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New insights into the health effects of dietary saturated and omega-6 and omega-3 polyunsaturated fatty acids
Cardiovascular diseases and cancers are leading causes of morbidity and mortality. Reducing dietary saturated fat and replacing it with polyunsaturated fat is still the main dietary strategy to prevent cardiovascular diseases, although major flaws have been reported in the analyses supporting this approach. Recent studies introducing the concept of myocardial preconditioning have opened new avenues to understand the complex interplay between the various lipids and the risk of cardiovascular diseases. The optimal dietary fat profile includes a low intake of both saturated and omega-6 fatty acids and a moderate intake of omega-3 fatty acids. This profile is quite similar to the Mediterranean diet. On the other hand, recent studies have found a positive association between omega-6 and breast cancer risk. In contrast, omega-3 fatty acids do have anticancer properties. It has been shown that certain (Mediterranean) polyphenols significantly increase the endogenous synthesis of omega-3 whereas high intake of omega-6 decreases it. Finally, epidemiological studies suggest that a high omega-3/omega-6 ratio may be the optimal strategy to decrease breast cancer risk. Thus, the present high intake of omega-6 in many countries is definitely not the optimal strategy to prevent CVD and cancers. A moderate intake of plant and marine omega-3 in the context of the traditional Mediterranean diet (low in saturated and omega-6, but high in plant monounsaturated fat) appears to be the best approach to reduce the risk of both cardiovascular diseases and cancers, in particular breast cancer.
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Common variants in mismatch repair genes associated with increased risk of sperm DNA damage and male infertility
Background:
The mismatch repair (MMR) pathway plays an important role in the maintenance of the genome integrity, meiotic recombination and gametogenesis. This study investigated whether genetic variations in MMR genes are associated with an increased risk of sperm DNA damage and male infertility.
Methods:
We selected and genotyped 21 tagging single nucleotide polymorphisms (SNPs) in five MMR genes (MLH1, MLH3, PMS2, MSH4 and MSH5) using the SNPstream 12-plex platform in a case-control study of 1,292 idiopathic infertility patients and 480 fertile controls in a Chinese population. Sperm DNA damage levels were detected with the Tdt-mediated dUTP nick end labelling (TUNEL) assay in 450 cases. Fluorescence resonance energy transfer (FRET) and co-immunoprecipitation techniques were employed to determine the effects of functional variants.
Results:
One intronic SNP in MLH1 (rs4647269) and two non-synonymous SNPs in PMS2 (rs1059060, Ser775Asn) and MSH5 (rs2075789, Pro29Ser) seem to be risk factors for the development of azoospermia or oligozoospermia. Meanwhile, we also identified a possible contribution of PMS2 rs1059060 to the risk of male infertility with normal sperm count. Among patients with normal sperm count, MLH1 rs4647269 and PMS2 rs1059060 were associated with increased sperm DNA damage. Functional analysis revealed that the PMS2 rs1059060 can affect the interactions between MLH1 and PMS2.
Conclusions:
Our results provide evidence supporting the involvement of genetic polymorphisms in MMR genes in the aetiology of male infertility.
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Novel regulatory therapies for prevention of GVHD
Graft-versus-host disease is one of the major transplant-related complications in allogeneic hematopoietic stem cell transplantation. Continued efforts have been made to prevent the occurrence of severe graft-versus-host disease by eliminating or suppressing donor-derived effector T cells. Conventional immunosuppression does not adequately prevent graft-versus-host disease, especially in mismatched transplants. Unfortunately, elimination of donor-derived T cells impairs stem cell engraftment, and delays immunologic reconstitution, rendering the recipient susceptible to post-transplant infections and disease relapse, with potentially lethal consequences. In this review, we discuss the role of dynamic immune regulation in controlling graft-versus-host disease, and how cell based therapies are being developed using regulatory T cells and other tolerogenic cells for the prevention and treatment of graft-versus-host disease. In addition, advances in the design of cytoreductive conditioning regimens to selectively target graft-versus-host disease-inducing donor-derived T cells that have improved the safety of allogeneic stem cell transplantation are reviewed. Finally, we discuss advances in our understanding of the tolerogenic facilitating cell population, a phenotypically and functionally distinct population of bone marrow-derived cells which promote hematopoietic stem cell engraftment while reducing the risk of graft-versus-host disease.
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Lifestyle interventions for overweight and obese pregnant women to improve pregnancy outcome: systematic review and meta-analysis
Background:
Overweight and obesity pose a big challenge to pregnancy as they are associated with adverse maternal and perinatal outcome. Evidence of lifestyle intervention resulting in improved pregnancy outcome is conflicting. Hence the objective of this study is to determine the efficacy of antenatal dietary, activity, behaviour or lifestyle interventions in overweight and obese pregnant women to improve maternal and perinatal outcomes.
Methods:
A systematic review and meta-analyses of randomised and non-randomised clinical trials following prior registration (CRD420111122 http://www.crd.york.ac.uk/PROSPERO) and PRISMA guidelines was employed. A search of the Cochrane Library, EMBASE, MEDLINE, CINAHL, Maternity and Infant care and eight other databases for studies published prior to January 2012 was undertaken. Electronic literature searches, study selection, methodology and quality appraisal were performed independently by two authors. Methodological quality of the studies was assessed according to Cochrane risk of bias tool. All appropriate randomised and non-randomised clinical trials were included while exclusions consisted of interventions in pregnant women who were not overweight or obese, had pre-existing diabetes or polycystic ovarian syndrome, and systematic reviews. Maternal outcome measures, including maternal gestational weight gain, gestational diabetes and Caesarean section, were documented. Fetal outcomes, including large for gestational age and macrosomia (birth weight > 4 kg), were also documented.
Results:
Thirteen randomised and six non-randomised clinical trials were identified and included in the meta-analysis. The evidence suggests antenatal dietary and lifestyle intervention in obese pregnant women reduces maternal pregnancy weight gain (10 randomised clinical trials; n = 1228; -2.21 kg (95% confidence interval -2.86 kg to -1.59 kg)) and a trend towards a reduction in the prevalence of gestational diabetes (six randomised clinical trials; n = 1,011; odds ratio 0.80 (95% confidence interval 0.58 to 1.10)). There were no clear differences reported for other outcomes such as Caesarean delivery, large for gestational age, birth weight or macrosomia. All available studies were assessed to be of low to medium quality.
Conclusion:
Antenatal lifestyle intervention is associated with restricted gestational weight gain and a trend towards a reduced prevalence of gestational diabetes in the overweight and obese population. These findings need to be interpreted with caution as the available studies were of poor to medium quality.
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The regulation of mobile health applications
In July 2011, the United States Food and Drug Administration issued draft guidance concerning the regulation of mobile medical applications (applications on a wireless device that are used as accessories to medical devices or to convert a mobile platform to a medical device). While the suggestion of regulation is rooted in patient safety, concerns about limits on innovation and discovery as well as the evolving nature of both mobile health and current health care delivery have emerged. This article discusses the prevalence of mobile health, the context of regulation concerning mobile medical applications, and implications for the future.
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Lifestyle factors affecting gastroesophageal reflux disease symptoms: a cross-sectional study of healthy 19864 adults using FSSG scores
Background:
Gastroesophageal reflux disease (GERD) is a very common disorder worldwide, comprised of reflux esophagitis (RE) and non-erosive reflux disease (NERD). As more than half of GERD patients are classified into the NERD group, precise evaluation of bothersome epigastric symptoms is essential. Nevertheless, compared with many reports targeting endoscopic reflux esophagitis, large-scale studies focusing on GERD symptoms have been very scarce.
Methods:
To elucidate lifestyle factors affecting GERD symptoms, 19,864 healthy adults in Japan were analyzed. Sub-analyses of 371 proton pump inhibitor (PPI) users and 539 histamine H2-receptor antagonist (H2RA) users were also performed. Using the FSSG (Frequency Scale for the Symptoms of GERD) score as a response variable, 25 lifestyle-related factors were univariately evaluated by Student's t-test or Pearson's correlation coefficient, and were further analyzed with multiple linear regression modelling.
Results:
Average FSSG scores were 4.8 ± 5.2 for total subjects, 9.0 ± 7.3 for PPI users, and 8.2 ± 6.6 for H2RA users. Among the total population, positively correlated factors and standardized coefficients (β) for FSSG scores are inadequate sleep (β = 0.158), digestive drug users (β = 0.0972 for PPI, β = 0.0903 for H2RA, and β = 0.104 for others), increased body weight in adulthood (β = 0.081), dinner just before bedtime (β = 0.061), the habit of midnight snack (β = 0.055), lower body mass index (β = 0.054), NSAID users (β = 0.051), female gender (β = 0.048), lack of breakfast (β = 0.045), lack of physical exercise (β = 0.035), younger age (β = 0.033), antihyperglycemic agents non-users (β = 0.026), the habit of quick eating (β = 0.025), alcohol drinking (β = 0.025), history of gastrectomy (β = 0.024), history of cardiovascular disease (β = 0.020), and smoking (β = 0.018). Positively correlated factors for PPI users are female gender (β = 0.198), inadequate sleep (β = 0.150), lack of breakfast (β = 0.146), antihypertensive agent non-users (β = 0.134), and dinner just before bedtime (β = 0.129), whereas those for H2RA users are inadequate sleep (β = 0.248), habit of midnight snack (β = 0.160), anticoagulants non-users (β = 0.106), and antihypertensive agents non-users (β = 0.095).
Conclusions:
Among many lifestyle-related factors correlated with GERD symptoms, poor quality of sleep and irregular dietary habits are strong risk factors for high FSSG scores. At present, usual dose of PPI or H2RA in Japan cannot fully relieve GERD symptoms.
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Stem cells and other innovative intraarticular therapies for osteoarthritis: what does the future hold?
Osteoarthritis (OA), the most common type of arthritis in the world, is associated with suffering due to pain, productivity loss, decreased mobility and quality of life. Systemic therapies available for OA are mostly symptom modifying and have potential gastrointestinal, renal, hepatic and cardiac side effects. BMC Musculoskeletal Disorders recently published a study showing evidence of reparative effects demonstrated by homing of intra-articularly (IA) injected autologous bone marrow stem cells in damaged cartilage in an animal model of OA, along with clinical and radiographic benefit. This finding adds to the growing literature showing the potential benefit of IA bone marrow stem cells. Other potential IA therapies include IL-1 receptor antagonists, conditioned autologous serum, botulinum toxin and bone morphogenetic protein-7. For each of these therapies, trial data in humans has been published, but more studies are needed to establish that they are safe and effective. Several promising new OA treatments are on the horizon, but challenges remain to finding safe and effective local and systemic therapies for OA.Please see related article: http://www.biomedcentral.com/1471-2474/12/259
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A new analysis approach of epidermal growth factor receptor pathway activation patterns provides insights into cetuximab resistance mechanisms in head and neck cancer
The pathways downstream of the epidermal growth factor receptor (EGFR) have often been implicated to play crucial roles in development and progression of various cancer types. Different authors have proposed models in cell lines in which they study the modes of pathway activities after perturbation experiments. It is prudent to believe that a better understanding of these pathway activation patterns might lead to novel treatment concepts for cancer patients or at least allow a better stratification of patient collectives into different risk groups or into groups that might respond to different treatments. Traditionally such analyses focused on the individual players of the pathways. More recently in the field of Systems Biology a plethora of approaches has been developed that take a more holistic view on the signaling pathways and their downstream transcriptional targets. Fertig et al. have recently developed a new method to identify patterns and biological process activity from transcriptomics data and they demonstrate the utility of this methodology to analyze gene-expression activity downstream of EGFR in head and neck squamous cell carcinoma (HNSCC) to study cetuximab resistance.Please see related article: http://www.biomedcentral.com/1471-2164/13/160
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New race and ethnicity standards: elucidating health disparities in diabetes
The concepts of race and ethnicity are useful for understanding the distribution of disease in the population and for identifying at-risk groups for prevention and treatment efforts. The U.S. Department of Health and Human Services recently updated the race and ethnicity classifications in order to more effectively monitor health disparities. Differences in chronic disease mortality rates are contributing to race and ethnic health disparities in life expectancy in the United States. The prevalence of diabetes is higher in African Americans and Hispanics compared to white Americans, and parallel trends are seen in diabetes risk factors, including physical inactivity, dietary patterns and obesity. Further research is required to determine the extent to which the observed differences in diabetes prevalence are attributable to differences in lifestyle versus other characteristics across race and ethnic groups.
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The role of nutrition in integrated programs to control neglected tropical diseases
There are strong and direct relationships between undernutrition and the disease caused by infectious organisms, including the diverse pathogens labeled as neglected tropical diseases (NTDs). Undernutrition increases the risk of infection, the severity of disease and the risk that children will die, while the physical damage, loss of appetite, and host responses during chronic infection can contribute substantially to undernutrition. These relationships are often synergistic. This opinion article examines the role of nutrition in controlling NTDs and makes the point that mass drug treatment - the major strategy currently proposed to control several diseases - is crucial to controlling disease and transmission, but is only the start of the process of physical recovery. Without adequate energy and nutrients to repair damaged tissues or recover lost growth and development, the benefits of treatment may not be evident quickly; the effects of control programs may be not appreciated by beneficiaries; while vulnerability to reinfection and disease may not be reduced. There is substantial potential for nutritional interventions to be added to large scale programs to deliver drug treatments and thereby contribute, within a broad strategy of public health interventions and behavior change activities, to controlling and preventing neglected tropical diseases in populations, and to restoring their health.
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