Impacts of increased ocean temperatures on a low-latitude coral reef fish - Processes related to oxygen uptake and delivery.

Increasing temperatures are expected to significantly affect the physiological performance of ectotherms, particularly in tropical locations. The shape of an organism's thermal reaction norm can provide important information on its capacity to persist under climate change scenarios; however, difficulty lies in choosing a measurable trait that best depicts physiological performance. This study investigated the effects of elevated temperatures on processes related to oxygen uptake and delivery, including oxygen consumption, haematology, and tissue health for a low-latitude population of coral reef damselfish. Acanthochromis polyacanthus were collected from the Torres Strait (10°31-46'S, 142°20-35'E) and maintained at current average ocean temperatures (+0 °C; seasonally cycling), + 1.5 °C and + 3 °C higher than present day temperatures for 10 months. Aerobic performance indicated a limit to metabolic function at + 3 °C (33 °C), following an increase in aerobic capacity at + 1.5 °C (31.5 °C). Neither haematological parameters nor gill morphology showed the same improvement in performance at + 1.5 °C. Gill histopathology provided the first indicator of a decline in organism health, which corresponded with mortality observations from previous research. Findings from this study suggest thermal specialisation in this low-latitude population as well as variation in thermal sensitivity, depending on the physiological trait.

Effects of probiotics on body weight, body mass index, fat mass and fat percentage in subjects with overweight or obesity: a systematic review and meta-analysis of randomized controlled trials.

A systematic review and meta-analysis of randomized controlled trials was conducted to examine the effects of probiotic supplementation on body weight, body mass index (BMI), fat mass and fat percentage in subjects with overweight (BMI 25-29.9 kg m-2 ) or obesity (BMI ≥30 kg m-2 ). MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched for studies published between 1946 and September 2016. A meta-analysis, using a random effects model, was performed to calculate the weighted mean difference between the intervention and control groups. Of 800 studies identified through the literature search, 15 were finally included. The studies comprised a total of 957 subjects (63% women), with the mean BMI being 27.6 kg m-2 and the duration of the interventions ranging from 3 to 12 weeks. Administration of probiotics resulted in a significantly larger reduction in body weight (weighted mean difference [95% confidence interval]; -0.60 [-1.19, -0.01] kg, I2  = 49%), BMI (-0.27 [-0.45, -0.08] kg m-2 , I2  = 57%) and fat percentage (-0.60 [-1.20, -0.01] %, I2  = 19%), compared with placebo; however, the effect sizes were small. The effect of probiotics on fat mass was non-significant (-0.42 [-1.08, 0.23] kg, I2  = 84%).

Treatment with methylnaltrexone is associated with increased survival in patients with advanced cancer.

BACKGROUND: Methylnaltrexone (MNTX), a peripherally acting µ-opioid receptor (MOR) antagonist, is FDA-approved for treatment of opioid-induced constipation (OIC). Preclinical data suggest that MOR activation can play a role in cancer progression and can be a target for anticancer therapy. PATIENTS AND METHODS: Pooled data from advanced end-stage cancer patients with OIC, despite laxatives, treated in two randomized (phase III and IV), placebo-controlled trials with MNTX were analyzed for overall survival (OS) in an unplanned post hoc analysis. MNTX or placebo was given subcutaneously during the double-blinded phase, which was followed by the open-label phase, allowing MNTX treatment irrespective of initial randomization. RESULTS: In two randomized, controlled trials, 229 cancer patients were randomized to MNTX (117, 51%) or placebo (112, 49%). Distribution of patients' characteristics and major tumor types did not significantly differ between arms. Treatment with MNTX compared with placebo [76 days, 95% confidence interval (CI) 43-109 versus 56 days, 95% CI 43-69; P = 0.033] and response (laxation) to treatment compared with no response (118 days, 95% CI 59-177 versus 55 days, 95% CI 40-70; P < 0.001) had a longer median OS, despite 56 (50%) of 112 patients ultimately crossing over from placebo to MNTX. Multivariable analysis demonstrated that response to therapy [hazard ratio (HR) 0.47, 95% CI 0.29-0.76; P = 0.002) and albumin ≥3.5 (HR 0.46, 95% CI 0.30-0.69; P < 0.001) were independent prognostic factors for increased OS. Of interest, there was no difference in OS between MNTX and placebo in 134 patients with advanced illness other than cancer treated in these randomized studies (P = 0.88). CONCLUSION: This unplanned post hoc analysis of two randomized trials demonstrates that treatment with MNTX and, even more so, response to MNTX are associated with increased OS, which supports the preclinical hypothesis that MOR can play a role in cancer progression. Targeting MOR with MNTX warrants further investigation in cancer therapy. CLINICAL TRIALS NUMBER: NCT00401362, NCT00672477.

Breath carbon stable isotope ratios identify changes in energy balance and substrate utilization in humans.

Rapid detection of shifts in substrate utilization and energy balance would provide a compelling biofeedback tool for individuals attempting weight loss. As a proof of concept, we tested whether the natural abundance of exhaled carbon stable isotope ratios (breath δ(13)C) reflects shifts between negative and positive energy balance. Volunteers (n=5) consumed a 40% energy-restricted diet for 6 days followed by 50% excess on day 7. Breath was sampled immediately before and 1 h and 2 h after breakfast, lunch and dinner. Exhaled breath δ(13)C values were measured by cavity ring-down spectroscopy. Using repeated measures analysis of variance (ANOVA) followed by Dunnett's contrasts, pre-breakfast breath values on days 2-6 were compared with day 1, and postprandial day 7 time points were compared with pre-breakfast day 7. Energy restriction diminished pre-breakfast breath δ(13)C by day 3 (P<0.05). On day 7, increased energy intake was first detected immediately before dinner (-23.8±0.6 vs -21.9±0.7‰, P=0.002 (means±s.d.)), and breath δ(13)C remained elevated at least 2 h post dinner. In conclusion, when shifting between negative and positive energy balance, breath δ(13)C showed anticipated isotopic changes. Although additional research is needed to determine specificity and repeatability, this method may provide a biomarker for marked increases in caloric intake.

Transformation by Hras(G12V) is consistently associated with mutant allele copy gains and is reversed by farnesyl transferase inhibition.

RAS-driven malignancies remain a major therapeutic challenge. The two-stage 7,12-dimethylbenz(a)anthracene (DMBA)/12-o-tetradecanoylphorbol-13-acetate (TPA) model of mouse skin carcinogenesis has been used to study mechanisms of epithelial tumor development by oncogenic Hras. We used mice with an Hras(G12V) knock-in allele to elucidate the early events after Hras activation, and to evaluate the therapeutic effectiveness of farnesyltransferase inhibition (FTI). Treatment of Caggs-Cre/FR-Hras(G12V) mice with TPA alone was sufficient to trigger papilloma development with a shorter latency and an ∼10-fold greater tumor burden than DMBA/TPA-treated WT-controls. Hras(G12V) allele copy number was increased in all papillomas induced by TPA. DMBA/TPA treatment of Hras(G12V) knock-in mice induced an even greater incidence of papillomas, which either harbored Hras(G12V) amplification or developed an Hras(Q61L) mutation in the second allele. Laser-capture microdissection of normal skin, hyperplastic skin and papillomas showed that amplification occurred only at the papilloma stage. HRAS-mutant allelic imbalance was also observed in human cancer cell lines, consistent with a requirement for augmented oncogenic HRAS signaling for tumor development. The FTI SCH66336 blocks HRAS farnesylation and delocalizes it from the plasma membrane. NRAS and KRAS are not affected as they are alternatively prenylated. When tested in lines harboring HRAS, NRAS or KRAS mutations, SCH66336 delocalized, inhibited signaling and preferentially inhibited growth only of HRAS-mutant lines. Treatment with SCH66336 also induced near-complete regression of papillomas of TPA-treated Hras(G12V) knock-in mice. These data suggest that farnesyl transferase inhibitors should be reevaluated as targeted agents for human HRAS-driven cancers, such as those of bladder, thyroid and other epithelial lineages.

Arterial stiffness, lifestyle intervention and a low-calorie diet in morbidly obese patients-a nonrandomized clinical trial.

OBJECTIVE: Arterial stiffness is an independent predictor of cardiovascular morbidity and mortality. This study aimed to compare the 7-week effect of a low-calorie diet (LCD) and an intensive lifestyle intervention program (ILI) on arterial stiffness in morbidly obese individuals. DESIGN AND METHODS: Nonrandomized clinical trial. The LCD provided 900 kcal/day, and participants in the LCD group were instructed to maintain their habitual physical activity level. The ILI included two 90-min supervised training sessions 3 days a week at moderate to high intensity (4-8 METs) and a caloric restriction of 1000 kcal/day. RESULTS: A total of 179 individuals completed the study, 88 (56 women) in the ILI group and 91 (57 women) in the LCD group. High-fidelity applanation tonometry (Millar(®) , Sphygmocor(®) ) was used to measure carotid-femoral pulse wave velocity (PWV). After adjustment for relevant confounders, the ILI group had a significantly greater reduction in PWV than the LCD group; -0.4 (-0.6, -0.1) m/s, P = 0.004. When compared to the LCD group, the ILI group showed a larger reduction in systolic and diastolic blood pressure -5 (-9, -1) and -5 (-7, -2) mmHg, P = 0.038 and P ≤ 0.001 respectively, whereas no difference was observed regarding pulse pressure, P = 0.661. No significant differences between groups were found regarding the loss of fat mass, P = 0.259, but the loss of muscle mass was larger in the LCD group, 0.8 (0.5, 1.1) kg, P ≤ 0.001. CONCLUSION: Despite the limitations of a nonrandomized design, our findings indicate that for morbidly obese individuals a moderate caloric restriction combined with aerobic physical exercise is associated with a greater decline in PWV than a LCD alone.

Effect of clothing weight on body weight.

BACKGROUND: In clinical settings, it is common to measure weight of clothed patients and estimate a correction for the weight of clothing, but we can find no papers in the medical literature regarding the variability in clothing weight of adults with weather, season and gender. METHODS: Fifty adults (35 women) were weighed four times during a 12-month period with and without clothing. Clothing weights were determined and regressed against minimum, maximum and average daily outdoor temperature. RESULTS: The average clothing weight (±s.d.) throughout the year was significantly greater in men than in women (1.2±0.3 vs 0.8±0.3 kg, P<0.0001). The average within-person minimum and the average within-person maximum clothing weights across the year were 0.9±0.2 and 1.5±0.4 kg for men, and 0.5±0.2 and 1.1±0.4 kg for women, respectively. The within-person s.d. in clothing weight was 0.3 kg for both men and women. Over the 55 °C range in the lowest to the highest outdoor temperatures, the regressions predicted a maximal change in clothing weight of only 0.4 kg in women and 0.6 kg in men. CONCLUSION: The clothing weight of men is significantly greater than that of women, but there is little variability throughout the year. Therefore, a clothing adjustment of approximately 0.8 kg for women and 1.2 kg for men is appropriate regardless of outdoor temperature.

Impact of gender on vitamin D deficiency in morbidly obese patients: a cross-sectional study.

BACKGROUND/OBJECTIVE: Obesity is associated with vitamin D deficiency (25-hydroxyvitamin D (25(OH)D) <50 nmol/l). We aimed to examine the effect of gender on vitamin D status in severe obesity. SUBJECTS/METHODS: Cross-sectional study of 2026 morbidly obese patients examined consecutively at a tertiary care centre between November 2005 and June 2010. Serum 25(OH)D concentration and use of vitamin D supplements were registered in all patients. Total vitamin D intake (µg/day) was assessed in a subgroup of 154 patients using a validated food frequency questionnaire. RESULTS: The male (n=690) and female (n=1336) patients had a mean (s.d.) age of 45.0 (12.1) years and 42.2 (12.2) years (P<0.001), body mass index (BMI) of 44.6 (6.0) kg/m(2) and 44.3 (5.9) kg/m(2) (P=0.30) and waist circumference (WC) of 140 (13) cm and 127 (13) cm (P<0.001), respectively. Male patients had significantly lower mean 25(OH)D concentrations than female patients 50.0 (22.0) nmol/l versus 53.6 (22.4) nmol/l (P=0.001) and a higher rate of vitamin D deficiency (56% versus 47%; P<0.001). Obese men had significantly higher odds of vitamin D deficiency than women (odds ratio=1.41; 95% confidence interval: 1.17-1.70, P<0.001), also after adjustment for season, age, current smoking, intake of vitamin D supplements, BMI and WC (odds ratio=1.39; 95% confidence interval: 1.10-1.76). CONCLUSIONS: Morbidly obese Norwegian men seeking weight loss treatment have significantly higher odds of vitamin D deficiency than women. Monitoring of 25(OH)D concentrations in obese patients should therefore take gender into account.

Increased vegetable and fruit consumption during weight loss effort correlates with increased weight and fat loss.

BACKGROUND: Individuals who focused on calorie counting lost more weight than those who focused on increasing vegetable and fruit (V&F) intake in a weight loss program. We now present serum carotenoid data (biomarkers of V&F intake) from both groups and test whether these biomarkers correlate with changes in weight and body fat. DESIGN: Sixty obese volunteers were randomized to one of the following weight loss programs: 500 kcal per day reduction (Reduction) or a focus on consuming eight vegetables per day and 2-3 fruits per day (HiVeg). Volunteers in the Reduction group were 36.8±10.3 years with a body mass index of 33.5; 83% were white, 17% chose not to report race; 70% were not Hispanic or Latino, 13% were Hispanic or Latino and 17% chose not to report ethnicity. Volunteers in the HiVeg group were 30.4±6.6 years with a body mass index of 33.2: 74% white, 11% Asian, 5% black or African American, 5% multiracial and 5% chose not to report race; 89% were not Hispanic or Latino, 5% were Hispanic or Latino and 5% chose not to report ethnicity. Subjects were taught basic nutrition principles, received breakfast and lunch 5 days per week for 3 months, meals 2 days per week during month 4, then regular phone calls to month 12. RESULTS: Total serum carotenoid concentrations increased from baseline to 3 months and remained elevated at 12 months, but there was no difference between groups. Changes in weight, fat and % fat correlated negatively with serum carotenoid concentrations. CONCLUSION: Increased serum carotenoids (a biomarker for V&F intake) correlated with improved weight and fat loss indicating that increased V&F consumption is an appropriate strategy for weight loss. However, in light of the fact that the Reduction group lost more weight, the consumption of increased V&F for the purpose of weight loss should happen within the context of reducing total caloric intake.

Obesity-related cardiovascular risk factors after weight loss: a clinical trial comparing gastric bypass surgery and intensive lifestyle intervention.

OBJECTIVE: Weight reduction improves several obesity-related health conditions. We aimed to compare the effect of bariatric surgery and comprehensive lifestyle intervention on type 2 diabetes and obesity-related cardiovascular risk factors. DESIGN: One-year controlled clinical trial (ClinicalTrials.gov identifier NCT00273104). METHODS: Morbidly obese subjects (19-66 years, mean (s.d.) body mass index 45.1 kg/m(2) (5.6), 103 women) were treated with either Roux-en-Y gastric bypass surgery (n=80) or intensive lifestyle intervention at a rehabilitation centre (n=66). The dropout rate within both groups was 5%. RESULTS: Among the 76 completers in the surgery group and the 63 completers in the lifestyle group, mean (s.d.) 1-year weight loss was 30% (8) and 8% (9) respectively. Beneficial effects on glucose metabolism, blood pressure, lipids and low-grade inflammation were observed in both groups. Remission rates of type 2 diabetes and hypertension were significantly higher in the surgery group than the lifestyle intervention group; 70 vs 33%, P=0.027, and 49 vs 23%, P=0.016. The improvements in glycaemic control and blood pressure were mediated by weight reduction. The surgery group experienced a significantly greater reduction in the prevalence of metabolic syndrome, albuminuria and electrocardiographic left ventricular hypertrophy than the lifestyle group. Gastrointestinal symptoms and symptomatic postprandial hypoglycaemia developed more frequently after gastric bypass surgery than after lifestyle intervention. There were no deaths. CONCLUSIONS: Type 2 diabetes and obesity-related cardiovascular risk factors were improved after both treatment strategies. However, the improvements were greatest in those patients treated with gastric bypass surgery.

Neuroendocrine carcinoma of the liver and gallbladder in a cow.

A 15-year-old Limousin-cross cow was presented for examination with neurological signs and serum biochemical changes consistent with liver disease. Necropsy revealed enlargement of the liver with multifocal firm, depressed, pale, circumscribed lesions throughout the parenchyma. Within the gallbladder there were exophytic and villiform mucosal masses. Microscopically, hepatic structure was displaced by neoplastic cells forming trabeculae, nests and rosettes. There was transmural infiltration of the gallbladder by similar cells. The histological pattern of growth of the neoplastic cells, the presence of silver-stained cytoplasmic granules within these cells and the immunohistochemical demonstration of chromogranin A supported the diagnosis of neuroendocrine carcinoma. Bovine liver and gallbladder neuroendocrine carcinomas are rare and this is the first detailed documentation of the disease in the United Kingdom.

Histological observations of bovine tuberculosis in lung and lymph node tissues from British deer.

Deer are recognized as hosts of Mycobacterium bovis and assessing the role of wild cervids in perpetuating tuberculosis among cattle has motivated extensive research on several continents. In this paper, the histopathology of lymph node and lung tuberculous granulomas in M. bovis positive British deer is presented. The overall aim was to seek further insights into the potential for onward transmission from infected deer to other species, including cattle. Samples were obtained from an extensive survey of wild mammals in South-West England and from statutory tuberculosis surveillance. M. bovis culture-positive samples were characterised microscopically as to their stage of lesion advancement, number of acid-fast bacilli and granuloma encapsulation. Seventy percent of the deer developed granulomas containing far greater numbers of M. bovis bacilli than typically reported in cattle. Red and fallow deer had the largest number of poorly encapsulated granulomas often containing many hundreds of bacilli. The results are consistent with infected wild British deer being a potential source of environmental contamination and onward transmission to other species. However, further work on levels of bacillary shedding is required before this can be confirmed.

Scanning optical pyrometer for measuring temperatures in hollow cathodes.

Life-limiting processes in hollow cathodes are determined largely by the temperature of the electron emitter. To support cathode life assessment, a noncontact temperature measurement technique which employs a stepper motor-driven fiber optic probe was developed. The probe is driven inside the hollow cathode and collects light radiated by the hot interior surface of the emitter. Ratio pyrometry is used to determine the axial temperature profile. Thermocouples on the orifice plate provide measurements of the external temperature during cathode operation and are used to calibrate the pyrometer system in situ with a small oven enclosing the externally heated cathode. The diagnostic method and initial measurements of the temperature distribution in a hollow cathode are discussed.

Metabolic influences of fiber size in aerobic and anaerobic locomotor muscles of the blue crab, Callinectes sapidus.

Diameters of some white locomotor muscle fibers in the adult blue crab, Callinectes sapidus, exceed 500 microm whereas juvenile white fibers are <100 microm. It was hypothesized that aerobically dependent processes, such as metabolic recovery following burst contractions, will be significantly impeded in the large white fibers. In addition, dark aerobic fibers of adults, which rely on aerobic metabolism for both contraction and recovery, grow as large as the white fibers. These large aerobic fibers are subdivided, however, thus decreasing the effective diameter of each metabolic functional unit and enabling aerobic contraction. The two goals of this study were: (1) to characterize the development of subdivisions in the dark levator muscle fibers and (2) to monitor post-contractile metabolism as a function of fiber size in aerobic and anaerobic levator muscles. Dark levator muscle fibers from crabs ranging from <0.1 g to >190 g were examined with transmission electron microscopy to determine the density of mitochondria and subdivision diameters. Across all size classes, there was a constant mitochondrial fractional area (25% of the total subdivision area) and subdivision size (mean diameter of 36.5+/-2.7 microm). Thus, blue crab dark levator fibers are unusual in having metabolic functional units (subdivisions) that do not increase in size during development while the contractile functional units (fibers) grow hypertrophically. The body mass scaling of post-contractile lactate dynamics was monitored during recovery from anaerobic, burst exercise in white and dark muscle, and in hemolymph. There were no differences among size classes in lactate accumulation during exercise in either muscle. However, in white fibers from large crabs, lactate continued to increase after exercise, and lactate removal from tissues required a much longer period of time relative to smaller crabs. Differences in lactate removal among size classes were less pronounced in dark fibers, and post-contractile lactate accumulation was significantly higher in white than in dark fibers from large animals. These data suggest that the large white fibers invoke anaerobic metabolism following contraction to accelerate certain phases of metabolic recovery that otherwise would be overly slow. This implies that, in addition to the typical mass-specific decrease in oxidative capacity that accompanies increases in animal mass, aerobic metabolic processes become increasingly limited by surface area to volume and intracellular diffusion constraints in developing white muscle fibers.

Granulomatous skin lesions in moray eels caused by a novel Mycobacterium species related to Mycobacterium triplex.

An outbreak of granulomatous dermatitis was investigated in a captive population of moray eels. The affected eels had florid skin nodules concentrated around the head and trunk. Histopathological examination revealed extensive granulomatous inflammation within the dermis and subcutaneous fascial plane between the fat and axial musculature. Acid-fast rods were detected within the smallest lesions, which were presumably the ones that had developed earliest. Eventually, after several months of incubation at room temperature, a very slowly growing acid-fast organism was isolated. Sequencing of the 16S rRNA gene identified it as a Mycobacterium species closely related (0.59% divergence) to M. triplex, an SAV mycobacterium. Intradermal inoculation of healthy green moray eels with this organism reliably reproduced the lesion. Experimentally induced granulomatous dermatitis appeared within 2 weeks of inoculation and slowly but progressively expanded during the 2 months of the experiment. Live organisms were recovered from these lesions at all time points, fulfilling Koch's postulates for this bacterium. In a retrospective study of tissues collected between 1993 and 1999 from five spontaneous disease cases, acid-fast rods were consistently found within lesions, and a nested PCR for the rRNA gene also demonstrated the presence of mycobacteria within affected tissues.

[Diet and secondary prevention of coronary heart disease--are our recommendations good enough?]. / Kosthold og sekundaerforebygging av koronar hjertesykdom--er våre anbefalinger gode nok?

BACKGROUND: Dietary treatment plays an important role in prevention of coronary heart disease. In Norway as in other European countries, patients with established coronary heart disease are advised to follow a cholesterol-lowering diet. However, epidemiological observations have suggested that Mediterranean and other diets may have cardioprotective characteristics beyond their effects on serum total and LDL cholesterol levels. MATERIAL AND METHODS: We describe the results of randomised, controlled clinical trials that have investigated the effect of diet on secondary prevention of coronary heart disease. RESULTS: Diets characterised by high contents of oleic acid (18: 1n-9), alpha-linolenic acid (18: 3n-3) and fish or fish oil and near-vegetarian diets have reduced cardiovascular morbidity and mortality in patients with coronary heart disease. INTERPRETATION: Several characteristics of the Mediterranean diet seem to have additional anti-atherothrombogenic effects beyond those observed with the usually recommended cholesterol-lowering diet. We ask whether Norwegian dietary recommendations for secondary prevention, should emphasise more strongly the type of fat used and fruit and vegetable intake, in line with the principles of the Mediterranean diet. Such dietary advice should be incorporated into the medical treatment given to all patients with coronary heart disease, regardless of their lipid profile.

Oocyte donor screening: the selection process and cost analysis.

OBJECTIVE: To evaluate the selection process and cost of screening oocyte donors. DESIGN: Retrospective analysis. SETTING: University-based IVF program. PATIENT(S): Potential oocyte donors. INTERVENTION(S): Outcomes of all inquiries by individuals responding to recruitment advertisements for oocyte donors over a 10-month period were assessed. Recruitment and screening costs to bring a single donor into the program were calculated. MAIN OUTCOME MEASURE(S): The attrition rate for each step of the oocyte donor screening process was determined. The costs assessed over the study period included the following: advertisement, administrative, professional, ultrasound, and blood screening. The total cost to bring a single donor into the program was calculated. RESULT(S): Advertisements led to 315 phone inquiries from potential oocyte donors. Of these, a total of 223 (71%) voluntarily withdrew from the screening process, 54 (17%) were screened out for medical or psychological reasons, and 38 (12%) entered the active donor pool. The total cost to bring a single donor into the program was approximately 1,869 dollars. CONCLUSION(S): There was significant attrition in the screening process for oocyte donation that needs to be taken into account in determining the costs of managing the program.