SummaryBackgroundData on liver transplantation (LT) in acute on chronic liver failure (ACLF) are scanty.AimTo perform meta‐analysis on outcomes after LT for ACLF compared with ACLF patients not receiving LT or with LT recipients for indications other than ACLF.MethodsWe pooled data from 12 studies on LT outcomes among ACLF patients.ResultsAmong nine studies, 22 238 LT recipients for ACLF vs 30 791 for non‐ACLF were younger by 1.1 years, less males (64% vs 66.4%), and higher model for end‐stage disease score by 14.5 (14.4‐14.6), P < 0.01 for all. Post‐transplant patient survival at 30 day, 90 day, 6 months, 1 year and 5 years was lower in ACLF: 96.2% vs 98.1%, 92.6% vs 96.2%, 89.9% vs 94.4%, 86.0% vs 91.9%, 66.9% vs 80.7% respectively, P < 0.01 for all. ACLF patients stayed longer in hospital and ICU by 5.7 and 10.5 days respectively, P < 0.001, with similar post‐transplant complications [74.4% vs 55.5%, P = 0.12]. Among three studies, 441 LT recipients for ACLF vs 301 ACLF patients not selected for LT had better 30 day and 1 year survival: 95.2% vs 60% and 85.3% vs 28.2% respectively, P < 0.001. Outcomes were worse in ACLF‐3 and better for ACLF‐1 and ACLF‐2 patients at the time of LT.ConclusionIn this pooled analysis with a large sample size across the globe, LT for select patients with ACLF provided survival benefit. However, larger prospective studies are needed to further refine selection criteria, especially for ACLF‐3 patients as basis for improving outcomes and optimal utilisation of scarce donor pool.

Background Fetal Alcohol Spectrum Disorders (FASD) comprise a continuum of lifelong outcomes in those born prenatally exposed to alcohol. Although studies have shown no differences in rates by race, FASD is of particular concern for American Indian communities. One tribally-run prevention program is the Oglala Sioux Tribe (OST) CHOICES Program, which is modeled after the evidence-based CHOICES program that was focused on preconceptional prevention of alcohol-exposed pregnancy (AEP) by reducing risky drinking in women at-risk for pregnancy and/or preventing unintended pregnancy. Methods The OST CHOICES Program was made culturally appropriate for American Indian women and implemented with three communities, two on the reservation and one off. Data on drinking, sexual activity, and contraception use were collected at baseline and 3- and 6-months post-intervention. Data were analyzed using descriptive statistics, one-way ANOVA, and a random intercept generalized estimating equation (GEE) model. Results A total of 193 non-pregnant American Indian women enrolled in the OST CHOICES Program, and all were at-risk for AEP because of binge drinking and being at-risk for an unintended pregnancy. Fifty-one percent of participants completed both 3- and 6-month follow-up. Models showed a significant decrease in AEP risk from baseline at both 3- and 6-month follow-ups, indicating the significant impact of the OST CHOICES intervention. Women in the OST CHOICES Program were more likely to reduce their risk for AEP by utilizing contraception, rather than decreasing binge drinking. Conclusions Even with minor changes to make the CHOICES intervention culturally and linguistically appropriate and the potential threats to program validity those changes entail, we found a significant impact in reducing AEP risk. This highlights the capacity for the CHOICES intervention to be implemented in a wide variety of settings and populations.

Objective To evaluate the ability of thio-urethane oligomers to improve the properties of restorative composite resins. Materials and methods Oligomers were synthesized by combining 1,6-hexanediol-diissocyante (aliphatic) with pentaerythritol tetra-3-mercaptopropionate (PETMP) or 1,3-bis(1-isocyanato-1-methylethyl)benzene (aromatic) with trimethylol-tris-3-mercaptopropionate (TMP), at 1:2 isocyanate:thiol, leaving pendant thiols. Oligomers were added at 0–20 wt% to BisGMA-TEGDMA (70–30 wt%). Silanated inorganic fillers were added (70 wt%). Materials were photoactivated at 800 mW/cm2 filtered to 320–500 nm. Near-IR was used to follow degree of methacrylate conversion (DC). Mechanical properties were evaluated in three-point bending with 2 mm × 2 mm × 25 mm bars for flexural strength/modulus and toughness (FS/E, and T) according to ISO 4049, and 2 mm × 5 mm × 25 mm notched specimens for fracture toughness (KIC). Polymerization stress (PS) was measured on the Bioman. Results were analyzed with ANOVA/Tukey’s test (α = 5%). Results Significant increase in DC was observed in thio-urethane-containing materials especially for the group with 20 wt% of aliphatic version. Materials composed by oligomers also promoted higher FS, E, and KIC in comparison to controls irrespective of thio-urethane type. A significant increase in toughness was detected by ANOVA, but not distinguished in the groups. The PS was significantly reduced by the presence of thio-urethane for almost all groups. Conclusions The use of thio-urethane oligomer to compose methacrylate-based restorative composite promote increase in DC, FS, E and KIC while significant reduces PS.

IMPORTANCE Research to date has not determined a safe level of alcohol or tobacco use during pregnancy. Electroencephalography (EEG) is a noninvasive measure of cortical function that has previously been used to examine effects of in utero exposures and associations with neurodevelopment. OBJECTIVE To examine the association of prenatal exposure to alcohol (PAE) and tobacco smoking (PTE) with brain activity in newborns.

Overexpression of the oncoprotein mortalin in cancer cells and its protein partners enables mortalin to promote multiple oncogenic signaling pathways and effectively antagonize chemotherapy-induced cell death. A UBX-domaincontaining protein, UBXN2A, acts as a potential mortalin inhibitor. This current study determines whether UBXN2A effectively binds to and occupies mortalin's binding pocket, resulting in a direct improvement in the tumor's sensitivity to chemotherapy. Molecular modeling of human mortalin's binding pocket and its binding to the SEP domain of UBXN2A followed by yeast two-hybrid and His-tag pulldown assays revealed that three amino acids (PRO442, ILE558, and LYS555) within the substrate-binding domain of mortalin are crucial for UBXN2A binding to mortalin. As revealed by chase experiments in the presence of cycloheximide, overexpression of UBXN2A seems to interfere with the mortalin-CHIP E3 ubiquitin ligase and consequently suppresses the C-terminus of the HSC70-interacting protein (CHIP)-mediated destabilization of p53, resulting in its stabilization in the cytoplasm and upregulation in the nucleus. Overexpression of UBXN2A causes a significant inhibition of cell proliferation and the migration of colon cancer cells. We silenced UBXN2A in the human osteosarcoma U2OS cell line, an enriched mortalin cancer cell, followed by a clinical dosage of the chemotherapeutic agent 5-fluorouracil (5-FU). The UBXN2A knockout U2OS cells revealed that UBXNA is essential for the cytotoxic effect achieved by 5-FU. UBXN2A overexpression markedly increased the apoptotic response of U2OS cells to the 5-FU. In addition, silencing of UBXN2A protein suppresses apoptosis enhanced by UBXN2A overexpression in U2OS. The knowledge gained from this study provides insights into the mechanistic role of UBXN2A as a potent mortalin inhibitor and as a potential chemotherapy sensitizer for clinical application.

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Introduction Precision oncology (PO) is a growing treatment approach in the era of next-generation sequencing (NGS) and matched therapies. Effective delivery of PO in the community has not been extensively studied. Our program developed a virtual molecular tumor board (MTB) strategy to help guide PO care. Materials and Methods Over 18 months, eligible adult patients with advanced, incurable solid tumor malignancies were enrolled in a molecular profiling (MP) study using the Foundation Medicine NGS panel. Results were reviewed through a weekly, videoconferenced MTB conducted across our largely rural integrated health system. Recommendations from the MTB were used to identify actionable alterations (AAs). Feasibility of PO care delivery was assessed as the primary outcome. Secondary outcomes included the frequency of AAs, genomic matched treatments, genomic matched clinical trial enrollment, and clinical outcomes. Results A total of 120 participants with a variety of advanced tumor types were enrolled. Of these, 109 (90.8%) had successful MP. Treatment on the basis of an AA was recommended by the MTB in 58% of patients (63 of 109) who had a successful MP result. For those completing MP, treatments included enrollment in a genomic matched clinical trial (n = 16; 14.6%) and genomic matched treatment with a Food and Drug Administration–approved agent (n = 23; 21.1%). Response and survival data were similar regardless of the matched treatment option chosen. Conclusion A video-conferenced MTB-facilitated NGS testing and treatment delivery system was implemented in our integrated community oncology program. Continued use of this model aims to increase understanding of the impact of PO in this setting.