Holcknoble7236

Background Despite the divergent disease biology of cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC), waitlist prioritization is identical for both diagnoses. Methods We compared waitlist and post-transplant outcomes between CCA and HCC liver transplant patients with MELD exceptions using Scientific Registry of Transplant Recipients data. 408 CCA candidates listed between 2003 and mid-2017 were matched to two HCC cohorts by listing date (±2 months, n=816), and OPTN region and date (±6 months, n=408). Cumulative incidence competing-risk regression examined the effects of diagnosis, OPTN region, and center-level CCA listing volume on waitlist removal due to death/being too ill (dropout). Cox models evaluated the effects of diagnosis, OPTN region, center-level CCA volume, and waiting time on graft failure among deceased donor liver transplant (DDLT) recipients. Results After adjusting for OPTN region and CCA listing volume (all P≥0.07), both HCC cohorts had a reduced likelihood of waitlist dropout compared to CCA candidates (SHR≤0.63, 95%CI0.41-0.93; P≤0.02). The cumulative incidence rates of waitlist dropout at 6 and 12 months were 13.2% (95%CI10-17) and 23.9% (95%CI20-29) for CCA candidates, 7.3% (95%CI5-10) and 12.7% (95%CI10-17) for HCC candidates with region and listing date matching, and 7.1% (95%CI5-9) and 12.6% (95%CI10-15) for HCC candidates with listing date matching only. Additionally, HCC DDLT recipients had a 57% reduced risk of graft failure compared to CCA recipients (P less then 0.001). Waiting time was unrelated to graft failure (P=0.57) and there was no waiting time by diagnosis cohort interaction effect (P=0.47). Conclusion When identically prioritized, LT candidates with CCA have increased waitlist dropout compared to those with HCC. More granular data are necessary to discern ways to mitigate this waitlist disadvantage and improve survival for patients with CCA.Intraventricular hemorrhage is a common cause of morbidity and mortality in premature infants. The rupture of the germinal zone into the ventricles entails loss of neural stem cells and disturbs the normal cytoarchitecture of the region, compromising late neurogliogenesis. Here we demonstrate that neural stem cells can be easily and robustly isolated from the hemorrhagic cerebrospinal fluid obtained during therapeutic neuroendoscopic lavage in preterm infants with severe intraventricular hemorrhage. Our analyses demonstrate that these neural stem cells, although similar to human fetal cell lines, display distinctive hallmarks related to their regional and developmental origin in the germinal zone of the ventral forebrain, the ganglionic eminences that give rise to interneurons and oligodendrocytes. These cells can be expanded, cryopreserved, and differentiated in vitro and in vivo in the brain of nude mice and show no sign of tumoral transformation 6 months after transplantation. This novel class of neural stem cells poses no ethical concerns, as the fluid is usually discarded, and could be useful for the development of an autologous therapy for preterm infants, aiming to restore late neurogliogenesis and attenuate neurocognitive deficits. Furthermore, these cells represent a valuable tool for the study of the final stages of human brain development and germinal zone biology.Objective Despite the joint pain and significant dysfunction that characterizes arthritis, many people with arthritis continue to carry out everyday duties and responsibilities. Our objective was to describe participation in informal caregiving (unpaid assistance to someone with a health issue or limitation) among people with arthritis. Methods Analysis of the baseline data from the Canadian Longitudinal Study on Aging (CLSA), a nationally representative sample of people aged 45-85 (n=21,241). The questionnaire covered socio-demographic, health, and caregiving variables. ANA12 The caregiving variables examined characteristics of the person who received the most care from the respondent, as well as the types (e.g., hands-on vs. hands-off tasks) and amount (e.g., hours/week) of care provided. Results There was no difference in the proportion of people with and without arthritis who provided informal care (46%). Individuals with arthritis reported worse health, but this did not affect the likelihood of providing care, nor the types or amount of care provided. Caregivers with and without arthritis were most likely to provide fewer than 7 hours/week of care, and the most common type was hands-off care, particularly transportation assistance. Men were just as likely to provide care as women, but were less likely to provide high intensity care or perform hands-on tasks. Conclusion Despite on average reporting worse health, people with arthritis were just as likely to provide informal care as people without arthritis. The need to provide informal care among people with arthritis may impact their ability to engage in self-management activities for their arthritis.Poly (ADP-ribose) polymerase 1 (PARP1) is a master regulator of diverse biological processes such as DNA repair, oxidative stress, and apoptosis. PARP1 can be activated by aggregated α-synuclein, and this process in turn exacerbates toxicity of α-synuclein. This circle is closely linked to the evolution of Parkinson's disease (PD) that characterized by progressive neurodegeneration and motor deficits. Here, we reported the PARP1, as a novel upstream molecular of transcription factor EB (TFEB), participates in regulation of autophagy in α-synuclein aggregated cells and mice. PARP1 inhibition not only enhances the nuclear transcription of TFEB via SIRT1 mediated down-regulation of mTOR signaling but also reduces nuclear export of TFEB by attenuating the TFEB-CRM1 interaction. Our results revealed that PARP1 inhibition lessened the accumulation of α-synuclein in PD models. Also, oral administration of PARP1 inhibitor Veliparib prevented neurodegeneration and improved motor ability in α-synucleinA53T transgenic mice. These findings identify that PARP1 signaling pathway regulates TFEB-mediated autophagy, pointing to potential therapeutic strategy of PD via enhancing protein degradation systems.