Bi(OTf)3-Catalyzed Multicomponent α-Amidoalkylation Reactions.

A bismuth(III) triflate catalyzed three-component synthesis of α-substituted amides starting from amides, aldehydes, and (hetero)arenes is reported. The reaction has a broad substrate scope, encompassing formaldehyde as well as aryl and alkyl aldehydes. Low catalyst loadings are required, and water is formed as the only side product. The scope and limitation of this method will be discussed.

Higher glucose concentrations following protein- and fat-rich meals - the Tuebingen Grill Study: a pilot study in adolescents with type 1 diabetes.

OBJECTIVE: Traditionally insulin dosage is focused on the carbohydrate amount of meals. We investigated the influence of a fat- and protein-rich meal in the evening on glucose concentration over night in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: Fifteen patients, mean age 16.8 [standard deviation (SD) 2.9] yr participated in the study. Mean glycated hemoglobin (HbA1c) was 6.9 (range: 6.0-8.9) %. On two consecutive days the patients received a standard meal (SM) and a fat-protein-rich evening meal (FPRM). The carbohydrate amount remained identical and insulin was adjusted to this carbohydrate amount with the individual carbohydrate bolus. Glucose was measured continuously over night with the Enlite sensor and the Guardian system (Medtronic) during the following 12 h after the meal. RESULTS: Glucose area under the curve (AUC) for SM was 1400 (SD 580) mg/dL/12 h and for FPRM 1968 (SD 394) mg/dL/12 h (p < 0.05). There was a significant difference in the AUC between 4 and 12 h after the meal. Maximal AUC difference was 6 h after the meal. Glucose concentration in the morning (12 h after the meal) differed: 91 (SD 34) mg/dL after SM and 153 (SD 60) mg/dL after FPRM (p < 0.05). For SM 31% of glucose level were <80 mg/dL and 24% >150 mg/dL, for FPRM it was 3 and 48%. CONCLUSIONS: Twelve hours after a FPRM glucose concentration is significantly higher. Dietary counseling should include the effect of protein and fat on glucose levels in adolescents with type 1 diabetes. The data indicate clearly a need for additional insulin for fat-protein-rich meals.

Bi(OTf)3-catalyzed three-component synthesis of α-amino acid derivatives.

A highly efficient Bi(OTf)3-catalyzed multicomponent synthesis of arylglycines from readily available starting materials is described. The reaction proceeds under mild conditions and provides a general route to various N-protected arylglycines.

Coping styles as predictors for quality of life and prognosis in patients at risk for or with a diagnosis of heart failure: Results from the observational DIAST-CHF study.

OBJECTIVE: Patients with heart failure often experience impaired health-related quality of life (HRQOL) and have an increased risk of cardiovascular and cerebrovascular events. The aim of this study was to investigate the predictive role of different coping styles on outcome. METHODS: This longitudinal study included 1536 participants who either had cardiovascular risk factors or were diagnosed with heart failure. Follow-ups took place one, two, five and ten years after recruitment. Coping and HRQOL were investigated using self-assessment questionnaires (Freiburg Questionnaire for Coping with Illness, Short Form-36 Health Survey). Somatic outcome was quantified by incidence of major adverse cardiac and cerebrovascular events (MACCE) and 6-min-walking-distance. RESULTS: Pearson correlation and multiple linear regression analysis showed significant associations between the coping styles used at the first three time points and HRQOL after five years. After adjusting for baseline HRQOL, minimization and wishful thinking predicted worse mental HRQOL (ß = -0.106; p = 0.006), while depressive coping predicted worse mental (ß = -0.197; p < 0.001) and physical HRQOL (ß = -0.085; p = 0.03; n = 613). Active problem-oriented coping could not significantly predict HRQOL. Only minimization and wishful thinking was significantly associated with an increased 10-year-risk for MACCE (hazard ratio = 1.06; 95% confidence interval: 1.01-1.11; p = 0.02; n = 1444) and reduction in 6-min-walking-distance at 5 years (ß = -0.119; p = 0.004; n = 817) in adjusted analyses. CONCLUSIONS: Depressive coping and minimization and wishful thinking were associated with worse quality of life in patients at risk for or with diagnosed heart failure. Minimization and wishful thinking also predicted worse somatic outcome. Therefore, patients using those coping styles might benefit from early psychosocial interventions.

Investigation of the Sympathetic Regulation in Delayed Onset Muscle Soreness: Results of an RCT.

Sports-related pain and injury is directly linked to tissue inflammation, thus involving the autonomic nervous system (ANS). In the present experimental study, we disable the sympathetic part of the ANS by applying a stellate ganglion block (SGB) in an experimental model of delayed onset muscle soreness (DOMS) of the biceps muscle. We included 45 healthy participants (female 11, male 34, age 24.16 ± 6.67 years [range 18-53], BMI 23.22 ± 2.09 kg/m2) who were equally randomized to receive either (i) an SGB prior to exercise-induced DOMS (preventive), (ii) sham intervention in addition to DOMS (control/sham), or (iii) SGB after the induction of DOMS (rehabilitative). The aim of the study was to determine whether and to what extent sympathetically maintained pain (SMP) is involved in DOMS processing. Focusing on the muscular area with the greatest eccentric load (biceps distal fifth), a significant time × group interaction on the pressure pain threshold was observed between preventive SGB and sham (p = 0.034). There was a significant effect on pain at motion (p = 0.048), with post hoc statistical difference at 48 h (preventive SGB Δ1.09 ± 0.82 cm VAS vs. sham Δ2.05 ± 1.51 cm VAS; p = 0.04). DOMS mediated an increase in venous cfDNA -as a potential molecular/inflammatory marker of DOMS- within the first 24 h after eccentric exercise (time effect p = 0.018), with a peak at 20 and 60 min. After 60 min, cfDNA levels were significantly decreased comparing preventive SGB to sham (unpaired t-test p = 0.008). At both times, 20 and 60 min, cfDNA significantly correlated with observed changes in PPT. The 20-min increase was more sensitive, as it tended toward significance at 48 h (r = 0.44; p = 0.1) and predicted the early decrease of PPT following preventive stellate blocks at 24 h (r = 0.53; p = 0.04). Our study reveals the broad impact of the ANS on DOMS and exercise-induced pain. For the first time, we have obtained insights into the sympathetic regulation of pain and inflammation following exercise overload. As this study is of a translational pilot character, further research is encouraged to confirm and specify our observations.

Additional Insulin for Coping with Fat- and Protein-Rich Meals in Adolescents with Type 1 Diabetes: The Protein Unit.

OBJECTIVE: Dietary proteins raise blood glucose levels; dietary fats delay this rise. We sought to assess the insulin amount required to normalize glucose levels after a fat- and protein-rich meal (FPRM). METHODS: Sixteen adolescents (5 female) with type 1 diabetes (median age: 18.2 years; range: 15.2-24.0; duration: 7.1 years; 2.3-14.3; HbA1c: 7.2%; 6.2-8.3%) were included. FPRM (carbohydrates 57 g; protein 92 g; fat 39 g; fibers 7 g; calories 975 Kcal) was served in the evening, with 20 or 40% extra insulin compared to a standard meal (SM) (carbohydrates 70 g; protein 28 g; fat 19 g; fibers 10 g; calories 579 Kcal) or carbohydrates only. Insulin was administered for patients on intensified insulin therapy or as a 4-hour-delayed bolus for those on pump therapy. The 12-hour post-meal glucose levels were compared between FPRM and SM, with the extra insulin amount calculated based on 100 g proteins as a multiple of the carbohydrate unit. RESULTS: Glucose levels (median, mg/dL) 12-hour post-meal with 20% extra insulin vs. 40% vs. insulin dose for SM were 116 vs. 113 vs. 91. Glucose-AUC over 12-hour post-meal with 20% extra insulin vs. 40% vs. insulin dose for SM was 1603 mg/dL/12 h vs. 1527 vs. 1400 (no significance). Glucose levels in the target range with 20% extra insulin vs. 40% were 60% vs. 69% (p=0.1). Glucose levels <60 mg/dL did not increase with 40% extra insulin. This corresponds to the 2.15-fold carbohydrate unit for 100 g protein. CONCLUSIONS: We recommend administering the same insulin dose given for 1 carbohydrate unit (10 g carbs) to cover 50 g protein.

Similar mating and sperm displacement patterns in two highly divergent D. simulans populations from Africa and Europe.

The frequency of remating in Drosophila melanogaster is affected by both genetic and ecological factors. We studied the remating behaviour in one European (Italy) and one African (Uganda) Drosophila simulans population using six highly polymorphic microsatellite markers. Despite that the populations were genetically distinct (F(ST) = 0.18) and originated from very dissimilar ecological settings with different population densities, we inferred a very similar mating pattern. The remating parameter alpha was similar in both populations (a = 1.3-1.4). No more than two distinct paternal genotypes per family were detected in each population.