Irisin and Fibronectin Type III Domain-Containing 5 Responses to Exercise in Different Environmental Conditions

International Journal of Exercise Science 10(5): 666-680, 2017. Fibronectin type III domain-containing 5 (FNDC5) is a skeletal muscle membrane-bound precursor to the myokine irisin. Irisin is involved in stimulating adipose tissue to become more metabolically active in order to produce heat. The purpose of this study was to determine the effects of exercise in a hot (33 °C), cold (7 °C), and room temperature (RT, 20 °C) environment on the skeletal muscle gene expression of FNDC5 and the plasma concentrations of irisin. Twelve recreationally trained males completed three separate, 1 h cycling bouts at 60% of Wmax in a hot, cold, and RT environment followed by three hours of recovery at room temperature. Blood samples were taken from the antecubital vein and muscle biopsies were taken from the vastus lateralis pre-, post-, and 3 h post-exercise. Plasma concentrations of irisin did not change from pre- (9.23 ± 2.68 pg·mL-1) to post-exercise (9.6 ± 0.2 pg·mL-1, p = 0.068), but did decrease from post-exercise to 3 h post-exercise (8.9 ± 0.5 pg·mL-1, p = 0.047) regardless of temperature. However, when plasma volume shifts were considered, no differences were found in irisin (p = 0.086). There were no significant differences between trials for irisin plasma concentrations (p \u3e 0.05). No significant differences in FNDC5 were observed between the hot, cold, or RT or pre-, post-, or 3 h post-exercise time points (p \u3e 0.05). These data indicate that the temperature in which exercise takes place does not influence FNDC5 transcription or circulating irisin in a human model

Interobserver agreement for single operator choledochoscopy imaging: can we do better?

Background. The SpyGlass Direct Visualization System (Boston Scientific, Natick, MA) is routinely used during single operator choledochoscopy (SOC) to identify biliary lesions or strictures with a diagnostic accuracy up to 88%. The objective of this study was to determine the interobserver agreement (IOA) of modified scoring criteria for diagnosing biliary lesions/strictures. Methods. 27 SPY SOC video clips were reviewed and scored by 9 interventional endoscopists based on published criteria that included the presence and severity of surface structure, vasculature visualization, lesions, and findings. Results. Overall IOA was slight for all variables. The K statistics are as follows: surface (K = 0.12, SE = 0.02); vessels (K = 0.14, SE = 0.02); lesions (K = 0.11, SE = 0.02); findings (K = 0.08, SE = 0.03); and final diagnosis (K = 0.08, SE = 0.02). The IOA for findings and final diagnosis was also only slight. The final diagnosis was malignant (11), benign (11), and indeterminate (5). Conclusion. IOA using the modified criteria of SOC images was slight to almost poor. The average accuracy was less than 50%. These findings reaffirm that imaging criteria for benign and malignant biliary pathology need to be formally established and validated

Exercise-Induced Interleukin-6 and Metabolic Responses in Hot, Temperate, and Cold Conditions

The purpose of this study was to determine the effects of exercise in hot, cold, and temperate environments on plasma interleukin-6 (IL-6). Eleven recreationally trained males (age = 25 ± 4 years, height = 178 ± 5 cm, weight = 79.4 ± 13.5 kg, body fat = 14.7 ± 3.6%, VO2 peak = 54.6 ± 11.5 ml kg-1 min-1) performed a 1 hr cycling bout in hot (33 °C), cold (7 °C), and temperate (20 °C) environments at 60% of Wmax followed by 3 hr of supine recovery in temperate conditions. Expired gases were measured every 15 min during exercise and once every hour during recovery. Heart rate was continuously measured throughout the trials. Blood samples were obtained from the antecubital vein pre-exercise, immediately post-exercise, and 3 hr post-exercise. Blood samples were analyzed for plasma concentrations of IL-6 using a commercial ELISA kit. Plasma IL-6 concentrations were significantly higher immediately post-exercise (14.8 ± 1.6 pg ml-1, p = 0.008) and 3 hr post-exercise (14.8 ± 0.9 pg ml-1, p = 0.018) compared to pre-exercise (11.4 ± 2.4 pg ml-1), across all trials. There were no differences in plasma IL-6 concentrations (p = 0.207) between temperature conditions.Oxygen consumption and heart rate were higher and respiratory exchange ratio was lower in the hot compared to other conditions (p \u3c 0.05). These data indicate that the temperature in which exercise occurs does not affect acute plasma IL-6 response despite differences in metabolic state

Quality of Life in Chronic Pancreatitis is Determined by Constant Pain, Disability/Unemployment, Current Smoking, and Associated Co-Morbidities

OBJECTIVES: Chronic pancreatitis (CP) has a profound independent effect on quality of life (QOL). Our aim was to identify factors that impact the QOL in CP patients. METHODS: We used data on 1,024 CP patients enrolled in the three NAPS2 studies. Information on demographics, risk factors, co-morbidities, disease phenotype, and treatments was obtained from responses to structured questionnaires. Physical and mental component summary (PCS and MCS, respectively) scores generated using responses to the Short Form-12 (SF-12) survey were used to assess QOL at enrollment. Multivariable linear regression models determined independent predictors of QOL. RESULTS: Mean PCS and MCS scores were 36.7+/-11.7 and 42.4+/-12.2, respectively. Significant (P \u3c 0.05) negative impact on PCS scores in multivariable analyses was noted owing to constant mild-moderate pain with episodes of severe pain or constant severe pain (10 points), constant mild-moderate pain (5.2), pain-related disability/unemployment (5.1), current smoking (2.9 points), and medical co-morbidities. Significant (P \u3c 0.05) negative impact on MCS scores was related to constant pain irrespective of severity (6.8-6.9 points), current smoking (3.9 points), and pain-related disability/unemployment (2.4 points). In women, disability/unemployment resulted in an additional 3.7 point reduction in MCS score. Final multivariable models explained 27% and 18% of the variance in PCS and MCS scores, respectively. Etiology, disease duration, pancreatic morphology, diabetes, exocrine insufficiency, and prior endotherapy/pancreatic surgery had no significant independent effect on QOL. CONCLUSIONS: Constant pain, pain-related disability/unemployment, current smoking, and concurrent co-morbidities significantly affect the QOL in CP. Further research is needed to identify factors impacting QOL not explained by our analyses

Mechanisms of CFTR Functional Variants That Impair Regulated Bicarbonate Permeation and Increase Risk for Pancreatitis but Not for Cystic Fibrosis

CFTR is a dynamically regulated anion channel. Intracellular WNK1-SPAK activation causes CFTR to change permeability and conductance characteristics from a chloride-preferring to bicarbonate-preferring channel through unknown mechanisms. Two severe CFTR mutations (CFTRsev) cause complete loss of CFTR function and result in cystic fibrosis (CF), a severe genetic disorder affecting sweat glands, nasal sinuses, lungs, pancreas, liver, intestines, and male reproductive system. We hypothesize that those CFTR mutations that disrupt the WNK1-SPAK activation mechanisms cause a selective, bicarbonate defect in channel function (CFTRBD) affecting organs that utilize CFTR for bicarbonate secretion (e.g. the pancreas, nasal sinus, vas deferens) but do not cause typical CF. To understand the structural and functional requirements of the CFTR bicarbonate-preferring channel, we (a) screened 984 well-phenotyped pancreatitis cases for candidate CFTRBD mutations from among 81 previously described CFTR variants; (b) conducted electrophysiology studies on clones of variants found in pancreatitis but not CF; (c) computationally constructed a new, complete structural model of CFTR for molecular dynamics simulation of wild-type and mutant variants; and (d) tested the newly defined CFTRBD variants for disease in non-pancreas organs utilizing CFTR for bicarbonate secretion. Nine variants (CFTR R74Q, R75Q, R117H, R170H, L967S, L997F, D1152H, S1235R, and D1270N) not associated with typical CF were associated with pancreatitis (OR 1.5, p = 0.002). Clones expressed in HEK 293T cells had normal chloride but not bicarbonate permeability and conductance with WNK1-SPAK activation. Molecular dynamics simulations suggest physical restriction of the CFTR channel and altered dynamic channel regulation. Comparing pancreatitis patients and controls, CFTRBD increased risk for rhinosinusitis (OR 2.3, p<0.005) and male infertility (OR 395, p<<0.0001). WNK1-SPAK pathway-activated increases in CFTR bicarbonate permeability are altered by CFTRBD variants through multiple mechanisms. CFTRBD variants are associated with clinically significant disorders of the pancreas, sinuses, and male reproductive system.Fil: LaRusch, Jessica. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Jung, Jinsei. Yonsei University College of Medicine; Corea del SurFil: General, Ignacio. University of Pittsburgh; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lewis, Michele D.. Mayo Clinic. Division of Gastroenterology and Hepatology; Estados UnidosFil: Park, Hyun Woo. Yonsei University College of Medicine; Corea del SurFil: Brand, Randall E.. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Gelrud, Andres. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Anderson, Michelle A.. University of Michigan; Estados UnidosFil: Banks, Peter A.. Brigham and Women’s Hospital. Division of Gastroenterology; Estados UnidosFil: Conwell, Darwin. Brigham and Women’s Hospital. Division of Gastroenterology; Estados UnidosFil: Lawrence, Christopher. Medical University of South Carolina; Estados UnidosFil: Romagnuolo, Joseph. Medical University of South Carolina; Estados UnidosFil: Baillie, John. University of Duke; Estados UnidosFil: Alkaade, Samer. St. Louis University. School of Medicine; Estados UnidosFil: Cote, Gregory. Indiana University; Estados UnidosFil: Gardner, Timothy B.. Dartmouth-Hitchcock Medical Center; Estados UnidosFil: Amann, Stephen T.. North Mississippi Medical Center; Estados UnidosFil: Slivka, Adam. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Sandhu, Bimaljit. Virginia Commonwealth University Medical Center; Estados UnidosFil: Aloe, Amy. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Kienholz, Michelle L.. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Yadav, Dhiraj. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Barmada, M. Michael. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Bahar, Ivet. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Lee, Min Goo. Yonsei University College of Medicine; Corea del SurFil: Whitcomb, David C.. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: North American Pancreatitis Study Group. No especifica

The University of Akron Human Powered Vehicle Team

The University of Akron Human Powered Vehicle Team’s 2016 vehicle, Klokan, was designed, manufactured and tested with safety, reliability, performance and ease of use in mind. The vehicle is a fully faired tadpole trike with a lightweight aluminum frame constructed from 6061-T6 tubing having a total weight of 8.9 lbs. To complement the lightweight frame, the fairing is constructed from polycarbonate, PETG and carbon fiber strips which combine into a lightweight, easy to manufacture weather barrier and aerodynamic structure. Klokan was designed to be a safe and efficient mode of everyday transportation which ensures that riders are sufficiently protected by a rollover protection system (RPS) which was designed to meet the ASME HPVC requirements with a minimum safety factor of two. The project scope includes all aspects of design and fabrication to create a vehicle that is easy to manufacture, easy to use, safe, and low cost to facilitate its usability in everyday situations. The team completed research on how to improve the manufacturability, reliability, and performance through analysis of designs, computer based modeling, and physical testing to validate that the bike meets team goals as well as exceeding the requirements set by the ASME Human Powered Vehicle Competition. The frame was designed in a manner that reduces welding through the use of bends and allows for precision fixturing to be manufactured and used to construct multiple frames quickly and efficiently. The fairing’s modular construction reduces the need for specialized tooling while minimizing weight and construction time. The team designed and successfully implemented an innovative rollover warning system which actively monitors the percentage of vehicle load on each tire and warns the driver through audible tone and visual warning light prior to a dangerous rollover becoming imminent

Use and perceived effectiveness of non-analgesic medical therapies for chronic pancreatitis in the United States

Aliment Pharmacol Ther 2011; 33: 149–159Effectiveness of medical therapies in chronic pancreatitis has been described in small studies of selected patients.To describe frequency and perceived effectiveness of non-analgesic medical therapies in chronic pancreatitis patients evaluated at US referral centres.Using data on 516 chronic pancreatitis patients enrolled prospectively in the NAPS2 Study, we evaluated how often medical therapies [pancreatic enzyme replacement therapy (PERT), vitamins/antioxidants (AO), octreotide, coeliac plexus block (CPB)] were utilized and considered useful by physicians.Oral PERT was commonly used (70%), more frequently in the presence of exocrine insufficiency (EI) (88% vs. 61%, P  < 0.001) and pain (74% vs. 59%, P  < 0.002). On multivariable analyses, predictors of PERT usage were EI (OR 5.14, 95% CI 2.87–9.18), constant (OR 3.42, 95% CI 1.93–6.04) or intermittent pain (OR 1.98, 95% CI 1.14–3.45). Efficacy of PERT was predicted only by EI (OR 2.16, 95% CI 1.36–3.42). AO were tried less often (14%) and were more effective in idiopathic and obstructive vs. alcoholic chronic pancreatitis (25% vs. 4%, P  = 0.03). Other therapies were infrequently used (CPB – 5%, octreotide – 7%) with efficacy generally <50%.Pancreatic enzyme replacement therapy is commonly utilized, but is considered useful in only subsets of chronic pancreatitis patients. Other medical therapies are used infrequently and have limited efficacy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79114/1/j.1365-2036.2010.04491.x.pd

Effect of Covered Metallic Stents Compared With Plastic Stents on Benign Biliary Stricture Resolution A Randomized Clinical Trial

Importance Endoscopic placement of multiple plastic stents in parallel is the first-line treatment for most benign biliary strictures; it is possible that fully covered, self-expandable metallic stents (cSEMS) may require fewer endoscopic retrograde cholangiopancreatography procedures (ERCPs) to achieve resolution. Objective To assess whether use of cSEMS is noninferior to plastic stents with respect to stricture resolution. Design, Setting, and Participants Multicenter (8 endoscopic referral centers), open-label, parallel, randomized clinical trial involving patients with treatment-naive, benign biliary strictures (N = 112) due to orthotopic liver transplant (n = 73), chronic pancreatitis (n = 35), or postoperative injury (n = 4), who were enrolled between April 2011 and September 2014 (with follow-up ending October 2015). Patients with a bile duct diameter less than 6 mm and those with an intact gallbladder in whom the cystic duct would be overlapped by a cSEMS were excluded. Interventions Patients (N = 112) were randomized to receive multiple plastic stents or a single cSEMS, stratified by stricture etiology and with endoscopic reassessment for resolution every 3 months (plastic stents) or every 6 months (cSEMS). Patients were followed up for 12 months after stricture resolution to assess for recurrence. Main Outcomes and Measures Primary outcome was stricture resolution after no more than 12 months of endoscopic therapy. The sample size was estimated based on the noninferiority of cSEMS to plastic stents, with a noninferiority margin of −15%. Results There were 55 patients in the plastic stent group (mean [SD] age, 57 [11] years; 17 women [31%]) and 57 patients in the cSEMS group (mean [SD] age, 55 [10] years; 19 women [33%]). Compared with plastic stents (41/48, 85.4%), the cSEMS resolution rate was 50 of 54 patients (92.6%), with a rate difference of 7.2% (1-sided 95% CI, −3.0% to ∞; P < .001). Given the prespecified noninferiority margin of −15%, the null hypothesis that cSEMS is less effective than plastic stents was rejected. The mean number of ERCPs to achieve resolution was lower for cSEMS (2.14) vs plastic (3.24; mean difference, 1.10; 95% CI, 0.74 to 1.46; P < .001). Conclusions and Relevance Among patients with benign biliary strictures and a bile duct diameter 6 mm or more in whom the covered metallic stent would not overlap the cystic duct, cSEMS were not inferior to multiple plastic stents after 12 months in achieving stricture resolution. Metallic stents should be considered an appropriate option in patients such as these

Mechanisms of CFTR Functional Variants That Impair Regulated Bicarbonate Permeation and Increase Risk for Pancreatitis but Not for Cystic Fibrosis

CFTR is a dynamically regulated anion channel. Intracellular WNK1-SPAK activation causes CFTR to change permeability and conductance characteristics from a chloride-preferring to bicarbonate-preferring channel through unknown mechanisms. Two severe CFTR mutations (CFTRsev) cause complete loss of CFTR function and result in cystic fibrosis (CF), a severe genetic disorder affecting sweat glands, nasal sinuses, lungs, pancreas, liver, intestines, and male reproductive system. We hypothesize that those CFTR mutations that disrupt the WNK1-SPAK activation mechanisms cause a selective, bicarbonate defect in channel function (CFTRBD) affecting organs that utilize CFTR for bicarbonate secretion (e.g. the pancreas, nasal sinus, vas deferens) but do not cause typical CF. To understand the structural and functional requirements of the CFTR bicarbonate-preferring channel, we (a) screened 984 well-phenotyped pancreatitis cases for candidate CFTRBD mutations from among 81 previously described CFTR variants; (b) conducted electrophysiology studies on clones of variants found in pancreatitis but not CF; (c) computationally constructed a new, complete structural model of CFTR for molecular dynamics simulation of wild-type and mutant variants; and (d) tested the newly defined CFTRBD variants for disease in non-pancreas organs utilizing CFTR for bicarbonate secretion. Nine variants (CFTR R74Q, R75Q, R117H, R170H, L967S, L997F, D1152H, S1235R, and D1270N) not associated with typical CF were associated with pancreatitis (OR 1.5, p = 0.002). Clones expressed in HEK 293T cells had normal chloride but not bicarbonate permeability and conductance with WNK1-SPAK activation. Molecular dynamics simulations suggest physical restriction of the CFTR channel and altered dynamic channel regulation. Comparing pancreatitis patients and controls, CFTRBD increased risk for rhinosinusitis (OR 2.3, p<0.005) and male infertility (OR 395, p≪0.0001). WNK1-SPAK pathway-activated increases in CFTR bicarbonate permeability are altered by CFTRBD variants through multiple mechanisms. CFTRBD variants are associated with clinically significant disorders of the pancreas, sinuses, and male reproductive system. © 2014 Whitcomb et al