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Das, M.,Du, Y.,Mortensen, J.,Ribeiro, O.,Hariharan, P.,Guan, L.,Loland, C.,Kobilka, B.,Byrne, B.,Chae, P. THE ROYAL SOCIETY OF CHEMISTRY 2017 Chemical Science Vol.8 No.2
<P>Amphiphile selection is a crucial step in membrane protein structural and functional study. As conventional detergents have limited scope and utility, novel agents with enhanced efficacy need to be developed. Although a large number of novel agents have been reported, so far there has been no systematically designed comparative study of the protein stabilization efficacy of stereo-isomeric amphiphiles. Here we designed and prepared a novel class of stereo-isomeric amphiphiles, designated butane-1,2,3,4-tetraolbased maltosides (BTMs). These stereoisomers showed markedly different behaviour for most of the targeted membrane proteins depending on the chirality of the linker region. These findings indicate an important role for detergent stereochemistry in membrane protein stabilization. In addition, we generally observed enhanced detergent efficacy with increasing alkyl chain length, reinforcing the importance of the balance between hydrophobicity and hydrophilicity in detergent design. The stereo-isomeric difference in detergent efficacy observed provides an important design principle for the development of novel amphiphiles for membrane protein manipulation.</P>
Sundstrup, Emil,Hansen, Ase M.,Mortensen, Erik L.,Poulsen, Otto M.,Clausen, Thomas,Rugulies, Reiner,Moller, Anne,Andersen, Lars L. Occupational Safety and Health Research Institute 2020 Safety and health at work Vol.11 No.3
Background: The study aimed to determine the association of individual cognitive ability in late midlife with labor market participation among older workers. Methods: This prospective cohort study estimates the risk of long-term sickness absence, disability pension, early retirement, and unemployment from scores on the Intelligenz-Struktur-Test 2000R by combining data from 5076 workers from the Copenhagen Aging and Midlife Biobank with a register on social transfer payments. Analyses were stepwise adjusted for age, gender, physical and psychosocial work environment, health behaviors, occupational social class, education, and chronic diseases. Results: In the fully adjusted model, low cognitive ability (≥1 standard deviation below the mean for each gender) and high cognitive ability (≥1 standard deviation above the mean for each gender) were not associated with risk of any of the four labor market outcomes. Conclusion: Individual cognitive ability in late midlife was not associated with risk of long-term sickness absence, disability pension, early retirement, and unemployment in the fully adjusted model. Thus, no direct effect of individual cognitive ability in late midlife was observed on the risk of permanently or temporarily leaving the labor market.
Winthrop, K L,Park, S-H,Gul, A,Cardiel, M H,Gomez-Reino, J J,Tanaka, Y,Kwok, K,Lukic, T,Mortensen, E,Ponce de Leon, D,Riese, R,Valdez, H BMJ Publishing Group 2016 Annals of the Rheumatic Diseases Vol.75 No.6
<P><B>Objectives</B></P><P>To evaluate the risk of opportunistic infections (OIs) in patients with rheumatoid arthritis (RA) treated with tofacitinib.</P><P><B>Methods</B></P><P>Phase II, III and long-term extension clinical trial data (April 2013 data-cut) from the tofacitinib RA programme were reviewed. OIs defined a priori included mycobacterial and fungal infections, multidermatomal herpes zoster and other viral infections associated with immunosuppression. For OIs, we calculated crude incidence rates (IRs; per 100 patient-years (95% CI)); for tuberculosis (TB) specifically, we calculated rates stratified by patient enrolment region according to background TB IR (per 100 patient-years): low (≤0.01), medium (>0.01 to ≤0.05) and high (>0.05).</P><P><B>Results</B></P><P>We identified 60 OIs among 5671 subjects; all occurred among tofacitinib-treated patients. TB (crude IR 0.21, 95% CI of (0.14 to 0.30)) was the most common OI (n=26); median time between drug start and diagnosis was 64 weeks (range 15–161 weeks). Twenty-one cases (81%) occurred in countries with high background TB IR, and the rate varied with regional background TB IR: low 0.02 (0.003 to 0.15), medium 0.08 (0.03 to 0.21) and high 0.75 (0.49 to 1.15). In Phase III studies, 263 patients diagnosed with latent TB infection were treated with isoniazid and tofacitinib concurrently; none developed TB. For OIs other than TB, 34 events were reported (crude IR 0.25 (95% CI 0.18 to 0.36)).</P><P><B>Conclusions</B></P><P>Within the global tofacitinib RA development programme, TB was the most common OI reported but was rare in regions of low and medium TB incidence. Patients who screen positive for latent TB can be treated with isoniazid during tofacitinib therapy.</P>