Cigarette smoking and associated risk of multiple sclerosis in the Iranian population

Exposure to cigarette smoke is emerging as an environmental risk factor for multiple sclerosis (MS). We investigated the possible association between environmental tobacco smoke, its cumulative exposure, and MS risk. We used data from the Iranian Multiple Sclerosis Registry to identify a case-control of 662 patients who had MS and a comparison group of 394 patients. Information regarding current smoking status, including the number of cigarettes smoked per day, duration, and smoking pack-years indicative of cumulative dose of tobacco smoked was obtained. We analyzed the incidence of MS among ever–smokers who had been smokers during their disease course and prior to disease onset in comparison with never–smokers who had never been exposed by calculating the odds ratio (OR) with a 95% confidence interval (CI) employing logistic regression. Of the 662 MS patients, there were 523 women (79.0%) and 139 men (21.0%), with a mean age of 31 ± 10.0 years at disease onset. The risk for MS was increased among ever–smokers (OR = 1.78, 95% CI = 1.22–2.59, p = 0.03) compared to never–smokers. As compared with never smokers, the OR for patients with 6–10 pack years was 2.91 for men (95% CI = 1.11–9.47, p = 0.03) and 1.69 for women (95% CI = 1.02–6.45, p = 0.04). Our results demonstrate that cigarette smoking is significantly associated with an increased risk for MS. The risk effects of smoking were more noticeable in male patients and at higher tobacco doses.     

Decreased mitochondrial proton leak and reduced expression of uncoupling protein 3 in skeletal muscle of obese diet-resistant women

Weight loss in response to caloric restriction is variable. Because skeletal muscle mitochondrial proton leak may account for a large proportion of resting metabolic rate, we compared proton leak in diet-resistant and diet-responsive overweight women and compared the expression and gene characteristics of uncoupling protein (UCP)2 and UCP3. Of 1,129 overweight women who completed the University of Ottawa Weight Management Clinic program, 353 met compliance criteria and were free of medical conditions that could affect weight loss. Subjects were ranked according to percent body weight loss during the first 6 weeks of a 900-kcal meal replacement protocol. The highest and lowest quintiles of weight loss were defined as diet responsive and diet resistant, respectively. After body weight had been stable for at least 10 weeks, 12 of 70 subjects from each group consented to muscle biopsy and blood sampling for determinations of proton leak, UCP mRNA expression, and genetic studies. Despite similar baseline weight and age, weight loss was 43% greater, mitochondrial proton leak-dependent (state 4) respiration was 51% higher (P = 0.0062), and expression of UCP3 mRNA abundance was 25% greater (P < 0.001) in diet-responsive than in diet-resistant subjects. There were no differences in UCP2 mRNA abundance. None of the known polymorphisms in UCP3 or its 5' flanking sequence were associated with weight loss or UCP3 mRNA abundance. Thus, proton leak and the expression of UCP3 correlate with weight loss success and may be candidates for pharmacological regulation of fat oxidation in obese diet-resistant subjects.     

Bone mineralization in newborns whose mothers received magnesium sulphate for tocolysis of premature labour

Prolonged maternal magnesium sulphate infusion therapy for tocolysis of premature labour may result in secondary fetal hypermagnesaemia, which has been associated with bony abnormalities in the newborn. We report on four infants, members of two twin pregnancies, who were exposed to prolonged fetal hypermagnesaemia. Three of the infants, all appropriate for gestational age, showed abnormal radiological findings consisting of abnormal mineralisation of long-bone metaphyses owing to fetal hypermagnesaemia. The fourth infant, who was growth retarded, had normal bones. Intrauterine growth restriction appears to be protective against magnesium sulphate-induced abnormal bone mineralisation in the newborn.     

Multi-functional magnetic nanoparticles for magnetic resonance imaging and cancer therapy

We have developed a multi-layer approach for the synthesis of water-dispersible superparamagnetic iron oxide nanoparticles for hyperthermia, magnetic resonance imaging (MRI) and drug delivery applications. In this approach, iron oxide core nanoparticles were obtained by precipitation of iron salts in the presence of ammonia and provided β-cyclodextrin and pluronic polymer (F127) coatings. This formulation (F127250) was highly water dispersible which allowed encapsulation of the anti-cancer drug(s) in β-cyclodextrin and pluronic polymer for sustained drug release. The F127250 formulation has exhibited superior hyperthermia effects over time under alternating magnetic field compared to pure magnetic nanoparticles (MNP) and β-cyclodextrin coated nanoparticles (CD200). Additionally, the improved MRI characteristics were also observed for the F127250 formulation in agar gel and in cisplatin resistant ovarian cancer cells (A12780CP) compared to MNP and CD200 formulations. Furthermore, the drug-loaded formulation of F127250 exhibited many folds of imaging contrast properties. Due to the internalization capacity of the F127250 formulation, its curcumin-loaded formulation (F127250-CUR) exhibited almost equivalent inhibition effects on A2780CP (ovarian), MDA-MB-231 (breast), and PC-3 (prostate) cancer cells even though curcumin release was only 40%. The improved therapeutic effects were verified by examining molecular effects using Western blotting and transmission electron microscopic (TEM) studies. F127250-CUR also exhibited haemocompatibility, suggesting a nanochemo-therapeutic agent for cancer therapy.     

The Effectiveness and Cost-Effectiveness of a Rural Employer-Based Wellness Program

Context: The cost-effectiveness of employer-based wellness programs has been previously investigated with favorable financial and nonfinancial outcomes being detected. However, these investigations have mainly focused on large employers in urban settings. Very few studies examined wellness programs offered in rural settings. Purpose: This paper aims to explore the effectiveness and cost-effectiveness of a rural employer-based wellness program. Methods: Six rural employers were categorized into 3 groups: a control group and 2 intervention groups with varying degrees of wellness activities. Participants were asked to complete an annual health risk assessment (HRA) that addressed 16 wellness areas. At the conclusion of 4 years, HRA and effectiveness data were utilized to examine program effectiveness and combined with program costs to estimate cost-effectiveness. Findings: The “Coaching and Referral” group—the highest in intensity of participant engagement—exhibited superior improvement in several wellness areas and in percentage of employees with good health indicators compared to the control and the Trail Marker, lower-intensity intervention groups. However, the Trail Markers had more favorable cost-effectiveness ratios. Conclusions: Rural worksite wellness programs have shown great potential in their effectiveness and cost-effectiveness. Such programs need not be too aggressive, tedious, and costly to generate a favorable return for employers and funders. However, employers should be encouraged to experiment with different levels of wellness program intensities until a more favorable outcome can be realized.     

What is the impact of the 2017 cochrane systematic review and meta-analysis that evaluated the use of PCSK9 inhibitors for lowering cardiovascular disease and mortality?

Introduction: In 2017, Schmidt et al. conducted a Cochrane systematic review and meta-analysis to evaluate the effect of using proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to reduce low-density-lipoprotein- cholesterol (LDL-C) and cardiovascular disease (CVD). The Cochrane review was a systematic review and meta-analysis of 20 randomized, double-blinded trials that compared the use of PCSK9 inhibitors with statins/ezetimibe, ezetimibe, or placebo for a treatment duration of at least 24 weeks. The use of PCSK9 inhibitors lowered the risk for CVD (OR 0.86 (0.80 to 0.92)) but not mortality (OR 1.02 (0.91 to 1.14)) when compared to placebo.

Areas covered: The following article evaluates the recently published Cochrane review and clarifies the efficacy of PCSK9 inhibitors for improving cardiovascular morbidity and mortality.

Expert opinion: The Cochrane review discussed suggests that PCSK9 inhibitors are effective in lowering LDL-C and the risk of CVD but not the risk of mortality. The higher price of PCSK9 inhibitors is a further deterrent for using them as a substitute for statins – cholesterol lowering medications with history showing they lower mortality. Statins should remain the gold-standard cholesterol-lowering drug class until PCSK9 inhibitors become more affordable and demonstrate consistent efficacy for reducing CVD and mortality.     

Cross-linked starch microspheres: Effect of cross-linking condition on the microsphere characteristics

Cross-linked starch microspheres were prepared using different kinds of cross-linking agents. The influence of several parameters on morphology, size, swelling ratio and drug release rate from these microspheres were evaluated. These parameters included cross-linker type, concentration and the duration of cross-linking reaction. Microspheres cross-linked with glutaraldehyde had smooth surface compared with those prepared with epichlorhydrine or formaldehyde. The particle size increased with increasing the cross-linking time and increasing the drug loading. Swelling ratio of the particles was a function of cross-linker type but not the concentration or time of cross-linking. Drug release from starch microspheres was measured in phosphate buffer and also in phosphate buffer containing alpha-amylase. Results showed that microspheres cross-linked with epichlorhydrine released all their drug content in the first 30 minutes. However, cross-linking of the starch microspheres with glutaraldehyde or formaldehyde decreased drug release rate. SEM and drug release studies showed that cross-linked starch microspheres were susceptible to the enzymatic degradation under the influence of alpha-amylase. Changing the enzyme concentration from 5000 to 10,000 IU/L, increased drug release rate but higher concentration of enzyme (20,000 IU/L) caused no more acceleration.     

Arsenic in soils and forages from poultry litter-amended pastures

In regions of concentrated poultry production, poultry litter (PL) that contains significant quantities of trace elements is commonly surface-applied to pastures at high levels over multiple years. This study examined the effect of long-term applications of PL on soil concentrations of arsenic (As), copper (Cu), Zinc (Zn), and the uptake of these elements by bermuda grass grown on Cecil (well-drained) and Sedgefield (somewhat poorly-drained) soils. The results showed that concentrations of As, Cu, and Zn in soils that had received surface-applied PL over a 14-year period were significantly greater than untreated soil at 0-2.5 and 2.5-7.5 cm depths. However, the levels were well below the USEPA loading limits established for municipal biosolids. Arsenic fractionation showed that concentrations of all As fractions were significantly greater in PL-amended soils compared to untreated soils at 0-2.5 and 2.5-7.5 cm depths. The residual fraction was the predominant form of As in all soils. The water-soluble and NaHCO(3)-associated As were only 2% of the total As. Significant differences were found in concentrations of these trace elements and phosphorus (P) in forage from PL-amended soils compared to that in untreated plots. The concentrations of Cu, Zn, As, and P were significantly greater in forage from Sedgefield amended soil compared to Cecil soil, but were in all cases below levels of environmental concern.