Associations of Cardiovascular and Non-Cardiovascular Comorbidities with Dementia Risk in Patients with Diabetes: Results from a Large UK Cohort Study.

BACKGROUND: Type 2 diabetes (T2D) is an established risk factor for dementia. However, it remains unclear whether the presence of comorbidities could further increase dementia risk in diabetes patients. OBJECTIVES: To examine the associations between cardiovascular and non-cardiovascular comorbidities and dementia risk in T2D patients. DESIGN: Population-based cohort study. SETTING: The UK Clinical Practice Research Datalink (CPRD). PARTICIPANTS: 489,205 T2D patients aged over 50 years in the UK CPRD. MEASUREMENTS: Major cardiovascular and non-cardiovascular comorbidities were extracted as time-varying exposure variables. The outcome event was dementia incidence based on dementia diagnosis or dementia-specific drug prescription. RESULTS: During a median of six years follow-up, 33,773 (6.9%) incident dementia cases were observed. Time-varying Cox regressions showed T2D patients with stroke, peripheral vascular disease, atrial fibrillation, heart failure or hypertension were at higher risk of dementia compared to those without such comorbidities (HR [95% CI] = 1.64 [1.59-1.68], 1.37 [1.34-1.41], 1.26 [1.22-1.30], 1.15 [1.11-1.20] or 1.10 [1.03-1.18], respectively). Presence of chronic obstructive pulmonary disease or chronic kidney disease was also associated with increased dementia risk (HR [95% CI] = 1.05 [1.01-1.10] or 1.11 [1.07-1.14]). CONCLUSIONS: A range of cardiovascular and non-cardiovascular comorbidities were associated with further increases of dementia risk in T2D patients. Prevention and effective management of these comorbidities may play a significant role in maintaining cognitive health in T2D patients.

Evidence-Based Tools for Dietary Assessments in Nutrition Epidemiology Studies for Dementia Prevention.

Increasing evidence proposes diet as a notable modifiable factor and viable target for the reduction of Alzheimer's Disease risk and age-related cognitive decline. However, assessment of dietary exposures is challenged by dietary capture methods that are prone to misreporting and measurement errors. The utility of -omics technologies for the evaluation of dietary exposures has the potential to improve reliability and offer new insights to pre-disease indicators and preventive targets in cognitive aging and dementia. In this review, we present a focused overview of metabolomics as a validation tool and framework for investigating the immediate or cumulative effects of diet on cognitive health.

Rheological properties of wheat starch influenced by amylose-lysophosphatidylcholine complexation at different gelation phases.

Amylose is able to form helical inclusion complexes with lysophosphatidylcholine (LPC). This complexation influences the functional and rheological properties of wheat starch; however it is well known that the formation of these complexes lead the starchy systems to a slower enzymatic hydrolysis. Based on this, to benefit from both the structuring properties of starch and also lower digestibility of the inclusion complexes, the objective of this study is the formation of amylose-LPC inclusion complexes while developing a firm network providing the desired functional properties in a starchy system. To investigate the influence of amylose-LPC complex formation at different stages of starch gelation on the viscosity behavior of wheat starch, 3% (w/w) LPC was added at three different points of the viscosity profile, obtained by rapid visco analyzer (RVA). LPC addition at all points affected the gelation behavior of wheat starch as compared with the reference. LPC addition at half-peak and peak of the viscosity profile resulted in a viscosity increase during cooling. Measuring the dynamic rheological properties of the freshly prepared gelatinized samples showed a decrease of storage modulus (G') and loss modulus (G") in the presence of LPC. During storage, in the presence of LPC, a lower elasticity was observed which indicates a lower rate of amylose retrogradation due to complexation with LPC.

Assessment of the influence of amylose-LPC complexation on the extent of wheat starch digestibility by size-exclusion chromatography.

Amylose forms inclusion complexes with lysophosphatidylcholine (LPC), that decrease the susceptibility of amylose to amylase degradation. This study on the influence of complexation on starch susceptibility to amylase explains the nature of this protective effect. Wheat starch suspensions (9% w/w) containing 0.5-5% LPC were subjected to hydrolysis by porcine pancreatic α-amylase at 37 °C for several digestion times. The digesta were analysed by size-exclusion chromatography (SEC). The molar mass distribution was closely dependent on the digestion time and amount of LPC. This study precisely demonstrates the alteration of the digestion profile of starch on a molecular level, influenced by amylose-LPC complexation; however the effect depends on the digestion time. During 15 and 30 min digestion, inclusion complexes not only protect amylopectin in the initial hydrolysis stage, but also demonstrate lower susceptibility of the molecular amylose complexes to amylase hydrolysis. Digestion for 240 min resulted in a lower oligosaccharide peak concentration, in the presence of a high LPC concentration, which is related to less degradation of complexed amylose fraction.

The influence of amylose-LPC complex formation on the susceptibility of wheat starch to amylase.

This study was aimed to assess the role of lysophosphatidylcholine (LPC) in the development of slowly digestible starch (SDS). The influence of LPC, on the enzymatic degradation of diluted 9% wheat starch suspensions (w/w) was investigated, using an in vitro digestion method. Wheat starch suspensions containing 0.5-5% LPC (based on starch) were heated in a Rapid Visco Analyser (RVA) till 95 °C and subjected to enzyme hydrolysis by porcine pancreatic α-amylase at 37 °C for several digestion periods. In vitro digestion measurements demonstrated that complexing starch with 5% LPC leads to a 22% decrease in rate of reducing sugar compared to the reference while the samples containing 0.5% LPC showed an equal digestibility comparable to the control. A clear decrease in the formation of reducing sugars was observed in presence of 2-5% LPC, since the results after 15 min digestion imply the formation of SDS due to the formation of amylose-LPC inclusion complexes. The DSC measurements proved the presence of amylose-LPC inclusion complexes even after 240 min digestion demonstrating the low susceptibility of amylose-V complexes to amylase.

Influence of lysophosphatidylcholine on the gelation of diluted wheat starch suspensions.

Starch is an omnipresent constituent which is used for its nutritional and structuring properties. Recently concerns have been raised since starch is a source of readily available glucose which is tightly correlated with diabetes type II and obesity. For this reason, the possibilities for modulating the digestibility of starch while preserving its functional properties were investigated; therefore the focus of this paper is on starch gelatinization and the effect of lysophosphatidylcholine (LPC) on the structuring properties of wheat starch. The effect of LPC on thermal properties and viscosity behavior of starch suspensions was studied using DSC and RVA, respectively. The influence on granular structure was observed by light microscopy. The RVA profile demonstrated no viscosity increase at high LPC concentrations which proves intact granular structure after gelatinization. LPC in intermediate concentrations resulted in a notable delay of pasting; however the peak and end viscosities were influenced as well. Lower LPC concentrations demonstrated a higher peak viscosity as compared with pure starch suspensions. DSC results imply that inclusion complexes of amylose-LPC might be formed during pasting time. Since the viscosity profiles are changed by LPC addition, swelling power and solubility of starch granules are influenced as well. LPC hinders swelling power and solubility of starch granules which are stimulated by heating.

Comparison of two different curricula in psychiatry clerkship at tehran university of medical sciences.

OBJECTIVES: The aim of this study was to evaluate the efficacy of a new psychiatry clerkship curriculum which was designed to improve the knowledge and skills of medical students of Tehran University of Medical Sciences (TUMS), Iran. METHODS: This quasi-experimental study was conducted in two consecutive semesters from February 2009 to January 2010. In total, 167 medical students participated in the study. In the first semester, as the control group, the clerks' training was based on the traditional curriculum. In the next semester, we constructed and applied a new curriculum based on the SPICES model (student-centered, problem-based, integrated, community-based, elective and systematic).At the end of the clerkship, the students were given two exams: Multiple Choice Questions (MCQ) to assess their knowledge, and Objective Structured Clinical Examination (OSCE) to assess their skills. Baseline data and test performance for each student were analyzed. RESULTS: Compared to the control group, students in the intervention group showed significantly higher OSCE scores (P= 0.01). With respect to MCQ score, no significant difference was found between the two groups. CONCLUSIONS: The results suggest that the revised curriculum is more effective than the traditional one in improving the required clinical skills in medical students during their psychiatry clerkship.

Burden of hip fracture in Iran.

To measure the burden caused by hip fracture in Iran and to compare it with other parts of the world, we applied the Global Burden of Disease (GBD) method created by the World Health Organization. The GBD method uses disability-adjusted life years (DALY), which is comprised of years of life lost (YLL) and years of life lived with disability (YLD). To calculate YLD, incidence of hip fracture was obtained from the Iranian Multicenter Study on Accidental Injuries, a large-scale nationwide prospective study. Disability weights were applied to the remaining duration of disease. To calculate YLL, remaining years of potential life at any age at death were calculated using the standard life table. A discount rate of 3% and age weighting were applied. Hip fracture generated 16,708 DALYs, comprising 8,812 (52.7%) YLL and 7,896 (47.3%) YLD. Iran accounted for 0.85% of the global burden of hip fracture and 12.4% of the burden of hip fracture in the Middle East. The female to male ratio in Iran (1.1) was lower than the global (2.2) and the Middle Eastern (1.4) ratios and higher than the ratios in China and India (1.0 and 0.9, respectively). In conclusion, hip fracture is not as much a cause of disease burden in Iran as in the developed regions of the world. We recommend utilization of the standardized GBD method to calculate burden of osteoporosis in different countries and to set local priorities according to these measures.

Bone mineral density and estimated height loss based on patients' recalls.

INTRODUCTION: Height loss has been shown to be an indicator of incident vertebral fractures. However, the relationship between height loss and bone mineral density (BMD) in different skeletal regions, as well as the power of human memory in estimation of height loss across the life span, has not yet been established. Given that the variation in BMD between populations is substantially less than the variation in fracture risk, we studied the relationship between height loss based on patient's recalls and BMD in Iranian men and women of all ages. METHODS: Randomized clustered sampling from all regions of Tehran was performed to recruit the study population. Participants were asked about their maximum recalled previously measured height, if they were confident. In the 457 participants included, the difference between the participants' maximum recalled and current measured height was calculated. RESULT: L1-L4 lumbar BMD, femoral neck BMD, and young adjusted T-scores were significantly lower in the group of participants with estimated height reduction of greater than 5 cm. In simple linear regression analysis, height loss was a significant predictor of femoral neck T-score (standardized beta coefficient=-0.15; p0.003) and L1-L4 lumbar T-score (beta=-0.08; p0.048). After adjustment for age, gender, and weight, height loss remained a significant predictor for femoral neck T-score (beta=-0.078; p0 .043). In multivariate models for lumbar T-score, height loss was an independent predictor only in participants equal to or younger than 50 years of age (beta=-0.144; p0.033). CONCLUSION: Higher estimated height loss according to patients' recalls was an indicator of lower BMD in our sample. Especially in the femoral neck region, this factor might be considered as a substitute case-finding tool for low BMD. Considering relatively young nature of our study group and biological differences between populations, our findings need to be validated in future prospective studies.

Relationship between erythrocyte lithium concentration and renal concentrating capacity.

BACKGROUND: Studies investigating possible correlations between plasma lithium concentration, lithium treatment duration, and frequency of lithium administration, and lithium nephrotoxicity have yielded conflicting results. OBJECTIVES: Our main objective was to investigate whether there was any relationship between erythrocyte lithium concentration (ELC) and renal side effects. Another objective of our study was to identify a parameter, which could be estimated inexpensively, for assessing possible renal side-effects of lithium. METHOD: Seventy Iranian inpatients with bipolar disorder entered this case-control study. Medications taken concurrently by the patients were recorded. A direct method of measuring ELC was used in this study. The cases were patients on lithium who had urine specific gravity (SG) of 1.006 or less after 8-10 h water deprivation at night and the controls consisted of patients on lithium with urine SG of 1.011 or more after this period. Blood urea nitrogen, serum creatinine, sodium and potassium and urine SG, sodium, and potassium were measured in all patients during this time. Renal indices were compared by using independent sample t-test at a significance level of a P-value of 0.05 or less. Non-parametric Spearman's rank correlation test was used to investigate the relationship between clinical variables and the indices of renal function. RESULTS: Results revealed that in case group mean serum sodium concentrations were significantly higher (P = 0.008) and mean urine sodium and potassium were significantly lower than those of controls (P = 0.004 and 0.007 respectively). We found no statistically difference in lithium ratios between the two groups. However, ELCs were significantly higher in the cases (P = 0.026). There were no significant correlation between concomitant use of neuroleptics, benzodiazepines or carbamazepine and ELC or lithium renal side-effects. CONCLUSION: This study showed that ELC may reflect lithium renal side-effects better than plasma lithium level.

Baclofen versus clonidine in the treatment of opiates withdrawal, side-effects aspect: a double-blind randomized controlled trial.

OBJECTIVE: Baclofen is known for the alleviation of signs and symptoms of spasticity. Reports from our previous study have suggested that it may be at least as effective as clonidine in the management of physical symptoms of opiate withdrawal syndromes and superior to clonidine in the management of mental symptoms. We now report on a randomized double-blind comparison of baclofen vs. clonidine in view of side-effects profile. METHODS: A total of 62 opiates addicts were randomly assigned to treatment with baclofen or clonidine during a 14-day, double-blind clinical trial. All patients met the DSM IV criteria for opioid dependence. Maximum daily doses were 40 mg for baclofen and 0.8 mg for clonidine. This trial medication was given three times per day in divided doses. The severity of side-effects was measured in days 0, 1, 2, 3, 4, 7 and 14. RESULTS: There was no significant difference between two treat7ments in terms of retention in treatment (dropout) and overall side-effect. Nevertheless, significantly more problems relating to hypotension were encountered with subjects on clonidine. CONCLUSION: We conclude that, the low incidence of hypotension with baclofen suggests that the drug may be suitable for outpatient ambulatory treatment of withdrawal from opiates.

Double-blind randomized controlled trial of baclofen vs. clonidine in the treatment of opiates withdrawal.

BACKGROUND: A variety of detoxification methods have been utilized for the treatment of opiate withdrawal syndrome, of which alpha-adrenergic agonists have attracted considerable attention over the last two decades. However, accumulating evidence in rats shows the efficacy of the GABAB receptor agonist, baclofen, in reducing alcohol intake and self-administration of cocaine. OBJECTIVE: To examine the ability of baclofen, in the management of opiate withdrawal. METHOD: A total of 62 opiate addicts randomly assigned to treatment with baclofen or clonidine during a 14-day, double-blind clinical trial. All patients met the DSM IV criteria for opioid dependence. Maximum daily doses were 40 mg for baclofen and 0.8 mg for clonidine given three times a day in divided doses. The severity of the opiate withdrawal syndrome was measured on days 0, 1, 2, 3, 4, 7 and 14 using the Short Opiate Withdrawal Scale (SOWS). RESULTS: Baclofen and clonidine were equally effective in treating the physical symptoms of withdrawal syndromes. However, baclofen showed a significant superiority over clonidine in the management of mental symptoms. CONCLUSION: These results suggest that baclofen might be a novel therapeutic agent for opiate withdrawal syndrome. However, a larger study to confirm our results is warranted.

The lithium ratio and the incidence of side effects.

1. During a prospective and outpatient study the correlation between the lithium ratio and the incidence of lithium side effects and type of comedications was studied in 51 Iranian bipolar patients by using new direct method of measuring erythrocyte lithium concentration. 2. Results revealed that patients who received lithium alone the incidence of lithium side effects was extremely lower than those with lithium and neuroleptics in combination. Both neurological and renal side effects of lithium were higher in patients who received lithium in combination with neuroleptics. 3. In patients on lithium alone the lithium ratio among patients with side effects were significantly lower than those without side effects, and the plasma lithium concentrations were significantly higher in those with side effects. In patients who received neuroleptics in combination with lithium, the lithium ratios were also significantly lower in those with serious side effects than those with slight side effects, but there were no significant correlation in plasma lithium concentrations between them. 4. Previous studies about the correlation of the lithium ratio and incidence of side effects have yielded inconsistent results, and methodological problems may be a reason for these discrepancies. By using the new direct method of measuring erythrocyte lithium concentration, repetition of previous studies on lithium ratio may elucidate its value as a tool in daily practice.