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Transmission of SARS-CoV-2 from humans to other mammals, including pet animals, has been reported. However, with the exception of farmed mink, there is no previous evidence that these infected animals can infect humans, resulting in sustained human-to-human transmission. Following a confirmed SARS-CoV-2 infection of a pet shop worker, animals in the shop and the warehouse supplying it were tested for evidence of SARS-CoV-2 infection. In this case study, viral swabs and blood samples were collected from animals in a pet shop and its corresponding warehouse in Hong Kong. Nasal swab or saliva samples from human COVID-19 patients epidemiologically linked to the pet shop and from subsequent local cases confirmed to be infected by SARS-CoV-2 delta variant were collected. Oral swabs were tested by quantitative RT-PCR (RT-qPCR) for SARS-CoV-2 and blood samples were serologically tested by a surrogate virus neutralisation test and plaque reduction neutralisation test. The SARS-CoV-2 RT-qPCR positive samples were sequenced by next generation viral full genome sequencing using the ISeq sequencing platform (Illumina), and the viral genomes were phylogenetically analysed. Eight (50%) of 16 individually tested Syrian hamsters in the pet shop and seven (58%) of 12 Syrian hamsters in the corresponding warehouse were positive for SARS-CoV-2 infection in RT-qPCR or serological tests. None of the dwarf hamsters (n=75), rabbits (n=246), guinea pigs (n=66), chinchillas (n=116), and mice (n=2) were confirmed positive for SARS-CoV-2 in RT-qPCR tests. SARS-CoV-2 viral genomes deduced from human and hamster cases in this incident all belong to the delta variant of concern (AY.127) that had not been circulating locally before this outbreak. The viral genomes obtained from hamsters were phylogenetically related with some sequence heterogeneity. Phylogenetic dating suggests infection in these hamsters occurred around Oct 14, 2021 (95% CI Sept 15 to Nov 9, 2021). Multiple zoonotic transmission events to humans were detected, leading to onward human-to-human transmission. Pet hamsters can be naturally infected with SARS-CoV-2. The virus can circulate among hamsters and lead to human infections. Both genetic and epidemiological results strongly suggest that there was more than one hamster-to-human transmission event in this study. This incident also led to onward human transmission. Importation of SARS-CoV-2-infected hamsters was a likely source of this outbreak. US National Institutes of Health, Research Grants Council of Hong Kong, Food and Health Bureau, and InnoHK.

Purpose Creating a healthy lifestyle is important across different life stages. Commercial smart wearable devices are an innovative and interesting approach as an early psychological intervention for modifying health-related behaviors. Therefore, the purpose of this study was to explore the effects of smart wearable devices on health-promoting lifestyles and quality of life. Methods The study design was a three-parallel randomized controlled trial with a 3-month intervention. Two commercial smart wearable devices (smartwatches and smart bracelets) with different levels of complicated functions were applied as a psychological intervention in comparison with a smartphone app as the control group. Participants were healthy young adults with a median age of 26 years. Outcome measurements were conducted by self-administered questionnaires. Chi-square tests and ANOVA were performed for testing the difference of participants at baseline, and generalized estimating equations were performed for testing the effect of the intervention. Results At the beginning, 81 participants were recruited and 73 participants completed the study. Results of a healthy lifestyle demonstrated significant group effects of exercise and a significant effect of the interaction for self-actualization and stress management in the experimental group with a smartwatch (Self-actualization: MD = 0.35[− 0.10,0.80]; Exercise: MD = 0.21[− 0.33 0.75]; Stress management: MD = 0.36[− 0.04,0.76]) by comparing with only using mobile app (Self-actualization: MD =  − 0.03[− 0.25,0.18]; Exercise: MD =  − 0.12[− 0.38,0.14]; Stress management, MD =  − 0.28[− 0.55,0.00]). The significant effect of group-by-time interaction for self-actualization was found in the experimental group with a smart bracelet (MD = 0.05[− 0.30,0.20]) by comparing with the control group. The GEE-adjusted model indicated significant effects of the interaction on the comprehensive, physical, and mental quality of life in the experimental group with the smartwatch (Comprehensive: MD = 0.24[− 0.04,0.52]; Physical: MD = 0.67[0.26,1.09]; Mental: MD = 0.72[0.29,1.16]) by comparing with the control group (Comprehensive: MD =  − 1.57[− 2.55, − 0.59]; Physical: MD = 0.25[0.00,0.50]; Mental: MD = 0.08[− 0.11,0.27]). Conclusion From a psychological perspective, smart wearable devices have potential benefits of shaping a healthy lifestyle and improving the quality of life. Enhancing the utility of commercial well-designed smart wearable devices is an innovative and effective strategy for promoting public health.

Chemotherapy for patients with advanced oesophageal squamous cell carcinoma offers poor long-term survival prospects. We report the final analysis from our study of the immune checkpoint PD-1 inhibitor nivolumab versus chemotherapy in patients with previously treated advanced oesophageal squamous cell carcinoma. We did a multicentre, randomised, open-label, phase 3 trial (ATTRACTION-3) at 90 hospitals and cancer centres in Denmark, Germany, Italy, Japan, South Korea, Taiwan, the UK, and the USA. We enrolled patients aged 20 years and older with unresectable advanced or recurrent oesophageal squamous cell carcinoma (regardless of PD-L1 expression), at least one measurable or non-measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, a baseline Eastern Cooperative Oncology Group performance status of 0–1, and who were refractory or intolerant to one previous fluoropyrimidine-based and platinum-based chemotherapy and had a life expectancy of at least 3 months. Patients were randomly assigned (1:1) to either nivolumab (240 mg for 30 min every 2 weeks) or investigator's choice of chemotherapy (paclitaxel 100 mg/m2 for at least 60 min once per week for 6 weeks then 1 week off; or docetaxel 75 mg/m2 for at least 60 min every 3 weeks), all given intravenously. Treatment continued until disease progression assessed by the investigator per RECIST version 1.1 or unacceptable toxicity. Randomisation was done using an interactive web response system with a block size of four and stratified according to geographical region (Japan vs rest of the world), number of organs with metastases, and PD-L1 expression. Patients and investigators were not masked to treatment allocation. The primary endpoint was overall survival, defined as the time from randomisation until death from any cause, in the intention-to-treat population that included all randomly assigned patients. Safety was assessed in all patients who received at least one dose of the assigned treatment. This trial is registered with ClinicalTrials.gov, number NCT02569242, and follow-up for long-term outcomes is ongoing. Between Jan 7, 2016, and May 25, 2017, we assigned 419 patients to treatment: 210 to nivolumab and 209 to chemotherapy. At the time of data cutoff on Nov 12, 2018, median follow-up for overall survival was 10·5 months (IQR 4·5–19·0) in the nivolumab group and 8·0 months (4·6–15·2) in the chemotherapy group. At a minimum follow-up time (ie, time from random assignment of the last patient to data cutoff) of 17·6 months, overall survival was significantly improved in the nivolumab group compared with the chemotherapy group (median 10·9 months, 95% CI 9·2–13·3 vs 8·4 months, 7·2–9·9; hazard ratio for death 0·77, 95% CI 0·62–0·96; p=0·019). 38 (18%) of 209 patients in the nivolumab group had grade 3 or 4 treatment-related adverse events compared with 131 (63%) of 208 patients in the chemotherapy group. The most frequent grade 3 or 4 treatment-related adverse events were anaemia (four [2%]) in the nivolumab group and decreased neutrophil count (59 [28%]) in the chemotherapy group. Five deaths were deemed treatment-related: two in the nivolumab group (one each of interstitial lung disease and pneumonitis) and three in the chemotherapy group (one each of pneumonia, spinal cord abscess, and interstitial lung disease). Nivolumab was associated with a significant improvement in overall survivaland a favourable safety profile compared with chemotherapy in previously treated patients with advanced oesophageal squamous cell carcinoma, and might represent a new standard second-line treatment option for these patients. ONO Pharmaceutical Company and Bristol-Myers Squibb.

Age-related macular degeneration (AMD) leads to gradual central vision loss and is the third leading cause of irreversible blindness worldwide. The underlying mechanisms for this progressive neurodegenerative disease remain unclear and there is currently no preventive treatment for dry AMD. Sodium iodate (NaIO3) has been reported to induce AMD-like retinal pathology in mice. We established a mouse model for AMD to evaluate the effects of quercetin on NaIO3-induced retinal apoptosis, and to investigate the pertinent underlying mechanisms. Our in vitro results indicated that quercetin protected human retinal pigment epithelium (ARPE-19) cells from NaIO3-induced apoptosis by inhibiting reactive oxygen species production and loss of mitochondrial membrane potential as detected by Annexin V-FITC/PI flow cytometry. We also evaluated the relative expression of proteins in the apoptosis pathway. Quercetin downregulated the protein expressions of Bax, cleaved caspase-3, and cleaved PARP and upregulated the expression of Bcl-2 through reduced PI3K and pAKT expressions. Furthermore, our in vivo results indicated that quercetin improved retinal deformation and increased the thickness of both the outer nuclear layer and inner nuclear layer, whereas the expression of caspase-3 was inhibited. Taken together, these results demonstrate that quercetin could protect retinal pigment epithelium and the retina from NaIO3-induced cell apoptosis via reactive oxygen species-mediated mitochondrial dysfunction, involving the PI3K/AKT signaling pathway. This suggests that quercetin has the potential to prevent and delay AMD and other retinal diseases involving NaIO3-mediated apoptosis.

Background: The recommended treatment for patients infected with hepatitis C virus genotype 2 (HCV2) is pegylated interferon (peginterferon) and ribavirin for 24 weeks. Aim: To assess whether a shorter 16-week treatment is as effective as a standard 24-week treatment. Methods: Patients with HCV2 infection were randomised in a 1:2 ratio to either 16 weeks (n = 50) or 24 weeks (n = 100) of treatment with peginterferon α-2a (180 μg/week) and weight-based ribavirin 1000–1200 mg/day, with a 24-week follow-up period. A rapid virological response (RVR) was defined as seronegative for HCV RNA at 4 weeks of treatment, and the primary end point, sustained virological response (SVR), as seronegative for HCV RNA at the 24-week follow-up. Results: The rate of RVR and SVR was 86% (43/50, 95% confidence interval (CI) 76% to 96%) and 94% (47/50, CI 87% to 100%), respectively, in the 16-week group, which was comparable to 87% (87/100, CI 80% to 94%) and 95% (95/100, CI 91% to 99%) in the 24-week group. Patients with RVR had a significantly higher SVR rate than patients without RVR in both 16-week (100% vs 57%, p = 0.015) and 24-week groups (98% vs 77%, p = 0.002). Multivariate analysis showed that RVR and age were independent factors associated with SVR. Both treatment arms were equally well tolerated. The incidence of alopecia was significantly higher in the 24-week group (49%) than in the 16-week group (20%, p = 0.001). Conclusion: 16 weeks and 24 weeks of peginterferon treatment with weight-based ribavirin at a dose of 1000–1200 mg/day provided equal efficacy in patients with HCV2 who achieved RVR at 4 weeks.

Background Lateral epicondylitis is frequently seen in racquet sport players and the treatments are usually symptomatic rather than curative. Taping therapy is cheap and easy to apply in the sport field. In this study we valued the effectiveness of Kinesio taping (KT) on immediate pain control for patients with chronic lateral epicondylitis. Methods We conducted a randomized, double-blinded, cross-over study with 15 patients with chronic lateral epicondylitis. All participants received two taping sessions in a random order with a 3-day interval in between: one with KT and the other with sham taping (ST). Pain perceived during resisted wrist extension and at rest using numeric rating scale (NRS), the pain-free grip strength, and the pressure pain threshold, were measured before and 15 min after the tape was applied. Results A significant reduction of 2.1 ± 1.6 (Z = − 3.081, P  = 0.002) and 0.7 ± 0.8 (Z = − 2.428, P  = 0.015) was found on a NRS with KT and ST, respectively, indicating that both taping sessions produced immediate pain relief for resisted wrist extension. Both taping sessions significantly improved the pain-free grip strength with increases of 3.31 ± 5.05 (Z = − 2.615, P  = 0.009) and 2.43 ± 3.31 (Z = − 2.783, P  = 0.005) kg found with KT and ST, respectively. Compared with ST, KT exhibited superiority in controlling pain experienced during resisted wrist extension (Z = − 2.168, P  = 0.030). Conclusions Taping produced unneglectable placebo effects on pain relief and painf-free grip strength for patients with lateral epicondylitis, and KT seemed to have additional effects on controlling pain that was elicited by resisted wrist extension. Trial registration ISRCTN13618356 (retrospectively registered on 13/02/2017).

Smart wearable technology has potential benefits for promoting physical activity and preventing sarcopenia. The purpose of this study was to explore the efficacy of a wearable activity tracker with 2-stage goal-setting for daily steps on older adults' physical activity and sarcopenia indicators. The study used a clustered trial design and was conducted in March to June 2022. Participants were community-dwelling adults older than 60 years who were recruited from 4 community centers in Taipei City. The intervention was designed with 2-stage goals set to 5000 steps/day in the first 4 weeks and 7500 steps/day in the final 4 weeks while wearing a commercial wearable activity tracker. Data were collected by self-reported questionnaires, a body composition analyzer, a handle grip tester, and 5 sit-to-stand tests. All 27 participants in the experimental group and 31 participants in the control group completed the 8-week intervention. Total and light-intensity physical activities, skeletal muscle index, and muscle strength increased, while sedentary time, BMI, and the waist circumference of participants decreased in the experimental group, with significant group-by-time interactions compared to the control group. A wearable activity tracker with gradual goal-setting is an efficient approach to improve older adults' physical activity and sarcopenia indicators. Smart wearable products with behavioral change techniques are recommended to prevent sarcopenia in older adult populations.

Immunotherapy with immune checkpoint inhibitors combined with an anti-angiogenic tyrosine-kinase inhibitor (TKI) has been shown to improve overall survival versus anti-angiogenic therapy alone in advanced solid tumours, but not in hepatocellular carcinoma. Therefore, a clinical study was conducted to compare the efficacy and safety of the anti-PD-1 antibody camrelizumab plus the VEGFR2-targeted TKI rivoceranib (also known as apatinib) versus sorafenib as first-line treatment for unresectable hepatocellular carcinoma. This randomised, open-label, international phase 3 trial (CARES-310) was done at 95 study sites across 13 countries and regions worldwide. Patients with unresectable or metastatic hepatocellular carcinoma who had not previously received any systemic treatment were randomly assigned (1:1) to receive either camrelizumab 200 mg intravenously every 2 weeks plus rivoceranib 250 mg orally once daily or sorafenib 400 mg orally twice daily. Randomisation was done via a centralised interactive response system. The primary endpoints were progression-free survival, as assessed by the blinded independent review committee per Response Evaluation Criteria in Solid Tumours version 1.1, and overall survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of the study drugs. We report the findings from the prespecified primary analysis for progression-free survival and interim analysis for overall survival. This study is registered with ClinicalTrials.gov (NCT03764293). Between June 28, 2019, and March 24, 2021, 543 patients were randomly assigned to the camrelizumab–rivoceranib (n=272) or sorafenib (n=271) group. At the primary analysis for progression-free survival (May 10, 2021), median follow-up was 7·8 months (IQR 4·1–10·6). Median progression-free survival was significantly improved with camrelizumab–rivoceranib versus sorafenib (5·6 months [95% CI 5·5–6·3] vs 3·7 months [2·8–3·7]; hazard ratio [HR] 0·52 [95% CI 0·41–0·65]; one-sided p<0·0001). At the interim analysis for overall survival (Feb 8, 2022), median follow-up was 14·5 months (IQR 9·1–18·7). Median overall survival was significantly extended with camrelizumab–rivoceranib versus sorafenib (22·1 months [95% CI 19·1–27·2] vs 15·2 months [13·0–18·5]; HR 0·62 [95% CI 0·49–0·80]; one-sided p<0·0001). The most common grade 3 or 4 treatment-related adverse events were hypertension (102 [38%] of 272 patients in the camrelizumab–rivoceranib group vs 40 [15%] of 269 patients in the sorafenib group), palmar-plantar erythrodysaesthesia syndrome (33 [12%] vs 41 [15%]), increased aspartate aminotransferase (45 [17%] vs 14 [5%]), and increased alanine aminotransferase (35 [13%] vs eight [3%]). Treatment-related serious adverse events were reported in 66 (24%) patients in the camrelizumab–rivoceranib group and 16 (6%) in the sorafenib group. Treatment-related death occurred in two patients: one patient in the camrelizumab–rivoceranib group (ie, multiple organ dysfunction syndrome) and one patient in the sorafenib group (ie, respiratory failure and circulatory collapse). Camrelizumab plus rivoceranib showed a statistically significant and clinically meaningful benefit in progression-free survival and overall survival compared with sorafenib for patients with unresectable hepatocellular carcinoma, presenting as a new and effective first-line treatment option for this population. Jiangsu Hengrui Pharmaceuticals and Elevar Therapeutics.

SummaryThe occurrence of osteoporosis in tuberculosis, a chronic infection, has rarely been evaluated. In this study, we found significantly higher incidence rates of osteoporosis (Adjusted hazard ratio (AHR) 1.82) and osteoporotic fracture (AHR 2.33) in tuberculosis patients than matched cohorts, which suggest that osteoporosis screening should be considered in tuberculosis patients’ follow-up program. The aim of this study is to determine the occurrence of incident osteoporosis in patients who completed anti-tuberculosis (TB) treatment.IntroductionChronic inflammatory disorders are associated with an increased risk of osteoporosis. Although TB is an infectious disease characterized by systemic inflammatory responses, the impact of active TB on incident osteoporosis is unclear. We used the Taiwan National Health Insurance Research Database to investigate the association between history of active TB and incident osteoporosis and osteoporotic fracture.MethodsIn this nationwide retrospective cohort study, active TB patients and their age- and sex-matched controls were identified from the National Health Insurance Research Database in Taiwan during 2000–2012. The occurrence of incident osteoporosis, osteoporotic fractures, and risk factors associated with osteoporosis among TB patients and matched controls were analyzed.ResultsWe observed incident osteoporosis in 2.2% (n = 86) of the TB patients and in 1.1% (n = 162) of the matched controls. The incidence rate of osteoporosis was 4.31 and 1.80 per 1000 person-years, which was significantly higher in TB patients (p < 0.001). In multivariate analysis, TB was an independent risk factor for osteoporosis. The other independent factors associated with osteoporosis were older age, female sex, chronic obstructive pulmonary disease, asthma, and lower income. Moreover, we demonstrated that the occurrence of osteoporotic fracture was significantly higher in TB patients.ConclusionsPatients with a history of active TB have a higher incidence rate of osteoporosis and osteoporotic fracture.

Urban parks provide connectedness to nature as a health resilience environment for promoting health. Virtual reality can provide opportunities for urban citizens to be exposed to natural elements with health benefits. The purpose was to explore the effects of actual and virtual parks on the quality of life and physical activity of urban residents. The study design was a cluster trial. Participants were healthy adults aged 20–50 years, recruited from three college campuses, and randomly assigned to two experimental groups ( n  = 30, 32) and one control group ( n  = 30). The intervention with virtual or actual parks was conducted for 30 min a session once a week for 12 weeks. Outcomes were measured using self-reported questionnaires, including the World Health Organization Quality-of-Life Scale-BREF and International Physical Activity Questionnaire-Short Form. In total, 84 participants completed the interventions and post-intervention measures. Results showed that participants who experienced actual parks had significant increases in the social quality of life and light-intensity physical activity and had decreased body weight. Participants who experienced the virtual parks experienced a significant increase in their mental quality of life. Participants in the experimental groups of both kinds of parks had significant improvements in their self-rated health, physical and environmental quality of life, and sedentary time after the intervention. Urban parks are an important natural resource for citizens’ health and physical activity promotion. Virtual parks can simulate actual parks and have similar health benefits and are thus are recommended for citizens who lack opportunities and motivation to go to actual parks.