Estimated Worldwide Mortality Attributed to Secondhand Tobacco Smoke Exposure, 1990-2016

Importance: The World Health Organization estimates that the 1 billion individuals who smoke worldwide contribute to the 880 000 secondhand smoke (SHS)-related deaths among individuals who do not smoke each year. A better understanding of the scale of harm of SHS to those who do not smoke could increase awareness of the consequences of smoking and help to design measures to protect individuals who do not smoke, especially children. Objective: To calculate the number of individuals who smoke associated with the death of 1 individual who died of SHS exposure both on a global scale and in various World Bank regions. Design, Setting, and Participants: In this cross-sectional epidemiologic assessment, data from Our World in Data were used to tabulate the number of individuals who smoke in each country and number of premature deaths related to SHS in that country from 1990 to 2016. The mean number of cigarettes consumed in all countries was also included in analyses. Data were collected for the following World Bank regions: North America, Latin America and the Caribbean, Europe and Central Asia, the Middle East and North Africa, sub-Saharan Africa, South Asia, and East Asia and the Pacific from 1990 and 2016. Statistical analysis was conducted in July 2019. Exposure: Secondhand smoke. Main Outcomes and Measures: The pack-year index, calculated as the number of pack-years associated with the death of 1 individual who does not smoke but was exposed to SHS, and the SHS index, calculated as the number of individuals who smoked for 24 years (ie, the mean duration of smoking) associated with the death of 1 individual who does not smoke. Results: Globally, the SHS index changed favorably, from 31.3 (95% CI, 30.6-32.0) individuals who smoked associated with the death of 1 individual who did not smoke in 1990 to 52.3 (95% CI, 51.2-53.5) individuals who smoked in 2016. There was a wide regional variation in the 2016 secondhand smoke index, from 42.6 (95% CI, 41.6-43.5) individuals who smoked in the Middle East and North Africa to 85.7 (95% CI, 83.8-87.7) individuals who smoked in North America. Worldwide, the pack-year index also changed favorably from 751.9 (95% CI, 736.3-770.7) pack-years associated with 1 death in 1990 to 1255.9 (95% CI, 1227.2-1284.4) pack-years in 2016. Conclu

Mutations in SCG10 Are Not Involved in Hirschsprung Disease

Hirschsprung disease (HSCR) is a congenital malformation characterized by the absence of enteric neurons in the distal part of the colon. Several genes have been implicated in the development of this disease that together account for 20% of all cases, implying that other genes are involved. Since HSCR is frequently associated with other congenital malformations, the functional characterization of the proteins encoded by the genes involved in these syndromes can provide insights into the protein-network involved in HSCR development. Recently, we found that KBP, encoded by the gene involved in a HSCR- associated syndrome called Goldberg-Shprintzen syndrome, interacts with SCG10, a stathmin-like protein. To determine if SCG10 is involved in the etiology of HSCR, we determined SCG10 expression levels during development and screened 85 HSCR patients for SCG10 mutations. We showed that SCG10 expression increases during development but no germline mutation was found in any of these patients. In conclusion, this study shows that SCG10 is not directly implicated in HSCR development. However, an indirect involvement of SCG10 cannot be ruled out as this can be due to a secondary effect caused by its direct interactors

Diversity-Oriented Enzymatic Synthesis of Cyclopropane Building Blocks

While biocatalysis is increasingly incorporated into drug development pipelines, it is less commonly used in the early stages of drug discovery. By engineering a protein to produce a chiral motif with a derivatizable functional handle, biocatalysts can be used to help generate diverse building blocks for drug discovery. Here we show the engineering of two variants of Rhodothermus marinus nitric oxide dioxygenase (RmaNOD) to catalyze the formation of cis- and trans-diastereomers of a pinacolboronate-substituted cyclopropane which can be readily derivatized to generate diverse stereopure cyclopropane building blocks

Diversity-Oriented Enzymatic Synthesis of Cyclopropane Building Blocks

While biocatalysis is increasingly incorporated into drug development pipelines, it is less commonly used in the early stages of drug discovery. By engineering a protein to produce a chiral motif with a derivatizable functional handle, biocatalysts can be used to help generate diverse building blocks for drug discovery. Here we show the engineering of two variants of Rhodothermus marinus nitric oxide dioxygenase (RmaNOD) to catalyze the formation of cis- and trans-diastereomers of a pinacolboronate-substituted cyclopropane which can be readily derivatized to generate diverse stereopure cyclopropane building blocks

Multiple health risk behaviors and mental health from a life course perspective:The Dutch TRAILS study

We examined trajectories of multiple health risk behavior (MHRB) patterns throughout adolescence, and changes in mental health from childhood to young adulthood. Further, we assessed how continuity or onset of MHRBs overall were associated with subsequent changes in mental health, and whether this varied by type of MHRBs. We used six waves of the prospective Dutch TRAILS study (2001-2016; n = 2229), covering ages 11 until 23. We measured MHRBs (substance use: alcohol misuse, cannabis use, smoking; and obesity-related: overweight, physical inactivity, irregular breakfast intake) at three time points during adolescence. We assessed mental health as Youth/Adult Self-report total problems at ages 11 and 23. Latent class growth analyses and ANOVA were used to examine longitudinal trajectories and associations. We identified six developmental trajectories for the total of MHRBs and mental health. Trajectories varied regarding likelihood of MHRBs throughout adolescence, mental health at baseline, and changes in mental health problems in young adulthood. We found no associations for the continuity of overall MHRBs throughout adolescence, and neither for early, mid- or late onset, with changes in mental health problems in young adulthood. However, continuity of MHRBs in the obesity-related subgroup was significantly associated with an increase in mental health problems. Adolescents with the same MHRB patterns may, when reaching adulthood, have different levels of mental health problems, with mental health at age 11 being an important predictor. Further, involvement with obesity-related MHRBs continuously throughout adolescence is associated with increased mental health problems in young adulthood

Nickel-Catalyzed Conversion of Enol Triflates into Alkenyl Halides

A Ni‐catalyzed halogenation of enol triflates was developed and it enables the synthesis of a broad range of alkenyl iodides, bromides, and chlorides under mild reaction conditions. The reaction utilizes inexpensive, bench‐stable Ni(OAc)_2⋅4 H_2O as a precatalyst and proceeds at room temperature in the presence of sub‐stoichiometric Zn and either 1,5‐cyclooctadiene or 4‐(N,N‐dimethylamino)pyridine