Transforming outcome expectations into retention among hospital nurses: A cross-sectional study.

AIM: To examine the main effects and interaction effects of outcome expectations (e.g., anticipated satisfactory salary and benefits), nurse identity (a sense of membership in the nursing profession), and information-access efficiency of the electronic medical record system (how the system enables nurses to quickly retrieve the needed information) on nurses' retention. DESIGN: This study uses a cross-sectional survey and adopts proportionate random sampling to recruit a representative sample of nurses of a medical centre in Taiwan. METHODS: This study successfully obtained completed questionnaires from 430 nurses during December 2021 to January 2022. Data are analysed by using hierarchical regressions. RESULTS: Positive outcome expectations and identification as a member in the nursing profession are associated with retention. Information-access efficiency strengthens the link between outcome expectations and retention, while nurse identity weakens this link. CONCLUSION: Outcome expectations can help retain nurses, particularly those who perceive high levels of information-access efficiency and possess weak nurse identity. That is, outcome expectations have a complementary role with nurse identity in retaining nurses. IMPLICATIONS FOR THE PROFESSION: Nurse managers should devise means to build positive outcome expectations for nurses. In addition, either strengthening nurses' identification with the nursing profession or improving the information-access efficiency of the electronic medical system may also help retain nurses. IMPACT: This study examined how to transform outcome expectation to nurse retention, offering nurse managers to devise new means to retain nurses. REPORTING METHOD: STROBE statement was chosen as EQUATOR checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Portable robots for upper-limb rehabilitation after stroke: a systematic review and meta-analysis.

BACKGROUND: Robot-assisted upper-limb rehabilitation has been studied for many years, with many randomised controlled trials (RCTs) investigating the effects of robotic-assisted training on affected limbs. The current trend directs towards end-effector devices. However, most studies have focused on the effectiveness of rehabilitation devices, but studies on device sizes are relatively few. GOAL: Systematically review the effect of a portable rehabilitation robot (PRR) on the rehabilitation effectiveness of paralysed upper limbs compared with non-robotic therapy. METHODS: A meta-analysis was conducted on literature that included the Fugl-Meyer Assessment (FMA) obtained from the PubMed and Web of Science (WoS) electronic databases until June 2023. RESULTS: A total of 9 studies, which included RCTs, were completed and a meta-analysis was conducted on 8 of them. The analysis involved 295 patients. The influence on upper-limb function before and after treatment in a clinical environment is analysed by comparing the experimental group using the portable upper-limb rehabilitation robot with the control group using conventional therapy. The result shows that portable robots prove to be effective (FMA: SMD = 0.696, 95% = 0.099 to.293, p < 0.05). DISCUSSION: Both robot-assisted and conventional rehabilitation effects are comparable. In some studies, PRR performs better than conventional rehabilitation, but conventional treatments are still irreplaceable. Smaller size with better portability has its advantages, and portable upper-limb rehabilitation robots are feasible in clinical rehabilitation. CONCLUSION: Although portable upper-limb rehabilitation robots are clinically beneficial, few studies have focused on portability. Further research should focus on modular design so that rehabilitation robots can be decomposed, which benefits remote rehabilitation and household applications.

Feasibility and Design Factors for Home-Based Pulmonary Rehabilitation of Patients With Chronic Obstructive Pulmonary Disease and Chronic Lung Diseases Based on a People-Object-Environment Framework: Qualitative Interview Study.

BACKGROUND: The feasibility of implementing home-based pulmonary rehabilitation (PR) can be assessed from the perspectives of patients with chronic lung disease and health care professionals involved in PR. OBJECTIVE: Through a qualitative inquiry using interviews and the adoption of the people-object-environment framework, this study aims to understand the influences of interpersonal, environmental, and situational factors on the perceptions and considerations of individuals involved in home-based PR for patients with chronic lung disease. METHODS: One-on-one interviews were conducted with 20 patients with chronic lung disease and 20 health care professionals for investigating their attitudes and opinions based on their experiences regarding home-based PR as well as for identifying the key factors affecting the benefits and drawbacks of such therapies. This study further evaluates the feasibility of using digital tools for medical diagnosis and treatment by examining the technology usage of both parties. RESULTS: The 4 key issues that all participants were the most concerned about were as follows: distance to outpatient medical care, medical efficiency, internet connectivity and equipment, and physical space for diagnosis and treatment. Interviews with patients and health care professionals revealed that the use of technology and internet was perceived differently depending on age and area of residence. Most participants reported that digital tools and internet connectivity had many benefits but still could not solve all the problems; moreover, these same digital tools and network transmission could lead to problems such as information security and digital divide concerns. This study also emphasizes the significant impact of human behavior and thinking on shaping the design of health care interventions and technologies. Understanding user perspectives and experiences is crucial for developing effective solutions for unmet needs. CONCLUSIONS: The results of this study indicate that despite the different perspectives of patients and health care professionals, their considerations of the key issues are very similar. Therefore, the implementation of plans related to telemedicine diagnosis, treatment, or rehabilitation should take the suggestions and considerations of both parties into account as crucial factors for telehealth care design.

Effects of benzophenone-3 and its metabolites on the marine diatom Chaetoceros neogracilis: Underlying mechanisms and environmental implications.

The wide application of benzophenones (BPs), such as benzophenone-3 (BP3), as an ingredient in sunscreens, cosmetics, coatings, and plastics, has led to their global contamination in aquatic environments. Using the marine diatom Chaetoceros neogracilis as a model, this study assessed the toxic effects and mechanisms of BP3 and its two major metabolites (BP8 and BP1). The results showed that BP3 exhibited higher toxicity on C. neogracilis than BP8 and BP1, with their 72-h median effective concentrations being 0.4, 0.8 and 4 mg/L, respectively. Photosynthesis efficiencies were significantly reduced after exposure to environmentally relevant concentrations of the three benzophenones, while cell viability, membrane integrity, membrane potential, and metabolic activities could be further impaired at their higher concentrations. Comparative transcriptomic analysis, followed by gene ontology and KEGG pathway enrichment analyses unraveled that all the three tested benzophenones disrupted photosynthesis and nitrogen metabolism of the diatom through alteration of similar pathways. The toxic effect of BP3 was also attributable to its unique inhibitory effects on eukaryotic ribosome biosynthesis and DNA replication. Taken together, our findings underscore that benzophenones may pose a significant threat to photosynthesis, oxygen production, primary productivity, carbon fixation, and the nitrogen cycle of diatom in coastal waters worldwide.

Lipolysis products from triglyceride-rich lipoproteins induce stress protein ATF3 in osteoblasts.

High fat diets overwhelm the physiological mechanisms for absorption, storage, and utilization of triglycerides (TG); consequently TG, TG-rich lipoproteins (TGRL), and TGRL remnants accumulate, circulate systemically, producing dyslipidemia. This associates with, or is causative for increased atherosclerotic cardiovascular risk, ischemic stroke, fatty liver disease, and pancreatitis. TGRL hydrolysis by endothelial surface-bound lipoprotein lipase (LPL) generates metabolites like free fatty acids which have proinflammatory properties. While osteoblasts utilize fatty acids as an energy source, dyslipidemia is associated with negative effects on the skeleton. In this study we investigated the effects of TGRL lipolysis products (TGRL-LP) on expression of a stress responsive transcription factor, termed activating transcription factor 3 (ATF3), reactive oxygen species (ROS), ATF3 target genes, and angiopoietin-like 4 (Angptl4) in osteoblasts. As ATF3 negatively associates with osteoblast differentiation, we also investigated the skeletal effects of global ATF3 deletion in mice. TGRL-LP increased expression of Atf3, proinflammatory proteins Ptgs2 and IL-6, and induced ROS in MC3T3-E1 osteoblastic cells. Angptl4 is an endogenous inhibitor of LPL which was transcriptionally induced by TGRL-LP, while recombinant Angptl4 prevented TG-driven Atf3 induction. Atf3 global knockout male mice demonstrated increased trabecular and cortical microarchitectural parameters. In summary, we find that TGRL-LP induce osteoblastic cell stress as evidenced by expression of ATF3, which may contribute to the negative impact of dyslipidemia in the skeleton. Further, concomitant induction of Angptl4 in osteoblasts might play a protective role by reducing local lipolysis.

Association between interruption of intervention and language performance in young children with language delay-a cohort study during COVID-19 pandemic.

Introduction: To assess the association between a three-month interruption of language intervention programs and the language performance of children with language delay during the COVID-19 pandemic, and to identify which children are more vulnerable to such interruptions. Materials and methods: This is a retrospective study involving 33 children with language delay who experienced a three-month suspension of language interventions due to the COVID-19 pandemic. We collected their demographic data and language performance scores from the Comprehensive Developmental Inventory for Infants and Toddlers-Diagnostic test (CDIIT-DT) at four different time points. The scores were analyzed using a Wilcoxon Signed Ranks test. Results: The median scores of language comprehension and overall language ability showed a decreasing trend during the interruption period. However, resuming interventions post-interruption showed a statistically significant increase in all language domains. Children in the borderline delay group (CDIIT-DT DQ scores between 71 and 85) were more likely to experience a decline in their language abilities during the interruption. Discussion: This is the first study to reveal a decreasing trend in language performance during interruption periods, and highlighting the significance of post-interruption language interventions in facilitating improvements. Furthermore, our study brings attention to the heightened vulnerability of children exhibiting borderline language delay in overall language ability tests when faced with interruptions in language interventions.

Tilapia Fish Skin Treatment of Third-Degree Skin Burns in Murine Model.

This study explored the feasibility of using fish skin bandages as a therapeutic option for third-degree skin burns. Following the California wildfires, clinical observations of animals with third-degree skin burns demonstrated increased comfort levels and reduced pain when treated with tilapia fish skin. Despite the promises of this therapy, there are few studies explaining the healing mechanisms behind the application of tilapia fish skin. In this study, mice with third-degree burns were treated with either a hydrocolloid adhesive bandage (control) (n = 16) or fish skin (n = 16) 7 days post-burn. Mice were subjected to histologic, hematologic, molecular, and gross evaluation at days 7, 16, and 28 post-burn. The fish skin offered no benefit to overall wound closure compared to hydrocolloids. Additionally, we detected no difference between fish skin and control treatments in regard to hypermetabolism or hematologic values. However, the fish skin groups exhibited 2 times more vascularization and 2 times higher expression of antimicrobial defensin peptide in comparison to controls. Proteomic analysis of the fish skin revealed the presence of antimicrobial peptides. Collectively, these data suggest that fish skin can serve as an innovative and cost-effective therapeutic alternative for burn victims to facilitate vascularization and reduce bacterial infection.

A specific early eluting peak in Bio-Rad Variant II cation-exchange high-performance liquid chromatography (CE-HPLC) for the screening of alpha-thalassaemia in a Chinese population.

The early eluting peaks in the first minute of cation-exchange high-performance liquid chromatography (CE-HPLC) are often not analysed in haemoglobin pattern studies, except for haemoglobin (Hb) Bart's and Hb H peaks. In this study, we described the presence of a specific α-thalassaemia early eluting peak (αEEP) at the retention time of 0.24 min generated by Variant II CE-HPLC (ß-Thalassaemia Short Program; Bio-Rad Laboratories). We have evaluated the utility of αEEP for the screening of α-thalassaemia trait in our local Chinese population in comparison to the Hb H inclusion body test. A total of 303 blood samples presenting with microcytosis were sent for haemoglobin pattern study and were analysed for the presence or absence of αEEP and Hb H inclusions. Twenty cases with a normal mean corpuscular volume were assessed as a control. Discordant results between the αEEP and the Hb H inclusion test were reviewed with the α-globin genotyping test performed. The concordance rate of the αEEP and the Hb H inclusion body test was 96.0% (κ=0.921, p<0.001). Eight of 303 cases (2.6%) were initially negative for the Hb H inclusion test but positive for the αEEP. All eight cases were found to have occasional Hb H inclusion bodies upon review. Four of 303 cases (1.3%) were negative for the αEEP but positive for the Hb H inclusion test. Of these four cases, two (50%) showed heterozygous Southeast Asian (SEA) type deletion, one (25%) showed Hb Quong Sze mutation, and one (25%) showed no mutation detected upon molecular testing. All the Hb E trait cases with no Hb H inclusions and the negative control group showed the absence of the αEEP. The sensitivity and specificity of αEEP for detecting SEA deletion were 93.8% and 100% respectively, which is superior to the Hb H inclusion test (sensitivity 81.3%, specificity 95.2%). The αEEP is found to be a more sensitive method than the Hb H inclusion body test in the screening of α-thalassaemia trait in our Chinese population, in which SEA type deletion is prevalent. Further study is needed to explore the utility of the αEEP in the screening of α-thalassaemia traits in other populations. The exact nature of the αEEP is yet to be defined.

Environmental-relevant bisphenol A exposure promotes ovarian cancer stemness by regulating microRNA biogenesis.

Bisphenol A (BPA) is a ubiquitous environmental xenobiotic impacting millions of people worldwide. BPA has long been proposed to promote ovarian carcinogenesis, but the detrimental mechanistic target remains unclear. Cancer stem cells (CSCs) are considered as the trigger of tumour initiation and progression. Here, we show for the first time that nanomolar (environmentally relevant) concentration of BPA can markedly increase the formation and expansion of ovarian CSCs concomitant. This effect is observed in both oestrogen receptor (ER)-positive and ER-defective ovarian cancer cells, suggesting that is independent of the classical ERs. Rather, the signal is mediated through alternative ER G-protein-coupled receptor 30 (GPR30), but not oestrogen-related receptor α and γ. Moreover, we report a novel role of BPA in the regulation of Exportin-5 that led to dysregulation of microRNA biogenesis through miR-21. The use of GPR30 siRNA or antagonist to inhibit GPR30 expression or activity, respectively, resulted in significant inhibition of ovarian CSCs. Similarly, the CSCs phenotype can be reversed by expression of Exportin-5 siRNA. These results identify for the first time non-classical ER and microRNA dysregulation as novel mediators of low, physiological levels of BPA function in CSCs that may underlie its significant tumour-promoting properties in ovarian cancer.

A convergent fragment coupling strategy to access quaternary stereogenic centers.

The formation of quaternary stereogenic centers via convergent fragment coupling is a longstanding challenge in organic synthesis. Here, we report a strategy for the formation of quaternary stereogenic centers in polycyclic systems based upon the semi-pinacol reaction. In the key transformation, two fragments of a similar size and complexity are joined by a 1,2-addition of an alkenyl lithium to an epoxy ketone, and the resulting epoxy silyl ether undergoes a semi-pinacol rearrangement catalyzed by N-(trimethylsilyl)bis(trifluoromethanesulfonyl)imide (TMSNTf2) or trimethylsilyl trifluoromethanesulfonate (TMSOTf). Polycyclic scaffolds were generated in high yields and the reaction conditions tolerated a variety of functional groups including esters, silyl ethers, enol ethers, and aryl triflates. This method provides a useful strategy for the synthesis of complex polycyclic natural product-like scaffolds with quaternary stereogenic centers from simplified fragments.

Trends in Severe Outcomes Among Adult and Pediatric Patients Hospitalized With COVID-19 in the Canadian Nosocomial Infection Surveillance Program, March 2020 to May 2022.

Importance: Trends in COVID-19 severe outcomes have significant implications for the health care system and are key to informing public health measures. However, data summarizing trends in severe outcomes among patients hospitalized with COVID-19 in Canada are not well described. Objective: To describe trends in severe outcomes among patients hospitalized with COVID-19 during the first 2 years of the COVID-19 pandemic. Design, Setting, and Participants: Active prospective surveillance in this cohort study was conducted from March 15, 2020, to May 28, 2022, at a sentinel network of 155 acute care hospitals across Canada. Participants included adult (aged ≥18 years) and pediatric (aged 0-17 years) patients hospitalized with laboratory-confirmed COVID-19 at a Canadian Nosocomial Infection Surveillance Program (CNISP)-participating hospital. Exposures: COVID-19 waves, COVID-19 vaccination status, and age group. Main Outcomes and Measures: The CNISP collected weekly aggregate data on the following severe outcomes: hospitalization, admission to an intensive care unit (ICU), receipt of mechanical ventilation, receipt of extracorporeal membrane oxygenation, and all-cause in-hospital death. Results: Among 1 513 065 admissions, the proportion of adult (n = 51 679) and pediatric (n = 4035) patients hospitalized with laboratory-confirmed COVID-19 was highest in waves 5 and 6 of the pandemic compared with waves 1 to 4 (77.3 vs 24.7 per 1000 patient admissions). Despite this, the proportion of patients with positive test results for COVID-19 who were admitted to an ICU, received mechanical ventilation, received extracorporeal membrane oxygenation, and died were each significantly lower in waves 5 and 6 when compared with waves 1 through 4. Admission to the ICU and in-hospital all-cause death rates were significantly higher among those who were unvaccinated against COVID-19 when compared with those who were fully vaccinated (incidence rate ratio, 4.3 and 3.9, respectively) or fully vaccinated with an additional dose (incidence rate ratio, 12.2 and 15.1, respectively). Conclusions and Relevance: The findings of this cohort study of patients hospitalized with laboratory-confirmed COVID-19 suggest that COVID-19 vaccination is important to reduce the burden on the Canadian health care system as well as severe outcomes associated with COVID-19.

Trust Your Gut: Strategies and Tactics for Intestinally Restricted Drugs.

Non-absorbable small-molecule drugs targeted to the gut represent an alternative approach to safe, non-systemic therapeutics. Such drugs remain confined to the gastrointestinal tract upon oral dosing by virtue of their limited passive permeability, increasing the local concentration at the site of action while minimizing exposure elsewhere in the body. Herein we review the latest advances in the field of gut-restricted therapeutics, highlighting the different strategies and tactics that medicinal chemists have employed in pursuit of drugs with minimal intestinal absorption.

Development and Evaluation of Neighborhood Care Volunteer Training Programs-Preparing for Older Adult Community Care in Taiwan.

BACKGROUND: The prevalence of chronic diseases and functional disorders is projected to escalate as the older adult population increases. Thus, the demand for and burdens of long-term care are increasing. Training middle-aged and older volunteers at the community level will enhance health promotion and disease prevention in communities. PURPOSE: In this study, multilevel volunteer training programs and related implementation methods were designed for neighborhood caregivers. METHODS: This study was divided into two phases. In Phase 1, an expert review was conducted using the modified Delphi method to congregate expert opinions into an interdisciplinary consensus and establish the content and methods of implementation of the multilevel training program. In Phase 2, the training programs were implemented and evaluated. RESULTS: In Phase 1, 17 experts in geriatric and long-term care were enrolled in the Delphi surveys. Consensus was defined as at least 80% agreement. These experts devised volunteer training programs for neighborhood caregivers at three levels: basic caregiver training, advanced caregiver training, and volunteer caregiver instructor training. The curriculum focused on fulfilling the health demands of neighborhood care; adopted disability-prevention and disability-delaying healthcare as the basic framework; and referred to the attention, relevance, confidence, and satisfaction model of motivational design. This model of motivational design drew on the attributes of volunteers and the current state of care programs, including interest, program difficulty, and feasibility of future services. In Phase 2, 50 community middle-aged and older volunteers enrolled in the training programs and, after completing the program, were asked to evaluate their satisfaction with the program content and program effectiveness. A high level of satisfaction was reported across all three levels. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The training programs achieved satisfactory consistency and convergence and were well received by the volunteer trainees. These programs may be referenced in the development of future training programs and the creation of a model of community healthcare services. The curriculum was designed from the learners' perspective with direct healthcare applications. A progressive multilevel set of neighborhood care volunteer training programs was offered to cultivate community volunteers.

Differential bone adaptation to mechanical unloading and reloading in young, old, and osteocyte deficient mice.

Mechanical unloading causes rapid loss of bone structure and strength, which gradually recovers after resuming normal loading. However, it is not well established how this adaptation to unloading and reloading changes with age. Clinically, elderly patients are more prone to musculoskeletal injury and longer periods of bedrest, therefore it is important to understand how periods of disuse will affect overall skeletal health of aged subjects. Bone also undergoes an age-related decrease in osteocyte density, which may impair mechanoresponsiveness. In this study, we examined bone adaptation during unloading and subsequent reloading in mice. Specifically, we examined the differences in bone adaptation between young mice (3-month-old), old mice (18-month-old), and transgenic mice that exhibit diminished osteocyte density at a young age (3-month-old BCL-2 transgenic mice). Mice underwent 14 days of hindlimb unloading followed by up to 14 days of reloading. We analyzed trabecular and cortical bone structure in the femur, mechanical properties of the femoral cortical diaphysis, osteocyte density and cell death in cortical bone, and serum levels of inflammatory cytokines. We found that young mice lost ~10% cortical bone volume and 27-42% trabecular bone volume during unloading and early reloading, with modest recovery of metaphyseal trabecular bone and near total recovery of epiphyseal trabecular bone, but no recovery of cortical bone after 14 days of reloading. Old mice lost 12-14% cortical bone volume and 35-50% trabecular bone volume during unloading and early reloading but had diminished recovery of trabecular bone during reloading and no recovery of cortical bone. In BCL-2 transgenic mice, no cortical bone loss was observed during unloading or reloading, but 28-31% trabecular bone loss occurred during unloading and early reloading, with little to no recovery during reloading. No significant differences in circulating inflammatory cytokine levels were observed due to unloading and reloading in any of the experimental groups. These results illustrate important differences in bone adaptation in older and osteocyte deficient mice, suggesting a possible period of vulnerability in skeletal health in older subjects during and following a period of disuse that may affect skeletal health in elderly patients.

Chromatin modifiers: A new class of pollutants with potential epigenetic effects revealed by in vitro assays and transcriptomic analyses.

A great variety of endocrine-disrupting chemicals (EDCs) have been used extensively and become widespread in the environment nowadays. Limited mammalian studies have shown that certain EDCs may target chromosome and epigenome of the germline, leading to adverse effects in subsequent generations, despite these progenies having never been exposed to the EDC before. However, the underlying mechanisms of chromosomal changes induced by these pollutants remain poorly known. Using the human ovarian granulosa tumor cell line COV434 as a model, we investigated and compared the transcriptomic changes induced by nine EDCs with diverse chemical structures (i.e. BDE-47, BPA, BP-3, DEHP, DHP, EE2, TCS, TDCPP and NP), to inquire if there is any common epigenetic modification associated with reproductive functions induced by these EDCs. Our results showed that COV434 cells were more responsive to BP-3, NP, DEHP and EE2, and more importantly, these four EDCs altered the expression of gene clusters related to DNA damage response, cell cycle, proliferation, and chromatin remodeling, which can potentially lead to epigenetic modifications and transgenerational inheritance. Furthermore, dysregulation of similar gene clusters was common in DEHP and NP treatments. Bioinformatics analysis further revealed that BP-3 disturbed signaling pathways associated with reproductive functions, whereas alterations in telomere-related pathways were highlighted upon EE2 exposure. Overall, this study highlighted chromatin modifications caused by a class of chemicals which that may potentially lead to epigenetic changes and transgenerational reproductive impairments.

Trends in Clostridioides difficile infection rates in Canadian hospitals during the coronavirus disease 2019 (COVID-19) pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has placed significant burden on healthcare systems. We compared Clostridioides difficile infection (CDI) epidemiology before and during the pandemic across 71 hospitals participating in the Canadian Nosocomial Infection Surveillance Program. Using an interrupted time series analysis, we showed that CDI rates significantly increased during the COVID-19 pandemic.

Nirmatrelvir-ritonavir use among adults hospitalized with COVID-19 during the Omicron phase of the COVID-19 pandemic, Canadian Nosocomial Infection Surveillance Program.

Background: Recent studies have demonstrated the effectiveness of nirmatrelvir-ritonavir in reducing the risk of progression to severe disease among outpatients with mild to moderate coronavirus disease 2019 (COVID-19); however, data are limited regarding the use and role of nirmatrelvir-ritonavir among hospitalized patients. This study describes the use and outcomes of nirmatrelvir-ritonavir among adults hospitalized with COVID-19 in a sentinel network of Canadian acute care hospitals during the Omicron variant phase of the pandemic. Methods: The Canadian Nosocomial Infection Surveillance Program conducts surveillance of hospitalized patients with COVID-19 in acute care hospitals across Canada. Demographic, clinical, treatment and 30-day outcome data were collected by chart review by trained infection control professionals using standardized questionnaires. Results: From January 1 to December 31, 2022, 13% (n=490/3,731) of adult patients (18 years of age and older) hospitalized with COVID-19 in 40 acute care hospitals received nirmatrelvir-ritonavir either at admission or during hospitalization. Most inpatients who received nirmatrelvir-ritonavir, 79% of whom were fully vaccinated, had at least one pre-existing comorbidity (97%) and were of advanced age (median=79 years). Few were admitted to an intensive care unit (2.3%) and among the 490 nirmatrelvir-ritonavir treated inpatients, there were 13 (2.7%) deaths attributable to COVID-19. Conclusion: These findings from a large sentinel network of Canadian acute-care hospitals suggest that nirmatrelvir-ritonavir is being used to treat adult COVID-19 patients at admission who are at risk of progression to severe disease or those who acquired COVID-19 in hospital. Additional research on the efficacy and indications for nirmatrelvir-ritonavir use in hospitalized patients is warranted to inform future policies and guidelines.

Aerodynamic Performance and Neuromuscular Control in Patients with Unilateral Vocal Fold Paralysis.

Unilateral vocal fold paralysis (UVFP) causes glottal incompetence and poor vocal efficiency. The influence of laryngeal neuromuscular control on aerodynamics in UVFP remains unclear. This study investigated the relationship between laryngeal muscle activities using quantitative laryngeal electromyography (LEMG) and aerodynamics in UVFP. This prospective study recruited patients with UVFP, and the diagnosis was confirmed with videolaryngostroboscopy and LEMG. The patient received aerodynamic assessment and LEMG of the thyroarytenoid-lateral cricoarytenoid (TA-LCA) muscle complex and the cricothyroid (CT) muscle. The relationship between quantitative LEMG and aerodynamic parameters was analyzed. A total of 134 UVFP patients without concurrent CT muscle involvement were enrolled. Compared with the normal side, the peak turn frequency of the lesioned side was lower in the TA-LCA (p < 0.001) and CT (p = 0.048) muscles. Stepwise linear regression revealed that the turn ratio of TA-LCA muscles was a robust factor in the decrease in peak expiratory airflow (ß = −0.34, p = 0.036), mean airflow during voicing (ß = −0.28, p = 0.014), and aerodynamic power (ß = −0.42, p = 0.019), and an increase in aerodynamic efficiency (ß = 27.91, p = 0.012). In addition, the turn ratio of CT muscles was a potent factor in inducing an increase in aerodynamic resistance (ß = 14.93, p = 0.029). UVFP without CT involvement still showed suppression of CT muscles on the lesioned side, suggesting that neurological impairment of the TA-LCA complex could cause asymmetrical compensation of CT muscles, further impeding aerodynamics. The residual function of TA-LCA muscle complexes facilitates less air leakage and power dissipation, enhancing aerodynamic efficiency. On the other hand, the symmetrical compensation of the CT muscles improves aerodynamic resistance.

Orphan Nuclear Receptor Nur77 Mediates the Lethal Endoplasmic Reticulum Stress and Therapeutic Efficacy of Cryptomeridiol in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) commonly possesses chronical elevation of IRE1α-ASK1 signaling. Orphan nuclear receptor Nur77, a promising therapeutic target in various cancer types, is frequently silenced in HCC. In this study, we show that cryptomeridiol (Bkh126), a naturally occurring sesquiterpenoid derivative isolated from traditional Chinese medicine Magnolia officinalis, has therapeutic efficacy in HCC by aggravating the pre-activated UPR and activating the silenced Nur77. Mechanistically, Nur77 is induced to sense IRE1α-ASK1-JNK signaling and translocate to the mitochondria, which leads to the loss of mitochondrial membrane potential (Δψm). The Bkh126-induced aggravation of ER stress and mitochondrial dysfunction result in increased cytotoxic product of reactive oxygen species (ROS). The in vivo anti-HCC activity of Bkh126 is superior to that of sorafenib, currently used to treat advanced HCC. Our study shows that Bkh126 induces Nur77 to connect ER stress to mitochondria-mediated cell killing. The identification of Nur77 as a molecular target of Bhk126 provides a basis for improving the leads for the further development of anti-HCC drugs.