Narrative review of home care for palliative patients in general practice.

In 2019, the International Association for Hospice and Palliative Care (IAHPC) presented for adoption and signing some very important documents, among which "New definition for Palliative Care", "Letter for National Palliative Care Advocates" (which was designated to be sent to government lead on Universal Health coverage, and UN negotiations) and "Suggested language changes to zero draft 'Political Declaration of the High-level Meeting on Universal Health Coverage'"-"Universal Health Coverage: Moving Together to Build a Healthier World". They are devoted to the constantly growing need of palliative care in addition to the diagnostics and treatment, and are essential part of the care both for the patients with chronic incurable life-threatening diseases (especially with serious health-related suffering) and their families. As the home is the natural place of illness, general practitioners (GPs) should be prepared and involved in the palliative care spectrum of activities. The authors present some aspects of the home-based care while focusing on some problems and challenges, and making comparison with some specific issues for palliative home-care. The overview of the new policies and documents for palliative care reveals the ultimate importance of "universal access to high-quality palliative care, integrated into all levels of health care systems in a continuum of care with disease prevention, early diagnosis, and treatment, to assure that any patient's or family caregiver's suffering is relieved to the greatest extent possible" and the key role of GPs in it.

The nuclear receptor PPAR gamma selectively inhibits Th17 differentiation in a T cell-intrinsic fashion and suppresses CNS autoimmunity.

T helper cells secreting interleukin (IL)-17 (Th17 cells) play a crucial role in autoimmune diseases like multiple sclerosis (MS). Th17 differentiation, which is induced by a combination of transforming growth factor (TGF)-beta/IL-6 or IL-21, requires expression of the transcription factor retinoic acid receptor-related orphan receptor gamma t (ROR gamma t). We identify the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR gamma) as a key negative regulator of human and mouse Th17 differentiation. PPAR gamma activation in CD4(+) T cells selectively suppressed Th17 differentiation, but not differentiation into Th1, Th2, or regulatory T cells. Control of Th17 differentiation by PPAR gamma involved inhibition of TGF-beta/IL-6-induced expression of ROR gamma t in T cells. Pharmacologic activation of PPAR gamma prevented removal of the silencing mediator for retinoid and thyroid hormone receptors corepressor from the ROR gamma t promoter in T cells, thus interfering with ROR gamma t transcription. Both T cell-specific PPAR gamma knockout and endogenous ligand activation revealed the physiological role of PPAR gamma for continuous T cell-intrinsic control of Th17 differentiation and development of autoimmunity. Importantly, human CD4(+) T cells from healthy controls and MS patients were strongly susceptible to PPAR gamma-mediated suppression of Th17 differentiation. In summary, we report a PPAR gamma-mediated T cell-intrinsic molecular mechanism that selectively controls Th17 differentiation in mice and in humans and that is amenable to pharmacologic modulation. We therefore propose that PPAR gamma represents a promising molecular target for specific immunointervention in Th17-mediated autoimmune diseases such as MS.