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During liver fibrogenesis, liver sinusoidal capillarization and extracellular matrix (ECM) deposition construct dual pathological barriers to drug delivery. Upon capillarization, the vanished fenestrae in liver sinusoidal endothelial cells (LSECs) significantly hinder substance exchange between blood and liver cells, while excessive ECM further hinders the delivery of nanocarriers to activated hepatic stellate cells (HSCs). Herein, an efficient nanodrug delivery system was constructed to sequentially break through the capillarized LSEC barrier and the deposited ECM barrier. For the first barrier, LSEC-targeting and fenestrae-repairing nanoparticles (named HA-NPs/SMV) were designed on the basis of the modification with hyaluronic acid and the loading of simvastatin (SMV). For the second barrier, collagenase I and vitamin A codecorated nanoparticles with collagen-ablating and HSC-targeting functions (named CV-NPs/siCol1α1) were prepared to deliver siCol1α1 with the goal of inhibiting collagen generation and HSC activation. Our in vivo results showed that upon encountering the capillarized LSEC barrier, HA-NPs/SMV rapidly released SMV and exerted a fenestrae-repairing function, which allowed more CV-NPs/siCol1α1 to enter the space of Disse to degrade deposited collagen and finally to achieve higher accumulation in activated HSCs. Scanning electronic microscopy images showed the recovery of liver sinusoids, and analysis of liver tissue sections demonstrated that HA-NPs/SMV and CV-NPs/siCol1α1 had a synergetic effect. Our pathological barrier-normalization strategy provides an antifibrotic therapeutic regimen.
Prior to the COVID-19 pandemic, there was evidence of challenges surrounding the psychological well-being of health care professionals (HCPs). HCPs already frayed psychological ability to cope risks being further compromised by COVID-19-related stresses.
Most research on stress, psychological distress, and coping among HCPs is done in a piecemeal manner without a theoretical model connecting these different but related phenomena. This critical advancement article aims to apply and extend Wheaton and Montazer's model of stressors, stress, and distress to the literature on HCPs, generally, and COVID-19, specifically, to summarize past and guide future research on HCPs' mental health, resilience, and coping. Our model describes how different sources of support buffer the effect of stressors on stress and how coping strategies moderate the effect of stress on psychological distress.
We extended the model by (a) distinguishing context from the support in HCPs' environment; (b) distinguishing adaptive from mas HCPs are facing, especially during the pandemic.Several models of genetic counseling have been proposed to tackle the increasing volume of individuals requiring access to BRCA testing. Few data are available on patient experience and retention of information with nurse-driven genetic counseling. We evaluated the experience and retention of information in women with an uninformative BRCA test result and who were not considered at high risk due to their personal/family history of cancer who underwent geneticist-supervised nurse-driven genetic counseling and who received their test result by phone. Women who received an uninformative BRCA test result between May 2017 and September 2019 were administered a questionnaire exploring experience with genetic counseling and retention of information provided. Of 366 eligible women, 299 (273 breast cancer patients and 26 women without breast cancer) completed the interview. Overall, 280 women (93.6%) positively valued their experience with genetic counseling and 287 (96.0%) considered it helpful with 57.5% of them feeling reassured for themselves and their family. Information on the clinical implications of the test result was correctly retained and women acted accordingly. Overall, 252 women (87.8%) accurately reported their test result as normal/negative. Only 67 (22.4%) recognized that despite a normal BRCA test result, a low probability of a hereditary syndrome remains. Most women showed a poor ability to estimate cancer risk in BRCA mutation carriers and in the general population. Geneticist-supervised nurse-driven genetic counseling process for women with uninformative BRCA test result is associated with a positive patient experience and an adequate retention of information concerning the management of their personal and familial cancer risk. The design and implementation of nurse-driven genetic counseling models may contribute to efficient and timely access to BRCA genetic testing.
This study aimed to investigate the efficacy of surgery in the treatment of small cell carcinoma of the esophagus (SCCE) and explore potential prognostic factors.
We screened patients with SCCE who underwent esophagectomy from 2010 to 2018 at three institutes. Differences in survival were analyzed using the Kaplan-Meier method and log-rank test. The prognostic factors were identified using univariate and multivariate analyses.
A total of 69 patients were included. Multivariate analysis showed that TNM stage (hazard ratio [HR] 4.10, 95% confidence interval [CI] 1.57-10.75, p = 0.004) and adjuvant therapy (HR 0.28, 95% CI 0.16-0.51, p < 0.001) were independent prognostic factors. Stage I, stage IIA, and stage IIB disease were merged into the surgery response disease (SRD), whereas stage III disease into the surgery nonresponse disease (SNRD). G Protein antagonist The SRD group had significantly improved survival compared to the SNRD group (HR 0.33, 95% CI 0.19-0.58, p < 0.001). In addition, adjuvant therapy increased survival benefit in the SNRD group (p < 0.001) but not in the SRD group (p = 0.061).
Surgery alone appears to be adequate for disease control in the SRD group, whereas multimodality therapy was associated with improved survival in the SNRD group.
Surgery alone appears to be adequate for disease control in the SRD group, whereas multimodality therapy was associated with improved survival in the SNRD group.Filtering nanoparticulate aerosols from air streams is important for a wide range of personal protection equipment (PPE), including masks used for medical research, healthcare, law enforcement, first responders, and military applications. Conventional PPEs capable of filtering nanoparticles less then 300 nm are typically bulky and sacrifice breathability to maximize protection from exposure to harmful nanoparticulate aerosols including viruses ∼20-300 nm from air streams. Here, we show that nanopores introduced into centimeter-scale monolayer graphene supported on polycarbonate track-etched supports via a facile oxygen plasma etch can allow for filtration of aerosolized SiO2 nanoparticles of ∼5-20 nm from air steams while maintaining air permeance of ∼2.28-7.1 × 10-5 mol m-2 s-1 Pa-1. Furthermore, a systematic increase in oxygen plasma etch time allows for a tunable size-selective filtration of aerosolized nanoparticles. We demonstrate a new route to realize ultra-compact, lightweight, and conformal form-factor filters capable of blocking sub-20 nm aerosolized nanoparticles with particular relevance for biological/viral threat mitigation.Systemic lupus erythematosus (SLE) is an autoimmune disorder with significant health disparities, as it disproportionately and more severely affects vulnerable and disadvantaged population groups in the United States and around the world, that is, women, ethnic minorities, individuals living in poverty, less educated, and lacking medical insurance. Both, genetic and non-genetic factors, contribute to these disparities. To overcome these health disparities and reduce poor outcomes among disadvantaged SLE populations, interventions on non-genetic amendable factors, especially on social health determinants, are necessary.Purpose The purposes of this study were to determine the moderation effects of affective attitude on the effects of cognitive attitude and intention on leisure-time moderate-to-vigorous physical activity (MVPA). Methods A total of 2100 undergraduate students completed validated instruments measuring their affective and cognitive attitude, intention to do MVPA, and leisure-time MVPA. Hierarchical regression analyses and Hayes' Process program (model 1 and model 58) were used to address the research questions. Results The results showed that affective attitude significantly moderated the effects of cognitive attitude on MVPA. It suggested that when affective attitude was negative, the effect of cognitive attitude on MVPA was not significant; when it was positive, the higher the value of affective attitude score, the larger the effects of cognitive attitude on MVPA. The results also showed that affective attitude significantly moderated the effect of intention on MVPA and the indirect effects of cognitive attitude on MVPA through intention. It suggested that the higher the value of the affective attitude, the larger the effects of intention on MVPA and the larger the indirect effects of cognitive attitude on MVPA through intention. ConclusionsThese results indicate that the moderating role of affective attitude in behavior change is important and should be considered for future theory development on the relationship between attitude and behavior. Practically, it suggests that people's affective attitude should be first understood and addressed when designing PA promotion programs.
Robotic surgery for rectal cancer is gaining popularity, but persuasive evidence on reducing surgical trauma is still lacking. This study compared robotic and laparoscopic abdominoperineal resections (APRs) for the risk of postoperative complications in low rectal cancer.
Between December 2013and 2016, patients with rectal cancer ≤5 cm from anal verge, cT1-T3 N0-1, or ycT1-T3 Nx stage, and no distant metastases were enrolled in a single-center, randomized,controlled trial. Eligible patients were randomly allocated to robotic or laparoscopic APRs at 11 ratio. The primary outcome was 30-day postoperative complication rate (Clavien-Dindo grade II or higher) of the intent-to-treat population. The trial registration number is NCT01985698 (http//www.
gov).
Totally 347 eligible patients were enrolled 174 in robotic and 173 in laparoscopic group. Robotic APRs significantly reduced postoperative complication rate (13.2% vs. 23.7%, p = 0.013), also reduced open conversion rate (0% vs. 2.9%, p = 0.030), intraoperative hemorrhage (median, 100 vs. 130 ml; p < 0.001), 30-day readmission rate (2.3% vs. 6.9%; p = 0.044), postoperative hospital stay (median, 5.0 vs. 7.0 days; p < 0.001), and improved urinary and sexual function. No significant difference was observed in long-term oncological outcomes.
Compared with laparoscopic APRs, robotic APRs significantly reduced surgical trauma and promoted postoperative recovery.
Compared with laparoscopic APRs, robotic APRs significantly reduced surgical trauma and promoted postoperative recovery.The carboxyl groups of a protein can be esterified by reaction with a diazo compound, 2-diazo-2-(p-methylphenyl)-N,N-dimethylacetamide. This esterification enables the entry of the protein into the cytosol of a mammalian cell, where the nascent ester groups are hydrolyzed by endogenous esterases. The low aqueous solubility of the ensuing esterified protein is, however, a major practical challenge. Solubility screening revealed that β-cyclodextrin (β-CD) is an optimal solubilizing agent for esterified green fluorescent protein (est-GFP). Its addition can increase the recovery of est-GFP by 10-fold. α-CD, γ-CD, and cucurbit-7-uril are less effective excipients. 1H NMR titration experiments revealed that β-CD encapsulates the hydrophobic tolyl group of ester conjugates with Ka = 321 M-1. Combining l-arginine and sucrose with β-CD enables the nearly quantitative recovery of est-GFP. Thus, the insolubility of esterified proteins can be overcome with excipients.
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