Differential Modulation of Intracellular Survival of Cytosolic and Vacuolar Pathogens by Curcumin

Curcumin, a principal component of turmeric, acts as an immunomodulator regulating the host defenses in response to a diseased condition. The role of curcumin in controlling certain infectious diseases is highly controversial. It is known to alleviate symptoms of Helicobacter pylori infection and exacerbate that of Leishmania infection. We have evaluated the role of curcumin in modulating the fate of various intracellular bacterial pathogens. We show that pretreatment of macrophages with curcumin attenuates the infections caused by Shigella flexneri (clinical isolates) and Listeria monocytogenes and aggravates those caused by Salmonella enterica serovar Typhi CT18 (a clinical isolate), Salmonella enterica serovar Typhimurium, Staphylococcus aureus, and Yersinia enterocolitica. Thus, the antimicrobial nature of curcumin is not a general phenomenon. It modulated the intracellular survival of cytosolic (S. flexneri and L. monocytogenes) and vacuolar (Salmonella spp., Y. enterocolitica, and S. aureus) bacteria in distinct ways. Through colocalization experiments, we demonstrated that curcumin prevented the active phagosomal escape of cytosolic pathogens and enhanced the active inhibition of lysosomal fusion by vacuolar pathogens. A chloroquine resistance assay confirmed that curcumin retarded the escape of the cytosolic pathogens, thus reducing their inter- and intracellular spread. We have demonstrated that the membrane-stabilizing activity of curcumin is crucial for its differential effect on the virulence of the bacteria.     

The Prevalence and Impact of Dental Anxiety Among Adult New Zealanders

ObjectiveTo describe the prevalence and impact of dental anxiety in the New Zealand adult population.MethodsSecondary analysis of data from the 2009 New Zealand national oral health survey. Dental anxiety was measured using the Dental Anxiety Scale (DAS).ResultsThe prevalence of dental anxiety was 13.3% (95% CI = 11.4, 15.6). On average, DAS scores were higher by 14% among females, lower among those in the oldest age group (55+), higher by 10% among those in the European/Other ethnic category, and higher by 10% among those residing in the most deprived neighbourhoods. Those who were dentally anxious had greater oral disease experience and were less likely to have visited a dentist within the previous 12 months. They also had poorer oral health-related quality of life, with the highest prevalence of OHIP-14 impacts observed in dentally anxious 35- to 54-year-olds.ConclusionsDental anxiety is a dental public health problem. It is an important contributor to poor oral health and care avoidance among New Zealanders. There is a need to develop both clinical and population-level interventions aimed at reducing the condition''s prevalence and impact.Key words: Dental anxiety, New Zealand, Quality of life, Dental utilisation     

Meeting KDOQI Guideline Goals at Hemodialysis Initiation and Survival during the First Year

Background and objectives: To determine, in a national cohort of incident hemodialysis patients, whether meeting a greater number of National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) guideline goals at dialysis initiation was independently associated, in a graded manner, with lower first-year mortality rates.Design, setting, participants, & measurements: Patients who initiated hemodialysis between June 1, 2005, and May 31, 2007, in the US were included in this retrospective cohort analysis. Guidelines examined were (1) use of arteriovenous fistula or graft at initiation; (2) hemoglobin ≥11 g/dl; and (3) albumin at goal. The primary predictor variable was number of guideline goals (zero, one, two, or three) met at dialysis initiation. Cox regression analysis was used to compare time to death, adjusting for baseline characteristics.Results: At dialysis initiation, 59%, 31%, 9%, and 1.6% of patients met zero, one, two, or three guideline goals, respectively (total n = 192,307). After multivariate adjustment, mortality hazard ratios (95% confidence intervals) were 0.81 (0.80 to 0.83) for patients who met one, 0.53 (0.51 to 0.56) for patients who met two, and 0.34 (0.30 to 0.39) for patients who met three guideline goals, compared with patients who met none. Meeting each individual goal was also associated with lower mortality.Conclusions: These findings suggest a graded association between meeting a greater number of evidence-based guideline goals at dialysis initiation and lower risk of death during the first year on dialysis.The number of patients with end-stage renal disease (ESRD) requiring dialysis is increasing (1,2). Patients with ESRD have exceedingly high morbidity and mortality rates, particularly in the first year after dialysis initiation, when mortality exceeds 25% (1). To improve outcomes of patients with ESRD, the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) developed evidence-based guidelines for the care of kidney disease patients. For patients with chronic kidney disease (CKD) approaching ESRD, the KDOQI guidelines recommend timely nephrology referral, nutritional consultation, fistula placement for dialysis access, and control of anemia, acidosis, and mineral and bone metabolism parameters (3). Evidence from prevalent dialysis patients (4) and from dialysis patients who survived on dialysis for at least 4 to 6 months (5,6) suggests that greater adherence to the KDOQI guidelines is associated with improved patient outcomes. Survival bias in these studies limits their generalizability to patients receiving renal replacement therapy who have survived beyond the initiation period. Whether guideline adherence at the time of dialysis initiation is associated with improved outcomes, particularly during the first year on dialysis, has not been examined.We aimed to determine, in a large nationally representative cohort of incident hemodialysis patients, whether meeting a greater number of KDOQI guideline goals, specifically goals related to vascular access, anemia management, and serum albumin, at dialysis initiation is independently associated, in a graded manner, with survival during the first dialysis year.     

Reduced renal function and sleep-disordered breathing in community-dwelling elderly men

BACKGROUND: Sleep-disordered breathing (SDB) may increase the risk of cardiovascular disease (CVD) and death in chronic kidney disease (CKD). However, the association between mild reductions in renal function and SDB is uncertain. METHODS: We studied 508 community-dwelling men aged>or=67 years (mean 76.0+/-5.3) who were enrolled at the Minnesota site for the Minneapolis center of the Outcomes of Sleep Disorders in Older Men (MrOS) sleep study and had serum cystatin-C and creatinine measured coincident with overnight polysomnography. CKD was defined as estimated glomerular filtration rate (eGFR)<60 ml/min/1.73 m2 using Cockcroft-Gault (CG), modification of diet in renal disease (MDRD) and Mayo Clinic formulae. SDB was defined by a respiratory disturbance index (RDI)>or=15 events/h. RESULTS: Mean cystatin-C was 1.21+/-0.30 mg/L, and mean creatinine was 1.09+/-0.23 mg/dL. Median RDI was 7.0 events/h (range 0-73). Higher quartiles of cystatin-C were associated with higher mean RDI (p for trend=0.007). This association persisted after adjustment for age and race (p for trend=0.03), but not after adjustment for body mass index (BMI, p for trend=0.34). After adjusting for age, race, BMI, diabetes, hypertension, and CVD, CKD defined by the Mayo Clinic formula, but not CG or MDRD, was associated with a higher odds of SDB [odds ratio (OR) 1.95, 95% confidence interval (CI) 1.04-3.65, p=0.04]. CONCLUSIONS: Older men with reduced renal function as defined by higher cystatin-C concentration have higher average RDI. This effect is explained by higher BMI in men with higher cystatin-C. CKD defined by the Mayo Clinic formula is independently associated with twofold higher odds for SDB. Therefore, reduced renal function may be associated with SDB in older men.     

The effect of raloxifene treatment in postmenopausal women with CKD

It is unknown whether treatment for osteoporosis with raloxifene is safe or effective in those with chronic kidney disease (CKD). With data from a multicenter, randomized, placebo-controlled trial of 7705 postmenopausal women with osteoporosis, the effect of raloxifene on rate of change of bone mineral density (BMD), incidence of fractures, and adverse events by stage of CKD was examined over 3 yr. Baseline serum creatinine values were available for 7316 women, and these values were used to assign a category of creatinine clearance (CrCl) using the Cockcroft-Gault formula (CrCl < 45, 45 to 59, and > or = 60 ml/min). BMD was measured at baseline and annually by dual x-ray absorptiometry. Within the placebo group, lower baseline CrCl was associated with a trend for higher annual losses of BMD at the femoral neck; however, within the raloxifene group, lower baseline CrCl was associated with greater increases in femoral neck BMD. This interaction between category of CrCl and treatment assignment was significant for rate of change of BMD at the hip. Irrespective of kidney function, raloxifene treatment was associated with a greater increase in spine BMD, a reduction in vertebral fractures, and no effect on nonvertebral fractures compared with placebo. Within each category of kidney function, adverse events were similar between the raloxifene and placebo groups. In conclusion, raloxifene increases BMD at both the hip and the spine and reduces the risk for vertebral fractures among individuals with CKD. The effect ofraloxifene on hip BMD is greater among those with mild to moderate CKD.     

Preferences for a Patient-Centered Role Orientation: Association with Patient-Information-Seeking Behavior and Clinical Markers of Health

BACKGROUND: Few data exist examining how patients' preferred role orientation (patient-centered or provider-centered) is associated with "patient-centered" behavior and clinical markers of health. PURPOSE: The purpose of the study is to investigate how patients' preferred role orientation is associated with information-seeking behavior and clinical markers of health in a chronically ill population. METHODS: Participants were 189 hypertensive patients, at two VA Medical Centers and four community-based clinics, who completed measures of preferred role orientation and medication information seeking. Lab values of patients' blood pressure, LDL cholesterol, and glycosylated hemoglobin A1c were used as clinical markers. RESULTS: Preference for a patient-centered role was associated with seeking medication information from various sources (e.g., the internet [OR = 1.14, 95% CI = 1.05-1.23]) and with the number of sources from which patients obtained information (beta = .21, p = 0.005). However, patient-centered preferences were also associated with higher systolic blood pressure (beta = 0.16, p = 0.04), higher diastolic blood pressure (beta = .15, p = 0.04), and higher LDL cholesterol (beta = 0.17, p = 0.04). There was no association with glycosylated hemoglobin A1c (beta = -0.10, p = 0.36). CONCLUSIONS: Patients who preferred a patient-centered role engaged in behavior consistent with their preferences, but had higher blood pressure and less favorable lipid levels. These findings are discussed in terms of the nature and treatment of certain chronic conditions that may explain why a patient-centered role orientation is associated with a less favorable clinical profile in some contexts.