Pilot case-control investigation of risk factors for hip fractures in the urban Indian population

<p>Abstract</p> <p>Background</p> <p>Despite the reported high prevalence of osteoporosis in India, there have been no previous studies examining the risk factors for hip fracture in the Indian population.</p> <p>Methods</p> <p>We carried out a case control investigation comprising 100 case subjects (57 women and 43 men) admitted with a first hip fracture into one of three hospitals across New Delhi. The 100 controls were age and sex matched subjects who were either healthy visitors not related to the case patients or hospital staff. Information from all subjects was obtained through a questionnaire based interview.</p> <p>Results</p> <p>There was a significant increase in the number of cases of hip fracture with increasing age. There were significantly more women (57%) than men (43%). Univariate analysis identified protective effects for increased activity, exercise, calcium and vitamin supplements, almonds, fish, paneer (cottage cheese), curd (plain yogurt), and milk. However, tea and other caffeinated beverages were significant risk factors. In women, hormone/estrogen therapy appeared to have a marginal protective effect. For all cases, decreased agility, visual impairment, long term medications, chronic illnesses increased the risk of hip fracture. The multivariate analysis confirmed a protective effect of increased activity and also showed a decrease in hip fracture risk with increasing body mass index (odds ratio (OR) 0.024, 95% confidence interval (CI) 0.006-0.10 & OR 0.81, 95% CI 0.68-0.97 respectively). Individuals who take calcium supplements have a decreased risk of hip fracture (OR 0.076; CI 0.017-0.340), as do individuals who eat fish (OR 0.094; CI 0.020-0.431), and those who eat paneer (OR 0.152; 0.031-0.741). Tea drinkers have a higher risk of hip fracture (OR 22.8; 95% CI 3.73-139.43). Difficulty in getting up from a chair also appears to be an important risk factor for hip fractures (OR 14.53; 95% CI 3.86-54.23).</p> <p>Conclusions</p> <p>In the urban Indian population, dietary calcium, vitamin D, increased body mass index, and higher activity levels have a significant protective effect on hip fracture. On the other hand, caffeine intake and decreased agility increase the risk of hip fracture. Future studies should be done in order to direct primary preventive programs for hip fracture in India.</p

Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid.

Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5-20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of D-glucose was lower than D-fructose. However, uptake of D-glucose was higher than D-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection

Polyglutamine Expansion Accelerates the Dynamics of Ataxin-1 and Does Not Result in Aggregate Formation

Polyglutamine expansion disorders are caused by an expansion of the polyglutamine (polyQ) tract in the disease related protein, leading to severe neurodegeneration. All polyQ disorders are hallmarked by the presence of intracellular aggregates containing the expanded protein in affected neurons. The polyQ disorder SpinoCerebellar Ataxia 1 (SCA1) is caused by a polyQ-expansion in the ataxin-1 protein, which is thought to lead to nuclear aggregates.Using advanced live cell fluorescence microscopy and a filter retardation assay we show that nuclear accumulations formed by polyQ-expanded ataxin-1 do not resemble aggregates of other polyQ-expanded proteins. Instead of being static, insoluble aggregates, nuclear accumulations formed by the polyQ-expanded ataxin-1 showed enhanced intracellular kinetics as compared to wild-type ataxin-1. During mitosis, ataxin-1 accumulations redistributed equally among daughter cells, in contrast to polyQ aggregates. Interestingly, polyQ expansion did not affect the nuclear-cytoplasmic shuttling of ataxin-1 as proposed before.These results indicate that polyQ expansion does not necessarily lead to aggregate formation, and that the enhanced kinetics may affect the nuclear function of ataxin-1. The unexpected findings for a polyQ-expanded protein and their consequences for ongoing SCA1 research are discussed

Laparoscopic versus open colectomy for colon cancer in an older population: a cohort study

<p>Abstract</p> <p>Background</p> <p>Laparoscopic colectomy for colon cancer has been compared with open colectomy in randomized controlled trials, but these studies may not be generalizable because of strict enrollment and exclusion criteria which may explicitly or inadvertently exclude older individuals due to associated comorbidities. Previous studies of older patients undergoing laparoscopic colectomy have generally focused on short-term outcomes. The goals of this cohort study were to identify predictors of laparoscopic colectomy in an older population in the United States and to compare short-term and long-term outcomes.</p> <p>Methods</p> <p>Patients aged 65 years or older with incident colorectal cancer diagnosed 1996-2002 who underwent colectomy within 6 months of cancer diagnosis were identified from the linked Surveillance, Epidemiology, and End Results-Medicare database. Laparoscopic and open colectomy patients were compared with respect to length of stay, blood transfusion requirements, intensive care unit monitoring, complications, 30-day mortality, and long-term survival. We adjusted for potential selection bias in surgical approach with propensity score matching.</p> <p>Results</p> <p>Laparoscopic colectomy cases were associated with left-sided tumors; areas with higher population density, income, and education level; areas in the western United States; and National Cancer Institute-designated cancer centers. Laparoscopic colectomy cases had shorter length of stay and less intensive care unit monitoring. Although laparoscopic colectomy patients (n = 424) had fewer complications (21.5% versus 26.3%), lower 30-day mortality (3.3% versus 5.8%), and longer median survival (6.6 versus 4.8 years) compared with open colectomy patients (n = 27,012), after propensity score matching these differences disappeared.</p> <p>Conclusions</p> <p>In this older population, laparoscopic colectomy practice patterns were associated with factors which likely correlate with tertiary referral centers. Although short-term and long-term survival are comparable, laparoscopic colectomy offers shorter hospitalizations and less intensive care.</p

On-line health companion contact among chronically ill in the Netherlands

A health companion is a patient who supports another patient or patient group with a similar health condition. Health companions deliver more and more support by the Internet. However, little is known about the characteristics of the users, their motivation, type of technology used and effects on health and the healthcare delivery process. The objective of the paper is to understand motivation, technology and effects of on-line health companion contact in the Netherlands concerning chronic diseases (DBM, COPD, CHF, CRD, CMD). The On-line Health Companion Contact Model was created to frame the research process. An extensive on-line questionnaire was taken from patients with various chronic disorders and using on-line health companion contact to obtain quantitative and qualitative data. Obtaining information was found the key motivation for applying on-line health companion contact and several characteristics play a role in the selection to use a specific website, including: closed access; the topics discussed; the easy use; the type of users and a clear structure. Respondents prefer website facilitated by a forum or social networking site. Other factors are the possibility to share experiences with other patients, to find recognition and understanding and to meet new people. These positive aspects are of greater importance than the perceived barriers including privacy concerns, negative stories and whining other users and concerns regarding the quality of information. On-line health companion contact can increase the quality of life and self-management because respondents perceived to be better informed, better able to accept their disease, better deal with their situation and to receive an increased amount of social support

Hedonic and incentive signals for body weight control

Here we review the emerging neurobiological understanding of the role of the brain’s reward system in the regulation of body weight in health and in disease. Common obesity is characterized by the over-consumption of palatable/rewarding foods, reflecting an imbalance in the relative importance of hedonic versus homeostatic signals. The popular ‘incentive salience theory’ of food reward recognises not only a hedonic/pleasure component (‘liking’) but also an incentive motivation component (‘wanting’ or ‘reward-seeking’). Central to the neurobiology of the reward mechanism is the mesoaccumbal dopamine system that confers incentive motivation not only for natural rewards such as food but also by artificial rewards (eg. addictive drugs). Indeed, this mesoaccumbal dopamine system receives and integrates information about the incentive (rewarding) value of foods with information about metabolic status. Problematic over-eating likely reflects a changing balance in the control exerted by hypothalamic versus reward circuits and/or it could reflect an allostatic shift in the hedonic set point for food reward. Certainly, for obesity to prevail, metabolic satiety signals such as leptin and insulin fail to regain control of appetitive brain networks, including those involved in food reward. On the other hand, metabolic control could reflect increased signalling by the stomach-derived orexigenic hormone, ghrelin. We have shown that ghrelin activates the mesoaccumbal dopamine system and that central ghrelin signalling is required for reward from both chemical drugs (eg alcohol) and also from palatable food. Future therapies for problematic over-eating and obesity may include drugs that interfere with incentive motivation, such as ghrelin antagonists

Immunobiological effects of gemcitabine and capecitabine combination chemotherapy in advanced pancreatic ductal adenocarcinoma

Background: Preclinical studies suggest that chemotherapy may enhance the immune response against pancreatic cancer. Methods: The levels of granulocyte macrophage-colony-stimulating factor (GM-CSF) and interleukin-6 (IL-6) and the associated inflammatory marker C-reactive protein (CRP) were assessed in 38 patients receiving gemcitabine and capecitabine combination chemotherapy for advanced pancreatic cancer within the TeloVac trial. Apoptosis (M30) and total immune response (delayed-type hypersensitivity and/or T-cell response) were also assessed and levels of apoptosis induction correlated with immune response. The telomerase GV1001 vaccine was given either sequentially (n=18) or concomitantly (n=24) with the combination chemotherapy. Results: There were no differences between baseline and post-treatment levels of CRP (P=0.19), IL-6 (P=0.19) and GM-CSF (P=0.71). There was a positive correlation between post-chemotherapy CRP and IL-6 levels (r=0.45, P=0.005) and between CRP with carbohydrate antigen-19-9 (CA19-9) levels at baseline (r=0.45, P=0.015) and post treatment (r=0.40, P=0.015). The change in CRP and IL-6 levels was positively correlated (r=0.40, P=0.012). Hazard ratios (95% CI) for baseline CA19-9 (1.30 (1.07–1.59), P=0.009) and CRP (1.55 (1.00–2.39), P=0.049) levels were each independently predictive of survival. The M30 mean matched differences between pre- and post-chemotherapy showed evidence of apoptosis in both the sequential (P=0.058) and concurrent (P=0.0018) chemoimmunotherapy arms. Respectively, 5 of 10 and 9 of 20 patients had a positive immune response but there was no association with apoptosis. Conclusions: Combination gemcitabine and capecitabine chemotherapy did not affect circulating levels of GM-CSF, IL-6 and CRP. Chemotherapy-induced apoptosis was not associated with the immunogenicity induced by the GV1001 vaccine in advanced pancreatic cancer

Parity and breastfeeding are protective against breast cancer in Nigerian women

As the relation between reproductive factors and breast cancer risk has not been systematically studied in indigenous women of sub-Saharan Africa, we examined this in a case–control study in Nigeria. In-person interviews were conducted using structured questionnaires to collect detailed reproductive history in 819 breast cancer cases and 569 community controls between 1998 and 2006. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI). Compared with women with menarcheal age <17 years, the adjusted OR for women with menarcheal age ⩾17 years was 0.72 (95% CI: 0.54–0.95, P=0.02). Parity was negatively associated with risk (P-trend=0.02) but age at first live birth was not significant (P=0.16). Importantly, breast cancer risk decreased by 7% for every 12 months of breastfeeding (P-trend=0.005). It is worth noting that the distribution of reproductive risk factors changed significantly from early to late birth cohorts in the direction of increasing breast cancer incidence. Our findings also highlight the heterogeneity of breast cancer aetiology across populations, and indicate the need for further studies among indigenous sub-Saharan women

Limits on WWZ and WW\gamma couplings from p\bar{p}\to e\nu jj X events at \sqrt{s} = 1.8 TeV

We present limits on anomalous WWZ and WW-gamma couplings from a search for WW and WZ production in p-bar p collisions at sqrt(s)=1.8 TeV. We use p-bar p -> e-nu jjX events recorded with the D0 detector at the Fermilab Tevatron Collider during the 1992-1995 run. The data sample corresponds to an integrated luminosity of 96.0+-5.1 pb^(-1). Assuming identical WWZ and WW-gamma coupling parameters, the 95% CL limits on the CP-conserving couplings are -0.33<lambda<0.36 (Delta-kappa=0) and -0.43<Delta-kappa<0.59 (lambda=0), for a form factor scale Lambda = 2.0 TeV. Limits based on other assumptions are also presented.Comment: 11 pages, 2 figures, 2 table