The Role of Endoscopy for Primary and Secondary Prophylaxis of Variceal Bleeding.

Cirrhosis is associated with a high morbidity and mortality. One of the most serious and unpredictable complication of cirrhosis, with a high mortality rate, is bleeding from esophagogastric varices. Endoscopic screening of varices followed by primary prophylactic treatment with beta blockers or band ligation in the presence of large esophageal varices will reduce the variceal bleeding rates and thereby reduce mortality risks in those with advanced cirrhosis. There is a paucity of data on primary prophylaxis of gastric varices but secondary prophylaxis includes glue injection, balloon-occluded retrograde transvenous obliteration, or transjugular intrahepatic portosystemic shunting with coil embolization.

Augmented mitochondrial apoptotic signaling impairs C2C12 myoblast differentiation following cellular aging through sequential passaging.

Aging is associated with the steady decline of several cellular processes. The loss of skeletal muscle mass, termed sarcopenia, is one of the major hallmarks of aging. Aged skeletal muscle exhibits a robust reduction in its regenerative capacity due to dysfunction (i.e., senescence, lack of self-renewal, and impaired differentiation) of resident muscle stem cells, called satellite cells. To replicate aging in vitro, immortalized skeletal muscle cells (myoblasts) can be treated with various agents to mimic age-related dysfunction; however, these come with their own set of limitations. In the present study, we used sequential passaging of mouse myoblasts to mimic impaired differentiation that is observed in aged skeletal muscle. Further, we investigated mitochondrial apoptotic mechanisms to better understand the impaired differentiation in these "aged" cells. Our data shows that sequential passaging (>20 passages) of myoblasts is accompanied with significant reductions in differentiation and elevated cell death. Furthermore, high-passage (HP) myoblasts exhibit greater mitochondrial-mediated apoptotic signaling through mitochondrial BAX translocation, CYCS and AIFM1 release, and caspase-9 activation. Finally, we show that inhibition of mitochondrial outer membrane permeability partly recovered differentiation in HP myoblasts. Together, our findings suggests that mitochondrial apoptotic signaling is a contributing factor to the diminished differentiation that is observed in aged myoblasts.

Use of a Caprine Model for Simulation and Training of Endoscopic Ear surgery.

BACKGROUND: The objective of this study was to evaluate the utility of a caprine model in endoscopic ear surgical education using the index procedures of tympanoplasty and ossiculoplasty. Specifically, this study assessed the face and content validity of the caprine model, and the potential impact of anatomical differences on trainee understanding of human middle ear anatomy. METHODS: Twelve otolaryngology trainees attended a 3-hour endoscopic ear surgery course utilizing the caprine model in which they completed canalplasty, tympanoplasty, and ossiculoplasty. Prior to the course, the trainees completed a self-reported needs assessment and knowledge assessment of human middle ear anatomy. Following the course, the trainees repeated the knowledge assessment and completed evaluation and validation questionnaires. Five-point Likert scores were used for the needs assessment and validation questionnaire. RESULTS: Of the 12 trainees, 9 participated in the study. All domains of the learner needs assessment showed an average improvement of 1 point on the post-course evaluation with 6 of 9 domains being significantly improved using the Wilcoxon signed-rank test (P< .05). The model achieved validation in the domains of face, content, and global content validity with an average Likert score > 4. Knowledge assessment scores increased by 7% (P=.23) after the course compared to before. CONCLUSION: The caprine model offers an effective surgical simulation model for endoscopic ear surgery training with good face and content validity. We find it to be readily available and affordable. We currently use it routinely to give otolaryngology residents the experience of endoscopic ear surgery before operating on patients.

Automated measurement of inter-arytenoid distance on 4D laryngeal CT: A validation study.

Changes to the voice are prevalent and occur early in Parkinson's disease. Correlates of these voice changes on four-dimensional laryngeal computed-tomography imaging, such as the inter-arytenoid distance, are promising biomarkers of the disease's presence and severity. However, manual measurement of the inter-arytenoid distance is a laborious process, limiting its feasibility in large-scale research and clinical settings. Automated methods of measurement provide a solution. Here, we present a machine-learning module which determines the inter-arytenoid distance in an automated manner. We obtained automated inter-arytenoid distance readings on imaging from participants with Parkinson's disease as well as healthy controls, and then validated these against manually derived estimates. On a modified Bland-Altman analysis, we found a mean bias of 1.52 mm (95% limits of agreement -1.7 to 4.7 mm) between the automated and manual techniques, which improves to a mean bias of 0.52 mm (95% limits of agreement -1.9 to 2.9 mm) when variability due to differences in slice selection between the automated and manual methods are removed. Our results demonstrate that estimates of the inter-arytenoid distance with our automated machine-learning module are accurate, and represents a promising tool to be utilized in future work studying the laryngeal changes in Parkinson's disease.

Topogivity: A Machine-Learned Chemical Rule for Discovering Topological Materials.

Topological materials present unconventional electronic properties that make them attractive for both basic science and next-generation technological applications. The majority of currently known topological materials have been discovered using methods that involve symmetry-based analysis of the quantum wave function. Here we use machine learning to develop a simple-to-use heuristic chemical rule that diagnoses with a high accuracy whether a material is topological using only its chemical formula. This heuristic rule is based on a notion that we term topogivity, a machine-learned numerical value for each element that loosely captures its tendency to form topological materials. We next implement a high-throughput procedure for discovering topological materials based on the heuristic topogivity-rule prediction followed by ab initio validation. This way, we discover new topological materials that are not diagnosable using symmetry indicators, including several that may be promising for experimental observation.

A Retrospective Review of 589 Percutaneous Tracheostomies in a Canadian Community Teaching Hospital.

OBJECTIVE: The primary objective of this study was to review the complication rate of percutaneous tracheostomies performed by a single surgeon in a community teaching hospital. METHODS: This retrospective study reviewed the patients who underwent percutaneous tracheostomy with bronchoscopic guidance in a community hospital setting between 2009 and 2017. Patients older than the age of 18 requiring percutaneous tracheostomy were chosen for this retrospective study. Patients who were medically unstable, had no palpable neck landmarks, and inadequate neck extension were excluded. Indications for percutaneous tracheostomy included patients who had failed to wean from mechanical ventilation, required pulmonary toileting, or in whom airway protection was required. RESULTS: Of the 600 patients who received percutaneous tracheostomy, 589 patients were included in the study. Intraoperative complication (2.6%) and postoperative complication rates (11.4%) compared similarly to literature reported rates. The most common intraoperative complications were bleeding, technical difficulties, and accidental extubation. Bleeding, tube obstruction, and infection were the most common postoperative complications. Overall burden of comorbidity, defined by Charlson Comorbidity Index, and coagulopathy were also found to be associated with higher complication rates. The decannulation rate at discharge was 46.3%. CONCLUSION: Percutaneous tracheostomy is a safe alternative to open tracheostomies in the community setting for appropriately selected patients.

Multivalent viral particles elicit safe and efficient immunoprotection against Nipah Hendra and Ebola viruses.

Experimental vaccines for the deadly zoonotic Nipah (NiV), Hendra (HeV), and Ebola (EBOV) viruses have focused on targeting individual viruses, although their geographical and bat reservoir host overlaps warrant creation of multivalent vaccines. Here we explored whether replication-incompetent pseudotyped vesicular stomatitis virus (VSV) virions or NiV-based virus-like particles (VLPs) were suitable multivalent vaccine platforms by co-incorporating multiple surface glycoproteins from NiV, HeV, and EBOV onto these virions. We then enhanced the vaccines' thermotolerance using carbohydrates to enhance applicability in global regions that lack cold-chain infrastructure. Excitingly, in a Syrian hamster model of disease, the VSV multivalent vaccine elicited safe, strong, and protective neutralizing antibody responses against challenge with NiV, HeV, or EBOV. Our study provides proof-of-principle evidence that replication-incompetent multivalent viral particle vaccines are sufficient to provide protection against multiple zoonotic deadly viruses with high pandemic potential.

Parkinson's disease, dopaminergic drugs and the plant world.

A large proportion of drugs used for the treatment of neurological disorders relate to naturally occurring compounds, many of which are plant alkaloids. This is particularly true of Parkinson's disease (PD). The pharmacopoeia of PD has strong botanical origins, while major discoveries about the neurochemistry of the basal ganglia came from the study of phytochemicals. This article narrates the development of pharmacotherapy for PD in terms of historically important plant-derived substances-tropane and hamala alkaloids, reserpine, levodopa, apomorphine, and ergoline dopamine receptor agonists. Alkaloids are nitrogen-containing secondary metabolic products that tend to be biologically active. They appear to be involved in plants' adaptation to herbivorous animals, though their exact purpose and the ways in which they work are uncertain. A sizable group of alkaloids influence animal dopaminergic systems, highlighting a key biological relationship. While animals must acquire the energy that plants harness, plants need to engage with the animal attribute that they lack-movement-in order to maximize their reproductive fitness. Neuroactive flowering plant compounds have been interacting with vertebrate and invertebrate motor systems for 100 million years. A deep evolutionary connection helps to explain why the pharmacological treatment of PD is imprinted with the power of these mysterious botanical chemicals.

Radiological correlates of vocal fold bowing as markers of Parkinson's disease progression: A cross-sectional study utilizing dynamic laryngeal CT.

OBJECTIVE: To determine whether arytenoid cartilage position and dynamics change with advancing duration and severity (as graded by MDS-UPDRS part III scores) in Parkinson's disease, in a cross-sectional study design, we performed laryngeal four-dimensional computed tomography (4D-CT) in people with Parkinson's disease and controls. METHODS: 31 people with Parkinson's disease covering a range of disease duration and severity and 19 controls underwent laryngeal 4D-CT whilst repeatedly vocalizing. We measured on each CT volume the glottic area (GA), inter-arytenoid distance (IAD), IAD-Area index (IAI) and arytenoid cartilage velocity ([Formula: see text]). RESULTS: People with Parkinson's disease had reductions in the mean/effective minimum IAD when compared to controls, while mean/effective minimum GA and mean/effective maximum IAI were increased. Arytenoid cartilage velocities showed no difference. On Spearman correlation analyses, advancing disease duration and severity of PD showed moderately strong and significant correlations with increasing mean/effective minimum GA, increasing mean/effective maximum IAI and decreasing effective minimum IAD. Linear mixed models which considered the effects of intra and inter-individual variation showed that both disease duration (b = -0.011, SEb = 0.053, 95% CI [-0.022, 0], t(27) = -2.10, p = 0.045) and severity (b = -0.069, SEb = 0.032, 95% CI [-0.14,-0.0039], t(27) = -2.17, p = 0.039) were significant predictors for IAD, and also for transformed values of the GA and IAI. CONCLUSIONS: There are progressive alterations in phonatory posturing as Parkinson's disease advances. The increases in GA despite reductions in IAD are concordant with prior observations of vocal fold bowing. Our study provides a basis for using laryngeal 4D-CT to assess disease progression in Parkinson's disease.

Outcomes in Hepatitis C Positive Liver Transplantation: Timing of Direct-Acting Antiviral Treatment and Impact on Graft Fibrosis.

Liver transplantation for hepatitis C virus (HCV)-related disease has the lowest five-year graft survival among all liver transplant recipients. Graft failure due to accelerated fibrosis from unrestrained HCV replication is common. Optimal timing of HCV treatment with direct-acting antiviral agents remains unknown. We compared HCV liver transplant recipients successfully treated for HCV before transplant to those treated within 1 year of transplant to determine if graft fibrosis, measured by Fib-4 scores, differs with timing of treatment. Fib-4 scores less than or equal to 1.45 defined minimal fibrosis and greater than 1.45 defined greater than minimal fibrosis. We identified 117 liver transplant recipients: 52 treated before transplantation and 65 treated within 1 year of transplantation. Overall, 34% of recipients had minimal fibrosis, and the likelihood of having minimal fibrosis following treatment and liver transplantation did not differ by timing of treatment. The odds ratio of having greater than minimal fibrosis was 0.65 (95% CI 0.30, 1.42) among those treated within 1 year after transplantation compared to those treated before transplantation (p-value 0.28). Importantly, nearly 2/3 of these patients had evidence of fibrosis progression one year after sustained virologic response, supporting recommendations for early antiviral-based treatment to prevent accumulation of HCV-related disease.

Examining interindividual differences in select muscle and whole-body adaptations to continuous endurance training.

NEW FINDINGS: What is the central question of the study? Do interindividual differences in trainability exist for morphological and molecular skeletal muscle responses to aerobic exercise training? What is the main finding and its importance? Interindividual differences in trainability were present for some, but not all, morphological and molecular outcomes included in our study. Our findings suggest that it is inappropriate, and perhaps erroneous, to assume that variability in observed responses reflects interindividual differences in trainability in skeletal muscle responses to aerobic exercise training. ABSTRACT: Studies have interpreted a wide range of morphological and molecular changes in human skeletal muscle as evidence of interindividual differences in trainability. However, these interpretations fail to account for the influence of random measurement error and within-subject variability. The purpose of the present study was to use the standard deviation of individual response (SDIR ) statistic to test the hypothesis that interindividual differences in trainability are present for some but not all skeletal muscle outcomes. Twenty-nine recreationally active males (age: 21 ± 2 years; BMI: 24 ± 3 kg/m2 ; V̇O2peak ; 45 ± 7 ml/kg/min) completed 4 weeks of continuous training (REL; n = 14) or control (n = 15). Maximal enzyme activities (citrate synthase and ß-hydroxyacyl-CoA dehydrogenase), capillary density, fibre type composition, fibre-specific succinate dehydrogenase activity and substrate storage (intramuscular triglycerides and glycogen), and markers of mitophagy (BCL2-interacting protein 3 (BNIP3), BNIP3-like protein, parkin and PTEN-induced kinase 1) were measured in vastus lateralis samples collected before and after the intervention. We also calculated SDIR values for V̇O2peak , peak work rate and the onset of blood lactate accumulation for the REL group and a separate group that exercised at the negative talk test stage. Although positive SDIR values - indicating interindividual differences in trainability - were obtained for aerobic capacity outcomes, maximal enzyme activities, capillary density, all fibre-specific outcomes and BNIP3 protein content, the remaining outcomes produced negative SDIR values indicating a large degree of random measurement error and/or within-subject variability. Our findings question the interpretation of heterogeneity in observed responses as evidence of interindividual differences in trainability and highlight the importance of including control groups when analysing individual skeletal muscle response to exercise training.

Increasing whole-body energetic stress does not augment fasting-induced changes in human skeletal muscle.

Fasting rapidly (≤ 6 h) activates mitochondrial biogenic pathways in rodent muscle, an effect that is absent in human muscle following prolonged (10-72 h) fasting. We tested the hypotheses that fasting-induced changes in human muscle occur shortly after food withdrawal and are modulated by whole-body energetic stress. Vastus lateralis biopsies were obtained from ten healthy males before, during (4 h), and after (8 h) two supervised fasts performed with (FAST+EX) or without (FAST) 2 h of arm ergometer exercise (~ 400 kcal of added energy expenditure). PGC-1α mRNA (primary outcome measure) was non-significantly reduced (p = 0.065 [ηp2 = 0.14]) whereas PGC-1α protein decreased (main effect of time: p < 0.01) during both FAST and FAST+EX. P53 acetylation increased in both conditions (main effect of time: p < 0.01) whereas ACC and SIRT1 phosphorylation were non-significantly decreased (both p < 0.06 [ηp2 = 0.15]). Fasting-induced increases in NFE2L2 and NRF1 protein were observed (main effects of time: p < 0.03), though TFAM and COXIV protein remained unchanged (p > 0.05). Elevating whole-body energetic stress blunted the increase in p53 mRNA, which was apparent during FAST only (condition × time interaction: p = 0.04). Select autophagy/mitophagy regulators (LC3BI, LC3BII, BNIP3) were non-significantly reduced at the protein level (p ≤ 0.09 [ηp2 > 0.13]) but the LC3II:I ratio was unchanged (p > 0.05). PDK4 mRNA (p < 0.01) and intramuscular triglyceride content in type IIA fibers (p = 0.04) increased similarly during both conditions. Taken together, human skeletal muscle signaling, mRNA/protein expression, and substrate storage appear to be unaffected by whole-body energetic stress during the initial hours of fasting.

A Method for Rapid Selection of Randomly Induced Mutations in a Gene of Interest Using CRISPR/Cas9 Mediated Activation of Gene Expression.

We have developed a CRISPR/Cas9 based method for isolating randomly induced recessive lethal mutations in a gene of interest (GOI) by selection within the F1 progeny of a single genetic cross. Our method takes advantage of the ability to overexpress a GOI using CRISPR/Cas9 mediated activation of gene expression. In essence, the screening strategy is based upon the idea that if overexpression of a wild type allele can generate a phenotype, then overexpression of a newly induced loss-of-function allele will lack this phenotype. As a proof-of-principle, we used this method to select EMS induced mutations of the Drosophila gene hindsight (hnt). From approximately 45,000 F1 progeny we recovered 8 new EMS induced loss-of-function hnt alleles that we characterized as an allelic series of hypomorphic mutations. This new method can, in theory, be used to recover randomly induced point mutants in a GOI and can be applied to any circumstance where CRISPR/Cas9 mediated activation of gene expression is associated with lethality or a visible phenotype.

Fiber-specific and whole-muscle LRP130 expression in rested, exercised, and fasted human skeletal muscle.

Leucine-rich pentatricopeptide repeat motif-containing protein (LRP130) is implicated in the control of mitochondrial gene expression and oxidative phosphorylation in the liver, partly due to its interaction with peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α). To investigate LRP130's role in healthy human skeletal muscle, we examined LRP130's fiber-type distribution and subcellular localization (n = 6), as well as LRP130's relationship with PGC-1α protein and citrate synthase (CS) maximal activity (n = 33) in vastus lateralis samples obtained from young males. The impact of an acute bout of exercise (endurance [END] and sprint interval training [SIT]) and fasting (8 h) on LRP130 and PGC-1α expression was also determined (n = 10). LRP130 protein content paralleled fiber-specific succinate dehydrogenase activity (I > IIA) and strongly correlated with the mitochondrially localized protein apoptosis-inducing factor in type I (r = 0.75) and type IIA (r = 0.85) fibers. Whole-muscle LRP130 protein content was positively related to PGC-1α protein (r = 0.49, p < 0.01) and CS maximal activity (r = 0.42, p < 0.01). LRP130 mRNA expression was unaltered (p > 0.05) following exercise, despite ~ 6.6- and ~ 3.8-fold increases (p < 0.01) in PGC-1α mRNA expression after END and SIT, respectively. Although unchanged at the group level (p > 0.05), moderate-to-strong positive correlations were apparent between individual changes in LRP130 and PGC-1α expression at the mRNA (r = 0.63, p < 0.05) and protein (r = 0.59, p = 0.07) level in response to fasting. Our findings support a potential role for LRP130 in the maintenance of basal mitochondrial phenotype in human skeletal muscle. LRP130's importance for mitochondrial remodeling in exercised and fasted human skeletal muscle requires further investigation.

Voice changes in Parkinson's disease: What are they telling us?

Emerging evidence suggests voice dysfunction is the earliest sign of motor impairment in Parkinson's disease (PD). The complexity and fine motor control involved in vocalization may result in dysfunction here before the limbs. The voice in PD demonstrates characteristic changes on perceptual and acoustic analyses. The physiological and anatomical correlates of these have been investigated through laryngoscopy, stroboscopy, photoglottography, laryngeal electromyography, computed-tomography, pulmonary function testing and aerodynamic assessments. These have revealed numerous abnormalities including incomplete glottic closure and vocal fold hypoadduction/bowing to account for these voice changes. Many of these phenomena are likely related to rigidity or bradykinesia of the laryngeal muscles. The early onset of voice changes is resonant with the pathophysiological insights offered by Braak's hypothesis and murine models of the disease. These physiological abnormalities and pathological models largely stand to support dopaminergic and non-dopaminergic mechanisms being implicated in the pathogenesis of voice dysfunction. This review focuses on characterizing the voice changes in PD. These stand as a promising area of enquiry to further our understanding of the pathophysiology of the disease and offer potential to be utilized as an early diagnostic biomarker or marker of disease progression.

Endoscope-assisted Partial Cochlectomy for Intracochlear Schwannoma With Simultaneous Cochlear Implantation: A Case Report.

INTRODUCTION: Intralabyrinthine schwannomas are a small subset of vestibular schwannomas which originate within the labyrinthine structures. Management typically consists of watch-and-wait strategies given that surgical intervention will sacrifice hearing. Endoscopic resection of primary intracochlear schwannoma with simultaneous cochlear implantation for a patient with progressive hearing loss and debilitating tinnitus is described. PATIENT: A 56-year-old male presenting with asymmetric left sensorineural hearing loss (SNHL) was diagnosed with intracochlear schwannoma on MRI. INTERVENTION: Surgery was indicated due to tumor growth on serial imaging, worsening SNHL, and severe tinnitus. Partial cochlectomy was performed via transcanal endoscopic approach. Cochlear implantation via mastoidectomy and posterior tympanotomy was simultaneously performed with a CI512 Contour Advanced implant (Cochlear, Sydney, Australia). MAIN OUTCOME MEASURES: Post partial cochlectomy speech performance. RESULTS: Preoperative audiometry showed left profound SNHL with 20% speech recognition score despite maximal amplification. Speech perception testing 5 months postoperatively demonstrated good unilateral discrimination when testing the implanted ear alone (BKB sentences 66%, CUNY sentences 79%), open-set comprehension, and excellent binaural performance. CONCLUSION: The endoscope offers an additional viable approach to the otic capsule for the removal of intracochlear schwannoma and good audiologic outcomes can be achieved with simultaneous cochlear implantation even after partial cochlectomy.

A comparison of pain responses, hemodynamic reactivity and fibre type composition between Bergström and microbiopsy skeletal muscle biopsies.

This study tested the hypotheses that 1) skeletal muscle biopsies performed with the Bergström needle evoke larger perceptions of pain and greater hemodynamic reactivity compared to biopsies performed with the microbiopsy needle, and 2) both needles yield samples with similar fibre type compositions when samples are collected at similar skeletal muscle depths. Fourteen healthy (age: 21.6 ±â€¯3.2 years; VO2peak: 41.5 ±â€¯5.8 mL/kg/min) males (n = 7) and females (n = 7) provided two resting skeletal muscle biopsies, one with each needle type, following a randomized crossover design. Participants completed the short-form McGill Pain Questionnaire and the Brief Pain Inventory before, during, and after the skeletal muscle biopsies. Hemodynamic reactivity was assessed by measuring heart rate (HR) and mean arterial pressure (MAP) at rest and during the biopsy procedures. Immunofluorescence analysis was used to assess fibre type composition in vastus lateralis samples. Compared to the microbiopsy needle, the Bergström needle elicited a larger perception of pain but similar hemodynamic reactivity during the biopsy. Both needles yielded skeletal muscle samples with similar fibre type composition and resulted in similar perceptions of pain and pain-related interference during the post-biopsy recovery period. Collectively, these findings suggest that studies should consider using the microbiopsy needle rather than the Bergström needle unless large amounts of muscle tissue or certain muscle fibre lengths are required. However, future work should determine whether our findings are generalizable to biopsies performed with different procedures and/or types of Bergström/microbiopsy needles.

Otology/Neurotology recommendations - Choosing Wisely campaign.

The Choosing Wisely Canada Campaign aims to raise awareness amongst physicians and patients regarding unnecessary tests and treatment. The otology/neurotology subspecialty group within the Canadian Society of Otolaryngology - Head & Neck Society developed a list of five common otologic presentations to help physicians deliver high quality effective care: (1) Don't order specialized audiometric and vestibular testing to screen for peripheral vestibular disease, (2) Don't perform computed tomography or blood work in the evaluation of sudden sensorineural hearing loss, (3) Don't perform auditory brain responses (ABR) in patients with asymmetrical hearing loss, (4) Don't prescribe oral antibiotics as first line treatment for patients with painless otorrhea associated with tympanic membrane perforation or tympanostomy tube, and (5) Don't perform particle repositioning maneuvers without a clinical diagnosis of posterior canal benign paroxysmal positional vertigo.

Repeatability of exercise-induced changes in mRNA expression and technical considerations for qPCR analysis in human skeletal muscle.

NEW FINDINGS: What is the central question of this study? Are individual changes in exercise-induced mRNA expression repeatable (i.e. representative of the true response to exercise rather than random error)? What is the main finding and its importance? Exercise-induced changes in mRNA expression are not repeatable even under identical experimental conditions, thereby challenging the use of mRNA expression as a biomarker of adaptive potential and/or individual responsiveness to exercise. ABSTRACT: It remains unknown if (1) the observed change in mRNA expression reflects an individual's true response to exercise or random (technical and/or biological) error, and (2) the individual responsiveness to exercise is protocol-specific. We examined the repeatability of skeletal muscle PGC-1α, PDK4, NRF-1, VEGF-A, HSP72 and p53 mRNA expression following two identical endurance exercise (END) bouts (END-1, END-2; 30 min of cycling at 65% of peak work rate (WRpeak ), n = 11) and inter-individual variability in PGC-1α and PDK4 mRNA expression following END and sprint interval training (SIT; 8 × 20 s cycling intervals at ∼170% WRpeak , n = 10) in active young males. The repeatability of key gene analysis steps (RNA extraction, reverse transcription, qPCR) and within-sample fibre-type distribution (n = 8) was also determined to examine potential sources of technical error in our analyses. Despite highly repeatable exercise bout characteristics (work rate, heart rate, blood lactate; ICC > 0.71; CV < 10%; r > 0.85, P < 0.01), gene analysis steps (ICC > 0.73; CV < 24%; r > 0.75, P < 0.01), and similar group-level changes in mRNA expression, individual changes in PGC-1α, PDK4, VEGF-A and p53 mRNA expression were not repeatable (ICC < 0.22; CV > 20%; r < 0.21). Fibre-type distribution in two portions of the same muscle biopsy was highly variable and not significantly related (ICC = 0.39; CV = 26%; r = 0.37, P = 0.37). Since individual changes in mRNA expression following identical exercise bouts were not repeatable, inferences regarding individual responsiveness to END or SIT were not made. Substantial random error exists in changes in mRNA expression following acute exercise, thereby challenging the use of mRNA expression for analysing individual responsiveness to exercise.

The impact of human papillomavirus (HPV) status on functional outcomes and quality of life (QOL) after surgical treatment of oropharyngeal carcinoma with free-flap reconstruction.

BACKGROUND: To determine the impact of Human Papillomavirus (HPV) status on speech, swallowing, and quality of life (QOL) outcomes after surgical treatment of oropharyngeal cancer (OPSCC). METHODS: A retrospective review of a prospectively collected database of all patients with OPSCC diagnosed and treated from 1998 to 2009. Speech, swallowing, and quality of life data were gathered at 3 different evaluation points. HPV status was determined using p16 positivity as a surrogate marker. Univariate and multivariate statistical analyses were performed to identify whether p16 status is a significant predictor of functional outcome and QOL. RESULTS: One hundred twelve patients with OPSCC and known p16 status were treated with primary surgery between 1998 and 2009, with mean age of 56 years. Out of those patients 63 (56%) were p16 positive. Speech intelligibility remained high at 1-year post operation (95.4%). Only 11.5% of the patients required a feeding tube at 1 year after surgery to maintain their daily caloric requirements and the risk of aspiration after surgery was not significant (p = 0.097). There was no statistically or clinically significant difference in speech, swallowing ability, swallowing safety and QOL outcomes between p16-positive and negative OPSCC. CONCLUSIONS: Surgically treated OPSCC patients demonstrate excellent swallowing function and can achieve excellent speech perception. P16 status may not be predictive of functional outcomes or QOL in surgically treated OPSCC.