Dietary flavanols and procyanidin oligomers from cocoa (Theobroma cacao) inhibit platelet function

<b>BACKGROUND:b> Flavonoids may be partly responsible for some health benefits, including antiinflammatory action and a decreased tendency for the blood to clot. An acute dose of flavanols and oligomeric procyanidins from cocoa powder inhibits platelet activation and function over 6 h in humans. <b>OBJECTIVE: b>This study sought to evaluate whether 28 d of supplementation with cocoa flavanols and related procyanidin oligomers would modulate human platelet reactivity and primary hemostasis and reduce oxidative markers in vivo. <b>DESIGN: b>Thirty-two healthy subjects were assigned to consume active (234 mg cocoa flavanols and procyanidins/d) or placebo (< or = 6 mg cocoa flavanols and procyanidins/d) tablets in a blinded parallel-designed study. Platelet function was determined by measuring platelet aggregation, ATP release, and expression of activation-dependent platelet antigens by using flow cytometry. Plasma was analyzed for oxidation markers and antioxidant status. <b>RESULTS:b> Plasma concentrations of epicatechin and catechin in the active group increased by 81% and 28%, respectively, during the intervention period. The active group had significantly lower P selectin expression and significantly lower ADP-induced aggregation and collagen-induced aggregation than did the placebo group. Plasma ascorbic acid concentrations were significantly higher in the active than in the placebo group (P < 0.05), whereas plasma oxidation markers and antioxidant status did not change in either group. <b>CONCLUSIONS:b> Cocoa flavanol and procyanidin supplementation for 28 d significantly increased plasma epicatechin and catechin concentrations and significantly decreased platelet function. These data support the results of acute studies that used higher doses of cocoa flavanols and procyanidins.<br />

Ice and pulsed electromagnetic field to reduce pain and swelling after distal radius fractures

<b>Objective: b>To examine the relative effectiveness of ice therapy and/or pulsed electromagnetic field in reducing pain and swelling after the immobilization period following a distal radius fracture.<b>Methods:b> A total of 83 subjects were randomly allocated to receive 30 minutes of either ice plus pulsed electromagnetic field (group A); ice plus sham pulsed electromagnetic field (group B); pulsed electromagnetic field alone (group C), or sham pulsed electromagnetic field treatment for 5 consecutive days (group D). All subjects received a standard home exercise programme. A visual analogue scale was used for recording pain; volumetric displacement for measuring the swelling of the forearm; and a hand-held goniometer for measuring the range of wrist motions before treatment on days 1, 3 and 5.Results: At day 5, a significantly greater cumulative reduction in the visual analogue scores as well as ulnar deviation range of motion was found in group A than the other 3 groups. For volumetric measurement and pronation, participants in group A performed better than subjects in group D but not those in group B.<b>Conclusion:b> The addition of pulsed electromagnetic field to ice therapy produces better overall treatment outcomes than ice alone, or pulsed electromagnetic field alone in pain reduction and range of joint motion in ulnar deviation and flexion for a distal radius fracture after an immobilization period of 6 weeks.<br />

Discriminative ability of functional loading tests for adolescent jumper

<b>Objectiveb>: To investigate the reliability and validity of five squat-based loading tests that are clinically appropriate for jumper's knee. The loading tests were step up, double leg squat, double leg squat on a 25-degree decline (decline squat), single leg decline squat, and decline hop. <b>Designb>: Cross-sectional controlled cohort. Subjects without knee pain comprised controls, those with extensor tendon pain comprised the jumper's knee group. <b>Settingb>: Institutional athlete study group in Australia. <b>Participantsb>: Fifty-six elite adolescent basketball players participated in this study, thirteen comprised the jumper's knee group, fifteen athletes formed a control group. <b>Interventionb>: Each subject performed each loading test for baseline and reliability data on the first testing day. Subjects then performed three days of intensive (6 h daily) basketball training, after which each loading test was reexamined. <b>Main outcome measuresb>: Eleven point interval scale for pain. <b>Resultsb>: The tests that best detected a change in pain due to intensive workload were the single leg decline squat and single leg decline hop. This study found that decline tests have better discriminative ability than the standard squat to detect change in jumper's knee pain due to intensive training. The typical error for these tests ranged from 0.3 to 0.5, however, caution should be exercised in the interpretation of these reliability figures due to relatively low scores. <b>Conclusionsb>: The single leg decline squat is recommended in the physical assessment of adolescent jumper's knee. The decline squat was selected as the best clinical test over the decline hop because it was easier to standardise performance.<br />

Preventing the onset of depressive disorders : a meta-analytic review of psychological interventions

<b>OBJECTIVEb>: A growing number of studies have tested the efficacy of preventive interventions in reducing the incidence of depressive disorders. Until now, no meta-analysis has integrated the results of these studies. <b>METHODb>: The authors conducted a meta-analysis. After a comprehensive literature search, 19 studies were identified that met inclusion criteria. The studies had to be randomized controlled studies in which the incidence of depressive disorders (based on diagnostic criteria) in an experimental group could be compared with that of a control group. <b>RESULTS:b> The mean incidence rate ratio was 0.78, indicating a reduction of the incidence of depressive disorders by 22% in experimental compared with control groups. Heterogeneity was low to moderate (I²=33%). The number needed to treat to prevent one case of depressive disorder was 22. Moderator analyses revealed no systematic differences between target populations or types of prevention (universal, selective, or indicated). The data included indications that prevention based on interpersonal psychotherapy may be more effective than prevention based on cognitive-behavioral therapy. <b>CONCLUSIONS: b>Prevention of new cases of depressive disorders does seem to be possible. Prevention may become an important way, in addition to treatment, to reduce the enormous public health burden of depression in the coming years.<br />

Aspects of milk protein catabolism by lactobacilli

Lactobacillus plantarum and subspecies of Lactobacillus casei were isolated from good quality mature Cheddar cheese and characterized with respect to metabolic functions that would allow their use in cheesemaking. In this way microbiological control of the maturation process with particular emphasis on protein catabolism was achieved. The lactobacilli isolated were selected for low growth rates (and acid production) in milk, and low proteinase activity to allow for their addition in high numbers to cheesemilk together with the normal starter flora (group N streptococci). The growth and acid production of the starter bacteria were unaffected by the presence of the lactobacilli during cheese manufacture and it was found that the added lactobacilli were able to grow and function under the conditions prevalent in Cheddar cheese during maturation. It was also demonstrated that the lactobacilli could be grown in an artificial medium to high numbers under controlled conditions and could be harvested for the preparation of cell concentrates, a necessary characteristic for commercialization. The lactobacilli also metabolized citrate, a potential problem in cheese maturation associated with C02 production but this did not adversely affect the maturation process under the conditions used. Compared to the group N streptococci the non-starter lactobacilli possessed a proteinase system that had a higher temperature optimum and was less affected by heat and sodium chloride. They also possessed a more active peptidase system although both the lactobacilli and the starter organisms possessed a similar range of peptidases. Non-starter lactobacilli were added to normal cheese and cheese made with proteinase negative starter. The added organisms did not adversely affect manufacturing parameters and did not metabolize citrate or lead to the formation of biogenic amines. However protein catabolism rates, particularly with respect to peptide degradation, were increased, as was flavour development and intensity. It was observed that the body and texture of the cheeses was unaffected by the treatment. By controlling both the starter and non-starter microflora in the cheeses a practical system for favourably influencing cheese maturation was possible. The investigation has demonstrated that carefully selected and characterized non-starter lactobacilli can be incorporated into Cheddar cheese manufacture in order to influence flavour development during maturation. Moreover the organisms can be added to the vat stage of manufacture without causing problems to the manufacturing process. This approach is a simple cost effective means of improving the cost of Cheddar cheese production and provides an unique opportunity to improve and control quality of all Cheddar cheese produced.

Effect of an arginine-containing nutritional supplement on pressure ulcer healing in community spinal patients

<b>Objective:b> To determine whether or not the use of an arginine-containing nutritional supplement could result in signifi cantly shorter pressure ulcer (PU) healing times in people with spinal cord injuries living in the community, compared with a comparative historical control group. <b>Method:b> Eighteen spinal-cord-injured patients (all part of a hospital spinal outreach service) received 9g of a commercial powdered arginine supplement per day until full PU healing occurred. Healing rates were compared against 17 historical control patients (as assessed by medical history audit).&nbsp;<br /> <b>Results:b> Baseline characteristics (age, gender, injury level and time) were similar between groups. Mean ulcer healing times were 10.5 ± 1.3 weeks versus 21 ± 3.7 weeks (p<0.05) in the intervention and control groups respectively. Comparison of healing rates in the intervention group against expected healing rates derived from the medical literature showed that intervention patients had a signifi cantly shorter mean healing time (category 2 PU: 5.5±1.3 weeks versus 13.4 weeks; category 3 PU: 12.5 ± 1.9 weeks versus 18.2 weeks; category 4 PU: 14.4 ± 4.8 weeks versus 22.1 weeks). A diagnosis of diabetes did not significantly alter healing rates in either group. Conclusion: Results from this observational study show a promising benefit of arginine supplementation on PU healing for individuals with spinal cord injury living in the community.<br />

The inclusion of ‘then-test’ questions in post-test questionnaires alters post-test responses: a randomized study of bias in health program evaluation

<b>Objectivesb> Program evaluations are frequently based on ‘then-test’ data, i.e., pre-test collected in retrospect. While the application of the then-test has practical advantages, little is known about the validity of then-test data. Because of the collection of then-test in close proximity to post-test questions, this study was aimed at exploring whether the presence of then-test questions in post-test questionnaires influenced subjects’ responses to post-test.<br /><b>Patients and methodsb> To test the influence of then-test questions, we designed a randomized three-group study in the context of chronic disease self-management programs. Interventions had comparable goals and philosophies, and all 949 study participants filled out identical Health Education Impact Questionnaires (heiQ) at pre-test. At post-test, participants were then randomized to one of the following three groups: Group A responded to post-test questions only (n = 331); Group B filled out transition questions in addition to post-test (n = 304); and Group C filled out then-test questions in addition to post-test (n = 314).<br /><b>Resultsb> Significant post-test differences were found in six of eight heiQ scales, with respondents who filled out then test questions reporting significantly higher post-test scores than respondents of the other groups.<br /><b>Conclusions b>This study provides evidence that the inclusion of then-test questions alters post-test responses,<br />suggesting that change scores based on then-test data be interpreted with care.<br />

The role of lipogenesis in the development of obesity and diabetes in Israeli sand rats (Psammomys obesus)

Obesity and diabetes in Israeli sand rats, Psammomys obesus, occur with the sequential transition of animals from normal insulin sensitivity to impaired insulin sensitivity, accompanied by increased adiposity, prior to insulin resistance and obesity, in a manner similar to susceptible human populations. The current study was designed to examine the role of de novo lipid synthesis in the development of excessive weight gain in P. obesus. Sand rats were classified at 12 wk of age into three groups: A, normoglycemic normoinsulinemic; B, normoglycemic hyperinsulinemic; C, hyperglycemic hyperinsulinemic, based on glucose and insulin responses in fed sand rats. Body weight, liver weight, white adipose tissue (WAT) mass and food intake were significantly elevated in Group C compared to Group A (P < 0.05). Lipogenic rate was measured by the amount of 3H incorporated into subscapular brown adipose tissue (BAT), epidiymal WAT and liver per hour, from sand rats with and without access to food. No difference in lipogenic rate was found between the groups in BAT, indicating that this tissue is of minor importance in whole body lipogenesis in P. obesus. In the WAT there was a greater lipogenic rate with the development of obesity and hyperinsulinemia (Group B vs. Group A) but no difference in the liver. However, the onset of hyperglycemia (Group C) further stimulated WAT lipogenesis and initiated increased hepatic lipogenesis, both of which contributed to the pre-existing obesity. This study suggests that elevated lipogenesis is not the primary cause of obesity in P. obesus, as lipogenic rate only markedly increases after obesity is already present in hyperglycemic animals.<br />

Falls and mobility in Parkinson’s disease : protocol for a randomised controlled clinical trial

<b>Backgroundb> Although physical therapy and falls prevention education are argued to reduce falls and disability in people with idiopathic Parkinson's disease, this has not yet been confirmed with a large scale randomised controlled clinical trial. The study will investigate the effects on falls, mobility and quality of life of (i) movement strategy training combined with falls prevention education, (ii) progressive resistance strength training combined with falls prevention education, (iii) a generic life-skills social program (control group). <b><br />Methods/Designb> People with idiopathic Parkinson's disease who live at home will be recruited and randomly allocated to one of three groups. Each person shall receive therapy in an out-patient setting in groups of 3-4. Each group shall be scheduled to meet once per week for 2 hours for 8 consecutive weeks. All participants will also have a structured 2 hour home practice program for each week during the 8 week intervention phase. Assessments will occur before therapy, after the 8 week therapy program, and at 3 and 12 months after the intervention. A falls calendar will be kept by each participant for 12 months after outpatient therapy. Consistent with the recommendations of the Prevention of Falls Network Europe group, three falls variables will be used as the primary outcome measures: the number of fallers, the number of multiple fallers and the falls rate. In addition to quantifying falls, we shall measure mobility, activity limitations and quality of life as secondary outcomes. <b><br />Discussionb> This study has the potential to determine whether outpatient movement strategy training combined with falls prevention education or progressive resistance strength training combined with falls prevention education are effective for reducing falls and improving mobility and life quality in people with Parkinson's disease who live at home.

Cancer stem cells in prostate cancer chemoresistance

There is currently no cure for metastatic castration-resistant prostate cancer (CRPC). Chemoresistance and metastatic disease remain the main causes of treatment failure and mortality in CaP patients. Although several advances have been made in the control of CRPC with some newly developed drugs, there is still an urgent need to investigate the mechanisms and pathways of prostate cancer (CaP) metastasis and chemoresistance, identify useful therapeutic targets, develop novel treatment approaches, improve current therapeutic modalities and increase patients' survival. Cancer stem cells (CSCs), a minority population of cancer cells characterised by self-renewal and tumor initiation, have gained intense attention as they not only play a crucial role in cancer recurrence but also contribute substantially to chemoresistance. As such, a number of mechanisms in chemoresistance have been identified to be associated with CSCs. Therefore, a thorough and integral understanding of these mechanisms can identify novel biomarkers and develop innovative therapeutic strategies for CaP treatment. Our recent data have demonstrated CSCs are associated with CaP chemosensitivity. In this review, we discuss the roles of putative CSC markers in CaP chemoresistance and elucidate several CSC-associated signaling pathways such as PI3K/Akt/mTOR, Wnt/&beta;-catenin and Notch pathways in the regulation of CaP chemoresistance. Moreover, we will summarize emerging and innovative approaches for the treatment of CRPC and address the challenging CRPC that is driven by CSCs. Understanding the link between CSCs and metastatic CRPC will facilitate the development of novel therapeutic approaches to overcome chemoresistance and improve the clinical outcomes of CaP patients.

Effects of study design and allocation on participant behaviour-ESDA: study protocol for a randomized controlled trial

BACKGROUND: What study participants think about the nature of a study has been hypothesised to affect subsequent behaviour and to potentially bias study findings. In this trial we examine the impact of awareness of study design and allocation on participant drinking behaviour. METHODS/DESIGN: A three-arm parallel group randomised controlled trial design will be used. All recruitment, screening, randomisation, and follow-up will be conducted on-line among university students. Participants who indicate a hazardous level of alcohol consumption will be randomly assigned to one of three groups. Group A will be informed their drinking will be assessed at baseline and again in one month (as in a cohort study design). Group B will be told the study is an intervention trial and they are in the control group. Group C will be told the study is an intervention trial and they are in the intervention group. All will receive exactly the same brief educational material to read. After one month, alcohol intake for the past 4 weeks will be assessed. DISCUSSION: The experimental manipulations address subtle and previously unexplored ways in which participant behaviour may be unwittingly influenced by standard practice in trials. Given the necessity of relying on self-reported outcome, it will not be possible to distinguish true behaviour change from reporting artefact. This does not matter in the present study, as any effects of awareness of study design or allocation involve bias that is not well understood. There has been little research on awareness effects, and our outcomes will provide an indication of the possible value of further studies of this type and inform hypothesis generation. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000846022.

Social desirability bias in the reporting of alcohol consumption: a randomized trial

OBJECTIVE: To investigate reporting of alcohol consumption, we manipulated the contexts of questions in ways designed to induce social desirability bias. METHOD: We undertook a two-arm, parallel-group, individually randomized trial at an Australian public university. Students were recruited by email to a web-based "Research Project on Student Health Behavior." Respondents answered nine questions about their physical activity, diet, and smoking. They were unknowingly randomized to a group presented with either (A) three questions about their alcohol consumption or (B) seven questions about their alcohol dependence and problems (under a prominent header labeled "Alcohol Use Disorders Identification Test"), followed by the same three alcohol consumption questions from (A). RESULTS: A total of 3,594 students (mean age = 27, SD = 10) responded and were randomized: 1,778 to Group A and 1,816 to Group B. Outcome measures were the number of days they drank alcohol, the typical number of drinks they consumed per drinking day, and the number of days they consumed six or more drinks. The primary analysis included participants with any alcohol consumption in the preceding 4 weeks (1,304 in Group A; 1,340 in Group B) using between-group, two-tailed t tests. RESULTS: In Groups A and B, respectively, means (and SDs) of the number of days drinking were 5.89 (5.92) versus 6.06 (6.12), p = .49; typical number of drinks per drinking day: 4.02 (3.87) versus 3.82 (3.76), p = .17; and number of days consuming six or more drinks: 1.69 (2.94) versus 1.67 (3.25), p = .56. CONCLUSIONS: We could not reject the null hypothesis because earlier questions about alcohol dependence and problems showed no sign of biasing the respondents' subsequent reports of alcohol consumption. These data support the validity of university students' reporting of alcohol consumption in web-based studies.

Effects of multivitamin, mineral and herbal supplement on cognition in younger adults and the contribution of B group vitamins

Cognitive benefits of multivitamins have been observed in the elderly, but fewer trials have investigated younger, healthy cohorts. This randomised, double-blind, placebo-controlled study investigated the cognitive effects of 16-week multivitamin supplementation in adults aged 20-49 years.

A combination of omega-3 fatty acids, folic acid and B-group vitamins is superior at lowering homocysteine than omega-3 alone: a meta-analysis

The aim of the study was to assess whether omega-3 polyunsaturated fatty acid supplementation alone or in combination with folic acid and B-group vitamins is effective in lowering homocysteine. The Medline Ovid, Embase and Cochrane databases were searched for randomized-controlled trial studies that intervened with omega-3 supplementation (with or without folic acid) and measured changes in homocysteine concentration. Studies were pooled using a random effects model for meta-analysis. Three different models were analyzed: all trials combined, omega-3 polyunsaturated fatty acid trials, and omega-3 polyunsaturated fatty acids with folic acid and B-group vitamin trials. Nineteen studies were included, consisting of 3267 participants completing 21 trials. Studies were heterogeneous; varying by dose, duration and participant health conditions. Across all trials, omega-3 supplementation was effective in lowering homocysteine by an average of 1.18μmol/L (95%CI: (-1.89, -0.48), P=.001). The average homocysteine-lowering effect was greater when omega-3 supplementation was combined with folic acid and B-group vitamins (-1.37μmol/L, 95%CI: (-2.38, -0.36), P<.01) compared to omega-3 supplementation alone (-1.09μmol/L 95%CI: (-2.04, -0.13), P=.03). Omega-3 polyunsaturated fatty acid supplementation was associated with a modest reduction in homocysteine. For the purposes of reducing homocysteine, a combination of omega-3s (0.2-6g/day), folic acid (150 - 2500μg/day) and vitamins B6 and B12 may be more effective than omega-3 supplementation alone.

Incorporation of group 14 elements into siloxane-bridged paracyclophanes cyclo-[p,p´-Me2SiC6H4EMe2C6H4SiMe2O]2 (E = C, Si, Ge, Sn)§

The bis(arylene silanes) p,p'-HMeb>2b>SiCb>6b>Hb>4b>EMeb>2b>Cb>6b>Hb>4b>SiMeb>2b>H (E = C (<b>10b>), Si (<b>11b>), Ge (<b>12b>), Sn(<b>13b>)) were prepared by the in situ Grignard reaction of p,p'-BrCb>6b>Hb>4b>CMeb>2b>Cb>6b>Hb>4b>Br, Mg turnings, and HSiMeb>2b>Cl (for <b>10b>) and the Grignard reaction using p-HMeb>2b>SiCb>6b>Hb>4b>Br, Mg turnings, and Meb>2b>EClb>2b> (E = Si for <b>11b>, Ge for <b>12b>, Sn for <b>13b>). The oxidation of <b>10-13 b>using Pearlman's catalyst, Pd(OH)b>2b>/C, in aqueous THF provided the bis(arylene silanols) p,p'-HOMeb>2b>SiCb>6b>Hb>4b>EMeb>2b>Cb>6b>Hb>4b>SiMeb>2b>OH (E = C (<b>14b>), Si (<b>15b>), Ge (<b>16b>), Sn(<b>17b>)). The HCl-catalyzed condensation of <b>14-17b> in highly diluted solutions of acetone/water afforded the siloxane-bridged paracyclophanes cyclo-[p,p'-Meb>2b>SiCb>6b>Hb>4b>EMeb>2b>Cb>6b>Hb>4b>SiMeb>2b>O]b>2b> (<b>6-9b>) that incorporate the group 14 elements E = C, Si, Ge, and Sn. Compounds<b> 6-17b> were investigated by multinuclear solution and solid-state NMR spectroscopy and <b>6b> and <b>9b> also by X-ray crystallography.<br />