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Participant recommendations included improved education for LTRs and caregivers about CVD risk factors, electronic health record alerts for providers, clearly defined CVD care provider roles, increased use of the transplant pharmacist, and multidisciplinary provider meetings to discuss care plans for LTRs. Multiple barriers to CVD care after LT were identified, and targeted recommendations were proposed by participants. Transplant centers should integrate participants' recommendations when designing interventions to optimize CVD care for LTRs.Many cancer cells maintain enhanced aerobic glycolysis due to irreversible defective mitochondrial oxidative phosphorylation (OXPHOS). This phenomenon, known as the Warburg effect, is recently challenged because most cancer cells maintain OXPHOS. However, how cancer cells coordinate glycolysis and OXPHOS remains largely unknown. Here, we demonstrate that OMA1, a stress-activated mitochondrial protease, promotes colorectal cancer development by driving metabolic reprogramming. OMA1 knockout suppresses colorectal cancer development in AOM/DSS and xenograft mice models of colorectal cancer. OMA1-OPA1 axis is activated by hypoxia, increasing mitochondrial ROS to stabilize HIF-1α, thereby promoting glycolysis in colorectal cancer cells. On the other hand, under hypoxia, OMA1 depletion promotes accumulation of NDUFB5, NDUFB6, NDUFA4, and COX4L1, supporting that OMA1 suppresses OXPHOS in colorectal cancer. Therefore, our findings support a role for OMA1 in coordination of glycolysis and OXPHOS to promote colorectal cancer development and highlight OMA1 as a potential target for colorectal cancer therapy.The tumor suppressor gene TP53 is the most frequently mutated gene in cancer. The compound APR-246 (PRIMA-1Met/Eprenetapopt) is converted to methylene quinuclidinone (MQ) that targets mutant p53 protein and perturbs cellular antioxidant balance. APR-246 is currently tested in a phase III clinical trial in myelodysplastic syndrome (MDS). By in vitro, ex vivo, and in vivo models, we show that combined treatment with APR-246 and inhibitors of efflux pump MRP1/ABCC1 results in synergistic tumor cell death, which is more pronounced in TP53 mutant cells. This is associated with altered cellular thiol status and increased intracellular glutathione-conjugated MQ (GS-MQ). Due to the reversibility of MQ conjugation, GS-MQ forms an intracellular drug reservoir that increases availability of MQ for targeting mutant p53. Our study shows that redox homeostasis is a critical determinant of the response to mutant p53-targeted cancer therapy.

Autoantibodies such as anti-citrullinated protein antibodies (ACPA) have been described to induce bone loss in RA, which could also be reflected in bone mineral density (BMD). We therefore examined the association between autoantibodies and osteoporosis in two independent RA-cohorts.

Dual X-ray absorptiometry (DXA) of lumbar spine (LS) and left hip (LH) was performed in 408 Dutch and 198 Swedish early RA-patients during five and ten years respectively. The longitudinal effect of ACPA and other autoantibodies on several BMD measures was studied using generalized estimating equations.

In the Dutch cohort, ACPA-positive patients had a significantly lower baseline BMD compared to ACPA-negative patients (LH Estimated Marginal Means (Confidence Interval) 0.92 (0.91-0.93) versus 0.95 (0.03-0.97) g/cm

(p=0.01)). Terephthalic price In accordance, significantly lower baseline Z-scores were observed in the ACPA-positive group compared to the ACPA-negative group (LH 0.18 (0.08-0.29) vs 0.48 (0.33-0.63) (p<0.01)). However, despite clear baseline differences, ACPA-positivity was not associated with greater decrease in absolute BMD or Z-score over time. Furthermore, there was no association between BMD and higher ACPA levels or other autoantibodies (RF and anti-CarP). In the Swedish cohort, ACPA-positive patients tended to have a higher baseline prevalence of osteopenia (p=0.04), but again, ACPA-positivity was not associated with more osteopenia or osteoporosis over time.

The presence of ACPA is associated with a significantly lower baseline BMD, but not with greater BMD loss over time in treated RA-patients. These results suggest that ACPA alone do not appear to contribute to bone loss after disease onset when disease activity is well managed.

The presence of ACPA is associated with a significantly lower baseline BMD, but not with greater BMD loss over time in treated RA-patients. These results suggest that ACPA alone do not appear to contribute to bone loss after disease onset when disease activity is well managed.Kabuki syndrome (OMIM #147920 and 300867) is a rare genetic disorder characterized by a distinctive facial gestalt, intellectual disability and multiple congenital anomalies. We summarized the clinical features and molecular findings of the Kabuki syndrome (KS) patients diagnosed in Hong Kong between January 1991 and December 2019. There were 21 molecularly confirmed KS. Twenty of them were due to pathogenic KMT2D variants and one patient had KDM6A deletion. Nine KMT2D variants were novel. The clinical phenotype of our Chinese KS patients was largely comparable with that reported in patients of other ethnicities. This study expands the mutation spectrum but also provide important natural history information of Chinese KS in literature.Tilapia lake virus (TiLV) is an emerging viral disease that affects several tilapia species in different countries since 2014. In 2017-2018, 129 samples were collected from 14 tilapia farms in Israel. Ninety samples represented mortality events (ME), and 39 were used as control samples (CS). RT-qPCR was performed on 89 and 39 duplicate brain and liver tissue samples from ME samples and CS, respectively. TiLV was diagnosed in 37 (41.6%) ME, while only two of the CS samples (5%) were positive for TiLV (OR = 13.2, 95% CI = 3.0-58.1). Additional RT-PCR was performed on positive samples, and amplified products were sequenced. Maximum likelihood phylogenetic analysis of segment-3 revealed three distinct clades the first clade (A) includes 25 sequences of TiLV, detected previously in Israel (2011), Ecuador (2012), Egypt (2015), Thailand (2015-2019), India (2017), Peru (2018) and USA (2018-2019) and 11 sequences of TiLV from the current study (2017-2018); the second clade (B) includes only four sequences from Thailand (2018) and Bangladesh (2017 and 2019); and a third clade (C) which includes a single sequence from Bangladesh (2019).