Single-Cell Sequencing of Peripheral Mononuclear Cells Reveals Distinct Immune Response Landscapes of COVID-19 and Influenza Patients.

The coronavirus disease 2019 (COVID-19) pandemic poses a current world-wide public health threat. However, little is known about its hallmarks compared to other infectious diseases. Here, we report the single-cell transcriptional landscape of longitudinally collected peripheral blood mononuclear cells (PBMCs) in both COVID-19- and influenza A virus (IAV)-infected patients. We observed increase of plasma cells in both COVID-19 and IAV patients and XIAP associated factor 1 (XAF1)-, tumor necrosis factor (TNF)-, and FAS-induced T cell apoptosis in COVID-19 patients. Further analyses revealed distinct signaling pathways activated in COVID-19 (STAT1 and IRF3) versus IAV (STAT3 and NFκB) patients and substantial differences in the expression of key factors. These factors include relatively increase of interleukin (IL)6R and IL6ST expression in COVID-19 patients but similarly increased IL-6 concentrations compared to IAV patients, supporting the clinical observations of increased proinflammatory cytokines in COVID-19 patients. Thus, we provide the landscape of PBMCs and unveil distinct immune response pathways in COVID-19 and IAV patients.

Cell transcriptomic atlas of the non-human primate Macaca fascicularis.

Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell-cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs.

Factors associated with long-term opioid use among patients with axial spondyloarthritis or psoriatic arthritis who initiated opioids.

OBJECTIVE: Up to one in five patients with axial spondyloarthritis (AxSpA) or psoriatic arthritis (PsA) newly initiated on opioids transition to long-term use within the first year. This study aimed to investigate individual factors associated with long-term opioid use among opioid new users with AxSpA/PsA. METHODS: Adult patients with AxSpA/PsA and without prior cancer who initiated opioids between 2006-2021 were included from Clinical Practice Research Datalink Gold, a national UK primary care database. Long-term opioid use was defined as having ≥3 opioid prescriptions issued within 90 days, or ≥ 90 days of opioid supply, in the first year of follow-up. Individual factors assessed included sociodemographic, lifestyle factors, medication use and comorbidities. A mixed-effects logistic regression model with patient-level random intercept was used to examine the association of individual characteristics with the odds of long-term opioid use. RESULTS: In total 10 300 opioid initiations were identified from 8,212 patients (3037 AxSpA; 5175 PsA). The following factors were associated with long-term opioid use: being a current smoker (OR : 1.62; 95%CI : 1.38,1.90), substance use disorder (OR : 2.34, 95%CI : 1.05,5.21), history of suicide/self-harm (OR : 1.84; 95%CI : 1.13,2.99), co-existing fibromyalgia (OR : 1.62; 95%CI : 1.11,2.37), higher Charlson Comorbidity Index (OR : 3.61; 95%CI : 1.69,7.71 for high scores), high MME/day at initiation (OR : 1.03; 95%CI : 1.02,1.03) and gabapentinoid (OR : 2.35; 95%CI : 1.75,3.16) and antidepressant use (OR : 1.69; 95%CI : 1.45,1.98). CONCLUSIONS: In AxSpA/PsA patients requiring pain relief, awareness of lifestyle, sociodemographic and prescribing characteristics associated with higher risk of long-term opioid use can prompt timely interventions such as structured medication reviews and smoking cessation to promote safer prescribing and better patient outcomes.

Trends for opioid prescribing and the impact of the COVID-19 pandemic in patients with rheumatic and musculoskeletal diseases between 2006 and 2021.

OBJECTIVE: To investigate opioid prescribing trends and assess the impact of the COVID-19 pandemic on opioid prescribing in rheumatic and musculoskeletal diseases (RMDs). METHODS: Adult patients with RA, PsA, axial spondyloarthritis (AxSpA), SLE, OA and FM with opioid prescriptions between 1 January 2006 and 31 August 2021 without cancer in UK primary care were included. Age- and gender-standardized yearly rates of new and prevalent opioid users were calculated between 2006 and 2021. For prevalent users, monthly measures of mean morphine milligram equivalents (MME)/day were calculated between 2006 and 2021. To assess the impact of the pandemic, we fitted regression models to the monthly number of prevalent opioid users between January 2015 and August 2021. The time coefficient reflects the trend pre-pandemic and the interaction term coefficient represents the change in the trend during the pandemic. RESULTS: The study included 1 313 519 RMD patients. New opioid users for RA, PsA and FM increased from 2.6, 1.0 and 3.4/10 000 persons in 2006 to 4.5, 1.8 and 8.7, respectively, in 2018 or 2019. This was followed by a fall to 2.4, 1.2 and 5.9, respectively, in 2021. Prevalent opioid users for all RMDs increased from 2006 but plateaued or dropped beyond 2018, with a 4.5-fold increase in FM between 2006 and 2021. In this period, MME/day increased for all RMDs, with the highest for FM (≥35). During COVID-19 lockdowns, RA, PsA and FM showed significant changes in the trend of prevalent opioid users. The trend for FM increased pre-pandemic and started decreasing during the pandemic. CONCLUSION: The plateauing or decreasing trend of opioid users for RMDs after 2018 may reflect the efforts to tackle rising opioid prescribing in the UK. The pandemic led to fewer people on opioids for most RMDs, providing reassurance that there was no sudden increase in opioid prescribing during the pandemic.

Single-nucleus transcriptome inventory of giant panda reveals cellular basis for fitness optimization under low metabolism.

BACKGROUND: Energy homeostasis is essential for the adaptation of animals to their environment and some wild animals keep low metabolism adaptive to their low-nutrient dietary supply. Giant panda is such a typical low-metabolic mammal exhibiting species specialization of extremely low daily energy expenditure. It has low levels of basal metabolic rate, thyroid hormone, and physical activities, whereas the cellular bases of its low metabolic adaptation remain rarely explored. RESULTS: In this study, we generate a single-nucleus transcriptome atlas of 21 organs/tissues from a female giant panda. We focused on the central metabolic organ (liver) and dissected cellular metabolic status by cross-species comparison. Adaptive expression mode (i.e., AMPK related) was prominently displayed in the hepatocyte of giant panda. In the highest energy-consuming organ, the heart, we found a possibly optimized utilization of fatty acid. Detailed cell subtype annotation of endothelial cells showed the uterine-specific deficiency of blood vascular subclasses, indicating a potential adaptation for a low reproductive energy expenditure. CONCLUSIONS: Our findings shed light on the possible cellular basis and transcriptomic regulatory clues for the low metabolism in giant pandas and helped to understand physiological adaptation response to nutrient stress.

The Impact of Long-Term Conditions and Comorbidity Patterns on COVID-19 Infection and Hospitalisation: A Cohort Study.

INTRODUCTION: Older adults are more vulnerable to COVID-19 infections; however, little is known about which comorbidity patterns are related to a higher risk of COVID-19 infection. This study investigated the role of long-term conditions or comorbidity patterns on COVID-19 infection and related hospitalisations. METHODS: This study included 4,428 individuals from Waves 8 (2016-2017) and 9 (2018-2019) of the English Longitudinal Study of Ageing (ELSA) who also participated in the ELSA COVID-19 Substudy in 2020. Comorbidity patterns were identified using an agglomerative hierarchical clustering method. The relationships between comorbidity patterns or long-term conditions and COVID-19-related outcomes were examined using multivariable logistic regression. RESULTS: Among a representative sample of community-dwelling older adults in England, those with cardiovascular disease (CVD) and complex comorbidities had an almost double risk of COVID-19 infection (OR = 1.87, 95% CI = 1.42-2.46) but not of COVID-19-related hospitalisation. A similar pattern was observed for the heterogeneous comorbidities cluster (OR = 1.56, 95% CI = 1.24-1.96). The individual investigations of long-term conditions with COVID-19 infection highlighted primary associations with CVD (OR = 1.46, 95% CI = 1.23-1.74), lung diseases (OR = 1.40, 95% CI = 1.17-1.69), psychiatric conditions (OR = 1.40, 95% CI = 1.16-1.68), retinopathy/eye diseases (OR = 1.39, 95% CI = 1.18-1.64), and arthritis (OR = 1.27, 95% CI = 1.09-1.48). In contrast, metabolic disorders and diagnosed diabetes were not associated with any COVID-19 outcomes. CONCLUSION: This study provides novel insights into the comorbidity patterns that are more vulnerable to COVID-19 infections and hospitalisations, highlighting the vulnerability of those with CVD and other complex comorbidities. These findings facilitate crucial new evidence that should be considered for appropriate screening measures and tailored interventions for older adults in the ongoing global outbreak.

Assessment of recombinant antigens Tp0100 and Tp1016 of Treponema pallidum for serological diagnosis of syphilis.

OBJECTIVE: To discover novel serodiagnostic candidates for the serological diagnosis of syphilis. METHODS: Two recombinant Treponema pallidum proteins Tp0100 and Tp1016 were expressed, purified, and identified by Western Blotting. A total of 600 clinical serum samples were tested with the Tp0100-based ELISA, the Tp1016-based ELISA, and the commercial LICA Syphilis TP kit (ChIVD, Beijing, China). The sensitivities were determined by testing 340 samples from individuals with clinically diagnosed primary, secondary, latent, and tertiary syphilis. The specificities were determined by screening 260 samples from healthy controls and individuals with potentially cross-reactive infections, including leptospirosis, Lyme disease, hepatitis B, tuberculosis, rheumatoid arthritis, systemic lupus erythematosus. Kappa (κ) values were applied to compare the agreement between clinical syphilis diagnosis and the Tp0100-based ELISA, the Tp1016-based ELISA, or the LICA Syphilis TP test. RESULTS: Using clinical syphilis diagnosis as the gold standard, Tp0100 exhibited an overall sensitivity of 95.6% and specificity of 98.1% for testing IgG antibody while Tp1016 demonstrated only an overall sensitivity of 75.0% and specificity of 79.6%. In contrast, the LICA Syphilis TP test revealed an overall sensitivity of 97.6% and specificity of 96.2%. In addition, the overall percent agreement and corresponding κ values were 96.7% (95% CI 95.6%-97.8%) and 0.93 for the Tp0100-based ELISA, 77.0% (95% CI 74.3%-79.7%) and 0.54 for the Tp1016-based ELISA, and 97.0% (95% CI 96.0%-98.0%) and 0.94 for the LICA Syphilis TP test, respectively. CONCLUSION: The recombinant T. pallidum protein Tp0100 shows promise as a novel diagnostic antigen in the serological tests for syphilis.

The impact of high-risk medications on mortality risk among older adults with polypharmacy: evidence from the English Longitudinal Study of Ageing.

BACKGROUND: Polypharmacy is common among older people and is associated with an increased mortality risk. However, little is known about whether the mortality risk is related to specific medications among older adults with polypharmacy. This study therefore aimed to investigate associations between high-risk medications and all-cause and cause-specific mortality among older adults with polypharmacy. METHODS: This study included 1356 older adults with polypharmacy (5+ long-term medications a day for conditions or symptoms) from Wave 6 (2012/2013) of the English Longitudinal Study of Ageing. First, using the agglomerative hierarchical clustering method, participants were grouped according to the use of 14 high-risk medication categories. Next, the relationship between the high-risk medication patterns and all-cause and cause-specific mortality (followed up to April 2018) was examined. All-cause mortality was assessed by Cox proportional hazards model and competing-risk regression was employed for cause-specific mortality. RESULTS: Five high-risk medication patterns-a renin-angiotensin-aldosterone system (RAAS) inhibitors cluster, a mental health drugs cluster, a central nervous system (CNS) drugs cluster, a RAAS inhibitors and antithrombotics cluster, and an antithrombotics cluster-were identified. The mental health drugs cluster showed increased risks of all-cause (HR = 1.55, 95%CI = 1.05, 2.28) and cardiovascular disease (CVD) (SHR = 2.11, 95%CI = 1.10, 4.05) mortality compared with the CNS drug cluster over 6 years, while others showed no differences in mortality. Among these patterns, the mental health drugs cluster showed the highest prevalence of antidepressants (64.1%), benzodiazepines (10.4%), antipsychotics (2.4%), antimanic agents (0.7%), opioids (33.2%), and muscle relaxants (21.5%). The findings suggested that older adults with polypharmacy who took mental health drugs (primarily antidepressants), opioids, and muscle relaxants were at higher risk of all-cause and CVD mortality, compared with those who did not take these types of medications. CONCLUSIONS: This study supports the inclusion of opioids in the current guidance on structured medication reviews, but it also suggests that older adults with polypharmacy who take psychotropic medications and muscle relaxants are prone to adverse outcomes and therefore may need more attention. The reinforcement of structured medication reviews would contribute to early intervention in medication use which may consequently reduce medication-related problems and bring clinical benefits to older adults with polypharmacy.

Postoperative opioids administered to inpatients with major or orthopaedic surgery: A retrospective cohort study using data from hospital electronic prescribing systems.

BACKGROUND: Opioids administered in hospital during the immediate postoperative period are likely to influence post-surgical outcomes, but inpatient prescribing during the admission is challenging to access. Modified-release(MR) preparations have been especially associated with harm, whilst certain populations such as the elderly or those with renal impairment may be vulnerable to complications. This study aimed to assess postoperative opioid utilisation patterns during hospital stay for people admitted for major/orthopaedic surgery. METHODS: Patients admitted to a teaching hospital in the North-West of England between 2010-2021 for major/orthopaedic surgery with an admission for ≥1 day were included. We examined opioid administrations in the first seven days post-surgery in hospital, and "first 48 hours" were defined as the initial period. Proportions of MR opioids, initial immediate-release(IR) oxycodone and initial morphine milligram equivalents (MME)/day were calculated and summarised by calendar year. We also assessed the proportion of patients prescribed an opioid at discharge. RESULTS: Among patients admitted for major/orthopaedic surgery, 71.1% of patients administered opioids during their hospitalisation. In total 50,496 patients with 60,167 hospital admissions were evaluated. Between 2010-2017 MR opioids increased from 8.7% to 16.1% and dropped to 11.6% in 2021. Initial use of oxycodone IR among younger patients (≤70 years) rose from 8.3% to 25.5% (2010-2017) and dropped to 17.2% in 2021. The proportion of patients on ≥50MME/day ranged from 13% (2021) to 22.9% (2010). Of the patients administered an opioid in hospital, 26,920 (53.3%) patients were discharged on an opioid. CONCLUSIONS: In patients hospitalised with major/orthopaedic surgery, 4 in 6 patients were administered an opioid. We observed a high frequency of administered MR opioids in adult patients and initial oxycodone IR in the ≤70 age group. Patients prescribed with ≥50MME/day ranged between 13-22.9%. This is the first published study evaluating UK inpatient opioid use, which highlights opportunities for improving safer prescribing in line with latest recommendations.

All-cause and cause-specific mortality risk among men and women with hepatitis C virus infection.

BACKGROUND: Hepatitis C virus (HCV) infection affects men and women differently, yet few studies have investigated sex differences in long-term mortality risk among the HCV-infected population. We conducted a population-based study to elucidate all-cause and cause-specific mortality among men and women with HCV infection. METHODS: The study population consisted of adult participants from the 1999-2018 National Health and Nutrition Examination Survey, including 945 HCV-infected and 44,637 non-HCV-infected individuals. HCV infection was defined as either HCV seropositivity or detectable HCV RNA. Participants were followed until the date of death or December 31, 2019, to determine survival status. RESULTS: The HCV-infected population, both male and female, tended to be older, more likely to be Black, single, have lower income, lower BMI, higher prevalence of hypertension, and were more likely to be current smokers. During a median follow-up of 125.0 months, a total of 5,309 participants died, including 1,253 deaths from cardiovascular disease (CVD) and 1,319 deaths from cancer. The crude analysis showed that the risk of death from all causes and from cancer, but not from CVD, was higher in the HCV-infected population. After adjusting for potential confounders, we found that both HCV-infected men (HR 1.41, 95% CI 1.10-1.81) and women (HR 2.03, 95% CI 1.36-3.02) were equally at increased risk of all-cause mortality compared to their non-HCV infected counterparts (p for interaction > 0.05). The risk of cancer-related mortality was significantly increased in HCV-infected women (HR 2.14, 95% CI 1.01-4.53), but not in men, compared to non-HCV-infected counterparts. Among HCV-infected population, there was no difference in the risks of all-cause, CVD-related, or cancer-related death between men and women. CONCLUSION: Both men and women with HCV infection had an increased risk of death from all causes compared to their non-HCV infected counterparts, but we did not observe a significant sex difference.

Machine learning identifies risk factors associated with long-term opioid use in fibromyalgia patients newly initiated on an opioid.

OBJECTIVES: Fibromyalgia is frequently treated with opioids due to limited therapeutic options. Long-term opioid use is associated with several adverse outcomes. Identifying factors associated with long-term opioid use is the first step in developing targeted interventions. The aim of this study was to evaluate risk factors in fibromyalgia patients newly initiated on opioids using machine learning. METHODS: A retrospective cohort study was conducted using a nationally representative primary care dataset from the UK, from the Clinical Research Practice Datalink. Fibromyalgia patients without prior cancer who were new opioid users were included. Logistic regression, a random forest model and Boruta feature selection were used to identify risk factors related to long-term opioid use. Adjusted ORs (aORs) and feature importance scores were calculated to gauge the strength of these associations. RESULTS: In this study, 28 552 fibromyalgia patients initiating opioids were identified of which 7369 patients (26%) had long-term opioid use. High initial opioid dose (aOR: 31.96, mean decrease accuracy (MDA) 135), history of self-harm (aOR: 2.01, MDA 44), obesity (aOR: 2.43, MDA 36), high deprivation (aOR: 2.00, MDA 31) and substance use disorder (aOR: 2.08, MDA 25) were the factors most strongly associated with long-term use. CONCLUSIONS: High dose of initial opioid prescription, a history of self-harm, obesity, high deprivation, substance use disorder and age were associated with long-term opioid use. This study underscores the importance of recognising these individual risk factors in fibromyalgia patients to better navigate the complexities of opioid use and facilitate patient-centred care.

What is Parental Monitoring?

Parental monitoring is a construct of longstanding interest in multiple fields-but what is it? This paper makes two contributions to the ongoing debate. First, we review how the published literature has defined and operationalized parental monitoring. We show that the monitoring construct has often been defined in an indirect and nonspecific fashion and measured using instruments that vary widely in conceptual content. The result has been a disjointed empirical literature that cannot accurately be described as the unified study of a single construct nor is achieving a cumulative scientific character. Second, we offer a new formulation of the monitoring construct intended to remedy this situation. We define parental monitoring as the set of all behaviors performed by caregivers with the goal of acquiring information about the youth's activities and life. We introduce a taxonomy identifying 5 distinct types of monitoring behaviors (Types 1-5), with each behavior varying along five dimensions (performer, target, frequency, context, style). We distinguish parental monitoring from 16 other parenting constructs it is often conflated with and position monitoring as one element within the broader parent-youth monitoring process: the continuous, dyadic interplay between caregivers and youth as they navigate caregivers attempts' to monitor youth. By offering an explicit and detailed conceptualization of monitoring, we aim to foster more rigorous and impactful research in this area.

Association between soluble α-klotho and mortality risk in middle-aged and older adults.

Introduction: Studies on association of α-klotho levels with mortality risk in general population are relatively scarce and inconclusive. Therefore, we conducted a population-based cohort study to investigate the relationship between soluble α-klotho and all-cause mortality in a nationally representative sample of middle-aged and older adults in the United States (U.S.). Methods: The study population was 2007-2016 National Health and Nutrition Examination Survey (NHANES) participants, totaling 13,583 adults aged 40-79 years. Participants were divided into 7 groups by septile of α-klotho levels. We linked the NHANES data to the National Death Index to determine participants' survival status. End of follow-up was participants' death date or December 31, 2019. Results: We observed that males, current smokers, older age, higher body mass index, and lower estimated glomerular filtration rate correlated to lower α-klotho levels, while hepatitis C virus infection correlated to higher α-klotho. The population mortality rate was 11.8 per 10,000 person-months (1,490 deaths); group 1 (the first septile) had higher mortality risk compared with group 2 through group 7. By weighted Cox regression with adjustment for potential confounders, we found that group 2 through group 6, but not group 7, were associated with 25% to 35% lower risk of all-cause mortality compared with group 1. When compared with group 4, we observed that both group 1 (HR: 1.46, 95% CI 1.13-1.88) and group 7 (HR: 1.38, 95% CI 1.09-1.74) were associated with higher mortality risk. Conclusion: In summary, among middle-aged and older U.S. adults, we observed a non-linear association between soluble α-klotho and all-cause mortality, with individuals at the two extremes at increased risk of death.

Lower product of magnesium × potassium is associated with higher mortality in chronic hemodialysis patients: a cohort study.

This study aimed to investigate the Mg × K product on the mortality risk of hemodialysis patients with concomitant hypokalemia and lower magnesium levels. This was a prospective observational study of patients in a HD center in southern Taiwan. A total of 444 HD patients were divided into 5 groups by the Mg × K product: group 1, bottom quintile, median Mg × K: 7.87, IQR: 7.03-8.12 (n = 89, age: 64 ± 13 years old); group 2, median Mg × K: 9.37, IQR: 8.97-9.86 (n = 89, age:62 ± 13 years old); group 3, median Mg × K: 10.95, IQR: 10.50-11.26 (n = 89, age:64 ± 13 years old); group 4, median Mg × K: 12.30, IQR: 11.87-12.82 (n = 89, 61 ± 12 years old); and group 5, top quintile, median Mg × K: 14.92, IQR:14.07-16.23 (n = 88, 62 ± 11 years old). The patients were followed up for 2 years to determine the risk of all-cause mortality. Patients with a lower Mg × K product had more comorbidities, malnutrition-inflammation status, and a higher mortality risk. Using multivariable Cox regression analysis, a higher Mg × K [HR, 0.89; 95%CI (0.81-0.98)] was found to be an independent predictor of better survival. HD patients with a lower Mg × K product had more comorbidities, a marked malnutrition-inflammation status, and were associated with long-term mortality. A higher Mg × K value is a favorable survival factor.

Remimazolam versus propofol for procedural sedation: a meta-analysis of randomized controlled trials.

Background: To improve patient tolerability and satisfaction as well as minimize complications, procedural sedation has been widely used. Propofol is the most widely used agent for induction of anesthesia and sedation by anesthesiologists. With a different mechanism compared to propofol, remimazolam is a new short-acting GABA-A receptor agonist. It is an ester-based benzodiazepine. This meta-analysis aims to clarify the efficacy and safety of remimazolam versus propofol for procedure sedation. Methods: Electronic databases were searched for randomized controlled trials (RCTs) comparing efficacy or safety of remimazolam versus propofol. Meta-analysis were conducted using RStudio with "metafor" package with random-effects model. Results: A total of twelve RCTs were included in the meta-analysis. The pooled results demonstrated that patients with remimazolam for procedural sedation had lower risk of bradycardia (OR 0.28, 95% CI [0.14-0.57]), hypotension (OR 0.26, 95% CI [0.22-0.32]), and respiratory depression (OR 0.22, 95% CI [0.14-0.36]). There was no difference in the risk of developing postoperative nausea and vomiting (PONV) (OR 0.65, 95% CI [0.15-2.79]) and dizziness (OR 0.93, 95% CI [0.53-1.61]) between the remimazolam and propofol groups. Using remimazolam for procedural sedation is significantly associated with less injection pain compared to propofol (OR 0.06, 95% CI [0.03-0.13]). Regarding the sedation efficacy, there was no difference in sedation success rate or time to loss of consciousness, recover and discharge between the remimazolam and the propofol groups. Conclusions: Based on our meta-analysis, patients receiving procedural sedation with remimazolam had lower risk of bradycardia, hypotension, respiratory depression and injection pain compared with propofol. On the other hand, there was no difference in sedation success rate, risk of PONV, dizziness, time to LOC, recovery and discharge between these two sedatives. PROSPERO registration number: CRD42022362950.

The impact of long-term conditions and comorbidity patterns on COVID-19 infection and hospitalisation: a cohort study.

Introduction: Older adults are usually more vulnerable to COVID-19 infections; however, little is known about which comorbidity patterns are related to a higher probability of COVID-19 infection. This study investigated the role of long-term conditions or comorbidity patterns on COVID-19 infection and related hospitalisations. Methods: This study included 4,428 individuals from Waves 8 (2016-2017) and 9 (2018-2019) of the English Longitudinal Study of Ageing (ELSA), who also participated in the ELSA COVID-19 Substudy in 2020. Comorbidity patterns of chronic conditions were identified using an agglomerative hierarchical clustering method. The relationships between comorbidity patterns or long-term conditions and COVID-19 related outcomes were examined using multivariable logistic regression. Results: Among a representative sample of community-dwelling older adults in England, those with cardiovascular disease (CVD) and complex comorbidities had an almost double risk of COVID-19 infection (OR=1.87, 95% CI=1.42-2.46) but not of COVID-19 related hospitalisation. A similar pattern was observed for the heterogeneous comorbidities cluster (OR=1.56, 95% CI=1.24-1.96). The individual investigations of long-term conditions with COVID-19 infection highlighted primary associations with CVD (OR=1.46, 95% CI=1.23-1.74), lung diseases (OR=1.40, 95% CI=1.17-1.69), psychiatric conditions (OR=1.40, 95% CI=1.16-1.68), retinopathy/eye diseases (OR=1.39, 95% CI=1.18-1.64), and arthritis (OR=1.27, 95% CI=1.09-1.48). In contrast, metabolic disorders and diagnosed diabetes were not associated with any COVID-19 outcomes. Discussion/Conclusion: This study provides novel insights into the comorbidity patterns that are more vulnerable to COVID-19 infections and highlights the importance of CVD and complex comorbidities.These findings facilitate crucial new evidence for appropriate screening measures and tailored interventions for older adults in the ongoing global outbreak.

Impact of perioperative α1-antagonists on postoperative urinary retention in orthopaedic surgery: meta-analysis.

BACKGROUND: Postoperative urinary retention (POUR) is a common complication following orthopaedic surgery. Previous studies attempted to establish the preventative role of α1-antagonist in POUR in the general surgical population; however, there is still no consensus regarding its use in orthopaedic surgery due to limited evidence. METHODS: Electronic databases of Cochrane Library, Embase, MEDLINE, and ClinicalTrials.gov were searched by two independent investigators from inception to 1 March 2022 to identify relevant randomized clinical trials. Two reviewers independently completed a critical appraisal of included trials by using the Cochrane Risk of Bias tool version 2.0 and extracted data from included articles. Risk of POUR was summarized as risk ratio (RR) with 95 per cent confidence intervals (c.i.). Mean difference (MD) was used for meta-analysis of continuous outcomes. RESULTS: Five randomized clinical trials involving 878 patients (α1-antagonist, 434; placebo, 444) undergoing hip/knee arthroplasty and spine surgeries were included. One study was assessed as high risk of bias from the randomization process and was excluded from the final meta-analysis. There was no difference in the risk of POUR between patients taking α1-antagonist and the placebo in arthroplasty (RR, 0.64; 95 per cent c.i., 0.36 to 1.14) and in spine surgeries (RR, 1.03; 95 per cent c.i., 0.69 to 1.55). There was no difference in length of stay (MD, -0.14 days; 95 per cent c.i., -0.33 to 0.05). Use of α1-antagonist was associated with a higher risk of adverse events (RR, 1.97; 95 per cent c.i., 1.27 to 3.06), with a composite of dizziness, light-headedness, fatigue, altered mental status, and syncope being the most commonly reported symptoms. CONCLUSION: In patients undergoing spinal surgery and joint arthroplasty, routine administration of perioperative α1-antagonist does not decrease risk of POUR but does increase perioperative dizziness, light-headedness, and syncope.

Chromosome-scale genomes reveal genomic consequences of inbreeding in the South China tiger: A comparative study with the Amur tiger.

The South China tiger (Panthera tigris amoyensis, SCT) is the most critically endangered subspecies of tiger due to functional extinction in the wild. Inbreeding depression is observed among the captive population descended from six wild ancestors, resulting in high juvenile mortality and low reproduction. We assembled and characterized the first SCT genome and an improved Amur tiger (P. t. altaica, AT) genome named AmyTig1.0 and PanTig2.0. The two genomes are the most continuous and comprehensive among any tiger genomes yet reported at the chromosomal level. By using the two genomes and resequencing data of 15 SCT and 13 AT individuals, we investigated the genomic signature of inbreeding depression of the SCT. The results indicated that the effective population size of SCT experienced three phases of decline, ~5.0-1.0 thousand years ago, 100 years ago, and since captive breeding in 1963. We found 43 long runs of homozygosity fragments that were shared by all individuals in the SCT population and covered a total length of 20.63% in the SCT genome. We also detected a large proportion of identical-by-descent segments across the genome in the SCT population, especially on ChrB4. Deleterious nonsynonymous single nucleotide polymorphic sites and loss-of-function mutations were found across genomes with extensive potential influences, despite a proportion of these loads having been purged by inbreeding depression. Our research provides an invaluable resource for the formulation of genetic management policies for the South China tiger such as developing genome-based breeding and genetic rescue strategy.

Immune response and homeostasis mechanism following administration of BBIBP-CorV SARS-CoV-2 inactivated vaccine.

The BBIBP-CorV severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccine has been authorized for emergency use and widely distributed. We used single-cell transcriptome sequencing to characterize the dynamics of immune responses to the BBIBP-CorV inactivated vaccine. In addition to the expected induction of humoral immunity, we found that the inactivated vaccine induced multiple, comprehensive immune responses, including significantly increased proportions of CD16+ monocytes and activation of monocyte antigen presentation pathways; T cell activation pathway upregulation in CD8+ T cells, along with increased activation of CD4+ T cells; significant enhancement of cell-cell communications between innate and adaptive immunity; and the induction of regulatory CD4+ T cells and co-inhibitory interactions to maintain immune homeostasis after vaccination. Additionally, comparative analysis revealed higher neutralizing antibody levels, distinct expansion of naive T cells, a shared increased proportion of regulatory CD4+ T cells, and upregulated expression of functional genes in booster dose recipients with a longer interval after the second vaccination. Our research will support a comprehensive understanding of the systemic immune responses elicited by the BBIBP-CorV inactivated vaccine, which will facilitate the formulation of better vaccination strategies and the design of new vaccines.