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Collectively, our observations show that mitochondrial functions are compromised in hlh-30 animals and that hlh-30 animals rewire their metabolism to largely depend on functional peroxisomes during starvation, underlining the importance of metabolic plasticity to maintain survival.ED crowding has been reported to reduce the quality of care. There are many proposed crowding metrics, but the metric most strongly associated with care quality remains unknown. The present study aims to determine the crowding metric with the strongest links with processes and outcomes of care linked to the Institute of Medicine quality domains. Systematic searches in healthcare databases were conducted using terms for 'crowding', 'metrics' and 'performance', supplemented by grey literature and citation searches. The level of evidence for each association was assessed using an explicit tool. The body of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. Evidence was synthesised using harvest plots. Titles and abstracts of 2052 studies were screened, 452 selected for full-text review and 183 included. Inter-observer agreement was moderate κ = 0.54 (95% confidence interval 0.50-0.59). Two thirds were from urban tertiary hospitals in North America (65%), Australasia (13%), Europe (12%) and Asia (8%). One third provided Level 3 or higher evidence. Metrics were based on occupancy (38%), time (31%), workload (19%) or combinations (9%). Data were synthesised from 25 607 375 patients, 2368 staff, 9089 hospitals and 101 177 sampling times. Almost all crowding metrics were patient-centred and reflect timeliness and efficiency. ED length of stay, boarding time and total occupancy had the strongest association with safety and effectiveness of care. ED length of stay was also associated with equity. The certainty of evidence for associations between crowding measures varied across domains of quality, from very low to moderate certainty.

To compare the performance and image quality of the handheld fundus camera to standard table-top fundus cameras in diabetic retinopathy (DR) screening. selleck chemical The reliability and diagnostic accuracy of DR grading performed by an ophthalmologist and a photographer reader were evaluated.

157 patients with diabetes, attending screening or follow-up of DR, were evaluated by fundus photographs taken in mydriasis by Optomed Aurora and Canon or Zeiss Visucam fundus cameras. The image quality and the severity of DR were evaluated independently by an ophthalmologist and experienced photographer. The sensitivity, specificity and reliability of the assessments were determined.

1884 fundus images from 314 eyes were analysed. In 53% of all eyes, DR was not present. 10% had mild non-proliferative diabetic retinopathy (NPDR), 16% moderate NPDR, 6% severe NPDR and 16% proliferative diabetic retinopathy (PDR). The DR grading outcomes by Aurora highly equalled to those of Canon or Zeiss (κ=0.93, 95% CI 0.91 to 0.94), and there was almost perfect agreement in grading between the ophthalmologist and photographer (κ=0.96, 95% CI 0.95 to 0.97). The image quality of Aurora was sufficient for reliable assessment according to both graders in 84-88% of the cases.

The Optomed Aurora fundus camera seems appropriate for DR screening. The sufficient image quality and high diagnostic accuracy for DR grading are supportive for a less expensive and easily transportable screening system for DR. Immediate image grading carried out by a photographer would further improve and speed up the screening process in all settings.

The Optomed Aurora fundus camera seems appropriate for DR screening. The sufficient image quality and high diagnostic accuracy for DR grading are supportive for a less expensive and easily transportable screening system for DR. Immediate image grading carried out by a photographer would further improve and speed up the screening process in all settings.

The risk of recurrent venous thromboembolism (VTE) after combined oral contraceptive (COC) use is variably reported. We assessed the long-term risk of recurrent VTE in women on COC at the time of a first VTE, in comparison to women without COC use. Our secondary aim assessed the impact of COC use on the recurrent VTE risk in high-risk and low-risk hyperpigmentation, edema, or redness in either leg; D-dimer level ≥250 μg/L; obesity with body mass index ≥30; or older age, ≥65 years (HERDOO2) subgroups.

The REVERSE cohort study derived the HERDOO2 clinical decision rule to predict recurrent VTE in patients who discontinued anticoagulation after 5-7months for a first unprovoked VTE. Incidence rates of recurrent VTE among women with and without COC exposure were calculated as the number of recurrent VTE over the number of person-years of follow-up, and Cox proportional hazards model was used to compare risks between groups.

The risk of recurrent VTE among COC users was 1.1% (95% confidence interval [CI] 0.3-2.9) per patient-year as compared with 3.2% per patient-year (95% CI 2.4-4.3) among nonusers (hazard ratio 0.37; 95% CI 0.1-1.0). Women who were COC users and high risk by HERDOO2 score had a recurrence rate of 3.5% (95% CI 0.4-12.5) compared with 6.1% (95% CI 4.3-8.5) among women who were non-COC users and at high risk by HERDOO2 score (HR 0.6, 95% CI 0.1-2.5).

Women who were COC users at the time of an otherwise unprovoked VTE event had a lower VTE recurrence rate during long-term follow-up, compared with nonusers. The use of HERDOO2 rule may help identify higher risk women with COC use.

Women who were COC users at the time of an otherwise unprovoked VTE event had a lower VTE recurrence rate during long-term follow-up, compared with nonusers. The use of HERDOO2 rule may help identify higher risk women with COC use.

Congenital hydrocephalus-3 with brain anomalies (HYC3, MIM 617967) is a rare form of congenital hydrocephalus characterized by severe hydrocephalus and cerebellar abnormalities, the onset of the disease occurs in utero even resulting in fetal death. A very limited spectrum of WDR81 pathogenic variants had been reported in three unrelated families with HYC3. This study aims at presenting novel compound heterozygous frameshift variants in WDR81 in a Chinese fetus.

Whole-exome sequencing (WES) was performed for a fetus with multiple congenital anomalies including sever hydrocephalus, cleft lip and palate, hydrops fetalis, hepatomegaly, and cerebellar hypoplasia. Sanger sequencing was performed to confirm the origin of the variants subsequently. Variants classification was based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines.

Two novel heterozygous variants c.146_147insG (p.Thr52fs) and c.673delC (p.Leu225fs) in WDR81 were identified. Sanger sequencing revealed that the c.146_147insG mutation was maternal origin and the c.673delC mutation was paternal origin. Both variants were pathogenic according to the ACMG/AMP guidelines.

The present study expands the mutation spectrum of WDR81 and help further define the genotype-phenotype correlations of HYC3. WDR81-related HYC3 were highly clinical heterogeneity. We suggested that fetal hydrocephalus with extracerebral manifestations may be suggestive of WDR81 deficiency and WES is effective for achieving a conclusive diagnosis for disorder.

The present study expands the mutation spectrum of WDR81 and help further define the genotype-phenotype correlations of HYC3. WDR81-related HYC3 were highly clinical heterogeneity. We suggested that fetal hydrocephalus with extracerebral manifestations may be suggestive of WDR81 deficiency and WES is effective for achieving a conclusive diagnosis for disorder.Mucosal melanoma is a rare form of melanoma which arises from melanocytes in the mucosal membranes and can be effectively treated with immune checkpoint blockade (ICB). However, response rates in mucosal melanoma are lower than those observed for cutaneous melanomas. Targeted sequencing of up to 447 genes (OncoPanel) was performed on tumors from all mucosal melanoma patients seen at the Dana-Farber Cancer Institute from 2011 until March 2019. We identified a total of 46 patients who received ICB with both tumor-genotype and ICB response data available. Within this cohort of patients, 16 (35%) had durable clinical benefit (DCB) to their first line of ICB. The average mutational burden/megabase was 6.23 and did not correlate with tumor response to ICB. Patients with KIT aberrations had a higher DCB rate compared with patients with wildtype KIT (71 vs. 28%), but this was not found to be statistically significant. For comparison, we analyzed tumor genotypes from an additional 50 mucosal melanoma tumors and 189 cutaneous melanoma tumors. The most frequent mutations in mucosal melanoma were in SF3B1 (27%), KIT (18%), and NF1 (17%), a pattern that is distinct from cutaneous melanomas. In addition, there were genetic differences observed based upon the site of origin of the mucosal melanoma. Our findings explore clinical features of response in patients with mucosal melanoma treated with ICB and demonstrate a low mutational burden that does not correlate with response. In addition, the lack of significant association between the genetic aberrations tested and response to ICB indicates the need for further exploration in this patient population.Phagosome maturation in macrophage is essential to the clearance of pathogenic materials in host defence but the dynamic features remain difficult to be measured in real time. Herein, we reported the multilayered Au@MnOx @SiO2 nanoparticle as a robust pH-sensitive plasmonic nanosensor for monitoring the dynamic acidification features over the phagosome maturation process in macrophage under darkfield microscopy. For this multilayered nanosensor, the gold nanoparticle core plays a role of signal reporter, the MnOx shell and the outmost SiO2 act as the sensing layer and the protecting layer, respectively. After subject to the acidic buffer solution, the MnOx layer in the multilayered nanoprobe could be decomposed rapidly, resulting in a remarkable spectral shift and color change under darkfield microscopy. We demonstrated this nanosensor for the investigation of single phagosome acidification dynamics by monitoring the color changes of nanoprobes after phagocytosis over time. The nanoprobes after phagocytosized in macrophage displayed a slight color change within the first hour and then cost several minutes to change from red to green in the next stage, indicating the phagosome undergoes a slow first and then fast acidification feature as well as a slow-to-fast acidification translation over the phagosome maturation process. Moreover, we validated that the slow-to-fast acidification translation was dependent on the activation of V-ATPase from the ATP depletion assay. We believed that this nanosensor is promising for studying the dynamic acidification features as well as disorders in phagosome maturation in phagocytic cells, which might provide valuable information for understanding the disease pathogenesis related to phagosome dysfunctions.

The pursuit of better management for haemorrhoidal disease (HD) is far from over, and even with the latest surgical procedures, none of the treatment options is close to perfect. The aims of this study were to review our experience with patients treated for symptomatic HD, compare the different treatment strategies in terms of complication and recurrence rates and determine predictors of recurrence.

A total of 1958 patients who underwent a procedure for HD performed by a single colorectal consultant surgeon between 2000 and 2015 were reviewed.

The treatment performed was rubber band ligation (RBL) in 73%, excisional haemorrhoidectomy (EH) in 16% and stapled haemorrhoidopexy (SH) in 11%. After a mean follow-up of 42.1 months, 242 patients (12%) developed recurrence. Logistic regression analysis of multiple factors showed that treatment received was a significant predictor of recurrence. RBL had the lowest post-operative complication rate but had the highest recurrence rate. EH had the lowest recurrence rate.