Aims
The current study aimed to assess the potential of a new high dose ultraviolet (UV) disinfection device to inactivate methicillin‐resistant Staphylococcus aureus (MRSA), Clostridium difficile ...and a norovirus surrogate on handheld mobile devices, and to compare the efficacy of the UV‐C device to hydrogen peroxide disinfection wipes.
Methods and Results
Suspensions of MRSA, C. difficile spores and a surrogate for norovirus (MS2) were inoculated onto glass or plastic coupons, with or without organic contamination and were exposed to continuous UV‐C light for 15–60 s (165–646 mJ cm−2) in a self‐contained UV‐C chamber or treated with hydrogen peroxide wipes. Increasing the UV‐C dose from 310 to 650 mJ cm−2 did not result in greater levels of inactivation. UV‐C light inactivated all three micro‐organisms, in the absence of organic contamination, by >2·9 log. Treatment of MRSA, C. difficile spores or MS2, in the presence of organic contamination, with UV‐C light (310–646 mJ cm−2) resulted in 2·3–3·7 log reductions. Treatment of MRSA with UV‐C light provided levels of inactivation comparable to treatment with hydrogen peroxide wipes used following the manufacturer’s instructions.
Conclusions
UV‐C light and hydrogen peroxide wipes had strong antimicrobial activity against MRSA, C. difficile spores and a norovirus surrogate, in the presence or absence of organic contamination.
Significance and Impact of the Study
Chemical disinfection wipes are widely used in healthcare facilities, but they are not recommended for use on handheld mobile devices which may harbour pathogenic micro‐organisms. The powerful bactericidal, sporicidal and virucidal activity of this high dose UV‐C light device, shows that this technology is a promising alternative to chemical disinfectants, particularly for control of MRSA.
The TIGER-3 (NCT02322281) study was initiated to compare the efficacy and safety of rociletinib, a third-generation EGFR tyrosine kinase inhibitor (TKI) that targets EGFR T790M and common ...EGFR-activating mutations, versus chemotherapy in patients with NSCLC who progressed on first- or second-generation EGFR TKIs.
Patients with advanced or metastatic EGFR-mutated NSCLC with disease progression on standard therapy (previous EGFR TKI and platinum-based chemotherapy) were randomized to oral rociletinib (500 or 625 mg twice daily) or single-agent chemotherapy (pemetrexed, gemcitabine, docetaxel, or paclitaxel).
Enrollment was halted when rociletinib development was discontinued in 2016. Of 149 enrolled patients, 75 were randomized to rociletinib (n = 53: 500 mg twice daily; n = 22: 625 mg twice daily) and 74 to chemotherapy. The median investigator-assessed progression-free survival (PFS) was 4.1 months (95% confidence interval CI: 2.6–5.4) in the rociletinib 500-mg group and 5.5 months (95% CI: 1.8–8.1) in the 625-mg group versus 2.5 months (95% CI: 1.4–2.9) in the chemotherapy group. An improved PFS was observed in patients with T790M-positive NSCLC treated with rociletinib (n = 25; 500 mg and 625 mg twice daily) versus chemotherapy (n = 20; 6.8 versus 2.7 mo; hazard ratio = 0.55, 95% CI: 0.28–1.07, p = 0.074). Grade 3 or higher hyperglycemia (24.0%), corrected QT prolongation (6.7%), diarrhea (2.7%), and vomiting (1.3%) were more frequent with rociletinib than chemotherapy (0%, 0%, 1.4%, and 0%, respectively).
Rociletinib had a more favorable median PFS versus chemotherapy but had higher rates of hyperglycemia and corrected QT prolongation in patients with advanced EGFR-mutated NSCLC who progressed on previous EGFR TKI. Incomplete enrollment prevented evaluation of the primary efficacy end point.
Cannabis use in adolescents and young adults is linked with aberrant brain structure, although findings to date are inconsistent. We examined whether aerobic fitness moderated the effects of cannabis ...on cortical surface structure and whether gender may play a moderating role. Seventy-four adolescents and young adults completed three-weeks of monitored abstinence, aerobic fitness testing, and structural magnetic resonance imaging (sMRI). Whole-sample linear regressions examined the effects of gender, VO
max, cannabis use, and their interactions on the surface area (SA) and local gyrification index (LGI). Cannabis use was associated with greater cuneus SA. Gender-by-cannabis predicted precuneus and frontal SA, and precentral, supramarginal, and frontal LGI; female cannabis users demonstrated greater LGI, whereas male cannabis users demonstrated decreased LGI compared to non-users. Aerobic fitness was positively associated with various SA and LGI regions. Cannabis-by-aerobic fitness predicted cuneus SA and occipital LGI. These findings demonstrate that aerobic fitness moderates the impact of cannabis on cortical surface structure, and gender differences are evident. These moderating factors may help explain inconsistencies in the literature and warrant further investigation. Present findings and aerobic fitness literature jointly suggest aerobic intervention may be a low-cost avenue for improving cortical surface structure, although the impact may be gender-specific.
In the JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial, rosuvastatin reduced major adverse cardiovascular events in patients with ...what historically was considered to be normal cholesterol levels, and the best outcomes were observed in patients who had significant reduction in inflammation as indicated by lowering of C-reactive protein levels (1). Benefit of statin therapy initiated 12 h prior to percutaneous coronary intervention was demonstrated in the ARMYDA (Atorvastatin for Reduction of Myocardial Damage During Angioplasty) study, which measured biomarkers of cardiac injury after intervention.
Mucus is known to contribute significantly to the prevention and repair of mucosal damage throughout the gastrointestinal tract. Although not normally expressed in the stomach, mucin-2 (MUC-2, ...encoded by the MUC2 gene) is expressed in certain disease states. The aim of this study was to determine in a mouse model whether the absence of Muc-2 would result in impaired susceptibility to and healing of gastric mucosal injury. Acute gastric damage was induced in mice deficient in Muc-2 and in wild-type controls, through oral administration of indomethacin. Chronic gastric ulcers were induced by serosal application of acetic acid. The extent of injury and the extent of healing of the damage over time were examined in both models. Indomethacin administration caused similar levels of gastric damage in Muc-2–deficient and wild-type mice, but the erosions healed more slowly in the former. Acetic acid–induced gastric ulcers were initially similar in size in Muc-2–deficient and wild-type mice of both sexes, but ulcer healing was significantly impaired in male Muc-2–deficient mice. Induction of cyclooxygenase-2 in the stomach, in response to indomethacin- or acetic acid–induced ulceration, was significantly reduced in male Muc-2–deficient mice. This phenomenon, and the sex specificity, was also apparent in bone marrow–derived macrophages stimulated with endotoxin. These results demonstrate a marked impairment of gastric mucosal repair in male Muc-2–deficient mice that may be related to an insufficient induction of cyclooxygenase-2, an enzyme known to contribute to mucosal repair.
Cholangiocytes, bile duct lining cells, actively adjust the amount of cholesterol and bile acids in bile through expression of enzymes and channels involved in transportation and metabolism of the ...cholesterol and bile acids. Herein, we report molecular mechanisms regulating bile acid biosynthesis in cholangiocytes. Among the cytochrome p450 (Cyp) enzymes involved in bile acid biosynthesis, sterol 27-hydroxylase (Cyp27) that is the rate-limiting enzyme for the acidic pathway of bile acid biosynthesis expressed in cholangiocytes. Expression of other Cyp enzymes for the basic bile acid biosynthesis was hardly detected. The
Cyp27
expression was negatively regulated by a hydrophobic bile acid through farnesoid X receptor (FXR), a nuclear receptor activated by bile acid ligands. Activated FXR exerted the negative effects by inducing an expression of fibroblast growth factor 15/19 (FGF15/19). Similar to its repressive function against cholesterol 7α-hydroxylase (
Cyp7a1
) expression in hepatocytes, secreted FGF15/19 triggered
Cyp27
repression in cholangiocytes through interaction with its cognate receptor fibroblast growth factor receptor 4 (FGFR4). The involvements of FXR and FGFR4 for the bile acid-induced
Cyp27
repression were confirmed in vivo using knockout mouse models. Different from the signaling in hepatocytes, wherein the FGF15/19-induced repression signaling is mediated by c-Jun N-terminal kinase (JNK), FGF15/19-induced
Cyp27
repression in cholangiocytes was mediated by p38 kinase. Thus, the results collectively suggest that cholangiocytes may be able to actively regulate bile acid biosynthesis in cholangiocytes and even hepatocyte by secreting FGF15/19. We suggest the presence of cholangiocyte-mediated intrahepatic feedback loop in addition to the enterohepatic feedback loop against bile acid biosynthesis in the liver.
PURPOSE:To assess the accuracy of crowdsourcing for grading optic nerve images for glaucoma using Amazon Mechanical Turk before and after training modules.
MATERIALS AND METHODS:Images (n=60) from 2 ...large population studies were graded for glaucoma status and vertical cup-to-disc ratio (VCDR). In the baseline trial, users on Amazon Mechanical Turk (Turkers) graded fundus photos for glaucoma and VCDR after reviewing annotated example images. In 2 additional trials, Turkers viewed a 26-slide PowerPoint training or a 10-minute video training and passed a quiz before being permitted to grade the same 60 images. Each image was graded by 10 unique Turkers in all trials. The mode of Turker grades for each image was compared with an adjudicated expert grade to determine accuracy as well as the sensitivity and specificity of Turker grading.
RESULTS:In the baseline study, 50% of the images were graded correctly for glaucoma status and the area under the receiver operating characteristic (AUROC) was 0.75 95% confidence interval (CI), 0.64-0.87. Post-PowerPoint training, 66.7% of the images were graded correctly with AUROC of 0.86 (95% CI, 0.78-0.95). Finally, Turker grading accuracy was 63.3% with AUROC of 0.89 (95% CI, 0.83-0.96) after video training. Overall, Turker VCDR grades for each image correlated with expert VCDR grades (Bland-Altman plot mean difference=−0.02).
CONCLUSIONS:Turkers graded 60 fundus images quickly and at low cost, with grading accuracy, sensitivity, and specificity, all improving with brief training. With effective education, crowdsourcing may be an efficient tool to aid in the identification of glaucomatous changes in retinal images.
Burnout is frequent among healthcare workers, and sleep problems are suspected risk factors. The sleep health framework provides a new approach to the promotion of sleep as a health benefit. The aim ...of this study was to assess good sleep health in a large sample of healthcare workers and to investigate its relationship with the absence of burnout among healthcare workers while considering anxiety and depressive symptoms. A cross-sectional Internet-based survey of French healthcare workers was conducted in summer 2020, at the end of the first COVID-19 lockdown in France (March to May 2020). Sleep health was assessed using the RU-SATED v2.0 scale (RegUlarity, Satisfaction, Alertness, Timing, Efficiency, Duration). Emotional exhaustion was used as a proxy for overall burnout. Of 1069 participating French healthcare workers, 474 (44.3%) reported good sleep health (RU-SATED > 8) and 143 (13.4%) reported emotional exhaustion. Males and nurses had a lower likelihood of emotional exhaustion than females and physicians, respectively. Good sleep health was associated with a 2.5-fold lower likelihood of emotional exhaustion and associations persisted among healthcare workers without significant anxiety and depressive symptoms. Longitudinal studies are needed to explore the preventive role of sleep health promotion in terms of the reduction in burnout risk.
PurposeThe COVID‐19 pandemic has disrupted many facets of life. We evaluated pandemic‐related health care experiences, COVID‐19 prevention behaviors and measures, health behaviors, and psychosocial ...outcomes among rural and urban cancer patients.MethodsAmong 1,472 adult cancer patients, who visited Huntsman Cancer Institute in the past 4 years and completed a COVID‐19 survey (August‐September 2020), we assessed the impact of the pandemic on medical appointments, prevention/health behaviors, and psychosocial factors, stratified by urbanicity.FindingsMean age was 61 years, with 52% female, 97% non‐Hispanic White, and 27% were residing in rural areas. Rural versus urban patients were more likely to be older, not employed, uninsured, former/current smokers, consume alcohol, and have pandemic‐related changes/cancellations in surgery appointments (all P<.05). Changes/cancellations in other health care access (eg, doctor's visits) were also common, particularly among urban patients. Urban versus rural patients were more likely to socially distance, use masks and hand sanitizer, and experience changes in exercise habits and in their daily lives (all P<.05). Less social interaction and financial stress were common among cancer patients but did not differ by urbanicity.ConclusionsThese findings suggest that the COVID‐19 pandemic had a substantial impact on cancer patients, with several challenges specific to rural patients. This comprehensive study provides unique insights into the first 6 months of COVID‐19 pandemic‐related experiences and continuity of care among rural and urban cancer patients predominantly from Utah. Further research is needed to better characterize the pandemic's short‐ and long‐term effects on rural and urban cancer patients and appropriate interventions.
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