Embryonal Control of Yellow Seed Coat Locus ECY1 Is Related to Alanine and Phenylalanine Metabolism in the Seed Embryo of Brassica napus

Seed coat colour is determined by the type of pigment deposited in the seed coat cells. It is related to important agronomic traits of seeds such as seed dormancy, longevity, oil content, protein content and fibre content. In Brassica napus inheritance of seed coat colour is related to maternal effects and pollen effects (xenia effects). In this research we isolated a mutation of yellow seeded B. napus controlled by a single Mendelian locus, which is named Embryonal Control of Yellow seed coat 1 (Ecy1). Microscopy of transverse sections of the mature seed show pigment is deposited only in the outer layer of seed coat. By Illumina Hiseq 2000 sequencing technology, a total of 12 G clean data, 116x coverage of coding sequences of B. napus, was achieved from seeds 26 days after pollination. It was assembled into 172,238 independent transcripts and 55,637 unigenes. A total of 139 orthologous genes of Arabidopsis transparent testa (TT) genes were mapped in silico to 19 chromosomes of B. napus. Only 49 of the TT orthologous genes are transcribed in seeds. However transcription of all the orthologs was independent of the embryonal control of seed coat colour. Only 55 genes were found to be differentially expressed between the brown seeds and yellow mutant. Among them 50 were up-regulated and 5 were down-regulated in the yellow seeds as compared to their brown counterparts. By KEGG classification, 14 metabolic pathways were significantly enriched. Of these, 5 pathways: phenylpropanoid biosynthesis, cyanoamino acid metabolism, plant hormone signal transduction, metabolic pathways and biosynthesis of secondary metabolites were related with seed coat pigmentation. Free amino acid quantification showed that Ala and Phe were present at higher levels in the embryo of yellow seeds as compared to brown seeds. This increase was not observed in the seed coat. Moreover, the excess amount of free Ala was exactly twice that of Phe in the embryo. The pigment substrate chalcone, is synthesized from two molecules of Ala and one molecule of Phe. The correlation between accumulation of Ala and Phe and disappearance of pigment in the yellow seeded mutant suggests that embryonal control of seed coat colour is related with Phe and Ala metabolism in the embryo of B. napus.

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Neurofibromin Loss of Function Drives Excessive Grooming in Drosophila

Neurofibromatosis I is a common genetic disorder that results in tumor formation and predisposes individuals to a range of cognitive/behavioral symptoms, including deficits in attention, visuospatial skills, learning, language development, sleep, and autism spectrum disorder-like traits. The nf1-encoded neurofibromin protein (Nf1) exhibits high conservation, from the common fruit fly, Drosophila melanogaster, to humans. Drosophila provide a powerful platform to investigate the signaling cascades upstream and downstream of Nf1, and the fly model exhibits similar behavioral phenotypes to mammalian models. In order to understand how loss of Nf1 affects motor behavior in flies, we combined traditional activity monitoring with video analysis of grooming behavior. In nf1 mutants, spontaneous grooming was increased up to 7x. This increase in activity was distinct from previously-described dopamine-dependent hyperactivity, as dopamine transporter mutants exhibited slightly decreased grooming. Finally, we found that relative grooming frequencies can be compared in standard activity monitors that measure infrared beam breaks, enabling the use of activity monitors as an automated method to screen for grooming phenotypes. Overall, these data suggest that loss of nf1 produces excessive activity that is manifested as increased grooming, providing a platform to dissect the molecular genetics of neurofibromin signaling across neuronal circuits.

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Myokine Expression in Muscle and Myotubes in Response to Exercise Stimulation

Purpose: Myokines have been shown to affect muscle physiology and exert systemic effects. We endeavored to investigate a panel of myokine mRNA expression after a single exercise bout (studies 1 and 2) to measure myokine mRNA in primary human myotubes in an in vitro exercise model (study 2). Methods: Vastus lateralis muscle biopsies were obtained from 20 healthy males (age, 24.0 ± 4.5 yr; BMI, 23.6 ± 1.8 kg·m−2) before and after a single exercise bout (650 kcal at 50% V˙O2max). Primary myotubes from active and sedentary male donors were treated with a pharmacological cocktail (palmitate, forskolin, and ionomycin (PFI)) to mimic exercise-stimulated contractions in vitro. Results: Interleukin 6 and 8 (IL-6 and IL-8), leukocyte-inducing factor, and connective tissue growth factor (CTGF) mRNA levels increased approximately 10-fold after a single exercise bout (all P

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Tear Fluid SIgA as a Noninvasive Biomarker of Mucosal Immunity and Common Cold Risk

Purpose: Research has not convincingly demonstrated the utility of saliva secretory immunoglobulin-A (SIgA) as a biomarker of upper respiratory tract infection (URTI) risk, and disagreement exists about the influence of heavy exercise ("open-window theory") and dehydration on saliva SIgA. Prompted by the search for viable alternatives, we compared the utility of tear and saliva SIgA to predict URTI prospectively (study 1) and assessed the influence of exercise (study 2) and dehydration (study 3) using a repeated-measures crossover design. Methods: In study 1, 40 subjects were recruited during the common-cold season. Subjects provided tear and saliva samples weekly and recorded upper respiratory symptoms (URS) daily for 3 wk. Real-time PCR confirmed common-cold pathogens in 9 of 11 subjects reporting URS (82%). Predictive utility of tear and saliva SIgA was explored by comparing healthy samples with those collected during the week before URS. In study 2, 13 subjects performed a 2-h run at 65% V˙O2peak. In study 3, 13 subjects performed exercise heat stress to 3% body mass loss followed by overnight fluid restriction. Results: Tear SIgA concentration and secretion rate were 48% and 51% lower, respectively, during URTI and 34% and 46% lower the week before URS (P 30%. Tear SIgA secretion rate >5.5 μg·min−1 or no decrease of >30% predicted subjects free of URS in >80% of cases. Tear SIgA concentration decreased after exercise (−57%, P

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Peripheral and Central Fatigue Development during All-Out Repeated Cycling Sprints

Purpose: We investigated the development and recovery of peripheral and central fatigue during repeated cycling sprints and its influence on power output. Methods: On six separate days, 12 healthy males performed the following tests: 1, 4, 6, 8, and 10 × 10 s sprints with 30 s of passive recovery between sprints, as well as 8 × 10 s sprints with 10 s of passive recovery. Peripheral and central fatigue levels were quantified via changes in preexercise- to postexercise-potentiated quadriceps twitch force, as evoked by supramaximal electrical stimulation of the femoral nerve (30 s through 6 min recovery), and quadriceps voluntary activation (VA), respectively. Root mean square of the vastus lateralis and the vastus medialis electromyogram during sprints were normalized by maximal M wave amplitude (RMS·Mmax−1). Results: From the first to the sixth sprint, we found significant and gradual reductions in power output (−25% ± 7%), RMS·Mmax−1 (−7% ± 4%), twitch force (−47% ± 11%) and VA (−11% ± 6%). During the subsequent sprints, no additional reduction in power output, RMS·Mmax−1, twitch force or VA, was found. Reduction in between-sprints recovery duration led to a significant reduction in power output and RMS·Mmax−1 but no change in peripheral and central fatigue. Conclusion: These findings are consistent with the hypothesis that central motor command and power output during all-out repeated sprints are limited in order to prevent excessive locomotor muscle fatigue. They also demonstrate that both the peripheral and central fatigue contribute significantly to the decline in power output elicited via repeated sprints.

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Biceps Femoris Architecture and Strength in Athletes with a Previous Anterior Cruciate Ligament Reconstruction

Purpose: This study aimed to determine whether limbs with a history of anterior cruciate ligament (ACL) injury reconstructed from the semitendinosus display different biceps femoris long head (BFlh) architecture and eccentric strength, assessed during the Nordic hamstring exercise, compared with the contralateral uninjured limb. Methods: The architectural characteristics of the BFlh were assessed at rest and at 25% of a maximal voluntary isometric contraction (MVIC) in the control group (n = 52) and in the group who had previous ACL injury (n = 15) using two-dimensional ultrasonography. Eccentric knee flexor strength was assessed during the Nordic hamstring exercise. Results: Fascicle length was shorter (P = 0.001; d range, 0.90–1.31) and pennation angle (P range, 0.001–0.006; d range, 0.87–0.93) was greater in the BFlh of the ACL-injured limb compared with those in the contralateral uninjured limb at rest and during a 25% MVIC. Eccentric strength was lower in the ACL-injured limb when compared with the contralateral uninjured limb. Fascicle length, MVIC, and eccentric strength were not different between the left and right limb in the control group. Conclusions: Limbs with a history of ACL injury reconstructed from the semitendinosus have shorter fascicles and greater pennation angles in the BFlh compared with those of the contralateral uninjured side. Eccentric strength during the Nordic hamstring exercise of the ACL-injured limb is significantly lower than that of the contralateral side. These findings have implications for ACL rehabilitation and hamstring injury prevention practices, which should consider altered architectural characteristics.

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High-Intensity Running and Energy Restriction Reduce Postprandial Lipemia in Girls

Purpose: This study examined the potency of combining acute high-intensity exercise and energy intake restriction on postprandial triacylglycerol concentrations ([TAG]) in healthy girls. Methods: Sixteen 11- to 13-yr-old girls (mean (SD) body mass, 45.1 (7.6) kg; peak oxygen uptake (V˙O2), 43 (6) mL·kg−1·min−1) completed three 2-d conditions in a counterbalanced crossover design separated by 14 d. On day 1, participants completed 10 × 1-min interval runs (HIIR) or 5 × 1-min interval runs combined with 0.82 (0.19) MJ energy intake restriction (HIIR-ER) or rested (CON). Exercise was completed at 100% maximal aerobic speed determined from an incremental peak V˙O2 test, with 1-min recovery between intervals. On day 2, capillary blood samples were taken in the fasted state and at predetermined intervals throughout the 6.5-h postprandial period. A standardized breakfast and lunch were consumed immediately and 4 h after the fasting sample, respectively. Results: Based on ratios of the geometric means (95% confidence intervals (CI) for ratios), fasting [TAG] was 16% and 8% lower than CON in HIIR (−24% to −7%; effect size (ES), 0.49; P = 0.002) and HIIR-ER (−17% to 1%; ES, 0.24; P = 0.09), respectively; HIIR was 8% lower than HIIR-ER (−17% to 1%; ES, 0.25; P = 0.08). The total area under the [TAG] versus time curve was 10% and 9% lower than CON in HIIR (−16% to −3%; ES, 0.30; P = 0.01) and HIIR-ER (−15% to −2%; ES, 0.28; P = 0.01), respectively; HIIR-ER and HIIR were similar (−1%; −8% to 6%; P = 0.80). Conclusions: Manipulations of HIIR and ER reduce postprandial [TAG] in girls. The magnitude of effect was marginally, although not meaningfully, greater after HIIR than that after HIIR-ER.

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Muscle Characteristics and Substrate Energetics in Lifelong Endurance Athletes

Purpose: The goal of this study was to explore the effect of lifelong aerobic exercise (i.e., chronic training) on skeletal muscle substrate stores (intramyocellular triglyceride [IMTG] and glycogen), skeletal muscle phenotypes, and oxidative capacity (ox), in older endurance-trained master athletes (OA) compared with noncompetitive recreational younger (YA) athletes matched by frequency and mode of training. Methods: Thirteen OA (64.8 ± 4.9 yr) exercising 5 times per week or more were compared with 14 YA (27.8 ± 4.9 yr) males and females. IMTG, glycogen, fiber types, succinate dehydrogenase, and capillarization were measured by immunohistochemistry in vastus lateralis biopsies. Fat-ox and carbohydrate (CHO)-ox were measured by indirect calorimetry before and after an insulin clamp and during a cycle ergometer graded maximal test. Results: V˙O2peak was lower in OA than YA. The OA had greater IMTG in all fiber types and lower glycogen stores than YA. This was reflected in greater proportion of type I and less type II fibers in OA. Type I fibers were similar in size, whereas type II fibers were smaller in OA compared with YA. Both groups had similar succinate dehydrogenase content. Numbers of capillaries per fiber were reduced in OA but with a higher number of capillaries per area. Metabolic flexibility and insulin sensitivity were similar in both groups. Exercise metabolic efficiency was higher in OA. At moderate exercise intensities, carbohydrate-ox was lower in OA but with similar Fat-ox. Conclusions: Lifelong exercise is associated with higher IMTG content in all muscle fibers and higher metabolic efficiency during exercise that are not explained by differences in muscle fibers types and other muscle characteristics when comparing older with younger athletes matched by exercise mode and frequency.

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Appetite and Energy Intake Responses to Acute Energy Deficits in Females versus Males

Purpose: To explore whether compensatory responses to acute energy deficits induced by exercise or diet differ by sex. Methods: In experiment one, 12 healthy women completed three 9-h trials (control, exercise-induced (Ex-Def) and food restriction–induced energy deficit (Food-Def)) with identical energy deficits being imposed in the Ex-Def (90-min run, ∼70% of V˙O2max) and Food-Def trials. In experiment two, 10 men and 10 women completed two 7-h trials (control and exercise). Sixty minutes of running (∼70% of V˙O2max) was performed at the beginning of the exercise trial. The participants rested throughout the remainder of the exercise trial and during the control trial. Appetite ratings, plasma concentrations of gut hormones, and ad libitum energy intake were assessed during main trials. Results: In experiment one, an energy deficit of approximately 3500 kJ induced via food restriction increased appetite and food intake. These changes corresponded with heightened concentrations of plasma acylated ghrelin and lower peptide YY3–36. None of these compensatory responses were apparent when an equivalent energy deficit was induced by exercise. In experiment two, appetite ratings and plasma acylated ghrelin concentrations were lower in exercise than in control, but energy intake did not differ between trials. The appetite, acylated ghrelin, and energy intake response to exercise did not differ between men and women. Conclusions: Women exhibit compensatory appetite, gut hormone, and food intake responses to acute energy restriction but not in response to an acute bout of exercise. Additionally, men and women seem to exhibit similar acylated ghrelin and PYY3–36 responses to exercise-induced energy deficits. These findings advance understanding regarding the interaction between exercise and energy homeostasis in women.

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Randomised clinical trial: Prucalopride, a colonic pro-motility agent, reduces the duration of post-operative ileus after elective gastrointestinal surgery

Alimentary Pharmacology and Therapeutics

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Incidence and risk factors for adverse events related to image-guided liver biopsy

Mayo Clinic Proceedings

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Distribution and characteristics of colonic diverticula in a United States screening population

Clinical Gastroenterology and Hepatology

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Apoptosis induced by cisplatin but not by 5-FU in colon cancer cells depends on Omi/Htra2 protein

BMC Cancer

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Can HCV direct-acting antiviral treatment as prevention reverse the HCV epidemic amongst men who have sex with men in the UK - epidemiological and modelling insights

Clinical Infectious Diseases

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Single-incision laparoscopic surgery (SILS) for children with Crohn's disease

Pediatric Surgery International

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Immunobiological effects of gemcitabine and capecitabine combination chemotherapy in advanced pancreatic ductal adenocarcinoma

British Journal of Cancer

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Faecal occult blood tests show lower colorectal cancer detection rates in the proximal colon in colonoscopy-verified diagnostic studies

Alimentary Pharmacology and Therapeutics

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Molecular biomarkers in the personalized treatment of colorectal cancer

Clinical Gastroenterology and Hepatology

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Impact of obesity and diabetes on waitlist survival, probability of liver transplantation, and post-transplant survival among chronic HCV patients

Liver International

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Knowledge and uptake of genetic counseling and colonoscopic screening among individuals at increased risk for Lynch syndrome and their endoscopists from the family health promotion project

The American Journal of Gastroenterology

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Viral hepatitis B and C outbreak related to parenteral treatment at an oncological department in Slovakia

Journal of Hospital Infection

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A phase I study of folfirinox plus IPI-926, a Hedgehog pathway inhibitor, for advanced pancreatic adenocarcinoma

Pancreas

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Parenteral Nutrition of Preterm Infants May Lead to Inadequate Phosphorus Supply.

No abstract available

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Golimumab Therapy in Six Patients with Severe Pediatric Onset Crohn's Disease.

Anti-TNF[alpha] blockade is so far the most effective therapy for extensive pediatric Crohn[Combining Acute Accent]s disease (CD), but loss of response is frequently encountered. We describe here the use of golimumab (Simponi) in six pediatric CD patients with antibody formation/loss of response to infliximab and adalimumab. Most patients had undergone surgery but had poor disease control. After introduction of golimumab, the levels of inflammatory markers and fecal calprotectin declined at first, but the response was not sustained. Each patient needed dose escalation of golimumab from 4 to 2 week intervals, in order to maintain response and to increase trough levels. Importantly, most patients were able to attend school when undergoing golimumab therapy. As with other anti-TNF[alpha] drugs, follow-up of drug levels is advisable. Although golimumab therapy failed in most patients, it is an alternate treatment option in pediatric patients with severe CD. The therapeutic response, however, is suboptimal in anti-TNF[alpha] exposed patients. (C) 2016 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Mucosal Healing of Pediatric Simple Ulcer Treated with Infliximab and Methotrexate.

No abstract available

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Hepatoblastoma in Explanted Livers of Patients with Biliary Atresia.

Objectives: Surveillance of hepatic nodules for malignant transformation to hepatocellular carcinoma is important in the monitoring of patients with Biliary Atresia (BA). To-date, only two published case reports describe the finding of Hepatoblastoma (HB) in this setting. This study aimed to investigate this association of HB and BA, and to assess the utility of alpha-fetoprotein (aFP) as a marker in the diagnosis. Methods: A retrospective study of all patients who underwent isolated liver transplantation (LTx) for the primary diagnosis of BA at a single center, between January 1999 and June 2014, was conducted. Patient demographics, pre-LTx aFP levels and histologic examination of native liver explants were reviewed. Results: 102 (44% male, median age 11 months) patients underwent LTx for BA. Two (2%) explants examinations were confirmatory for a co-diagnosis of HB; both patients had abnormally elevated aFP. Overall, 56 (55%) patients had available pre-LTx aFP levels. Recipients with persistently abnormal aFP levels (n = 20, 36%) were older at hepatoportoenterostomy (107d vs. 68d, P = 0.02) and younger at LTx surgery (359d vs. 1713d, P

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Quality of Reporting Nutritional Randomized Controlled Trials in Patients with Cystic Fibrosis.

Background: Randomized controlled trials (RCTs) have a major role in the making of evidence-based guidelines. We aimed to critically appraise the RCTs that addressed nutritional interventions in Cystic Fibrosis (CF) patients. Materials and Methods: Embase, PubMed and the Cochrane Library were systematically searched until July 2015. Methodology and reporting of nutritional RCTs were evaluated by the CONSORT checklist and additional dimensions relevant to CF patients. Results: 51 RCTs were included. Full details on methods were provided in a minority of studies. The mean duration of intervention was under 6 months. 56.9% of the RCTs did not define a primary outcome; 70.6% of studies did not provide details on sample size calculation; and only 31.4% reported on the subgroup or separated between important subgroups. Conclusions: The examined RCTs were characterized by a weak methodology, a small number of patients with no sample size calculations, a relatively short intervention, and many times did not examined outcomes that are important to the patient. Improvement over the years has been minor. (C) 2016 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Value of Gamma-Glutamyl Transpeptidase for Diagnosis of Biliary Atresia by Correlation with Age.

Objectives: Study the value of gamma-glutamyl transpeptidase (GGT) for distinguishing biliary atresia (BA) from non-BA for patients suspected of having neonatal obstructive jaundice (NOJ) by correlation with age. Methods: From January 2003 to March 2014, cholangiography and/or surgical exploration were undertaken in 1469 patients with suspicion of having NOJ. A total of 1338 patients were diagnosed with BA intraoperatively. Preoperative medical records were compared between BA and non-BA patients. Results: Preoperative levels of total bilirubin (TB), direct bilirubin (DB) and GGT were significantly higher in the BA group (p 121 days), BA groups had higher GGT levels (in IU/L) (i: 725.3+/-549.9; ii: 927.0+/-679.8; iii: 1114.3+/-823.1; iv: 767.5+/-666.7). The level of GGT in BA patients younger than 30 days was 834.2+/-475.3 IU/L. GGT levels had the highest diagnostic value (0.869) in group ii (61-90 days) and the lowest diagnosis value (0.712) in group iv (>121 days). At a cutoff of >303 IU/L in group ii (61-90 days), GGT had 82.8% sensitivity and 81.6% specificity for the discrimination of BA. Conclusions: GGT levels contribute to the diagnosis of BA before 120 days. Age must be considered if using GGT levels as a diagnostic test for BA. (C) 2016 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Local Drug Infiltration Analgesia During Knee Surgery to Reduce Postoperative Pain in Rats.

Background and Objectives: There is increasing interest in local infiltration analgesia (LIA) to reduce postoperative pain with knee surgery. Despite widespread use of LIA, wide variations in drug combinations, infiltration techniques, and the concomitant use of systemic analgesics have made it difficult to determine the optimal drug combination for LIA. Using a previously validated animal knee surgery model, we aimed to determine the optimal combination of medications to reduce postoperative pain, and the best anatomical location and timing for local drug injection during surgery. Methods: Knee surgery was performed in an adult rat model under isoflurane anesthesia. During surgery, combinations of bupivacaine, ketorolac, dexamethasone, and morphine were injected around the knee and compared to saline placebo. Similar medications were injected systemically as a comparator group. Postoperative pain was assessed by measuring spontaneous rearing activity. Injections were given after bone drilling and/or just before wound closure. Results: The 3-drug LIA combination of bupivacaine, ketorolac, and dexamethasone increased rearing (decreased pain) at 2 hours (P = 0.0198) and 24 hours (P = 0.0384) postsurgery compared to saline. The same drugs injected systemically had no effect. The ketorolac/dexamethasone combination for LIA was also effective at 2 hours (P = 0.0006) and 24 hours (P = 0.0279), and ketorolac alone reduced pain at 2 hours (P = 0.0045). Bupivacaine alone was less effective, and the addition of morphine had no effect. The 3-drug combination infiltrated just after creating holes in bone was more effective than when given into the wound just before wound closure. Conclusions: Our animal study suggests that clinical trials with LIA combinations of local anesthetic, nonsteroidal anti-inflammatory drug, and corticosteroid might be useful for reducing postoperative pain after knee surgery, with the nonsteroidal anti-inflammatory drug having the greatest effect. Perioperative physicians should consider delivering LIA earlier during the procedure as opposed to solely at the time of wound closure. Copyright (C) 2016 by American Society of Regional Anesthesia and Pain Medicine.

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