Aims ACHIEVE Control, a prospective pragmatic randomised real-life study in insulin-naïve adults with type 2 diabetes (T2D), demonstrated statistical superiority of insulin glargine 300 U/mL (Gla-300) over first-generation standard-of-care basal insulin analogues (SOC-BI; insulin glargine 100 U/mL or insulin detemir) for the primary composite endpoint of individualised HbA1c target achievement without documented symptomatic (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia at 6 months. Here, we report effectiveness and safety of Gla-300 versus SOC-BI in ACHIEVE Control at 12 months. Methods 3304 insulin-naïve adults with T2D and HbA1c 8%-11% after ≥1 year of treatment with ≥2 antihyperglycaemic agents were randomised to Gla-300 or SOC-BI. Key secondary endpoints included HbA1c target attainment without documented symptomatic or severe hypoglycaemia (≤3.9 mmol/L [≤70 mg/dL]) at 12 months. Results At 12 months, 26.1% (Gla-300) and 23.7% (SOC-BI) of adults achieved HbA1c targets without documented symptomatic (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia (odds ratio [OR] 1.14, 95% CI 0.97-1.35); 33.0% and 29.5%, respectively, achieved HbA1c targets without documented symptomatic ( less then 3.0 mmol/L [ less then 54 mg/dL]) or severe hypoglycaemia (OR 1.19, 95% CI 1.02-1.38). Odds ratio for HbA1c target achievement was 1.15 (95% CI 0.99-1.34) and favoured Gla-300 versus SOC-BI for absence of documented symptomatic or severe hypoglycaemia at 12 months for both ≤3.9 mmol/L (≤70 mg/dL) (OR 1.21, 95% CI 1.05-1.40) and less then 3.0 mmol/L ( less then 54 mg/dL) (OR 1.26, 95% CI 1.07-1.48). Conclusion Gla-300 tended to be associated with lower hypoglycemia risk than SOC-BI in real-world clinical practice during the 12-month follow-up. This article is protected by copyright. All rights reserved.Dehydration accrued during intense prolonged whole-body exercise in the heat compromises peripheral blood flow and cardiac output ( Q ˙ ). A markedly reduced stroke volume (SV) is a key feature of the dehydration-induced cardiovascular strain, but whether the lower output of the heart is mediated by peripheral or cardiac factors remains unknown. Therefore, we repeatedly quantified left ventricular (LV) volumes, LV mechanics (LV twist, a marker of systolic muscle function, and LV untwisting rate, an independent marker of LV muscle relaxation), left intra-ventricular pressure gradients, blood volume and peripheral blood flow during 2 hr of cycling in the heat with and without dehydration (DEH 4.0 ± 0.2% body mass loss and EUH euhydration control, respectively) in eight participants (three females and five males). While brachial and carotid blood flow, blood volume, SV, LV end-diastolic volume (LVEDV), cardiac filling time, systemic vascular conductance and Q ˙ were reduced in DEH compared to EUH after 2 hr, LV twist and untwisting rate tended to be higher (p = .09 and .06, respectively) and intra-ventricular pressure gradients were not different between the two conditions (p = .22). Furthermore, LVEDV in DEH correlated strongly with blood volume (r = .995, p less then .01), head and forearms beat volume (r = .98, p less then .05), and diastolic LV filling time (r = .98, p less then .05). These findings suggest that the decline in SV underpinning the blunted Q ˙ with exercise-induced dehydration is caused by compromised LV filling and venous return, but not intrinsic systolic or diastolic LV function.Objective To translate, cross-culturally adapt and test the psychometric properties of the Revised Fibromyalgia Impact Questionnaire (FIQR) in Nepali language (Nepali FIQR). Methods The translation was performed following the methodological standards described by Beaton. https://www.selleckchem.com/products/bromoenol-lactone.html Comprehensibility testing of the preliminary version was done in 40 fibromyalgia patients, and a pre-final version was prepared after making changes in the original version to maintain the equivalence with the target version. Psychometric testing was done in another group of 130 fibromyalgia patients to test for content validity and reliability. Construct validity was tested with visual analog score (VAS) for pain and Short Form (SF)-36. Results Nepali FIQR was comprehensible to 92.5% patients. The internal consistency was also acceptable with Cronbach's alpha of 0.900, 0.714 and 0.863 for function, overall and symptoms domain, respectively. Construct validity was also acceptable with a moderate correlation between Nepali FIQR and VAS and SF-36. Test-retest reliability of the total Nepali FIQR and of each item were acceptable with intraclass correlation coefficient (ICC) of >0.7 in all items except for question 1 of function domain (ICC 0.65). Conclusions Nepali FIQR is a comprehensible, reliable and valid tool for evaluation of the functional status of Nepalese patients with fibromyalgia and should be implemented in routine clinical care and research settings.Purpose Alpha-synuclein (α-syn) dopaminylation can lead to the death of dopaminergic neurons in the brain and is a risk factor of Parkinson's disease (PD). We aim to examine whether such a posttranslational modification (PTM) is presented in human blood plasma. Experimental design In vitro reaction simulation between α-syn and dopamine (DA) was conducted to study the biochemical mechanism. Then α-syn from human blood plasma samples was detected by using immunoprecipitation-mass spectrometry (IP-MS). Lastly the levels of endogenous α-syn and α-syn dopaminylation in 88 blood plasma samples from patients with PD, major depressive disorder (MDD) and healthy control (HC) were compared. Results DA modifies α-syn with the addition of dopamine-quinone (DAQ) into lysine sites of α-syn in vitro and the addition of DAQ and DOPAL (3,4-dihydroxyphenylacetaldehyde) in plasma samples. The unmodified α-syn between the PD and HC groups showed similar levels. The levels of two peptides, one with lysine 34 (34 K) DAQ modification and the other with lysine 23 (23 K) ubiquitination, were significantly higher in PD and MDD compared with HC. Conclusions and clinical relevance Thus, α-syn dopaminylation is measurable and might be used to indicatethe presence and progression of neurological disorders. This article is protected by copyright. All rights reserved.