Reducing Calorie Intake May Not Help You Lose Body Weight

Background Previously a meta-analysis found that multi-vitamin/mineral supplementation reduced mild psychiatric symptoms. To establish mechanisms, and to pin-point the individuals most likely to benefit, the role of various polymorphisms were examined. Supplementation was found to influence mild-psychiatric symptoms depending on the form of particular genes: genes that are risk factors for psychiatric disease and influence mechanisms by which drugs act. Methods In a double-blind trial young healthy males rated psychiatric symptoms, before and after taking vitamin/mineral supplements for three months, and the response was related to single nucleotide polymorphisms associated with catecholamines and serotonin. Outcomes With rs1800497 (Taq1A; dopamine D2 receptor), those with the CT allele benefitted from a vitamin/mineral supplement. Similarly with rs1800955 (DRD4 – dopamine D4 receptor), the mood of those with the CC allele benefitted selectively. With rs6296 (HTR1B) only those with the GC alleles responded, and with rs6311 (HTR2A) supplementation produced a beneficial response in those with the GG allele. With rs1050565 (5HTT gene - Human Serotonin Transporter gene) supplementation increased the mental health of those with the AA allele. Interpretation In a situation where a substantial proportion of patients do not benefit from drug therapy, and there is an element of trial and error when prescribing, it was proposed that future work should consider distinguishing patients depending on various polymorphisms and micro-nutrient status. In those with particular alleles, we should consider if drug administration and vitamin / mineral status interact synergistically to influence the therapeutic outcom

Sleep-disordered breathing-do we have to change gears in heart failure?

The majority of patients with heart failure have sleep-disordered breathing (SDB)-with central (rather than obstructive) sleep apnoea becoming the predominant form in those with more severe disease. Cyclical apnoeas and hypopnoeas are associated with sleep disturbance, hypoxaemia, haemodynamic changes, and sympathetic activation. Such patients have a worse prognosis than those without SDB. Mask-based therapies of positive airway pressure targeted at SDB can improve measures of sleep quality and partially normalise the sleep and respiratory physiology, but recent randomised trials of cardiovascular outcomes in central sleep apnoea have been neutral or suggested the possibility of harm, likely from increased sudden death. Further randomised outcome studies (with cardiovascular mortality and hospitalisation endpoints) are required to determine whether mask-based treatment for SDB is appropriate for patients with chronic systolic heart failure and obstructive sleep apnoea, for those with heart failure with preserved ejection fraction, and for those with decompensated heart failure. New therapies for sleep apnoea-such as implantable phrenic nerve stimulators-also require robust assessment. No longer can the surrogate endpoints of improvement in respiratory and sleep metrics be taken as adequate therapeutic outcome measures in patients with heart failure and sleep apnoea

Defining the Critical Hurdles in Cancer Immunotherapy

ABSTRACT: Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators, others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet be overcome to improve outcomes of patients with cancer

Associations of BCL-2 (RS17759659), CTLA-4 (RS231775), APO-1/FAS (RS2234767) genes polymorphisms with activity of proliferation and apoptosis in thyroid tissue of patients with nodular forms of goiter combined with autoimmune thyroiditis and thyroid adenoma

The study of apoptosis and proliferative activity in the thyroid gland (TG) tissue of patients with nodular goiter and autoimmune thyroiditis (NGAIT) and thyroid adenoma (TA) is based on the expression/density of Fas/FasL, BCL-2, p53, and Ki-67 markers assessment depending on the genetic polymorphisms of BCL-2 (rs17759659), CTLA-4 (rs231775) and APO-1/Fas (rs2234767) genes.Several mechanisms of thyroid cells' programmed killing are activated in NGAIT and TA with domination of Fas-induced apoptosis, which strongly associates with the BCL-2 gene's (rs17759659) promoter (F=25.33; p<0.001) and almost six fold weaker associates with the CTLA-4 gene's (rs231775) promoter (F=4.23, p=0.017). Factors that decrease the likelihood of NGAIT and TA regardless of the CTLA-4 (rs231775) and APO-1/Fas (rs2234767) genes' genotypes are the high Ki-67 density and reduction of cells containing p53 or BCL-2 proteins (OR=0.07-0.17; 95% CI OR: 0.03-0.36; p<0.001, and OR=0.08-0.11; 95% CI OR: 0.02-0.31; p<0.001, re­spectively). High expression of surface Fas and FasL in lymphoid infiltration and de­struction of thyroid cells (stronger in GG-genotype carriers of the BCL-2 gene by 18.54% (pAA=0.043) and 36.18% (pAG=0.018), respectively) indicates the initiation of the external pathway of apoptosis through the caspase mechanism (effector caspase- 8)

Поліморфізм генів apo-1 / fas, ctla-4 та bcl-2 у пацієнтів, оперованих із приводу вузлової патології щитоподібної залози

The aim of the work: to analyze the frequency of polymorphic variants of genes BCL-2 (rs17759659), CTLA-4 (rs231775), APO-1/ Fas (rs2234767) in patients, operated on nodular thyroid pathology with regard to its form (NGAIT, TA- thyroid adenoma).Materials and Methods. An analysis of the frequency of polymorphic variants of genes BCL-2 (rs17759659), CTLA-4 (rs231775), APO-1/Fas (rs2234767) in 125 patients, operated on nodular thyroid pathology with regard to its form (NGAIT, TA) was conducted. Also, we examined 25 healthy donors. The study of polymorphism of genes was carried out by the method of polymerase chain reac­tion in real time.Results and Discussion. Mutation of BCL-2 gene (rs17759659) and CTLA-4 (rs231775) in the homozygous state among patients, operated on nodular thyroid pathology occurs with a frequency 3.2–4.0 % no reliable difference between patients with thyroid pathology and healthy. Mutation of the gene APO-1/Fas (rs2234767) in the homozygous state among surveyed patients was not met at all.Цель работы: провести анализ частоты полиморфных вариантов генов BCL-2 ( rs17759659), CTLA-4 ( rs231775), APO-1/Fas (rs2234767) у пациентов, оперированных по поводу узловой патологии щитовидной железы (ЩЖ) с учетом ее вида (узловой зоб на фоне аутоиммунного тиреоидита, аденома щитовидной железы.Материалы и методы. Проведен анализ частоты полиморфных вариантов генов BCL-2 ( rs17759659), CTLA-4 (rs231775), APO-1/Fas (rs2234767) у 125 пациентов, оперированных по поводу узловой патологии щитовидной железы с учетом ее вида (узловой зоб на фоне аутоиммунного тиреоидита, аденома щитовидной железы). Также обследовано 25 практически здоровых доноров. Исследование полиморфизма генов проводили методом полимеразной цепной реакции в режиме реального времени.Результаты исследований и их обсуждение. Мутация генов BCL-2 ( rs17759659) и CTLA-4 ( rs231775) в гомозиготном состоянии среди пациентов, оперированных по поводу узловой патологии щитовидной железы, встречается с частотой 3,2– 4,0 % без достоверной разницы между больными на патологию щитовидной железы и здоровыми. Мутация гена APO-1/Fas (rs2234767) в гомозиготном состоянии среди обследованных не встречалась вообще.Мета роботи: провести аналіз частоти поліморфних варіантів генів BCL-2 (rs17759659), CTLA-4 (rs231775), APO-1/Fas (rs2234767) у хворих, оперованих із приводу вузлової патології щитоподібної залози із урахуванням її виду вузловий зоб на фоні автоімунного тиреоїдиту, аденома щитоподібної залози. Матеріали і методи. Проведено аналіз частоти поліморфних варіантів генів BCL-2 (rs17759659), CTLA-4 (rs231775), APO-1/Fas (rs2234767) у 125 хворих, оперованих з приводу вузлової патології щитоподібної залози із урахуванням її виду – вузлового зоба на фоні автоімунного тиреоїдиту, аденома щитоподібної залози. Також обстежено 25 практично здорових донорів. Дослідження поліморфізму генів проводили методом полімеразної ланцюгової реакції в режимі реального часу.Результати досліджень та їх обговорення. Мутація генів BCL-2 (rs17759659) та CTLA-4 (rs231775) у гомозиготному стані у хворих, оперованих з приводу вузлової патології щитоподібної залози, зустрічається із частотою 3,2–4,0 % без вірогідної різниці між хворими на патологію щитоподібної залози та здоровими. Мутація гена APO-1/Fas (rs2234767) у гомозиготному стані серед обстежених не траплялася взагалі

Effective transcription factor binding site prediction using a combination of optimization, a genetic algorithm and discriminant analysis to capture distant interactions

<p>Abstract</p> <p>Background</p> <p>Reliable transcription factor binding site (TFBS) prediction methods are essential for computer annotation of large amount of genome sequence data. However, current methods to predict TFBSs are hampered by the high false-positive rates that occur when only sequence conservation at the core binding-sites is considered.</p> <p>Results</p> <p>To improve this situation, we have quantified the performance of several Position Weight Matrix (PWM) algorithms, using exhaustive approaches to find their optimal length and position. We applied these approaches to bio-medically important TFBSs involved in the regulation of cell growth and proliferation as well as in inflammatory, immune, and antiviral responses (NF-κB, ISGF3, IRF1, STAT1), obesity and lipid metabolism (PPAR, SREBP, HNF4), regulation of the steroidogenic (SF-1) and cell cycle (E2F) genes expression. We have also gained extra specificity using a method, entitled SiteGA, which takes into account structural interactions within TFBS core and flanking regions, using a genetic algorithm (GA) with a discriminant function of locally positioned dinucleotide (LPD) frequencies.</p> <p>To ensure a higher confidence in our approach, we applied resampling-jackknife and bootstrap tests for the comparison, it appears that, optimized PWM and SiteGA have shown similar recognition performances. Then we applied SiteGA and optimized PWMs (both separately and together) to sequences in the Eukaryotic Promoter Database (EPD). The resulting SiteGA recognition models can now be used to search sequences for BSs using the web tool, SiteGA.</p> <p>Analysis of dependencies between close and distant LPDs revealed by SiteGA models has shown that the most significant correlations are between close LPDs, and are generally located in the core (footprint) region. A greater number of less significant correlations are mainly between distant LPDs, which spanned both core and flanking regions. When SiteGA and optimized PWM models were applied together, this substantially reduced false positives at least at higher stringencies.</p> <p>Conclusion</p> <p>Based on this analysis, SiteGA adds substantial specificity even to optimized PWMs and may be considered for large-scale genome analysis. It adds to the range of techniques available for TFBS prediction, and EPD analysis has led to a list of genes which appear to be regulated by the above TFs.</p

2014 Wild Blueberry Project Reports

FOOD SCIENCE AND NUTRITION PAGE 1. Development of effective intervention measures to maintain and improve food safety for wild blueberries 2. Role of wild blueberries on lipid metabolism and inflammation as related to obesity and the Metabolic Syndrome ENTOMOLOGY 3. Control tactics for blueberry pest insects, 2014 4. Pest biology and IPM, 2014 5. Biology of spotted wing drosophila, 2014 6. Biology of blueberry, beneficial insects, and blueberry pollination DISEASE MANAGEMENT 7. Research and control of mummy berry disease 8. Evaluation of fungicides for control of mummy berry on lowbush blueberry (2014) WEED MANAGEMENT 9. A 2014 preliminary trial for a Callisto-Matrix tank mix versus a traditional wild blueberry herbicide spray regimen EXTENSION 10. Wild blueberry Extension Education Program in 2014 INPUT SYSTEMS STUDY – SCRI GRANT 11. Systems approach to improving the sustainability of wild blueberry production, Year Five of a six-year study – experimental design 12. Food safety- Prevalence study of Escherichia coli O157:H7, Listeria monocytogenes and Salmonella spp. on lowbush blueberries (Vaccinium angustifolium) 13. Systems approach to improving the sustainability of wild blueberry production, Year 5 – reports from Frank Drummond 14. Systems approach to improving the sustainability of wild blueberry production, 2014, Year 5 of a six-year study, disease management results 15. Systems approach to improving the sustainability of wild blueberry production, Year Five of a six-year study, weed management results 16. Systems approach to improving the sustainability of wild blueberry production, Year Five of a six year study, plant productivity 17. 2014 economic analysis of Maine blueberry production systems including an introductory risk analysis 18. Biosensor development for food safety (ancillary study) 19. Ancillary projects in disease research (ancillary study) 20. Systems approach to improving the sustainability of wild blueberry production – Ancillary land-leveling study, Year Four of a four-year study (ancillary study) 21. 2013-14 evaluation of three pre-emergence herbicides alone and in combination with Velpar or Sinbar for effects on wild blueberry productivity and weed control – 2014 crop year results (ancillary study) 22. Evaluation of fall and spring combinations of preemergence herbicides to prevent weed resistance in wild blueberry fields, 2013-15 (ancillary study) 23. Post-harvest control of red sorrel in a non-crop blueberry field, 2012-2014 (ancillary study) 24. Post-harvest control of red sorrel in a non-crop blueberry field, 2013-2015 (ancillary study) 25. Effect of soil nutrient amendments on growth and yield of wild blueberries in Maine (ancillary study

Change in diet, physical activity, and body weight among young-adults during the transition from high school to college

<p>Abstract</p> <p>Background</p> <p>The freshmen year of college is likely a critical period for risk of weight gain among young-adults.</p> <p>Methods</p> <p>A longitudinal observational study was conducted to examine changes in weight, dietary intake, and other health-related behaviors among first-year college students (n = 186) attending a public University in the western United States. Weight was measured at the beginning and end of fall semester (August – December 2005). Participants completed surveys about dietary intake, physical activity and other health-related behaviors during the last six months of high school (January – June 2005) in August 2005 and during their first semester of college (August – December 2005) in December 2005.</p> <p>Results</p> <p>159 students (n = 102 women, 57 men) completed both assessments. The average BMI at the baseline assessment was 23.0 (standard deviation (SD) 3.8). Although the average amount of weight gained during the 15-week study was modest (1.5 kg), 23% of participants gained ≥ 5% of their baseline body weight. Average weight gain among those who gained ≥ 5% of baseline body weight was 4.5 kg. Those who gained ≥ 5% of body weight reported less physical activity during college than high school, were more likely to eat breakfast, and slept more than were those who did not gain ≥ 5% of body weight.</p> <p>Conclusion</p> <p>Almost one quarter of students gained a significant amount of weight during their first semester of college. This research provides further support for the implementation of education or other strategies aimed at helping young-adults entering college to achieve or maintain a healthy body weight.</p