Help needed in medication self-management for people with visual impairment: case-control study

Background: Visual impairment (VI) is rising in prevalence and contributing to increasing morbidity, particularly among older people. Understanding patients' problems is fundamental to achieving optimal health outcomes but little is known about how VI impacts on self-management of medication.

Aim: To compare issues relating to medication self-management between older people with and without VI.

Design and setting: Case-control study with participants aged =65 years, prescribed at least two long-term oral medications daily, living within the community.

Method: The study recruited 156 patients with VI (best corrected visual acuity [BCVA] 6/18 to 3/60) at low-vision clinics; community optometrists identified 158 controls (BCVA 6/9 or better). Researchers visited participants in their homes, administered two validated questionnaires to assess medication adherence (Morisky; Medication Adherence Report Scale [MARS]), and asked questions about medication self-management, beliefs, and support.

Results: Approximately half of the participants in both groups reported perfect adherence on both questionnaires (52.5% Morisky; 43.3%, MARS). Despite using optical aids, few (3%) with VI could read medication information clearly; 24% had difficulty distinguishing different tablets. More people with VI (29%) than controls (13%) (odds ratio [OR] = 2.8; 95% confidence interval [CI] = 1.6 to 5.0) needed help managing their medication, from friends (19% versus 10%) or pharmacists (10% versus 2.5%; OR = 4.4, 95% CI = 1.4 to 13.5); more received social service support (OR = 7.1; 95% CI = 3.9 to 12.9).

Conclusion: Compared to their peers without VI, older people with VI are more than twice as likely to need help in managing medication. In clinical practice in primary care, patients' needs for practical support in taking prescribed treatment must be recognised. Strategies for effective medication self-management should be explored.

Kingship by Descent or Kingship by Election? The Contested Title of James VI and I

Throughout the reign of Elizabeth I, a steady stream of tracts appeared in English print to vindicate the succession of the most prominent contenders, Mary and James Stuart of Scotland. This article offers a comprehensive account of the polemical battle between the supporters and opponents of the Stuarts, and further identifies various theories of English kingship, most notably the theory of corporate kingship, developed by the Stuart polemicists to defend the Scottish succession. James's accession to the English throne in March 1603 marked the protracted end of the debate over the succession. The article concludes by suggesting that, while powerfully renouncing the opposition to his succession, over the course of his attempt to unify his two kingdoms, James and his supporters ultimately departed from the polemic of corporate kingship, for a more assertive language of kingship by natural and divine law.

Regulation of Foxp3+ Inducible Regulatory T Cell Stability by SOCS2

Suppressor of cytokine signaling (SOCS) proteins are key regulators of CD4+ T cell differentiation, and in particular, we have recently shown that SOCS2 inhibits the development of Th2 cells and allergic immune responses. Interestingly, transcriptome analyses have identified SOCS2 as being preferentially expressed in both natural regulatory T cells (Tregs) and inducible Tregs (iTregs); however, the role of SOCS2 in Foxp3+ Treg function or development has not been fully elucidated. In this study, we show that despite having no effect on natural Treg development or function, SOCS2 is highly expressed in iTregs and required for the stable expression of Foxp3 in iTregs in vitro and in vivo. Indeed, SOCS2-deficient CD4+ T cells upregulated Foxp3 following in vitro TGF-ß stimulation, but failed to maintain stable expression of Foxp3. Moreover, in vivo generation of iTregs following OVA feeding was impaired in the absence of SOCS2 and could be rescued in the presence of IL-4 neutralizing Ab. Following IL-4 stimulation, SOCS2-deficient Foxp3+ iTregs secreted elevated IFN-? and IL-13 levels and displayed enhanced STAT6 phosphorylation. Therefore, we propose that SOCS2 regulates iTreg stability by downregulating IL-4 signaling. Moreover, SOCS2 is essential to maintain the anti-inflammatory phenotype of iTregs by preventing the secretion of proinflammatory cytokines. Collectively, these results suggest that SOCS2 may prevent IL-4-induced Foxp3+ iTreg instability. Foxp3+ iTregs are key regulators of immune responses at mucosal surfaces; therefore, this dual role of SOCS2 in both Th2 and Foxp3+ iTregs reinforces SOCS2 as a potential therapeutic target for Th2-biased diseases.

Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.