A strong association between functional disability and depressive symptoms in older people has frequently been reported. Some studies attribute this association to the disabling effects of depression, others to the depressogenic effects of physical health-related disability. The authors examined the reciprocal effects between depressive symptoms and functional disability and their temporal character in a community-based cohort of 753 older people with physical limitations who were assessed at yearly intervals. They compared structural equation models that differed in terms of direction and speed of effects between patient-reported disability in instrumental and basic activities of daily living (IADL/ADLs) and depressive symptoms. The association between disability and depression could be separated into three components: (a) a strong contemporaneous effect of change in disability on depressive symptoms, (b) a weaker 1-year lagged effect of change in depressive symptoms on disability (probably indirect through physical health), and (c) a weak correlation between the trait (or stable) components of depression and disability. IADL/ADL disability and depressive symptoms are thus mutually reinforcing over time. Compensatory forces like effective treatment and age-related adaptation may protect elders against this potential downward trend. To improve quality of life in elderly adults, treatment should target disability when it is new and depression when it is persistent.

Published 2 h BG levels for AGA babies are higher than 1 h values and are similar to audited 2 h levels in SGA and LGA babies. Clinically, 2 h levels are predictive of later hypoglycemia but may require repeat BG testing. Audit is an important tool to validate national guidelines, to minimize their burden and to maximize their utility.

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Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. Despite being an immunogenic tumor, single-agent checkpoint inhibitor therapy in the recurrent setting has been disappointing, raising the notion of suppressive factors in the tumor microenvironment (TME) as obstacles to immunotherapy. We previously observed that neutrophils acquire a complement dependent T cell suppressor phenotype in the TME, characterized by inhibition of T cell proliferation and activation through mechanisms distinct from myeloid-derived suppressor cells. Using ascites fluid supernatants (ASC) from patients with EOC as an authentic component of the TME, we identified ASC-activated neutrophils require multiple neutrophil effector functions including NADPH oxidase activation, SNARE-mediated exocytosis and degranulation. ASC-activated neutrophils also adhered to T cells and caused trogocytosis of T cell membranes. These injury and signaling cues resulted in T cell immunoparalysis, characterized by impaired CD3/CD28 stimulated Zap70 phosphorylation, NFAT translocation, IL2 production, glucose uptake, mitochondrial function, and mTOR activation. We also observed that in anti-CD3/CD28 pre-activated T cells, addition of neutrophils + ASC resulted significant reduction in Zap70 phosphorylation. Our results demonstrate complement-dependent priming of neutrophils in the TME inducing a T cell non-responsiveness distinct from established checkpoint pathways and identify targets for immunotherapy. Further studies will focus on the effects of neutrophil suppressors on the TCR signaling cascade and cell stress response pathways that may enable T cell survival in response to neutrophil damage at the expense of activation.