Influence of Glass Forming Ability on the Physical Stability of Supersaturated Amorphous Solid Dispersions

In this study, the influence of the glass-forming ability (GFA) of a drug on its physical stability in a supersaturated solid dispersion was investigated. Nine drugs were classified according to their GFA using their respective critical cooling rate. Their respective solubility in poly(vinylpyrrolidone-co-vinyl acetate) 6:4 (PVPVA64) was predicted using the melting point depression method based on the Flory-Huggins lattice theory. Supersaturated amorphous solid dispersions at a level of 25% w/w drug above saturation solubility in the polymer were prepared by film-casting, and their respective physical stability at temperatures of 10°C or 20°C above or below their respective T_g (dry conditions) was monitored by the use of polarized light microscopy. This study showed that drugs with good GFA (class 3) on average have higher physical stability in supersaturated amorphous solid dispersion compared to drug with modest GFA (class 2), which in turn have higher physical stability in supersaturated amorphous solid dispersion than drugs with poor GFA (class 1). These results indicate that the GFA of a drug and its physical stability in a supersaturated amorphous solid dispersion stored at a temperature above or below its T_g are correlated.     

The size-weight illusion in visual form agnosic patient DF

ABSTRACT

The size-weight illusion is a perceptual illusion where smaller objects are judged as heavier than equally weighted larger objects. A previous informal report suggests that visual form agnosic patient DF does not experience the size-weight illusion when vision is the only available cue to object size. We tested this experimentally, comparing the magnitudes of DF’s visual, kinesthetic and visual-kinesthetic size-weight illusions to those of 28 similarly-aged controls. A modified t-test found that DF’s visual size-weight illusion was significantly smaller than that of controls (z_cc = ?1.7). A test of simple dissociation based on the Revised Standardized Difference Test found that the discrepancy between the magnitude of DF’s visual and kinesthetic size-weight illusions was not significantly different from that of controls (z_dcc = ?1.054), thereby failing to establish a dissociation between the visual and kinesthetic conditions. These results are consistent with previous suggestions that visual form agnosia, following ventral visual stream damage, is associated with an abnormally reduced size-weight illusion. The results, however, do not confirm that this reduction is specific to the use of visual size cues to predict object weight, rather than reflecting more general changes in the processing of object size cues or in the use of predictive strategies for lifting.     

Overexpression of striatal D2 receptors reduces motivation thereby decreasing food anticipatory activity

Dopamine has been implicated in circadian timing underlying the food entrainable oscillator (FEO) circuitry and overexpression of the dopamine D2 receptor (D2R) in the striatum has been reported to reduce motivation to obtain food rewards in operant tasks. In the present study, we explored both of these mechanisms by examining food anticipatory activity (FAA) in dopamine D2 receptor‐overexpressing (D2R‐OE) mice under various durations of food availability. First, we noted that at baseline, there were no differences between D2R‐OE mice and their littermates in activity level, food intake, and body weight or in circadian activity. Under conditions of very restricted food availability (4 or 6 hr), both genotypes displayed FAA. In contrast, under 8‐hr food availability, control mice showed FAA, but D2R‐OE mice did not. Normalization of D2R by administration of doxycycline, a tetracycline analogue, rescued FAA under 8‐hr restricted food. We next tested for circadian regulation of FAA. When given ad libitum access to food, neither D2R‐OE nor controls were active during the daytime. However, after an interval of food restriction, all mice showed elevated locomotor activity at the time of previous food availability in the day, indicating circadian timing of anticipatory activity. In summary, motivation is reduced in D2R‐OE mice but circadian timing behavior is not affected. We conclude that an increase in striatal D2R reduces FAA by modulating motivation and not by acting on a clock mechanism.     

Physical Activity in Youth With Type 1 Diabetes: a Review

Youth with type 1 diabetes are at risk for developing cardiovascular disease, and regular physical activity is strongly recommended as one strategy for prevention, as well as for good glycemic control. Despite recommendations, families in this pediatric population face unique barriers to physical activity, including fear of hypoglycemia. Moreover, families are not routinely counseled in the specific health and psychosocial benefits of following physical activity recommendations for youth with type 1 diabetes. To bridge this gap, the recent literature regarding physical activity in children with type 1 diabetes is reviewed with particular focus on young children. A discussion of the limitations of the current body of research, and recommendations for objectively measured physical activity are provided. Specific recommendations for clinical practice are given, including provider endorsements for regular physical activity for longer than 60 minutes, at least three times a week.     

Examination of potential novel biochemical factors in relation to prostate cancer incidence and mortality in UK Biobank

Background Although prostate cancer is a leading cause of cancer death, its aetiology is not well understood. We aimed to identify novel biochemical factors for prostate cancer incidence and mortality in UK Biobank.Methods A range of cardiovascular, bone, joint, diabetes, renal and liver-related biomarkers were measured in baseline blood samples collected from up to 211,754 men at recruitment and in a subsample 5 years later. Participants were followed-up via linkage to health administrative datasets to identify prostate cancer cases. Hazard ratios (HRs) and 95% confidence intervals were calculated using multivariable-adjusted Cox regression corrected for regression dilution bias. Multiple testing was accounted for by using a false discovery rate controlling procedure.Results After an average follow-up of 6.9 years, 5763 prostate cancer cases and 331 prostate cancer deaths were ascertained. Prostate cancer incidence was positively associated with circulating vitamin D, urea and phosphate concentrations and inversely associated with glucose, total protein and aspartate aminotransferase. Phosphate and cystatin-C were the only biomarkers positively and inversely, respectively, associated with risk in analyses excluding the first 4 years of follow-up. There was little evidence of associations with prostate cancer death.Conclusion We found novel associations of several biomarkers with prostate cancer incidence. Future research will examine associations by tumour characteristics.Subject terms: Predictive markers, Prostate cancer, Risk factors     

HIV-negative children’s experiences and opinions towards parental HIV disclosure: a qualitative study in China

In HIV/AIDS research, few studies to date have evaluated ways to improve parental HIV disclosure practices using feedback from HIV-negative children who have recently experienced this event. We conducted semi-structured in-depth interviews with 20 children (aged 6–15) who were partially to fully aware of their parents’ HIV status in rural Guangxi, China. Of the 20 children, eight children who were of older age (11.38 years in average) endorsed parental HIV disclosure, five discouraged it and seven expressed uncertainty. Children’s different experiences and attitudes towards disclosure were seen to be associated with their family dynamics (especially the parent–child relationship), social support and care, experiences of stigma and discrimination, psychosocial suffering, comprehension of the disease and the children’s age. Our study contributes to building a child-centered comprehensive understanding for Chinese parental HIV disclosure. It is imperative that counselors and community advocates assess and help parents achieve optimal readiness preceding disclosure of their illness to their HIV-negative children.