Curriespears3916

We provocatively consider that TFIIH may have first evolved from evolutionary pressure for TCR to resolve arrested transcription blocks to DNA replication and later added its key roles in transcription initiation and global DNA repair. We anticipate that this level of mechanistic information will have significant impact on thinking about TFIIH, laying a robust foundation suitable to develop new paradigms for DNA transcription initiation and repair along with insights into disease prevention, susceptibility, diagnosis and interventions.

Our understanding of outcomes and disease time course of COVID-19 in patients with gastrointestinal (GI) symptoms remains limited. In this study we characterize the disease course and severity of COVID-19 among hospitalized patients with gastrointestinal manifestations in a large, diverse cohort from the Unites States.

This retrospective study evaluated hospitalized individuals with COVID-19 between March 11 and April 28, 2020 at two affiliated hospitals in New York City. We evaluated the association between GI symptoms and death, and also explored disease duration, from symptom onset to death or discharge.

Of 2,804 patients hospitalized with COVID-19, the 1,084 (38.7%) patients with GI symptoms were younger (aOR for age ≥75 0.59, 95% CI 0.45-0.77) and had more co-morbidities (aOR for modified Charlson comorbidity score ≥2 1.22, 95% CI 1.01-1.48) compared to those without GI symptoms. Individuals with GI symptoms had better outcomes, with a lower likelihood of intubation (aHR 0.66, 95% CI 0.55-0.79) and death (aHR 0.71, 95% CI 0.59-0.87), after adjusting for clinical factors. These patients had a longer median disease course from symptom onset to discharge (13.8 vs. 10.8 days, log-rank p = .048; among 769 survivors with available symptom onset time), which was driven by longer time from symptom onset to hospitalization (7.4 vs. 5.4 days, log-rank p < .01).

Hospitalized patients with GI manifestations of COVID-19 have a reduced risk of intubation and death, but may have a longer overall disease course driven by duration of symptoms prior to hospitalization.

Hospitalized patients with GI manifestations of COVID-19 have a reduced risk of intubation and death, but may have a longer overall disease course driven by duration of symptoms prior to hospitalization.

Esophageal remodeling in eosinophilic esophagitis (EoE) can lead to esophageal rigidity with eventual luminal compromise and stenoses. #link# Gauging esophageal functional alterations in EoE is challenging. An epithelial marker of functional remodeling would impact EoE management.

Esophageal biopsy specimens from children with and without EoE and primary human esophageal epithelial cells were used for PAI-1 immunohistochemistry, and cell proliferation experiments. PAI-1 immunostaining and basal cell hyperplasia were assessed in the context of concurrently obtained esophageal compliance measures on endoscopic functional lumen imaging probe (EndoFLIP).

EndoFLIPs were performed in 45 children (32 with and 13 without EoE). Epithelial PAI-1 was increased in patients with active EoE versus inactive or control patients (P < .01). Esophageal compliance was lower in EoE patients versus controls, particularly in the proximal esophagus (P < .001). Proximal compliance was the strongest predictor of EoE (AUROC 0.88, 95% CI 0.77, 0.98) with esophageal compliance of less than 2.6%mL/mmHg demonstrating 82% sensitivity and 84% specificity for EoE. PAI-1 inhibition significantly diminished esophageal epithelial cell proliferation, suggesting PAI-1 could trigger basal cell hyperplasia. A composite mid-esophageal BZH+ PAI-1 score was the strongest predictor of altered compliance (P = .02, AUROC 0.89 (95% CI 0.80, 0.99). PAI-1 inhibition decreased basal cell proliferation.

PAI-1 is significantly elevated in pediatric EoE and distinguishes altered compliance in children. PAI-1 may be a novel disease marker and therapeutic target.

PAI-1 is significantly elevated in pediatric EoE and distinguishes altered compliance in children. PAI-1 may be a novel disease marker and therapeutic target.

Surveillance recommendations for serrated polyps (SPs) are based on insufficient evidence. We aimed to evaluate the risk of metachronous advanced colorectal neoplasia (ACRN) associated with SPs.

We searched all relevant studies published through August 2020 that examined the risk of SPs for developing metachronous lesions. We performed meta-analyses of the risk of metachronous ACRN or colorectal cancer (CRC) between patients with SPs (or sessile serrated lesions [SSLs]) alone and those with conventional adenomas alone, and between patients with synchronous SPs (or SSLs) and conventional adenomas and those with conventional adenomas alone.

Eleven studies with 1,079,315 patients were included in the meta-analysis. selleck inhibitor in the risks of metachronous ACRN and CRC were found between the SPs alone and conventional adenomas alone groups (odds ratio [OR] [95% confidence interval [CI]] ACRN, 0.70 [0.27-1.82]; CRC, 0.74 [0.47-1.14]). The risks were similar between SSLs alone and conventional sed risk of metachronous ACRN, and further studies are needed to determine whether they require more intensive surveillance.

Patients with inflammatory bowel disease (IBD) are suggested to be at increased risk of urolithiasis, but the magnitude of risk and the impact of medical and surgical treatment on this risk remain unknown. We therefore aimed to determine overall and treatment-related risk of urolithiasis in patients with IBD in a nationwide population-based cohort study.

Using national registers, we identified all patients with IBD and all cases of urolithiasis in Denmark during 1977-2018. We obtained information on all IBD medications and surgical procedures during 1995-2018. IBD cases were matched 110 on age and sex to non-IBD individuals.

In total, 2,549 (3%) of 75,236 IBD patients and 11,258 (2%) of 767,403 non-IBD individuals developed urolithiasis, resulting in a 2-fold increased risk of urolithiasis (HR, 2.27; 95% CI, 2.17-2.38) in patients with IBD. The patients were also at increased risk of repetitive urolithiasis events (RR, 1.09; 95% CI 1.04-1.15) and had increased risk of urolithiasis prior to IBD diagnosis (OR, 1.