Diastereo-, Enantio-, and Z-Selective α,δ-Difunctionalization of Electron-Deficient Dienes Initiated by Rh-Catalyzed Conjugate Addition.

Metal-catalyzed enantioselective conjugate additions are highly reliable methods for stereoselective synthesis; however, multicomponent reactions that are initiated by conjugate arylation of acyclic π-systems are rare. These reactions generally proceed with poor diastereoselectivity while requiring basic, moisture sensitive organometallic nucleophiles. Here, we show that Rh-catalysts supported by a tetrafluorobenzobarrelene ligand (Ph-tfb) enable the enantio-, diastereo-, and Z-selective α,δ-difunctionalization of electron-deficient 1,3-dienes with organoboronic acid nucleophiles and aldehyde electrophiles to generate Z-homoallylic alcohols with three stereocenters. The reaction accommodates diene substrates activated by ester, amide, ketone, or aromatic groups and can be used to couple aryl, alkenyl, or alkyl aldehydes. Diastereoselective functionalization of the Z-olefin unit in the addition products allows for the generation of compounds with five stereocenters in high dr and ee. Mechanistic studies suggest aldehyde allylrhodation is the rate-determining step, and unlike reactions of analogous Rh-enolates, the Rh-allyl species generated by δ-arylation undergoes aldehyde trapping rather than protonolysis, even when water is present as a cosolvent. These findings should have broader implications in the use of privileged metal-catalyzed conjugate addition reactions as entry points toward the preparation of acyclic molecules containing nonadjacent stereocenters.

Multicountry Analysis of Spectrum of Clinical Manifestations of Children <5 Years of Age Hospitalized with Diarrhea.

After introduction of rotavirus vaccine, other pathogens might become leading causes of hospitalizations for severe diarrhea among children <5 years of age. Our study in 33 hospitals in 7 countries found acute gastroenteritis accounted for most (84%) reported hospitalizations of children with diarrhea. Bloody and persistent diarrhea each accounted for <1%.

Impact and Effectiveness of Monovalent Rotavirus Vaccine in Armenian Children.

BACKGROUND: The Republic of Armenia was 1 of the 2 earliest countries in the Newly Independent States to introduce rotavirus vaccine into its national immunization program to reduce the burden of rotavirus disease (documented to cause 38% of acute gastroenteritis hospitalizations [AGE] among children aged <5 years). In November 2012, RV1 (Rotarix) was introduced for Armenian infants at ages 6 and 12 weeks. METHODS: The established active surveillance system at 2 hospitals in the capital, Yerevan, whereby children aged <5 years hospitalized for AGE have stool sample tested for rotavirus antigen, was used to assess trends in rotavirus hospitalizations. Immunization records on children enrolled after vaccine introduction were obtained from clinics, and vaccine effectiveness (VE) was estimated using children with AGE who test negative for rotavirus as controls for the rotavirus-positive cases. RESULTS: Among infants, rotavirus hospitalizations were reduced by 48% within the first year after introduction, and by ≥75% in years 2 and 3 following introduction. Reductions of ≥30% in other young children too old to have been vaccinated suggest additional benefit through indirect protection; overall in year 3, rotavirus hospitalizations were reduced by 69% among children aged <5 years. The overall VE of 2 RV1 doses in protecting against rotavirus hospitalization (any severity) was 62% (95% confidence interval [CI], 36%-77%) among children aged 6-23 months; 68% (95% CI, 24%-86%) among those aged 6-11 months, and 60% (95% CI, 20%-80%) in children aged 12-23 months. Against more severe rotavirus disease, VE was 79% (95% CI, 55%-90%) and similarly high in both age groups. CONCLUSIONS: RV1 is effective in young Armenian children and substantially reduced rotavirus hospitalizations shortly after introduction.

Inflammation and Coagulation are Two Interconnected Pathophysiological Pathways in Atrial Fibrillation Pathogenesis.

Introduction: Atrial fibrillation (AF) is associated with elevated levels of clotting factors such as tissue factor (TF) and factor XII (FXII). Various inflammation markers, such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF- α), and high-sensitive C-reactive protein (hs-CRP), have also been associated with AF. This study explores the relationship between inflammation markers and coagulation activity, including their impact on heart structural changes in these patients. Methods: We observed 283 patients with nonvalvular AF who underwent a complete examination at admission, but only 183 patients have successful cardioversion. As a control group, similar patients without AF were examined. The markers of the coagulation and inflammation were studied by ELISA on the analyzer "Stat Fax 303 Plus". Studies were conducted using l statistical package SPSS 13.0. Results: It was revealed that patients with AF had significantly higher levels of hs-CRP, IL-6, and TNF-α and had elevated levels of TF and FXII compared with control group. The moderate correlations were observed between IL-6 and left atrial diameter (LAD), IL-6 and LA stiffness, hs-CRP and left atrial volume (LAV), TF and LAV. Conclusion: We have demonstrated that patients with AF have the relationship between elevated levels of inflammatory markers and coagulation activity, which contributes to structural atrial remodeling.

Using pneumococcal and rotavirus surveillance in vaccine decision-making: A series of case studies in Bangladesh, Armenia and the Gambia.

Pneumonia and diarrhea are the leading causes of child morbidity and mortality globally and are vaccine preventable. The WHO-coordinated Global Rotavirus and Invasive Bacterial Vaccine-Preventable Disease Surveillance Networks support surveillance systems across WHO regions to provide burden of disease data for countries to make evidence-based decisions about introducing vaccines and to demonstrate the impact of vaccines on disease burden. These surveillance networks help fill the gaps in data in low and middle-income countries where disease burden and risk are high but support to sustain surveillance activities and generate data is low. Through a series of country case studies, this paper reviews the successful use of surveillance data for disease caused by pneumococcus and rotavirus in informing national vaccine policy in Bangladesh, Armenia and The Gambia. The case studies delve into ways in which countries are leveraging and building capacity in existing surveillance infrastructure to monitor other diseases of concern in the country. Local institutions have been identified to play a critical role in making surveillance data available to policymakers. We recommend that countries review local or regional surveillance data in making vaccine policy decisions. Documenting use of surveillance activities can be used as advocacy tools to convince governments and external funders to invest in surveillance and make it a priority immunization activity.