Gut microbial differences in breast and prostate cancer cases from two randomised controlled trials compared to matched cancer-free controls.

Implicated in several chronic diseases, the gastrointestinal microbiome is hypothesised to influence carcinogenesis. We compared faecal microbiota of newly diagnosed treatment-naïve overweight and obese cancer patients and matched controls. Cases were enrolled in presurgical weight-loss trials for breast (NCT02224807) and prostate (NCT01886677) cancers and had a body mass index (BMI) ≥25 kg/m2. Cancer-free controls were matched 1:1 by age (±5 years), race, gender, and BMI (±5 kg/m2). All participants provided faecal samples; isolated bacterial DNA were PCR amplified at the V4 region of the 16S rRNA gene and analysed using the QIIME pipeline. Tests compared cases versus controls, then separately by gender. Microbial alpha-diversity and beta-diversity were assessed, and relative abundance of Operational Taxonomic Units (OTU's) were compared at the genus level, with false discovery rate (FDR) correction. 22 overweight and obese cancer patients were matched with 22 cancer-free controls, with an average BMI of 30.5±4.3 kg/m2, age 54.4±5.3 years, and 54.5% were black. Fourteen matches were made between breast cancer cases and healthy female controls, and 8 matches were made with prostate cancer cases and healthy male controls. Comparison of all cases and controls revealed no differences in alpha diversity, though prostate cancer patients had higher Chao1 (P=0.006) and Observed Species (P=0.036) than cancer-free males. Beta-diversity metrics were significantly different between cases and controls (P<0.03 for all tests in whole sample and in men), though only unweighted Unifrac was different in women (P=0.005). Kruskal Wallis tests indicated significant differences among 16 genera in all matches, 9 in female, and 51 in male. This study suggests the faecal microbiota of treatment-naive breast and prostate cancer patients differs from controls, though larger samples are needed to substantiate these findings. Trial registration: NIH Clinical Trials, NCT01886677, NCT02224807, registered 26 June 2013, 25 Aug 2014 (respectively) - retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT01886677; https://clinicaltrials.gov/ct2/show/NCT02224807.

Weight loss and improved metabolic outcomes amongst rural African American women in the Deep South: six-month outcomes from a community-based randomized trial.

BACKGROUND: Obesity is highly prevalent in African American women, especially those in the rural southern USA, resulting in persistent health disparities. OBJECTIVE: To test the effectiveness of an evidence-based behavioural weight loss intervention delivered by community health advisors to African American women in the rural south. DESIGN AND METHODS: Overweight or obese African American women (30-70 years) from eight counties in Mississippi and Alabama participated in a 24-month randomized controlled trial of an evidence-based behavioural weight loss programme augmented with community strategies to support healthy lifestyles (Weight Loss Plus, N = 154) compared to the weight loss programme alone (Weight Loss Only, N = 255). This study reports on 6-month outcomes on primary (weight change) and secondary (waist circumference, blood pressure, lipids, fasting blood glucose) outcomes, coinciding with the completion of the intensive weight loss phase. RESULTS: Weight Loss Only participants lost an average of 2.2 kg (P < 0.001). Weight Loss Plus participants lost an average of 3.2 kg (P < 0.001). The proportion of the total sample that lost at least 5% of their body weight was 27.1% with no difference between treatment groups. Similarly, we observed statistically significant reductions in blood pressure, waist circumference and triglycerides in each treatment group, with no statistical differences between groups. CONCLUSION: Trained lay health staff and volunteers from the rural southern USA were able to deliver a translation of a high-intensity behavioural intervention targeted to African American women, resulting in clinically meaningful weight loss and improvement in other metabolic outcomes in a significant proportion of participants.

Differences in weight loss and health outcomes among African Americans and whites in multicentre trials.

The efficacy of behavioural lifestyle interventions (BLI) for weight loss and prevention and treatment of diabetes and hypertension is well established but may vary among racial/ethnic subgroups. This report reviews literature from 1990 to 2012 to determine if outcomes were similar among African Americans (AA) and whites participating in multicentre BLIs funded by the National Institutes of Health. We identified seven relevant trials that reported subgroup analyses for AA. On average, AA lost less weight at 6 months (AA: -1.6 to -7.5 kg; whites: -3.8 to -8.2 kg), but also had less or similar weight regain compared with whites. There were no reported differences between races in diabetes incidence. Three analyses reported no differences in blood pressure; however, a fourth reported that AA women were the only group that did not experience a significant change in blood pressure. Despite increased attention to cultural relevance, race-specific differences in weight loss persist in trials spanning 20 years; however, risk factor modification was similar across race/ethnic groups. Additional research is needed to understand the mechanisms of risk factor modification, and potential for weight change to promote even greater risk factor modification for AA than has been observed to date.

Association of run-in periods with weight loss in obesity randomized controlled trials.

Study-level design characteristics that inform the optimal design of obesity randomized controlled trials (RCTs) have been examined in few studies. A pre-randomization run-in period is one such design element that may influence weight loss. We examined 311 obesity RCTs published between 1 January 2007 and 1 July 2009 that examine d weight loss or weight gain prevention as a primary or secondary end-point. Variables included run-in period, pre-post intervention weight loss, study duration (time), intervention type, percent female and degree of obesity. Linear regression was used to estimate weight loss as a function of (i) run-in (yes/no) and (ii) run-in, time, percent female, body mass index and intervention type. Interaction terms were also examined. Approximately 19% (18.6%) of the studies included a run-in period, with pharmaceutical studies having the highest frequency. Although all intervention types were associated with weight loss (Mean = 2.80 kg, SD = 3.52), the inclusion of a pre-randomization run-in was associated with less weight loss (P = 0.0017) compared with studies that did not include a run-in period. However, this association was not consistent across intervention types. Our results imply that in trials primarily targeting weight loss in adults, run-in periods may not be beneficial for improving weight loss outcomes in interventions.

Examining social influence on participation and outcomes among a network of behavioral weight-loss intervention enrollees.

Research suggests that social networks, social support, and social influence are associated with weight trajectories among treatment- and non-treatment-seeking individuals. This study examined the impact of having a social contact who participated in the same group behavioral weight-control intervention in the absence of specific social support training on women engaged in a weight-loss program. Participants (n = 92; 100% female; 54% black; mean age: 46 ± 10 years; mean BMI: 38 ± 6) were grouped based upon whether or not they reported a social contact enrolled previously/concurrently in our behavioral weight-control studies. Primary outcomes were 6-month weight change and treatment adherence (session attendance and self-monitoring). Half of the participants (53%) indicated that they had a social contact; black women were more likely to report a social contact than white women (67.3% versus 39.5%; P < 0.01). Among participants with a social contact, 67% reported at least one contact as instrumental in the decision to enroll in the program. Those with a contact lost more weight (5.9 versus 3.7 kg; P = 0.04), attended more group sessions (74% versus 54%; P < 0.01), and submitted more self-monitoring journals (69% versus 54%; P = 0.01) than those without a contact. Participants' weight change was inversely associated with social contacts' weight change (P = 0.04). There was no association between participant and contact's group attendance or self-monitoring. Social networks may be a promising vehicle for recruiting and engaging women in a behavioral weight-loss program, particularly black women. The role of a natural social contact deserves further investigation.

Current knowledge of water quality and safety for livestock.

Basic laboratory evaluation of water quality for livestock should include measurement of TDS, sulfate, nitrate-nitrite, and coliform bacteria. Supplementary water tests may include pH, sodium, iron, magnesium, chloride, calcium, potassium, manganese, and contaminants specific to the situation. Using the best-quality drinking water available contributes to the optimal production of livestock. Restricted quantity of drinking water or drinking water containing excessive levels of nitrate, TDS, sulfate, and other constituents can affect growth and production of all classes of animals. Drinking-water quality and availability should be evaluated as a cause of poor performance or nonspecific disease conditions in livestock. It is important that attempts to evaluate water quality include obtaining a thorough history, making astute observations, and asking intelligent questions. A thorough laboratory examination of animal specimens and water samples should be evaluated in view of existing standards for livestock drinking-water quality.

Characterization of an epizootic of pulmonary edema in swine associated with fumonisin in corn screenings.

In 1989, corn screenings were associated with acute interstitial pulmonary edema, hydrothorax, and death in swine. Attack rate was 5-50%, case fatality rate was 50-90%, and clinical course was 1-2 days. Screenings from farms with pigs affected with pulmonary edema contained 20-330 micrograms fumonisin B1 per gram. Screenings containing 92 micrograms fumonisin B1 per gram fed to weanling pigs caused pulmonary edema and death. Sterilized corn inoculated with Fusarium moniliforme and diluted 1:1 with clean corn contained fumonisin B1 (17 micrograms/g) and caused acute pulmonary edema when fed for 5 days. Survivors developed subacute hepatotoxicosis with individual hepatocellular necrosis, hepatomegalocytosis, and increased numbers of mitotic figures. Similar liver lesions occurred in pigs given fumonisin B1 intravenously at 0.8 mg/kg body weight for 14 days.

Fonofos toxicosis and milk residues in dairy cattle.

An organophosphate toxicosis due to fonofos was diagnosed in an Iowa Dairy herd. Fonofos was detected in the feed source and in the rumen contents, liver, and kidney tissue of one cow that died acutely. Bulk tank milk contained detectable levels of fonofos.

Acute monensin toxicosis in sheep: light and electron microscopic changes.

Monensin was administered orally to 3 sheep at dosages of 12 (the LD50), 16, and 24 mg/kg of body weight, respectively. Clinical signs of monensin toxicosis were observed in the sheep in 24 to 36 hours of administration. Clinical signs included CNS depression, anorexia, diarrhea, and stiffness. Increased serum creatine phosphokinase and aspartate aminotransferase activities identified possible muscle damage. Sheep were euthanatized at 54 hours after dosing; at necropsy, there were skeletal muscle hemorrhages, pale myocardium, and pulmonary edema. Ultrastructural lesions were in the liver, diaphragm, and myocardium; diaphragm and myocardium were most severely affected. Mitochondrial swelling and cristolysis, swollen sarcoplasmic reticulum, and disruption of myofibrillar architecture were prominent. These ultrastructural changes are consistent with the hypothesis that monensin causes muscle cell necrosis due to its ionophorous properties and disruption of cellular Na+:Ca2+ balance. It is proposed that this upset of normal ionic processes allows increased intracellular calcium, which directly leads to the functional and structural mitochondrial changes observed.

Effects of carbon monoxide exposure on pregnant sows and their fetuses.

Miniature and domestic sows at 108 to 110 days of the gestation were exposed to atmospheric carbon monoxide (CO) concentrations of 150 to 400 ppm for 48 to 96 hours. Overall stillbirth rates were 6.7%, 34.8%, 42.3%, and 80.0% in the sows exposed to CO in concentrations of 200, 250, 300, and 350 ppm, respectively. A significant linear relationship was determined between these concentrations of CO and the resultant maternal carboxyhemoglobin (COHb) concentration (P less than 0.01). The frequency of stillbirth increased significantly when maternal COHb concentration exceeded 23% saturation of hemoglobin. The COHb concentrations in new-delivered pigs (cesarean section) were greater than maternal COHb concentrations by 3 to 22%. Common gross lesions in stillborn pigs were cherry red discoloration of the subcutaneous tissues, muscle, and viscera and accumulation of a large volume of serosanguineous pleural effusion. Hypoxic ischemic leukoencephalopathy was found in new-delivered pigs from 3 of 14 litters. Lesions included focal leukoencephalomalacia, glial-vascular proliferation, multifocal hemorrhage, and vacuolation of the neuropile. Many extramedullary hematopoietic centers were present in liver sections.

Carboxyhemoglobin values in swine relative to carbon monoxide exposure: guidelines for monitoring animal and human health hazards in swine-confinement buildings.

Miniature pigs were exposed, in an environmental chamber, to 55 mg of CO/m3 of air, 110 mg/m3, 220 mg/m3, or 330 mg/m3. Blood samples were taken from the swine every hour over an exposure period of 6 or 8 hours. After the pigs were removed from the chamber, blood samples were taken every 30 minutes for an additional 3 hours. The blood samples were measured by spectrophotometry for the amount of carboxyhemoglobin (COHb). On exposure to CO, the COHb values in the pigs increased in a linear fashion during the first 2 hours, then began to level off, reaching a peak concentration at 6 to 8 hours. The percentage of COHb in the blood after 6 hours' exposure to the different amounts of CO were as follows: 55 mg/m3 - 5%, 110 mg/m3 - 10.5%, 220 mg/m3 - 20%, and 330 mg/m3 - 27.2%. There was a linear relationship between the amount of CO exposure and the peak blood value of COHb. The present data provide guidelines for the use of COHb measurement in swine as a means to monitor the environment in swine-confinement buildings for potentially dangerous amounts of CO for swine and persons and to aid in the diagnosis of CO-induced perinatal disease in swine.

Development of behavioral tests for the assessment of neurologic effects of lead in sheep.

Reports of neurologic impairment of children following recovery from acute lead encephalopathy have raised questions concerning the effects of chronic low-level lead exposure on the central nervous system. Behavioral toxicologic techniques have been employed to assess the effects of lead on the central nervous system in sheep. Mature sheep receiving daily doses of 100 mg lead/kg showed a significant decrease in performance on an auditory signal detection task. Daily oral doses of 120 and 230 mg lead/sheep for 27 weeks did not alter the performance of mature sheep on a fixed-interval schedule of reinforcement behavioral task. Prenatal exposure to maternal blood lead levels of 16 or 34 mug/100 ml during gestation and postnatal daily ingestion of 16, 8, 4, or 2 mg lead/kg did not alter performance of lambs on a closed-field maze task. Slowed learning was demonstrated in lambs prenatally exposed to maternal blood lead levels of 34 mug/100 ml during gestation when tested on nonspatial, two-choice visual discrimination problems at 10-15 months of age.