Differential Effects of Lipid-lowering Drugs in Modulating Morphology of Cholesterol Particles.

Treatment of dyslipidemia patients with lipid-lowering drugs leads to a significant reduction in low-density lipoproteins (LDL) level and a low to moderate level of increase in high-density lipoprotein (HDL) cholesterol in plasma. However, a possible role of these drugs in altering morphology and distribution of cholesterol particles is poorly understood. Here, we describe the in vitro evaluation of lipid-lowering drug effects in modulating morphological features of cholesterol particles using the plaque array method in combination with imaging flow cytometry. Image analyses of the cholesterol particles indicated that lovastatin, simvastatin, ezetimibe, and atorvastatin induce the formation of both globular and linear strand-shaped particles, whereas niacin, fibrates, fluvastatin, and rosuvastatin induce the formation of only globular-shaped particles. Next, purified very low-density lipoprotein (VLDL) and LDL particles incubated with these drugs showed changes in the morphology and image texture of cholesterol particles subpopulations. Furthermore, screening of 50 serum samples revealed the presence of a higher level of linear shaped HDL cholesterol particles in subjects with dyslipidemia (mean of 18.3%) compared to the age-matched normal (mean of 11.1%) samples. We also observed considerable variations in lipid-lowering drug effects on reducing linear shaped LDL and HDL cholesterol particles formation in serum samples. These findings indicate that lipid-lowering drugs, in addition to their cell-mediated hypolipidemic effects, may directly modulate morphology of cholesterol particles by a non-enzymatic mechanism of action. The outcomes of these results have potential to inform diagnosis of atherosclerosis and predict optimal lipid-lowering therapy

Personal and social norms for food portion sizes in lean and obese adults.

BACKGROUND: Portion size is an important component of dietary advice for weight control, but little is known about what portion sizes people consider 'normal'. This study determined the effect of body mass index (BMI), gender, dietary restraint and liking of the food on personal and social portion size norms for a range of foods and the degree of certainty over the norms. METHODS: Thirty lean (BMI 20-25 kg m(-)(2)) and 30 obese (BMI 30-35 kg m(-)(2)) men and women (aged 18-60 years) viewed 17 different portion sizes of 12 foods on a computer screen on two occasions a week apart. Participants responded 'more' or 'less' to each photograph reflecting personal portion size preference or perceived portion sizes of others. Personal and social norms for portion sizes of each food were determined using the method of constant stimuli giving a sigmoidal curve of the probability of answering 'less' over a range of portion sizes. The slope of the sigmoid at the norm gave a measure of certainty about the norm. Regression models were used to examine the effect of BMI, gender, dietary restraint and liking of the food on personal norms, social norms, the relationship between norms, and the slopes. RESULTS: Personal norms were significantly larger in the obese (P=0.026), men (P<0.001), those with lower dietary restraint (P<0.001), and those with higher liking for the food (P<0.001). Social norms were larger for women (P=0.012). The slopes at the norms were 30% shallower in the obese and in men (P<0.001). CONCLUSION: Larger personal norms for portion size among the obese, men, those with lower dietary restraint and those with higher liking for a food imply greater consumption, which may undermine weight control. Shallower slopes for norms in the obese and in men may imply less clearly defined habitual portion sizes.This study was supported by a program grant from the UK Medical Research Council (U105960389).This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ijo.2015.4

If the shoe fits : Development of an on-line tool to aid practitioner/patient discussions about 'healthy footwear'

Background: A previous study highlighted the importance of footwear to individuals' sense of their identity, demonstrating that shoes must 'fit' someone socially, as well as functionally. However, unhealthy shoes can have a detrimental effect on both foot health and mobility. This project utilises qualitative social science methods to enable podiatrists to understand the broader contribution of footwear to patients' sense of themselves and from this an online toolkit was developed to aid footwear education. Method: Semi-structured interviews were conducted with six podiatrists/shoe-fitters and 13 people with foot pathologies, some of whom also completed shoe diaries. These were supplemented with some follow-up interviews and photographs of participants' own shoes were taken to allow in-depth discussions. Results: Four areas related to 'fit' were identified; practicalities, personal, purpose and pressures, all of which need to be considered when discussing changes in footwear. These were incorporated into an online toolkit which was further validated by service users and practitioners in a focus group. Conclusion: This toolkit can support podiatrists in partnership with patients to identify and address possible barriers to changing footwear towards a more suitable shoe. Enabling patients to make healthier shoe choices will help contribute to improvements in their foot health and mobility

Pelvic girdle pain - associations between risk factors in early pregnancy and disability or pain intensity in late pregnancy: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Recent studies have shown high prevalence rates for pelvic girdle pain (PGP) in pregnancy. Some risk factors for developing PGP have been suggested, but the evidence is weak. Furthermore there is almost no data on how findings from clinical examinations are related to subsequent PGP. The main purpose for this study was to study the associations between socio-demographical, psychological and clinical factors measured at inclusion in early pregnancy and disability or pain intensity in gestation week 30.</p> <p>Methods</p> <p>This is a prospective cohort study following women from early to late pregnancy. Eligible women were recruited at their first attendance at the maternity care unit. 268 pregnant women answered questionnaires and underwent clinical examinations in early pregnancy and in gestation week 30. We used scores on disability and pain intensity in gestation week 30 as outcome measures to capture the affliction level of PGP. Multiple linear regression analysis was used to study the associations between potential risk factors measured in early pregnancy and disability or pain intensity in gestation week 30.</p> <p>Results</p> <p>Self-reported pain locations in the pelvis, positive posterior pelvic pain provocation (P4) test and a sum of pain provocation tests in early pregnancy were significantly associated with disability and pain intensity in gestation week 30 in a multivariable statistic model. In addition, distress was significantly associated with disability. The functional active straight leg raise (ASLR) test, fear avoidance beliefs and the number of pain sites were not significantly associated with either disability or pain intensity.</p> <p>Conclusions</p> <p>The results suggest that a clinical examination, including a few tests, performed in early pregnancy may identify women at risk of a more severe PGP late in pregnancy. The identification of clinical risk factors may provide a foundation for development of targeted prevention strategies.</p

Timing of birth for women with a twin pregnancy at term: a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>There is a well recognized risk of complications for both women and infants of a twin pregnancy, increasing beyond 37 weeks gestation. Preterm birth prior to 37 weeks gestation is a recognized complication of a twin pregnancy, however, up to 50% of twins will be born after this time.</p> <p>The aims of this randomised trial are to assess whether elective birth at 37 weeks gestation compared with standard care in women with a twin pregnancy affects the risk of perinatal death, and serious infant complications.</p> <p>Methods/Design</p> <p>Design: Multicentred randomised trial.</p> <p>Inclusion Criteria: women with a twin pregnancy at 36⁶weeks or more without contraindication to continuation of pregnancy.</p> <p>Trial Entry & Randomisation: Following written informed consent, eligible women will be randomised from 36⁺⁶weeks gestation. The randomisation schedule uses balanced variable blocks, with stratification for centre of birth and planned mode of birth. Women will be randomised to either elective birth or standard care.</p> <p>Treatment Schedules: Women allocated to the elective birth group will be planned for elective birth from 37 weeks gestation. Where the plan is for vaginal birth, this will involve induction of labour. Where the plan is for caesarean birth, this will involve elective caesarean section. For women allocated to standard care, birth will be planned for 38 weeks gestation or later. Where the plan is for vaginal birth, this will involve either awaiting the spontaneous onset of labour, or induction of labour if required. Where the plan is for caesarean birth, this will involve elective caesarean section (after 38 and as close to 39 weeks as possible).</p> <p>Primary Study Outcome: A composite of perinatal mortality or serious neonatal morbidity.</p> <p>Sample Size: 460 women with a twin pregnancy to show a reduction in the composite outcome from 16.3% to 6.7% with adjustment for the clustering of twin infants within mothers (p = 0.05, 80% power).</p> <p>Discussion</p> <p>This is a protocol for a randomised trial, the findings of which will contribute information about the optimal time of birth for women with an uncomplicated multiple pregnancy at and beyond 37 weeks gestation.</p> <p>Clinical Trial Registration</p> <p>Current Controlled Trials ISRCTN15761056</p

Prevalence of hallux valgus in the general population: a systematic review and meta-analysis

BACKGROUND: Hallux valgus (HV) is a foot deformity commonly seen in medical practice, often accompanied by significant functional disability and foot pain. Despite frequent mention in a diverse body of literature, a precise estimate of the prevalence of HV is difficult to ascertain. The purpose of this systematic review was to investigate prevalence of HV in the overall population and evaluate the influence of age and gender. METHODS: Electronic databases (Medline, Embase, and CINAHL) and reference lists of included papers were searched to June 2009 for papers on HV prevalence without language restriction. MeSH terms and keywords were used relating to HV or bunions, prevalence and various synonyms. Included studies were surveys reporting original data for prevalence of HV or bunions in healthy populations of any age group. Surveys reporting prevalence data grouped with other foot deformities and in specific disease groups (e.g. rheumatoid arthritis, diabetes) were excluded. Two independent investigators quality rated all included papers on the Epidemiological Appraisal Instrument. Data on raw prevalence, population studied and methodology were extracted. Prevalence proportions and the standard error were calculated, and meta-analysis was performed using a random effects model. RESULTS: A total of 78 papers reporting results of 76 surveys (total 496,957 participants) were included and grouped by study population for meta-analysis. Pooled prevalence estimates for HV were 23% in adults aged 18-65 years (CI: 16.3 to 29.6) and 35.7% in elderly people aged over 65 years (CI: 29.5 to 42.0). Prevalence increased with age and was higher in females [30% (CI: 22 to 38)] compared to males [13% (CI: 9 to 17)]. Potential sources of bias were sampling method, study quality and method of HV diagnosis. CONCLUSIONS: Notwithstanding the wide variation in estimates, it is evident that HV is prevalent; more so in females and with increasing age. Methodological quality issues need to be addressed in interpreting reports in the literature and in future research

Bee Venom Induces Unfolded Protein Response in A172 Glioblastoma Cell Line

Background: Glioblastoma is a type of brain tumor with poor response to available therapies, and shows high rate of mortality. Despite remarkable advancements in our knowledge about cytogenetic and pathophysiologic features of glioblastoma, current treatment strategies are mainly based on cytotoxic drugs; however, these therapeutic approaches are facing progressive failure because of the resistant nature of glioblastomas. In the recent years, however, promising results have emerged owing to targeted therapies toward molecular pathways within cancerous cells. Unfolded Protein Response (UPR) is a remarkable signaling pathway that triggers both apoptosis and survival pathways within cells, and therefore induces UPR-related apoptotic pathways in cancer cells by ER stress inducers. Objectives: Recently, the role of Bee venom (Bv), which contains powerful bioactive peptides, in inducing UPR-related apoptosis was revealed in cancer cell lines. Nevertheless, currently there are no reports of Bv potential ability in induction of UPR apoptotic routes in glioblastoma. The aim of current study was to evaluate possible role of Bee venome in inducing of UPR pathway within A172 glioblastoma cell line. Materials and Methods: We treated the A172 glioblastoma cell line with different Bv doses, and assessed UPR-related genes expression by real-time Polymerase Chain Reaction (PCR). Results: The IC50 of Bv for the studied cell line was 28 μg/mL. Furthermore, we observed that Bv can induce UPR target genes (Grp94 and Gadd153) over-expression through a dose-dependent mechanism. Conclusions: Our results suggest the potential role of Bv as a therapeutic agent for glioblastomas. Keywords: Glioblastoma; A172 Cell Line; Unfolded Protein Response; Bee Veno

Optimizing search strategies to identify randomized controlled trials in MEDLINE

BACKGROUND: The Cochrane Highly Sensitive Search Strategy (HSSS), which contains three phases, is widely used to identify Randomized Controlled Trials (RCTs) in MEDLINE. Lefebvre and Clarke suggest that reviewers might consider using four revisions of the HSSS. The objective of this study is to validate these four revisions: combining the free text terms volunteer, crossover, versus, and the Medical Subject Heading CROSS-OVER STUDIES with the top two phases of the HSSS, respectively. METHODS: We replicated the subject search for 61 Cochrane reviews. The included studies of each review that were indexed in MEDLINE were pooled together by review and then combined with the subject search and each of the four proposed search strategies, the top two phases of the HSSS, and all three phases of the HSSS. These retrievals were used to calculate the sensitivity and precision of each of the six search strategies for each review. RESULTS: Across the 61 reviews, the search term versus combined with the top two phases of the HSSS was able to find 3 more included studies than the top two phases of the HSSS alone, or in combination with any of the other proposed search terms, but at the expense of missing 56 relevant articles that would be found if all three phases of the HSSS were used. The estimated time needed to finish a review is 1086 hours for all three phases of the HSSS, 823 hours for the strategy versus, 818 hours for the first two phases of the HSSS or any of the other three proposed strategies. CONCLUSION: This study shows that compared to the first two phases of the HSSS, adding the term versus to the top two phases of the HSSS balances the sensitivity and precision in the reviews studied here to some extent but the differences are very small. It is well known that missing relevant studies may result in bias in systematic reviews. Reviewers need to weigh the trade-offs when selecting the search strategies for identifying RCTs in MEDLINE

'A good fit?' Bringing the Sociology of Footwear to the Clinical Encounter in Podiatry Services : A Narrative Review

Background: This narrative review explores the ways in which drawing on theories and methods used in sociological work on footwear and identity can contribute to healthcare research with podiatrists and their patients, highlighting recent research in this field, implications for practice and potential areas for future development. Traditionally, research within Podiatry Services has tended to adopt a quantitative, positivist focus, developing separately from a growing body of sociological work exploring the importance of shoes in constructing identity and self-image. Bringing qualitative research drawing on sociological theory and methods to the clinical encounter has real potential to increase our understanding of patient values, motivations and – crucially – any barriers to adopting ‘healthier’ footwear that they may encounter. Such work can help practitioners to understand why patients may resist making changes to their footwear practices, and help us to devise new ways for practitioners to explore and ultimately break down individual barriers to change (including their own preconceptions as practitioners). This, in turn, may lead to long-term, sustainable changes to footwear practices and improvements in foot health for those with complex health conditions and the wider population. Conclusion: A recognition of the complex links between shoes and identity is opening up space for discussion of patient resistance to footwear changes, and paving the way for future research in this field beyond the temporary ‘moment’ of the clinical encounter