Palliative Care Exposure in Internal Medicine Residency Education: A Survey of ACGME Internal Medicine Program Directors.

As the baby boomer generation ages, the need for palliative care services will be paramount and yet training for palliative care physicians is currently inadequate to meet the current palliative care needs. Nonspecialty-trained physicians will need to supplement the gap between supply and demand. Yet, no uniform guidelines exist for the training of internal medicine residents in palliative care. To our knowledge, no systematic study has been performed to evaluate how internal medicine residencies currently integrate palliative care into their training. In this study, we surveyed 338 Accreditation Council for Graduate Medical Education-accredited internal medicine program directors. We queried how palliative care was integrated into their training programs. The vast majority of respondents felt that palliative care training was "very important" (87.5%) and 75.9% of respondents offered some kind of palliative care rotation, often with a multidisciplinary approach. Moving forward, we are hopeful that the data provided from our survey will act as a launching point for more formal investigations into palliative care education for internal medicine residents. Concurrently, policy makers should aid in palliative care instruction by formalizing required palliative care training for internal medicine residents.

Drosophila Gyf/GRB10 interacting GYF protein is an autophagy regulator that controls neuron and muscle homeostasis.

Autophagy is an essential process for eliminating ubiquitinated protein aggregates and dysfunctional organelles. Defective autophagy is associated with various degenerative diseases such as Parkinson disease. Through a genetic screening in Drosophila, we identified CG11148, whose product is orthologous to GIGYF1 (GRB10-interacting GYF protein 1) and GIGYF2 in mammals, as a new autophagy regulator; we hereafter refer to this gene as Gyf. Silencing of Gyf completely suppressed the effect of Atg1-Atg13 activation in stimulating autophagic flux and inducing autophagic eye degeneration. Although Gyf silencing did not affect Atg1-induced Atg13 phosphorylation or Atg6-Pi3K59F (class III PtdIns3K)-dependent Fyve puncta formation, it inhibited formation of Atg13 puncta, suggesting that Gyf controls autophagy through regulating subcellular localization of the Atg1-Atg13 complex. Gyf silencing also inhibited Atg1-Atg13-induced formation of Atg9 puncta, which is accumulated upon active membrane trafficking into autophagosomes. Gyf-null mutants also exhibited substantial defects in developmental or starvation-induced accumulation of autophagosomes and autolysosomes in the larval fat body. Furthermore, heads and thoraxes from Gyf-null adults exhibited strongly reduced expression of autophagosome-associated Atg8a-II compared to wild-type (WT) tissues. The decrease in Atg8a-II was directly correlated with an increased accumulation of ubiquitinated proteins and dysfunctional mitochondria in neuron and muscle, which together led to severe locomotor defects and early mortality. These results suggest that Gyf-mediated autophagy regulation is important for maintaining neuromuscular homeostasis and preventing degenerative pathologies of the tissues. Since human mutations in the GIGYF2 locus were reported to be associated with a type of familial Parkinson disease, the homeostatic role of Gyf-family proteins is likely to be evolutionarily conserved.

Drosophila Fip200 is an essential regulator of autophagy that attenuates both growth and aging.

Autophagy-related 1 (Atg1)/Unc-51-like protein kinases (ULKs) are evolutionarily conserved proteins that play critical physiological roles in controlling autophagy, cell growth and neurodevelopment. RB1-inducible coiled-coil 1 (RB1CC1), also known as PTK2/FAK family-interacting protein of 200 kDa (FIP200) is a recently discovered binding partner of ULK1. Here we isolated the Drosophila RB1CC1/FIP200 homolog (Fip200/CG1347) and showed that it mediates Atg1-induced autophagy as a genetically downstream component in diverse physiological contexts. Fip200 loss-of-function mutants experienced severe mobility loss associated with neuronal autophagy defects and neurodegeneration. The Fip200 mutants were also devoid of both developmental and starvation-induced autophagy in salivary gland and fat body, while having no defects in axonal transport and projection in developing neurons. Interestingly, moderate downregulation of Fip200 accelerated both developmental growth and aging, accompanied by target of rapamycin (Tor) signaling upregulation. These results suggest that Fip200 is a critical downstream component of Atg1 and specifically mediates Atg1's autophagy-, aging- and growth-regulating functions.

ICOS-mediated signaling regulates cytokine production by human T cells and provides a unique signal to selectively control the clonal expansion of Th2 helper cells.

The CD28 homologue inducible costimulator (ICOS) has been demonstrated to regulate a number of T cell-dependent immune responses in vivo. However, the expression and functional importance of ICOS during APC-Th cell interaction in the human is not fully understood. Here, we demonstrate that ICOS-mediated signaling plays an important role in the production of selective cytokines during both primary and subsequent Th cell responses upon allospecific or superantigen activation. In contrast, ICOS does not play a role in the differentiation of naive cells into Th1 or Th2 effector cells, nor does it determine the type of effector function of memory cells upon subsequent allogeneic challenge. In addition, our data demonstrate that ICOS provides a novel and unique role in regulating DC-mediated Th2, but not Th1 cell clonal expansion. These data suggest that ICOS-mediated signaling plays a discrete role in the regulation of human T helper cell responses.