCD2, MLH1, MSH2, MSH6, PALB2, POLD1, POLE, PRKDC, and RAD50) and caretaker genes (BAP1, CDK12, MLL3, TP53, and BLM) and classified patients into 3 groups based on TMB level: low (< 5.5 mutations/Mb), intermediate (5.5-19.5 mutations/Mb), and high (≥ 19.5 mutations/Mb). We assessed MSI status and PD-1 & PD-L1 expression. 658 (86.6%) had at least 1 actionable GA. Direct DNA repair gene GAs were identified in 109 patients (14.2%), while 476 (62.6%) had GAs in caretaker genes. Both direct and caretaker DNA repair GAs were significantly associated with high TMB (P = 0.0005 and 0.0001, respectively). Tumor PD-L1 expression was positive in 119 (15.6%), with 17 (2.2%) being moderate or high. DNA repair GAs are relatively frequent in GBC and associated with coexisting actionable mutations and a high TMB.

High intensity exercise downregulates FTO mRNA expression during the early stages of recovery in young males and females.

BACKGROUND: Physical exercise and activity status may modify the effect of the fat mass- and obesity-associated (FTO) genotype on body weight and obesity risk. To understand the interaction between FTO's effect and physical activity, the present study investigated the effects of high and low intensity exercise on FTO mRNA and protein expression, and potential modifiers of exercise-induced changes in FTO in healthy-weighted individuals. METHODS: Twenty-eight untrained males and females (25.4 ± 1.1 years; 73.1 ± 2.0 kg; 178.8 ± 1.4 cm; 39.0 ± 1.2 ml.kg.min- 1 VO2peak) were genotyped for the FTO rs9939609 (T > A) polymorphism and performed isocaloric (400 kcal) cycle ergometer exercise on two separate occasions at different intensities: 80% (High Intensity (HI)) and 40% (Low Intensity (LO)) VO2peak. Skeletal muscle biopsies (vastus lateralis) and blood samples were taken pre-exercise and following 10 and 90 mins passive recovery. RESULTS: FTO mRNA expression was significantly decreased after HI intensity exercise (p = 0.003). No differences in basal and post-exercise FTO protein expression were evident between FTO genotypes. Phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and Akt substrate of 160 kDa (AS160) were significantly increased following HI intensity exercise (p < 0.05). Multivariate models of metabolomic data (orthogonal two partial least squares discriminant analysis (O2PLS-DA)) were unable to detect any significant metabolic differences between genotypes with either exercise trial (p > 0.05). However, skeletal muscle glucose accumulation at 10 mins following HI (p = 0.021) and LO (p = 0.033) intensity exercise was greater in AA genotypes compared to TT genotypes. CONCLUSION: Our novel data provides preliminary evidence regarding the effects of exercise on FTO expression in skeletal muscle. Specifically, high intensity exercise downregulates expression of FTO mRNA and suggests that in addition to nutritional regulation, FTO could also be regulated by exercise. TRIAL REGISTRATION: ACTRN12612001230842. Registered 21 November 2012 - Prospectively registered, https://www.anzctr.org.au/.

Isolated Intracranial Rosai-Dorfman Disease: Case Report and Review of the Literature.

BACKGROUND: Rosai-Dorfman disease (RDD) is a rare idiopathic benign proliferative disorder of histiocytes, predominantly affecting the lymph nodes. RDD can also present in extranodal tissues and is occasionally found within the central nervous system. CASE DESCRIPTION: We report the case of a 52-year-old man presenting with a short episode of dizziness. Imaging identified a right frontal, extraaxial, dural-based lesion, suspicious for a meningioma. The patient underwent a craniotomy for tumor resection and, although not entirely typical, the pathology was consistent with RDD. No other evidence of RDD was identified. CONCLUSIONS: RDD should be considered as a differential diagnosis of dural-based lesions, more commonly meningiomas.

Genomic profiling of cell-free circulating tumor DNA in patients with colorectal cancer and its fidelity to the genomics of the tumor biopsy.

BACKGROUND: Liquid biopsy offers the ability to non-invasively analyze the genome of a tumor through circulating tumor DNA (ctDNA) to identify targetable and prognostic genomic alterations. Few studies have rigorously analyzed ctDNA results and determined the fidelity with which they recapitulate the genomics of a sequenced tissue sample obtained from the same tumor. The clinical utility study (CUS) for the FoundationACT™ ctDNA assay (Foundation Medicine, Cambridge, MA, USA; NCT02620527) is a multi-center prospective clinical study for multiple solid tumor types to compare genomic profiling of paired tissue and blood samples from the same patient. In this subset of the study, paired specimens from 96 patients with colorectal cancer (CRC) were analyzed with comprehensive genomic profiling (CGP) of the tumor tissue sample (FoundationOne®) and blood sample (FoundationACT™). METHODS: Both samples underwent CGP using the hybrid capture-based Illumina Hi-Seq technology. Maximum somatic allele frequency (MSAF) was used to estimate the fraction of ctDNA in the sample. The set of genes and targeted regions common to both tumor and liquid were compared for each subject. RESULTS: Among these patients, 61% were male; 74% had clinical stage IV disease, 19% had clinical stage III disease, and 7% had clinical stage II disease. Time between the tissue biopsy and liquid biopsy (range, 0-709 days) had a significant impact on the positive percent agreement (PPA) between the two assays. Eighty percent of cases had evidence of ctDNA in the blood (MSAF >0). For all cases with MSAF >0, 171 base substitutions and insertions/deletions (indels) were identified in the tumor, and 79% (PPA) of these identical alterations were also identified in matched ctDNA samples; PPA increased to 87% for cases <270 days between the tissue and liquid biopsy, 95% for <90 days, and 100% PPA for <30 days. All known and likely short variants in KRAS, NRAS, and BRAF were analyzed independently as testing of these genes is recommended by the National Comprehensive Cancer Network (NCCN) for patients with CRC and have therapeutic implications. For NCCN genes, PPA was 80% for all time points for short variants; PPA increased to 90% for cases <270 days between the tissue and liquid biopsy. There was high concordance for KRAS G12X between tissue and liquid: overall percent agreement (97%), PPA (93%), negative percent agreement (NPA) (100%), positive predictive value (PPV) (100%), and negative predictive value (NPV) (96%) for the <270 day cohort. CONCLUSIONS: In cases where tumor tissue profiling is not possible, these results provide compelling evidence that genomic profiling of ctDNA in late stage CRC shows a high concordance with tumor tissue sequencing results and can be used to identify most clinically relevant alterations capable of guiding therapy for these patients.

Comprehensive characterization of RAS mutations in colon and rectal cancers in old and young patients.

Colorectal cancer (CRC) is increasingly appreciated as a heterogeneous disease, with factors such as microsatellite instability (MSI), cancer subsite within the colon versus rectum, and age of diagnosis associated with specific disease course and therapeutic response. Activating oncogenic mutations in KRAS and NRAS are common in CRC, driving tumor progression and influencing efficacy of both cytotoxic and targeted therapies. The RAS mutational spectrum differs substantially between tumors arising from distinct tissues. Structure-function analysis of relatively common somatic RAS mutations in G12, Q61, and other codons is characterized by differing potency and modes of action. Here we show the mutational profile of KRAS, NRAS, and the less common HRAS in 13,336 CRC tumors, comparing the frequency of specific mutations based on age of diagnosis, MSI status, and colon versus rectum subsite. We identify mutation hotspots, and unexpected differences in mutation spectrum, based on these clinical parameters.

Comprehensive Genomic Landscapes in Early and Later Onset Colorectal Cancer.

PURPOSE: The incidence rates of colorectal cancers are increasing in young adults. The objective of this study was to investigate genomic differences between tumor samples collected from younger and older patients with colorectal cancer. EXPERIMENTAL DESIGN: DNA was extracted from 18,218 clinical specimens, followed by hybridization capture of 3,769 exons from 403 cancer-related genes and 47 introns of 19 genes commonly rearranged in cancer. Genomic alterations (GA) were determined, and association with patient age and microsatellite stable/microsatellite instability high (MSS/MSI-H) status established. RESULTS: Overall genomic alteration rates in the younger (<40) and older (≥50) cohorts were similar in the majority of the genes analyzed. Gene alteration rates in the microsatellite stable (MSS) younger and older cohorts were largely similar, with several notable differences. In particular, TP53 (FDR < 0.01) and CTNNB1 (FDR = 0.01) alterations were more common in younger patients with colorectal cancer, and APC (FDR < 0.01), KRAS (FDR < 0.01), BRAF (FDR < 0.01), and FAM123B (FDR < 0.01) were more commonly altered in older patients with colorectal cancer. In the MSI-H cohort, the majority of genes showed similar rate of alterations in all age groups, but with significant differences seen in APC (FDR < 0.01), BRAF (FDR < 0.01), and KRAS (FDR < 0.01). CONCLUSIONS: Tumors from younger and older patients with colorectal cancer demonstrated similar overall rates of genomic alteration. However, differences were noted in several genes relevant to biology and response to therapy. Further study will need to be conducted to determine whether the differences in gene alteration rates can be leveraged to provide personalized therapies for young patients with early-onset sporadic colorectal cancer.

Comprehensive genetic alteration profiling in primary and recurrent glioblastoma.

INTRODUCTION: Glioblastoma (GBM) is heterogeneous and underlying genomic profiles influence evolution, resistance, and therapeutic responses. While extensive knowledge regarding genomic profiling of primary GBM exists, there remains a lack of understanding of genomic differences in recurrent GBM. METHODS: We used the FoundationOne® comprehensive genomic profiling assay (CGP) to analyze ten matched primary and recurrent GBM. Genomic alterations (GA) were compared to the cancer database Catalogue of Somatic Mutations in Cancer (COSMIC). RESULTS: All matched tumor pairs demonstrated differences in GA between the primary and recurrence including one resected without any intervening therapy. This suggests that time and/or therapeutic intervention contribute to GA. Although mutations were common to both the primary and recurrence, the percent reads varied substantially suggesting clonal expansions and contractions. For example, EGFR mutations were significantly expanded in three patients, and CNAs were increased in two patients at recurrence. Four genes that were commonly altered in both primary and recurrent GBM were more prevalent in our cohort than reported in COSMIC: CDKN2A (86% vs. 53%) and CDKN2B (86% vs. 54%) deletions, EGFR activating mutation (52% vs. 10%) or amplification (81% vs. 45%), and TERT mutation (95% vs. 51%). Lastly, PI3K pathway activating mutations were also commonly seen in our cohort (67%). CONCLUSIONS: CGP revealed that GA identified in GBM changed over time and with treatment. Mutations in TERT, CDKN2A/CDKN2B, EGFR, and PI3K pathway were commonly observed in both primary and recurrent GBM revealing their prognostic and therapeutic potential. This may have important implications for individualized therapies and needs further evaluation.

Clinical utility of tumor genomic profiling in patients with high plasma circulating tumor DNA burden or metabolically active tumors.

BACKGROUND: This retrospective study was undertaken to determine if the plasma circulating tumor DNA (ctDNA) level and tumor biological features in patients with advanced solid tumors affected the detection of genomic alterations (GAs) by a plasma ctDNA assay. METHOD: Cell-free DNA (cfDNA) extracted from frozen plasma (N = 35) or fresh whole blood (N = 90) samples were subjected to a 62-gene hybrid capture-based next-generation sequencing assay FoundationACT. Concordance was analyzed for 51 matched FoundationACT and FoundationOne (tissue) cases. The maximum somatic allele frequency (MSAF) was used to estimate the amount of tumor fraction of cfDNA in each sample. The detection of GAs was correlated with the amount of cfDNA, MSAF, total tumor anatomic burden (dimensional sum), and total tumor metabolic burden (SUVmax sum) of the largest ten tumor lesions on PET/CT scans. RESULTS: FoundationACT detected GAs in 69 of 81 (85%) cases with MSAF > 0. Forty-two of 51 (82%) cases had ≥ 1 concordance GAs matched with FoundationOne, and 22 (52%) matched to the National Comprehensive Cancer Network (NCCN)-recommended molecular targets. FoundationACT also detected 8 unique molecular targets, which changed the therapy in 7 (88%) patients who did not have tumor rebiopsy or sufficient tumor DNA for genomic profiling assay. In all samples (N = 81), GAs were detected in plasma cfDNA from cancer patients with high MSAF quantity (P = 0.0006) or high tumor metabolic burden (P = 0.0006) regardless of cfDNA quantity (P = 0.2362). CONCLUSION: This study supports the utility of using plasma-based genomic assays in cancer patients with high plasma MSAF level or high tumor metabolic burden.

Practice Patterns of Dentist Anesthesiologists in North America.

This study provides trends in the discipline of dental anesthesiology. A questionnaire-based survey was sent to 338 members of the American Society of Dentist Anesthesiologists to evaluate practice patterns. One focus of the study was modality of sedation/anesthesia used for dentistry in North America. Age, gender, years in practice, and geographic region of practice were also obtained. Data gathered from the returned questionnaires were entered into an Excel spreadsheet and then imported into JMP Statistical Discovery Software (v12.2 Pro) for descriptive analysis. A total of 112 surveys were completed electronically and 102 surveys were returned via post, for a total response rate of 63.3% ( N = 214). Data from this survey suggested a wide variation of therapeutic practices among dentist anesthesiologists in North America. Of the surveyed dentist anesthesiologists, 58.7% (SE = 4.2%) practice as mobile providers, 32.2% (SE = 3.1%) provide care in an academic environment, and 27.7% (SE = 2.8%) function as operator/anesthetists. The majority of anesthesia is provided for pediatric dentistry (47.0%, SE = 4.2%), oral and maxillofacial surgery (18.5%, SE = 3.9%), and special needs (16.7%, SE = 3.6%). Open-airway (58.7%, SE = 5.5%) sedation/anesthesia was the preferred modality of delivery, compared with the use of advanced airway (41.3%, SE = 4.6%). The demographics show diverse practice patterns of dentist anesthesiologists in multiple regions of the continent. Despite concerns regarding specialty recognition, reimbursement difficulties, and competition from alternative anesthesia providers, the overall perceptions of dentist anesthesiologists and the future of the field seem largely favorable.

Anatomy, radiology, and practical procedure education for foundation doctors in England: A National Observational Study.

There are concerns regarding the anatomy knowledge amongst medical school graduates and foundation doctors. Clinical procedures performed without relevant anatomical knowledge could result in serious harm to patients. The aim of this quantitative study was to assess education provision in the domains of anatomy, radiology and practical procedures for foundation year doctors during their first two years of training (FY1, FY2). A national survey of acute hospital trusts in England was conducted. Each trust completed a proforma relating to education provision for foundation year doctors between 6/8/2014 and 4/8/2015. A total of 95/161 (59%) acute hospital trusts in England responded. The mean number of teaching hours/year was 55.6±19.0 for FY1 and 57.3±30.4 hours/year for FY2. Anatomy education was provided in eight trusts with a mean of 2.3±1.0 hours/year for FY1 and 2.7±2.0 hours/year for FY2. The mean provision of practical procedure education was 2.2±1.3 hours/year for FY1 and 2.7±4.4 hours/year for FY2. The mean provision of radiology education was 10.5±18.7 hours/year for FY1 and 7.8±14.2 hours/year for FY2. Reasons for the lack of teaching included: lack of time, facilities, teaching staff, financial resources and absence of specific educational domains in the foundation curriculum. Medical education provision for foundation doctors is highly variable. There are wide discrepancies in postgraduate anatomy education, procedural skill training and radiology education between hospital trusts. Clin. Anat. 29:982-990, 2016. © 2016 Wiley Periodicals, Inc.

Use of opioid pain relievers following extraction of third molars.

Following extraction of third molars, it is common practice for oral and maxillofacial surgeons to provide a prescription for an opioid-containing analgesic such as hydrocodone with acetaminophen. Because the instructions for use most often indicate that these analgesics are to be taken "as needed for pain," it is unknown how many of the prescribed postoperative analgesic tablets are needed and actually taken. Therefore, an assessment of patient pain experiences and actual opioid analgesic usage was carried out using structured telephone interviews of patients performed 1 and 7 days following their thirdmolar extraction surgery. Forty-eight adolescents and young adults, ages 15 to 30 years, participated in this assessment. A review of the surgeon's notes indicated that the median number of prescribed opioid-containing analgesics (ie, Vicodin®, Norco®, Lorcet®, Percocet®) was 20 tablets (range 10 to 40). The median consumption during the first 24 hours was reported to be three tablets (range 0 to 10), and the total consumption for all 7 days was eight tablets (range 0 to 34). Four patients reported nausea or vomiting in the first 24 hours, and six patients reported nausea or vomiting during the following 6 days of recovery. The initial prescriptions provided adequate relief for 45 of the 48 patients. Higher consumption of opioid pain relievers (OPRs) was associated with a longer duration of surgery and the occurrence of postoperative infections.

Does early surgical decompression in cauda equina syndrome improve bladder outcome?

STUDY DESIGN: We analyzed retrospectively whether early surgery for cauda equina syndrome (CES) within 24, 48, or 72 hours of onset of autonomic symptoms made any difference to bladder function at initial outpatient follow-up. OBJECTIVE: CES potentially causes loss of autonomic control including bladder dysfunction, resulting in significant disability. There is significant debate regarding appropriate timing of surgery. SUMMARY OF BACKGROUND DATA AND METHODS: We conducted a retrospective cohort study of 200 patients between 2000 and 2011 who underwent decompressive surgery for CES at a regional neurosurgical center. Data collected were from clinical admission and at initial follow-up. Presentation was categorized into CES with retention (CESR) and incomplete CES (CESI) and duration of autonomic symptoms before surgical intervention. RESULTS: A total of 200 patients had complete clinical records; 61 cases with CESR and 139 cases with CESI. Average initial follow-up time was 96 days. For the 36 cases with CESI less than 24 hours, normal bladder function was seen at follow-up in all patients except 4 (11.1%), but with 103 cases with CESI more than 24 hours, 48 (46.6%) had bladder dysfunction (Pearson χP = 0.000). For the 64 cases with CESI less than 48 hours, normal bladder function was seen at follow-up in all except 10 (15.6%), but with 75 cases with CESI more than 48 hours, 42 (56%) had bladder dysfunction (Pearson χP = 0.000). For the 35 patients with CESR, operating within 24, 48, or 72 hours made no obvious difference to bladder outcome. Data were also reanalyzed changing the dataset groups to CESI less than 24 hours, 24 to 48 hours, and more than 48 hours to calculate odds ratios regarding normal bladder outcome. CONCLUSION: We identified that decompressive surgery within 24 hours of onset of autonomic symptoms in CESI reduces bladder dysfunction at initial follow-up, but no statistically significant difference in outcome was observed in CESR regarding timing of operation. LEVEL OF EVIDENCE: 3.

Defects in mitochondrial ATP synthesis in dystrophin-deficient mdx skeletal muscles may be caused by complex I insufficiency.

Duchenne Muscular Dystrophy is a chronic, progressive and ultimately fatal skeletal muscle wasting disease characterised by sarcolemmal fragility and intracellular Ca2+ dysregulation secondary to the absence of dystrophin. Mounting literature also suggests that the dysfunction of key energy systems within the muscle may contribute to pathological muscle wasting by reducing ATP availability to Ca2+ regulation and fibre regeneration. No study to date has biochemically quantified and contrasted mitochondrial ATP production capacity by dystrophic mitochondria isolated from their pathophysiological environment such to determine whether mitochondria are indeed capable of meeting this heightened cellular ATP demand, or examined the effects of an increasing extramitochondrial Ca2+ environment. Using isolated mitochondria from the diaphragm and tibialis anterior of 12 week-old dystrophin-deficient mdx and healthy control mice (C57BL10/ScSn) we have demonstrated severely depressed Complex I-mediated mitochondrial ATP production rate in mdx mitochondria that occurs irrespective of the macronutrient-derivative substrate combination fed into the Kreb's cycle, and, which is partially, but significantly, ameliorated by inhibition of Complex I with rotenone and stimulation of Complex II-mediated ATP-production with succinate. There was no difference in the MAPR response of mdx mitochondria to increasing extramitochondrial Ca2+ load in comparison to controls, and 400 nM extramitochondrial Ca2+ was generally shown to be inhibitory to MAPR in both groups. Our data suggests that DMD pathology is exacerbated by a Complex I deficiency, which may contribute in part to the severe reductions in ATP production previously observed in dystrophic skeletal muscle.

Effects of G-trainer, cycle ergometry, and stretching on physiological and psychological recovery from endurance exercise.

The purpose of this study was to compare the effectiveness of 3 treatment modes (Anti-Gravity Treadmill [G-trainer], stationary cycling [CompuTrainer], and static stretching) on the physiological and psychological recovery after an acute bout of exhaustive exercise. In a crossover design, 12 aerobically trained men (21.3 ± 2.3 years, 72.1 ± 8.1 kg, 178.4 ± 6.3 cm, (Equation is included in full-text article.): 53.7 ± 6.3 ml·kg·min) completed a 29-km stationary cycling time trial. Immediately after the time trial, subjects completed 30 minutes of G-trainer or CompuTrainer (40% (Equation is included in full-text article.)) or static stretching exercises. A significant time effect was detected for plasma lactate (p = 0.010) and serum cortisol (p = 0.039) after exercise. No treatment or treatment by time interaction was identified for lactate or cortisol, respectively. No main effects for time, treatment, or treatment by time interaction were identified for interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α). No differences were observed among treatments in skeletal muscle peak power output, mean power output, time to peak power, and rate to fatigue at 24 hours postexercise bout. Finally, no significant changes in mood status were observed after exercise and between treatment groups. When compared with stationary cycling and static stretching, exercise recovery performed on the G-trainer was unable to reduce systemic markers of stress and inflammation, blood lactate, or improve anaerobic performance and psychological mood states after an exhaustive bout of endurance exercise. Further research is warranted that includes individualized recovery modalities to create balances between the stresses of training and competition.