Effective critical micellar concentration of a zwitterionic detergent: A fluorimetric study on n-dodecyl phosphocholine

We have investigated the effect of ionic strength on the aggregation behavior of n-dodecyl phosphocholine. On the basis of the classical Corrin-Harkins relation, the critical micellar concentration of this detergent decreases with a biphasic trend on lithium chloride addition. It is nearly constant below 150 mM salt, with a mean value of 0.91 mM, whereas it undergoes a dramatic 80-fold decrease in 7 M LiCl. Such a drop in the critical micellar concentration could be explained by the effect of salting out and the implication of phosphocholine head groups on the organization of surrounding water. Knowledge of the effective critical micellar concentration of n-dodecyl phosphocholine could be useful in the purification of membrane proteins in non-denaturing conditions

Assessment of the management and clinical outcomes of patients with non-diabetic hyperglycaemia and newly diagnosed type 2 diabetes in primary care in England

Background It is unknown whether the detection of non-diabetic hyperglycaemia before the diagnosis of Type 2 diabetes is associated with vascular disease at time or following the diagnosis of Type 2 diabetes. Aim I assessed the association between glycaemic testing and detection of non-diabetic hyperglycaemia before the diagnosis of Type 2 diabetes is associated and vascular disease at time or following the diagnosis of Type 2 diabetes. Methods I identified 159,736 individuals with newly diagnosed Type 2 diabetes from the CPRD database in England between 2004 and 2017. I used logistic regression models to compare presence of vascular disease at the time of Type 2 diabetes diagnosis by prior glycaemic status. I employed time-partitioned Cox regression models to model differences in rates of vascular disease and mortality following the diagnosis of Type 2 diabetes. Results Half of the study population (49.9%) had at least one vascular disease, over one-third (37.4%) had microvascular disease, and almost a quarter (23.5%) had a diagnosed macrovascular disease at the time of Type 2 diabetes diagnosis. Individuals with prior non-diabetic hyperglycaemia were more likely to have microvascular disease and coronary heart disease at time of diagnosis of Type 2 diabetes. As compared with individuals with glycaemic values within the normal range in the three years before the diagnosis of Type 2 diabetes, those detected with non-diabetic hyperglycaemia had increased risk of microvascular disease that persisted up to 7.5 years. Conclusions Non-diabetic hyperglycaemia before diagnosis of Type 2 diabetes is associated with increased odds of microvascular disease and coronary heart disease in newly diagnosed Type 2 diabetes. It is also associated with increased rates of microvascular disease following the diagnosis of Type 2 diabetes. Detection of non-diabetic hyperglycaemia might represent an opportunity for a timely identification of NDH and specific clustering of NDH with other risk factors for T2D, which might prompt earlier assessment for risk factors and tailored cardiovascular risk reduction strategies during the NDH phase to reduce the burden of vascular disease.Open Acces

Management of vascular risk in people with multiple sclerosis at the time of diagnosis in England: A population-based study

Background: Vascular management in People with Multiple Sclerosis (PwMS) is important given the higher vascular burden than the general population, associated with increased disability and mortality. Objectives: We assessed differences in the prevalence of type 2 diabetes and hypertension; and the use of antidiabetic, antihypertensive and lipid-lowering medications at the time of the MS diagnosis. Methods: This is a population-based study including PwMS and matched controls between 1987 and 2018 in England. Results: We identified 12,251 PwMS and 72,572 matched controls. PwMS had a 30% increased prevalence of type 2 diabetes (95% confidence interval (CI) = 1.19, 1.42). Among those with type 2 diabetes, PwMS had a 56% lower prevalence of antidiabetic usage (95% CI = 0.33, 0.58). Prevalence of hypertension was 6% greater in PwMS (95% CI = 1.05, 1.06), but in those with hypertension, usage of antihypertensive was 66% lower in PwMS (95% CI = 0.28, 0.42) than controls. Treatment with lipid-lowering medications was 63% lower in PwMS (95% CI = 0.54, 0.74). PwMS had a 0.4-mm Hg lower systolic blood pressure (95% CI = −0.60, −0.13). 3.8% of PwMS were frail. Conclusion: At the time of diagnosis, PwMS have an increased prevalence of vascular risk factors, including hypertension and diabetes though paradoxically, there is poorer treatment. Clinical guidelines supporting appropriate vascular assessment and management in PwMS should be developed

A Cardiovascular Risk Score for Use in Occupational Medicine

Cardiovascular disease is one of the most frequent causes of long-term sickness absence from work. The study aims to develop and validate a score to assess the 10-year risk of unsuitability for work accounting for the cardiovascular risk. The score can be considered as a prevention tool that would improve the cardiovascular risk assessment during health surveillance visits under the assumption that a high cardiovascular risk might also translate into high risk of unsuitability for work. A total of 11,079 Italian workers were examined, as part of their scheduled occupational health surveillance. Cox proportional hazards regression models were employed to derive risk equations for assessing the 10-year risk of a diagnosis of unsuitability for work. Two scores were developed: the CROMA score (Cardiovascular Risk in Occupational Medicine) included age, sex, smoking status, blood pressure (systolic and diastolic), body mass index, height, diagnosis of hypertension, diabetes, ischemic heart disease, mental disorders and prescription of antidiabetic and antihypertensive medications. The CROMB score was the same as CROMA score except for the inclusion of only variables statistically significant at the 0.05 level. For both scores, the expected risk of unsuitability for work was higher for workers in the highest risk class, as compared with the lowest. Moreover results showed a positive association between most of cardiovascular risk factors and the risk of unsuitability for work. The CROMA score demonstrated better calibration than the CROMB score (11.624 (p-value: 0.235)). Moreover, the CROMA score, in comparison with existing CVD risk scores, showed the best goodness of fit and discrimination

NMR Structure and CD Titration with Metal Cations of Human Prion α2-Helix-Related Peptides

The 173–195 segment corresponding to the helix 2 of the C-globular prion protein domain could be one of several “spots” of intrinsic conformational flexibility. In fact, it possesses chameleon conformational behaviour and gathers several disease-associated point mutations. We have performed spectroscopic studies on the wild-type fragment 173–195 and on its D178N mutant dissolved in trifluoroethanol to mimic the in vivo system, both in the presence and in the absence of metal cations. NMR data showed that the structure of the D178N mutant is characterized by two short helices separated by a kink, whereas the wild-type peptide is fully helical. Both peptides retained these structural organizations, as monitored by CD, in the presence of metal cations. NMR spectra were however not in favour of the formation of definite ion-peptide complexes. This agrees with previous evidence that other regions of the prion protein are likely the natural target of metal cation binding

HDAC1 inhibition by MS-275 in mesothelial cells limits cellular invasion and promotes MMT reversal

Peritoneal fibrosis is a pathological alteration of the peritoneal membrane occurring in a variety of conditions including peritoneal dialysis (PD), post-surgery adhesions and peritoneal metastases. The acquisition of invasive and pro-fibrotic abilities by mesothelial cells (MCs) through induction of MMT, a cell-specific form of EMT, plays a main role in this process. Aim of this study was to evaluate possible effects of histone deacetylase (HDAC) inhibitors, key components of the epigenetic machinery, in counteracting MMT observed in MCs isolated from effluent of PD patients. HDAC inhibitors with different class/isoform selectivity have been used for pharmacological inhibition. While the effect of other inhibitors was limited to a partial E-cadherin re-expression, MS-275, a HDAC1-3 inhibitor, promoted: (i) downregulation of mesenchymal markers (MMP2, Col1A1, PAI-1, TGFβ1, TGFβRI) (ii) upregulation of epithelial markers (E-cadherin, Occludin), (iii) reacquisition of an epithelial-like morphology and (iv) marked reduction of cellular invasiveness. Results were confirmed by HDAC1 genetic silencing. Mechanistically, MS-275 causes: (i) increase of nuclear histone H3 acetylation (ii) rescue of the acetylation profile on E-cadherin promoter, (iii) Snail functional impairment. Overall, our study, pinpointing a role for HDAC1, revealed a new player in the regulation of peritoneal fibrosis, providing the rationale for future therapeutic opportunities

Multimorbidity and out-of-pocket expenditure on medicine in Europe:longitudinal analysis of 13 European countries between 2013-2015

BACKGROUND: Many European Health Systems are implementing or increasing levels of cost-sharing for medicine in response to the growing constrains on public spending on health despite their negative impact on population health due to delay in seeking care. OBJECTIVE: This study aims to examine the relationships between multimorbidity (two or more coexisting chronic diseases, CDs), complex multimorbidity (three or more CDs impacting at least three different body systems), and out-of-pocket expenditure (OOPE) for medicine across European nations. METHODS: This study utilized data on participants aged 50 years and above from two recent waves of the Survey of Health, Aging, and Retirement in Europe conducted in 2013 (n = 55,806) and 2015 (n = 51,237). Pooled cross-sectional and longitudinal study designs were used, as well as a two-part model, to analyse the association between multimorbidity and OOPE for medicine. RESULTS: The prevalence of multimorbidity was 50.4% in 2013 and 48.2% in 2015. Nearly half of those with multimorbidity had complex multimorbidity. Each additional CD was associated with a 34% greater likelihood of incurring any OOPE for medicine (Odds ratio = 1.34, 95% CI = 1.31–1.36). The average incremental OOPE for medicine was 26.4 euros for each additional CD (95% CI = 25.1–27·7), and 32.1 euros for each additional body system affected (95% CI 30.6–33.7). In stratified analyses for country-specific quartiles of household income the average incremental OOPE for medicine was not significantly different across groups. CONCLUSION: Between 2013 and 2015 in 13 European Health Systems increased prevalence of CDs was associated with greater likelihood of having OOPE on medication and an increase in the average amount spent when one occurred. Monitoring this indicator is important considering the negative association with treatment adherence and subsequent effects on health

Multimorbidity and out-of-pocket expenditure for medicines in China and India

Using nationally representative survey data from China and India, this study examined (1) the distribution and patterns of multimorbidity in relation to socioeconomic status and (2) association between multimorbidity and out-of-pocket expenditure (OOPE) for medicines by socioeconomic groups

Determinants of early working impairments in multiple sclerosis

IntroductionUnemployment can directly affect social status and identity. Assessing and adjusting determinants of early working impairments in a chronic disease can thus reduce its long-term burden. Hereby, we aim to evaluate differences in occupational history and early working impairments between people with multiple sclerosis (MS) and healthy workers.MethodsThis is a cross-sectional study comparing 71 workers with MS [age 41.7 ± 9.4 years; females 59.1%; EDSS 2.0 (1.0–6.0)] and 71 controls (age 42.6 ± 11.9 years; females 33.8%). All participants filled in Work Ability Index (WAI), Work Productivity and Activity Impairment (WPAI), European Questionnaire for Quality of Life (EuroQoL), Beck Depression Inventory II (BDI-II), and Pittsburgh Sleep Quality Index (PSQI). In MS, we further collected expanded disability status scale (EDSS), MS Questionnaire for Job difficulties (MSQ-Job), Fatigue severity scale (FSS), and the Brief International Cognitive Assessment for MS (BICAMS).ResultsWorkers with MS were more working disabled (p < 0.01), less exposed to workplace risks (p < 0.01), and more limited in fitness to work (p = 0.01), compared with controls. On linear regression models adjusted by age, sex, education, and type of contract, people with MS had worse WAI (Coeff=−5.47; 95% CI = −7.41, −3.53; p < 0.01), EuroQoL (Coeff = −4.24; 95% CI = −17.85, −6.50; p < 0.01), BDI-II (Coeff = 3.99; 95% CI = 2.37, 7.01; p < 0.01), and PSQI (Coeff = 4.74; 95% CI = 3.13, 7.61; p < 0.01), compared with controls, but no differences in WPAI (p = 0.60). EuroQoL, BDI-II, and PSQI were equally associated with both WAI and WPAI in MS and controls (all p< 0.01). In MS, worse MSQJob was associated with higher EDSS (Coeff = 5.22; 95% CI = 2.24, 7.95; p < 0.01), progressive disease (Coeff = 14.62; 95% CI = 5.56, 23.69; p < 0.01), EuroQoL (Coeff = 4.63; 95% CI = 2.92, 6.35; p < 0.01), FSS (Coeff = 0.55; 95% CI = 0.38, 0.72; p < 0.01), and cognitive impairment (Coeff = 4.42; 95% CI = 0.67, 8.22; p = 0.02).DiscussionEarly factors associated with working difficulties in MS include disability, fatigue, depression, and cognitive dysfunction. Early identification of clinical features potentially causing working difficulties should be considered to enhance job retention, along with targeted prevention and protection measures

Disability assessment using Google Maps

Objectives To evaluate the concordance between Google Maps  application (GM ) and clinical practice measurements of ambulatory function (e.g., Ambulation Score (AS) and respective Expanded Disability Status Scale (EDSS)) in people with multiple sclerosis (pwMS). Materials and methods This is a cross-sectional multicenter study. AS and EDSS were calculated using GM  and routine clinical methods; the correspondence between the two methods was assessed. A multinomial logistic model is investigated which demographic (age, sex) and clinical features (e.g., disease subtype, fatigue, depression) might have influenced discrepancies between the two methods. Results Two hundred forty-three pwMS were included; discrepancies in AS and in EDDS assessments between GM  and routine clinical methods were found in 81/243 (33.3%) and 74/243 (30.4%) pwMS, respectively. Progressive phenotype (odds ratio [OR] = 2.8; 95% confidence interval [CI] 1.1–7.11, p = 0.03), worse fatigue (OR = 1.03; 95% CI 1.01–1.06, p = 0.01), and more severe depression (OR = 1.1; 95% CI 1.04–1.17, p = 0.002) were associated with discrepancies between GM  and routine clinical scoring. Conclusion GM  could easily be used in a real-life clinical setting to calculate the AS and the related EDSS scores. GM  should be considered for validation in further clinical studies