Methodology of the INVestigating traIning assoCiated blasT pAthology (INVICTA) study.

BACKGROUND: Subconcussive blast exposure during military training has been the subject of both anecdotal concerns and reports in the medical literature, but prior studies have often been small and have used inconsistent methods. METHODS: This paper presents the methodology employed in INVestigating traIning assoCiated blasT pAthology (INVICTA) to assess a wide range of aspects of brain function, including immediate and delayed recall, gait and balance, audiologic and oculomotor function, cerebral blood flow, brain electrical activity and neuroimaging and blood biomarkers. RESULTS: A number of the methods employed in INVICTA are relatively easy to reproducibly utilize, and can be completed efficiently, while other measures require greater technical expertise, take longer to complete, or may have logistical challenges. CONCLUSIONS: This presentation of methods used to assess the impact of blast exposure on the brain is intended to facilitate greater uniformity of data collection in this setting, which would enable comparison between different types of blast exposure and environmental circumstances, as well as to facilitate meta-analyses and syntheses across studies.

Ulcerative Colitis Remission Status After Induction With Mesalazine Predicts Maintenance Outcomes: the MOMENTUM Trial.

BACKGROUND AND AIMS: This study assessed the efficacy of maintenance treatment with multimatrix mesalazine following achievement of complete or partial remission after induction treatment with high-dose multimatrix mesalazine. METHODS: In this phase 3b/4, open-label, multicentre, prospective, single-arm study, patients with mild-to-moderate ulcerative colitis were treated with multimatrix mesalazine 4.8g/day once daily for 8 weeks [induction phase]. At Week 8, those who achieved complete or partial remission, based on predefined clinical and endoscopic criteria, were eligible to receive 12 months of multimatrix mesalazine 2.4g/day once daily maintenance therapy. The primary endpoint was the proportion of patients in complete remission at Month 12. RESULTS: A total of 717 patients received induction treatment; 25.9% and 39.3% of patients achieved complete and partial remission, respectively, at Week 8. A total of 461 patients entered the maintenance phase. The likelihood of remaining in/achieving complete remission at Month 12 was higher for patients who entered the maintenance phase in complete remission compared with those who began maintenance in partial remission [47.8% vs 26.0%; p < 0.001]. At Month 12, mucosal healing [endoscopy score ≤ 1] was demonstrated in 76.4% [139/182] and 63.5% [176/277] of those who were in complete and partial remission, respectively, at the end of induction. CONCLUSION: Patients achieving complete remission before dose reduction were more likely to remain in remission at Month 12.

Provision of weight management advice for obese women during pregnancy: a survey of current practice and midwives' views on future approaches.

A semi-structured, web-based questionnaire was developed to survey midwives (n = 241) employed by NHS Tayside, UK, to identify current practice and views on weight management of obese women during pregnancy and the puerperium. A total of 78 (32%) midwives submitted responses following email invitation. Most respondents (79%) reported always calculating women's body mass index (BMI) at booking, with 73% routinely explaining the BMI category. In terms of future practice for obese women, although few respondents (15%) currently offer personalised advice regarding weight management based on a woman's diet and physical activity levels, 77% of respondents thought such advice would be appropriate and 69% thought it could possibly be feasible to offer such advice. The respondents viewed weight management to be of importance and felt that universal advice is appropriate, but confidence in discussing weight management and knowledge of the subject was low. Strategies to improve midwife confidence and weight management services should include training, ongoing support and definition of the midwife's role within the multidisciplinary team to support practice in the future.

Associations between diet and disease activity in ulcerative colitis patients using a novel method of data analysis.

BACKGROUND: The relapsing nature and varying geographical prevalence of ulcerative colitis (UC) implicates environmental factors such as diet in its aetiology. METHODS: In order to determine which foods might be related to disease activity in UC a new method of dietary analysis was developed and applied. Eighty-one UC patients were recruited at all stages of the disease process. Following completion of a 7 d diet diary, clinical assessment including a sigmoidoscopic examination (scale 0 (normal mucosa) to 6 (very active disease)) was conducted. Food weights for each person were adjusted (divided) by the person's calorific intake for the week. Each food consumed was given a food sigmoidoscopy score (FSS) calculated by summing the products of the (adjusted) weight of food consumed and sigmoidoscopy score for each patient and occurrence of food and dividing by the total (adjusted) weight of the food consumed by all 81 patients. Thus, foods eaten in large quantities by patients with very active disease have high FSSs and vice versa. Foods consumed by <10 people or weighing <1 kg for the whole group were excluded, leaving 75 foods. RESULTS: High FSS foods were characterized by high levels of the anti-thiamin additive sulfite (Mann-Whitney, p < 0.001), i.e. bitter, white wine, burgers, soft drinks from concentrates, sausages, lager and red wine. Caffeine also has anti-thiamin properties and decaffeinated coffee was associated with a better clinical state than the caffeine containing version. Beneficial foods (average intake per week) included pork (210 g), breakfast cereals (200 g), lettuce (110 g), apples and pears (390 g), milk (1250 ml), melon (350 g), bananas (350 g), bacon (120 g), beef and beef products (500 g), tomatoes (240 g), soup (700 g), citrus fruits (300 g), fish (290 g), yogurt (410 g), cheese (110 g), potatoes (710 g) and legumes (120 g). CONCLUSIONS: The dietary analysis method described provides a new tool for establishing relationships between diet and disease and indicates a potentially therapeutic diet for UC.

Contribution of dietary protein and inorganic sulfur to urinary sulfate: toward a biomarker of inorganic sulfur intake.

BACKGROUND: Sulfiting agents are widely used as food additives. Limits are set on their use in foods because they may adversely affect health. Sulfiting agents are excreted in urine as sulfate, which is indistinguishable from sulfate derived from sulfur amino acids. OBJECTIVE: The objective was to assess the contribution of inorganic sulfur to urinary sulfate excretion and of dietary protein to urinary sulfate and nitrogen excretion with the aim of developing a urinary biomarker of inorganic sulfur intake. DESIGN: Nine healthy men were fed a sequence of 3 diets for 15 d (n = 7), 5 diets for 10 d (n = 6), or both. The diets contained 51-212 g protein/d (0.43-1.71 g S/d) and 0.17-0.27 g inorganic S/d; p-aminobenzoic acid-validated 24-h urine samples (n = 47) were analyzed for sulfate and nitrogen. RESULTS: Dietary inorganic sulfur was efficiently excreted as sulfate in urine. Urinary sulfate derived from protein correlated strongly (r(2) = 0.86) with urinary nitrogen. Urinary recovery of protein sulfur and nitrogen decreased from 84% at average protein intakes (72 g/d) to 70% at high protein intakes (212 g/d). The nitrogen:sulfur ratio (in g) of the protein in the study diets was 18.9, which was maintained in urine (18.4 +/- 0.1) after dietary inorganic sulfur intake was subtracted from urinary sulfate. Therefore, inorganic sulfur intake (g/d) = urinary sulfur (g/d) - 0.054 x urinary nitrogen (g/d). For typical UK intakes of inorganic sulfur (0.25 g/d), this biomarker should produce mean (+/- SD) values of 0.24 +/- 0.10 g S/d. CONCLUSION: Twenty-four-hour urinary nitrogen and sulfate values can be used to predict inorganic sulfur intake.

The effects of bismuth, iron, zinc and nitrate on free sulfide in batch cultures seeded with fecal flora.

BACKGROUND: Hydrogen sulfide (H2S) and methanthiol (CH3SH) have been implicated as bacterially derived toxins which may be damaging to the gut mucosa. The addition of nitrate and metals that bind sulfide could potentially reduce the concentrations of these toxic gases. In this study, the effects of iron, zinc, bismuth and nitrate on free H2S concentrations in fecal batch cultures were investigated. METHODS: Stool samples were collected from six healthy subjects. Ten percent fecal slurries was made up with phosphate buffer. One milliliter of fecal slurry and 1 ml of metal solution were added to 28 ml anaerobic broth in a 30-ml vial giving final metal concentrations of 0.1, 0.5 and 1.0 mmol/l. For a control, the metal iron solution was replaced by 1 ml of water. After 24 h of incubation at 37 degrees C, 1 ml of the supernatant from the broth was distilled by microdistillation and sulfide determined by HPLC using amperometric detection. RESULTS: A significant reduction in H2S (P<0.05) of 57% was seen with 1.0 mmol/l zinc, but not with 0 and 0.5 mmol/l zinc treatments. Iron at 0.1, 0.5 and 1.0 mmol/l significantly reduced H2S concentrations (P<0.05) by 36%, 44% and 58%, respectively. Bismuth, the most effective metal, reduced H2S concentrations by more than 90% for all treatments. Both magnesium citrate and magnesium acetate did not affect sulfide concentrations, while 41% and 68% reductions were seen from the addition of 0.5 and 1.0 mmol/l magnesium nitrate, respectively (P<0.05). CONCLUSIONS: Bismuth, iron, zinc and nitrate are effective at reducing free H2S concentrations in batch cultures. Side effects of these metals may limit their use in vivo. Nitrate is considered toxic because of its contribution to the formation of the carcinogenic nitrite and nitrosamine, though results presented here may indicate a beneficial effect in the large intestine.

The effect of 5-aminosalicylic acid-containing drugs on sulfide production by sulfate-reducing and amino acid-fermenting bacteria.

The toxic, bacterial metabolite sulfide is implicated in ulcerative colitis. Ulcerative colitis patients taking 5-aminosalicylic acid-containing drugs have lower fecal sulfide levels than those not taking these drugs. The effects of sulfasalazine, balsalazide, olsalazine, and 5-aminosalicylic acid on sulfide production were studied in a three-stage chemostat pulsed on days 1 to 3 with 5 g sulfasalazine (40 mM) and in pure cultures of amino acid-fermenting and sulfate-reducing bacteria. By the third day of sulfasalazine addition to the chemostat, sulfide concentrations in vessels 1 through 3 had dropped from 1.73, 1.78, and 1.43 mM to 0.01, 0.15, and 0.9 mM, respectively. In pure cultures, 50% inhibition of sulfide production from amino acids occurred at 2.5 +/- 0.05 mM for sulfasalazine, 5 +/- 0.2 mM for olsalazine, 6 +/- 1 mM for balsalazide, and more than 20 mM for 5-aminosalicylic acid. Fifty percent inhibition of sulfide production from sulfate occurred at 0.25 +/- 0.05 mM for sulfasalazine, 0.7 +/- 0.2 mM for balsalazide, and 9.0 +/- 1.0 mM for 5-aminosalicylic acid. The order of effectiveness of equimolar concentrations of drugs (most effective first) in this assay was sulfasalazine, then olsalazine (though given clinically at half the dose of other 5-aminosalicylic acid prodrugs) and balsalazide, and lastly 5-aminosalicylic acid. Inhibition of sulfide production by 5-aminosalicylic acid-containing drugs may contribute to their therapeutic effect in ulcerative colitis.