Association between gestational weight gain, gestational diabetes risk, and obstetric outcomes: A randomized controlled trial post hoc analysis

Excess gestational weight gain (GWG) is associated with the development of gestational diabetes mellitus (GDM). Lifestyle trials have not achieved much GWG limitation, and have largely failed to prevent GDM. We compared the effect of substantial GWG limitation on maternal GDM risk. Pregnant women with a body mass index (BMI) ≥29 kg/m2 \u3c20 weeks gestation without GDM (n = 436) were randomized, in a multicenter trial, to usual care (UC), healthy eating (HE), physical activity (PA), or HE and PA lifestyle interventions. GWG over the median was associated with higher homeostasis model assessment insulin resistance (HOMA-IR) and insulin secretion (Stumvoll phases 1 and 2), a higher fasting plasma glucose (FPG) at 24–28 weeks (4.66 ± 0.43 vs. 4.61 ± 0.40 mmol/L, p \u3c 0.01), and a higher rate of caesarean section (38% vs. 27% p \u3c 0.05). The GWG over the median at 35–37 weeks was associated with a higher rate of macrosomia (25% vs. 16%, p \u3c 0.05). A post hoc comparison among women from the five sites with a GWG difference \u3e3 kg showed no significance difference in glycaemia or insulin resistance between HE and PA, and UC. We conclude that preventing even substantial increases in GWG after the first trimester has little effect on maternal glycaemia. We recommend randomized controlled trials of effective lifestyle interventions, starting in or before the first trimester

Control of Oxo-Group Functionalization and Reduction of the Uranyl Ion

yesUranyl complexes of a large, compartmental N8-macrocycle adopt a rigid, “Pacman” geometry that stabilizes the UV oxidation state and promotes chemistry at a single uranyl oxo-group. We present here new and straightforward routes to singly reduced and oxo-silylated uranyl Pacman complexes and propose mechanisms that account for the product formation, and the byproduct distributions that are formed using alternative reagents. Uranyl(VI) Pacman complexes in which one oxo-group is functionalized by a single metal cation are activated toward single-electron reduction. As such, the addition of a second equivalent of a Lewis acidic metal complex such as MgN″2 (N″ = N(SiMe3)2) forms a uranyl(V) complex in which both oxo-groups are Mg functionalized as a result of Mg−N bond homolysis. In contrast, reactions with the less Lewis acidic complex [Zn(N″)Cl] favor the formation of weaker U−O−Zn dative interactions, leading to reductive silylation of the uranyl oxo-group in preference to metalation. Spectroscopic, crystallographic, and computational analysis of these reactions and of oxo-metalated products isolated by other routes have allowed us to propose mechanisms that account for pathways to metalation or silylation of the exo-oxogroup

Predictive Models of Cognitive Fatigue in Multiple Sclerosis

Objective: Cognitive fatigue (CF) can be defined as decreased performance with sustained cognitive effort. The present study examined the interrelatedness of disease severity, fatigue, depression, and sleep quality in order to evaluate their predictive roles of CF in MS. Four theoretical models examining these variables were assessed. Methods: Fifty-eight individuals with a diagnosis of MS were recruited. CF was measured by examining last third versus first third performance on the Paced Auditory Serial Addition Test (PASAT). The PASAT and self-report measures of fatigue, depression, and sleep quality were administered. Path analysis was used to evaluate each of the models. Results: CF was correlated only with depression (r = .362, p = .006) and sleep quality (r = .433, p = .001). Sleep quality was the greatest significant independent predictor of CF (β = .433, t(1,55) = 3.53, p < .001), accounting for 17.3% of the total variance. The best fitting model showed sleep quality as the largest contributor to CF; however, depression played a smaller predictive role. Furthermore, depression emerged as the strongest predictor of sleep quality and fatigue. Disease severity weakly predicted depression. Conclusions: Sleep quality is the most significant predictor of CF in MS. As such, sleep quality may be a treatable cause of CF. Sleep quality itself, however, accounted for only 17.3% of the variance in C

A longitudinal evaluation of cognitive fatigue on a task of sustained attention in early relapsing-remitting multiple sclerosis

Background: Cognitive fatigue can be objectively measured on tasks of sustained attention and can be defined as decreased performance as a result of sustained cognitive effort. Individuals with multiple sclerosis (MS) early in their disease are vulnerable to cognitive fatigue, although this has yet to be evaluated longitudinally. We aimed to evaluate cognitive fatigue over a 3-year interval in individuals with early-phase relapsing-remitting MS (RRMS). The sensitivity of the Paced Auditory Serial Addition Test (PASAT) at detecting cognitive fatigue was evaluated, as was the impact of scoring method. Methods: 32 people with MS and 32 controls completed the 3- and 2-second PASAT (PASAT-3" and -2") as a measure of sustained attention at baseline and 3-year follow-up. Results: Performance on the PASAT remained stable across time, with improvement noted on the PASAT- 2" likely due to practice and the small sample size. Cognitive fatigue was noted at both times, although sensitivity varied based on scoring method. No evidence of worsening cognitive fatigue was noted over time. The MS group performed worse only when cognitive fatigue was the outcome variable. Conclusions: Although individuals with MS continue to be vulnerable to cognitive fatigue at follow-up, severity does not seem to increase with time. Cognitive fatigue may be a more sensitive marker of cognitive impairment than overall task performance in those with early-phase RRMS, which has important implications given t

Cognitive Fatigability Interventions in Neurological Conditions: A Systematic Review

Introduction: Although fatigue is a well-studied concept in neurological disease, cognitive fatigability (CF) is less understood. While most studies measure fatigue using subjective self-report, fewer have measured CF objectively. Given the negative impact of CF on quality-of-life, there is a need for targeted interventions. The objective of this review was to determine which procedural, behavioural and pharmacological treatments for objectively measured CF are available to people living with neurological conditions. Methods: In accordance with the PRISMA guidelines, systematic searches for randomized control trials (RCTs), case-controlled studies and case reports/series were conducted across the Ovid Medline, PsycInfo, EMBASE and Cochrane Library databases. English-language articles published between 1980 and February 2019 were considered for eligibility. Included were those that objectively measured CF in individuals with neurological disease/disorder/dysfunction between the ages of 18 and 65 years. Studies were reviewed using a modified Cochrane Data Extraction Template. Risk of bias was assessed using the Cochrane Risk of Bias tool. The review process was facilitated using Covidence software (www.covidence.org). Two authors reviewed articles independently, with a third resolving conflicts regarding article inclusion. Results: The search identified 450 records. After duplicates were removed and remaining titles/abstracts were screened for eligibility, 28 full-text articles were assessed, and two studies were included in the qualitative synthesis. Studies were a priori divided into those with pharmacological, procedural or behavioural interventions. Two studies met eligibility criteria; both of these included participants with multiple sclerosis. One s

Longitudinal stability of cognition in early-phase relapsing-remitting multiple sclerosis; Does cognitive reserve play a role?

Background: Up to 70% of people with multiple sclerosis (MS) experience cognitive impairment. Some remain cognitively intact despite advanced disease. Cognitive reserve (CR) theory postulates that individuals with higher levels of intellectual enrichment can tolerate more pathology than others before exhibiting cognitive impairment. Methods: Thirty-two individuals with early-phase relapsing-remitting MS with mild physical disability and disease duration less than 10 years and 32 controls were recruited. At baseline and after 3 years, participants completed neuropsychological tests evaluating several cognitive domains. The CR was assessed via a cognitive reserve index (CRI) using educational levels and North American Adult Reading Test scores. Change in cognition was assessed using a reliable change index. Results: At baseline, people with MS performed worse than controls on visual memory. There were no significant group difference

Cognitive fatigue in individuals with multiple sclerosis undergoing immunoablative therapy and hematopoietic stem cell transplantation

Background Fatigue presents as a significant problem in multiple sclerosis (MS). Cognitive fatigue (CF) can be defined as a decrease in, or inability to maintain task performance throughout the duration of a continuous cognitive task. CF was evaluated using the Paced Auditory Serial Addition Test (PASAT) both pre- and post-immunoablation and hematopoietic stem cell transplantation (IA-HSCT) over a 3-year follow-up period. The magnitude of CF was examined and the impact of scoring methodology was evaluated. Methods Twenty-three individuals with rapidly progressive MS and poor prognosis underwent high dose immunosuppression and subsequent HSCT. Individuals completed the 3″ and 2″ PASAT at baseline and every 6 months thereafter over a period of 36 months. As scoring methodology can impact its sensitivity to CF, the PASAT was s