Structural biology of retroviral DNA integration

Three-dimensional macromolecular structures shed critical light on biological mechanism and facilitate development of small molecule inhibitors. Clinical success of raltegravir, a potent inhibitor of HIV-1 integrase, demonstrated the utility of this viral DNA recombinase as an antiviral target. A variety of partial integrase structures reported in the past 16 years have been instrumental and very informative to the field. Nonetheless, because integrase protein fragments are unable to functionally engage the viral DNA substrate critical for strand transfer inhibitor binding, the early structures did little to materially impact drug development efforts. However, recent results based on prototype foamy virus integrase have fully reversed this trend, as a number of X-ray crystal structures of active integrase-DNA complexes revealed key mechanistic details and moreover established the foundation of HIV-1 integrase strand transfer inhibitor action. In this review we discuss the landmarks in the progress of integrase structural biology during the past 17 years.     

Interpersonal discrimination and health-related quality of life among black and white men and women in the United States

Objective

We assessed associations between discrimination and health-related quality of life among black and white men and women in the United States.

Methods

We examined data from the National Health Measurement Study, a nationally representative sample of 3,648 adults aged 35–89 in the non-institutionalized US population. These data include self-reported lifetime and everyday discrimination as well as several health utility indexes (EQ-5D, HUI3, and SF-6D). Multiple regression was used to compute mean health utility scores adjusted for age, income, education, and chronic diseases for each race-by-gender subgroup.

Results

Black men and women reported more discrimination compared to white men and women. Health utility tended to be worse as reported discrimination increased. With a few exceptions, differences between mean health utility scores in the lowest and highest discrimination groups exceeded the 0.03 difference generally considered to be a clinically significant difference.

Conclusions

Persons who experienced discrimination tended to score lower on health utility measures. The study also revealed a complex relationship between experiences of discrimination and race and gender. Because of these differential social and demographic relationships caution is urged when interpreting self-rated health measures in research, clinical, and policy settings.     

Erratum to: Interpersonal discrimination and health-related quality of life among black and white men and women in the United States

Objective

We assessed associations between discrimination and health-related quality of life among black and white men and women in the United States.

Methods

We examined data from the National Health Measurement Study, a nationally representative sample of 3,648 adults aged 35–89 in the non-institutionalized US population. These data include self-reported lifetime and everyday discrimination as well as several health utility indexes (EQ-5D, HUI3, and SF-6D). Multiple regression was used to compute mean health utility scores adjusted for age, income, education, and chronic diseases for each race-by-gender subgroup.

Results

Black men and women reported more discrimination than white men and women. Health utility tended to be worse as reported discrimination increased. With a few exceptions, differences between mean health utility scores in the lowest and highest discrimination groups exceeded the 0.03 difference generally considered to be a clinically significant difference.

Conclusions

Persons who experienced discrimination tended to score lower on health utility measures. The study also revealed a complex relationship between experiences of discrimination and race and gender. Because of these differential social and demographic relationships caution is urged when interpreting self-rated health measures in research, clinical, and policy settings.     

Analysis of the surgical treatment of rectal cancer]

Radical surgery was performed in 242 cases of rectal cancer. Female patients made up 60.3% of the group. Stage distribution was as follows: T1-13.3%, T2-21, T3-53.7 and T4-12% of patients. Lower ampullar part of the rectum was affected in 21.5% of cases whereas mid- and upper ampullar and rectosigmoid parts--in 28.1, 30.6 and 19.8% of cases, respectively. Exophytic tumors were registered in 49.6% of patients. Sphincter-saving surgery was performed in 68.2% of cases. In a group of 73 patients in whom abdomino-anal resection was performed prior to introduction of revascularization of withdrawn intestine, withdrawal was carried out in 65.8% of cases whereas in 34.2% anus preternaturalis was formed. Subsequently, local necrosis was encountered in 14.6% of cases while extensive one--in 8.3%. After the advent of revascularization, withdrawal was carried out in 95.4% of 44 operated patients. No necrotic changes were observed.     

A Study of the Photoorientation Phenomena in Cholesteric Polymer Systems Containing Photochromic Diarylethene Derivatives

Summary: Photoorientation processes in two cholesteric mixtures were studied. Mixture I contained a nematogenic phenylbenzoate homopolymer, a photochromic diarylethene dopant and a chiral dopant. Mixture II consisted of a binary comb‐shaped nematogenic copolymer with fluorescent perylene side groups and the same chiral and photochromic dopants. Irradiation of the mixtures with a polarized UV light did not induce photoorientation of the photoinduced “closed” form of the diarylethene dopant. However, the action of a polarized visible light on films of mixtures irradiated with UV light led to the appearance of dichroism. This phenomenon is associated with the photoselection process of the photochromic diarylethene molecules in the cholesteric matrix. An investigation of the kinetics of the photosensitized back photoreaction of the photochromic molecules in the cholesteric mixture showed that the polarized energy transfer from the fluorescent groups to the photochromic diarylethene dopant caused an increase in the photoselection rate. The thermal stability of dichroism in films of the mixtures was studied and it was shown that the disappearance of the dichroism of the diarylethene molecules occurred with a noticeable rate even at room temperature.

Scheme of photophysical and photochemical processes under the indirect excitation of diarylethene molecules.