An ERK5-NRF2 Axis Mediates Senescence-Associated Stemness and Atherosclerosis.

BACKGROUND: ERK5 (extracellular signal-regulated kinase 5) is a dual kinase transcription factor containing an N-terminal kinase domain and a C-terminal transcriptional activation domain. Many ERK5 kinase inhibitors have been developed and tested to treat cancer and inflammatory diseases. However, recent data have raised questions about the role of the catalytic activity of ERK5 in proliferation and inflammation. We aimed to investigate how ERK5 reprograms myeloid cells to the proinflammatory senescent phenotype, subsequently leading to atherosclerosis. METHODS: A ERK5 S496A (dephosphorylation mimic) knock in (KI) mouse model was generated using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9), and atherosclerosis was characterized by hypercholesterolemia induction. The plaque phenotyping in homozygous ERK5 S496A KI and wild type (WT) mice was studied using imaging mass cytometry. Bone marrow-derived macrophages were isolated from hypercholesterolemic mice and characterized using RNA sequencing and functional in vitro approaches, including senescence, mitochondria reactive oxygen species, and inflammation assays, as well as by metabolic extracellular flux analysis. RESULTS: We show that atherosclerosis was inhibited in ERK5 S496A KI mice. Furthermore, ERK5 S496 phosphorylation mediates both senescence-associated secretory phenotype and senescence-associated stemness by upregulating AHR (aryl hydrocarbon receptor) in plaque and bone marrow-derived macrophages isolated from hypercholesterolemic mice. We also discovered that ERK5 S496 phosphorylation could induce NRF2 (NFE2-related factor 2) SUMOylation at a novel K518 site to inhibit NRF2 transcriptional activity without altering ERK5 catalytic activity and mediates oxidized LDL (low-density lipoprotein)-induced senescence-associated secretory phenotype. Specific ERK5 kinase inhibitors (AX15836 and XMD8-92) also inhibited ERK5 S496 phosphorylation, suggesting the involvement of ERK5 S496 phosphorylation in the anti-inflammatory effects of these ERK5 kinase inhibitors. CONCLUSIONS: We discovered a novel mechanism by which the macrophage ERK5-NRF2 axis develops a unique senescence-associated secretory phenotype/stemness phenotype by upregulating AHR to engender atherogenesis. The finding of senescence-associated stemness phenotype provides a molecular explanation to resolve the paradox of senescence in proliferative plaque by permitting myeloid cells to escape the senescence-induced cell cycle arrest during atherosclerosis formation.

[Reflections on the Prospective Professional Competency of Taiwan Public Health Nurses].

Societal ageing, the rising prevalence of chronic diseases, and the COVID-19 pandemic have changed the global healthcare environment dramatically. These challenges have significantly burdened community medical and healthcare systems and complicated the work of public health nursing. As an important care provider on the frontlines of primary care, public health nurses (PHNs) must keep up with the current state of the medical environment and statistical data interpretation, scientific data translation, community resource sharing, and telehealth applications. These demands have greatly impacted the traditional routines and existing professional core competencies of PHNs. Discussions among 12 Taiwanese public healthcare experts and the definition of public health nursing capacity from World Health Organization were considered in this review. In addition to reflecting on social changes and the professional development of public health nursing, eight prospective recommendations were provided in this review to enhance the professional competence of PHNs and better prepare them for future changes in the health environment and primary healthcare. The suggestions provide a reference for updating the position statement of PHNs.

Walking for hypertension.

BACKGROUND: Increased physical activity has been recommended as an important lifestyle modification for the prevention and control of hypertension. Walking is a low-cost form of physical activity and one which most people can do. Studies testing the effect of walking on blood pressure have revealed inconsistent findings. OBJECTIVES: To determine the effect of walking as a physical activity intervention on blood pressure and heart rate. SEARCH METHODS: We searched the following databases up to March 2020: the Cochrane Hypertension Specialised Register, CENTRAL (2020, Issue 2), Ovid MEDLINE, Ovid Embase, CINAHL, PsycINFO, SPORTDiscus, PEDro, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also searched the following Chinese databases up to May 2020: Index to Taiwan Periodical Literature System; National Digital Library of Theses and Dissertation in Taiwan; China National Knowledge Infrastructure (CNKI) Journals, Theses & Dissertations; and Wanfang Medical Online. We contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions. SELECTION CRITERIA: Randomised controlled trials of participants, aged 16 years and over, which evaluated the effects of a walking intervention compared to non-intervention control on blood pressure and heart rate were included. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Where data were not available in the published reports, we contacted authors. Pooled results for blood pressure and heart rate were presented as mean differences (MDs) between groups with 95% confidence intervals (CIs). We undertook subgroup analyses for age and sex. We undertook sensitivity analyses to assess the effect of sample size on our findings. MAIN RESULTS: A total of 73 trials met our inclusion criteria. These 73 trials included 5763 participants and were undertaken in 22 countries. Participants were aged from 16 to 84 years and there were approximately 1.5 times as many females as males. The characteristics of walking interventions in the included studies were as follows: the majority of walking interventions was at home/community (n = 50) but supervised (n = 36 out of 47 reported the information of supervision); the average intervention length was 15 weeks, average walking time per week was 153 minutes and the majority of walking intensity was moderate. Many studies were at risk of selection bias and performance bias. Primary outcome We found moderate-certainty evidence suggesting that walking reduces systolic blood pressure (SBP) (MD -4.11 mmHg, 95% CI -5.22 to -3.01; 73 studies, n = 5060). We found moderate-certainty evidence suggesting that walking reduces SBP in participants aged 40 years and under (MD -4.41 mmHg, 95% CI -6.17 to -2.65; 14 studies, n = 491), and low-certainty evidence that walking reduces SBP in participants aged 41 to 60 years (MD -3.79 mmHg, 95% CI -5.64 to -1.94, P < 0.001; 35 studies, n = 1959), and those aged 60 years of over (MD -4.30 mmHg, 95% CI -6.17 to -2.44, 24 studies, n = 2610). We also found low certainty-evidence suggesting that walking reduces SBP in both females (MD -5.65 mmHg, 95% CI -7.89 to -3.41; 22 studies, n = 1149) and males (MD -4.64 mmHg, 95% CI -8.69 to -0.59; 6 studies, n = 203). Secondary outcomes We found low-certainty evidence suggesting that walking reduces diastolic blood pressure (DBP) (MD -1.79 mmHg, 95% CI -2.51 to -1.07; 69 studies, n = 4711) and heart rate (MD -2.76 beats per minute (bpm), 95% CI -4.57 to -0.95; 26 studies, n = 1747). We found moderate-certainty evidence suggesting that walking reduces DBP for participants aged 40 years and under (MD -3.01 mmHg, 95% CI -4.44 to -1.58; 14 studies, n = 491) and low-certainty evidence suggesting that walking reduces DBP for participants aged 41 to 60 years (MD -1.74 mmHg, 95% CI -2.95 to -0.52; 32 studies, n = 1730) and those aged 60 years and over (MD -1.33 mmHg, 95% CI -2.40 to -0.26; 23 studies, n = 2490). We found moderate-certainty evidence that suggests walking reduces DBP for males (MD -2.54 mmHg, 95% CI -4.84 to -0.24; 6 studies, n = 203) and low-certainty evidence that walking reduces DBP for females (MD -2.69 mmHg, 95% CI -4.16 to -1.23; 20 studies, n = 1000). Only 21 included studies reported adverse events. Of these 21 studies, 16 reported no adverse events, the remaining five studies reported eight adverse events, with knee injury being reported five times. AUTHORS' CONCLUSIONS: Moderate-certainty evidence suggests that walking probably reduces SBP. Moderate- or low-certainty evidence suggests that walking may reduce SBP for all ages and both sexes. Low-certainty evidence suggests that walking may reduce DBP and heart rate. Moderate- and low-certainty evidence suggests walking may reduce DBP and heart rate for all ages and both sexes.

[Application of the Risk of Bias 2 Tool].

The Cochrane risk of bias (RoB) tool is used widely in systematic review studies and evidence-based healthcare. However, how this tool is used and how domains and signaling questions are interpreted may vary significantly across studies. This article was written to illustrate the limitations of the Risk of Bias tool version 1, which have been addressed in the new version of this tool, Risk of Bias version 2 (RoB 2). In addition to introducing the five domains (including risk of bias due to the randomization process, deviations from the intended interventions, missing outcome data, measurement of the outcome, and selection of reported results) and the assessment of overall bias risk, the procedure of using the RoB 2 tool to assess randomized controlled trials when conducting a systematic review study and evidence-based practice is also introduced. The structure of pre-, during-, and post-assessment is used in this article to describe clearly the procedure of bias assessment. An overall introduction to the relevant resources related to RoB 2 (such as guidance, software, and websites) is also addressed, to further enhance the familiarity with RoB 2 of nursing staffs and systematic review researchers and to increase their ability to use this tool effectively.

Effect of exercise on slowing breastfeeding-induced bone loss: A meta-analysis and trial sequential analysis.

AIM: This study systematically reviewed evidence regarding the effectiveness of exercise in slowing breastfeeding-induced bone loss. METHODS: The evidence-based approach of a systematic review (PROSPERO registration No. CRD42019111623) was adopted. The inclusion criteria were randomized controlled trials or observational studies. Study samples were breastfeeding women, the intervention was any form of exercise, and bone mineral density (BMD) of the total body, lumbar spine and hip/femur neck before 6 months and at 1 year were the outcome measures. Meta-analyses were performed using a random effect model, and calculations of mean differences of BMD change and 95% confidence intervals (CIs) were carried out. Studies were further evaluated through trial sequential meta-analysis (TSA), and the 'Grading of Recommendations Assessment, Development and Evaluation' methodology was used to assess the certainty of evidence (CoE). RESULTS: A total of 1049 studies were screened, and 4 met the inclusion criteria. Weight-bearing aerobic exercise and resistance training before the 6-month evaluation slowed breastfeeding-induced bone loss in the lumbar spine (1.62% BMD change [95% CI = 0.53-2.71]; I2 = 8%). The TSA Z-curve revealed crossing of the TSA boundary and line of information size, indicating sufficient sampling and significance. The CoE of exercise benefit in the lumbar spine at 6 months was low, whereas the CoE for other areas ranged from low to very low. CONCLUSION: This first systematic review and meta-analysis provided some evidence of the advantages of exercise for slowing breastfeeding-induced bone loss. However, additional randomized controlled trials are warranted to generate more conclusive evidence.

[Comparing the Health Needs of Older Aboriginal and Older Ethnic Chinese Individuals in Taiwan].

BACKGROUND: Providing healthcare to older people is an essential policy in Taiwan. Previous studies have assessed the health needs of older people residing in urban areas. Evidence related to the differences in healthcare needs between older aboriginal and older ethnic Chinese people in Taiwan is insufficient. As both groups exhibit mutually distinct physical and socio-cultural attributes, understanding their different health needs is necessary to provide tailored and effective healthcare. PURPOSE: To investigate the distinct health needs of older aboriginal and older ethnic Chinese using a comprehensive health-needs assessment tool. METHODS: A cross-sectional study design was used. Older people aged 65 or over were proportionally sampled from communities. The Elderly Assessment System Care Standard instrument was used to collect data through interviews held in participant homes or in community activity centers between October 20th and December 20th, 2011. RESULTS: A total of 180 older people were recruited. A majority of participants had at least one chronic disease, disability, or frailty. Across a range of dimensions and categories of health needs, older aboriginal people had statistically significant higher health needs than non-aboriginal ones. However, older ethnic Chinese participants had higher levels of need in the domains of housing/financing and social participation/isolation. Regression analysis found that independence, risk of frailty, and risk of falls explained the majority of health needs, with R2 values of 64% and 69.6% for older aboriginal and older ethnic Chinese participants, respectively. However, the respective impact of these three categories on overall health needs varied between the two groups. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Based on our findings, healthcare providers should focus on improving the self-care capabilities of older aboriginal people and on reducing the risk of breakdowns in care for older ethnic Chinese people in order to enhance the quality of elderly care in Taiwan.

Health needs of older Aboriginal people in Taiwan: a community-based assessment using a multidimensional instrument.

AIMS AND OBJECTIVES: To explore the health needs of older Aboriginal people, using a multidimensional instrument. The gender differences related to their health needs were also addressed. BACKGROUND: Health status and life expectancy between Aborigines and non-Aborigines have been shown to differ. The investigation of the health needs of Aboriginal people is however scarce, particularly among the older adult population. There is a need to address unmet health needs and improve information on the health needs assessment of the older Aboriginal population. DESIGN: A cross-sectional design was used. METHODS: Aboriginal people aged 65 and over were randomly sampled to take part in the present study. A multidimensional instrument consisting of eight domains and three cross-domain categories was used to assess their health needs. RESULTS: A group of older Aboriginal people was recruited (n = 90, mean age = 73·5). The top three identified needs were 'mental health and well-being', 'staying healthy' and 'social participation'. The female participants had statistically significant higher scores for the 'mental health and well-being', 'getting around' domains and in the 'risk of falls' than the male ones. A regression model demonstrated that the health need of 'looking after oneself' was associated with all cross-domain categories of health need, which are 'independence', 'risk of breakdown in care' and 'risk of falls'. CONCLUSIONS: The present study has revealed major health needs among older Aboriginal people and found that older female Aborigines have more health needs than older male Aborigines. Further study to identify effective approaches to address these needs among this group is warranted. RELEVANCE TO CLINICAL PRACTICE: The findings can be used to identify effective approaches to addressing health needs among older Aboriginal people with a consideration of gender. Only then can resources be allocated and prioritised in a culturally sensitive and gender-specific manner nationally and globally.

Strand invasion of DNA quadruplexes by PNA: comparison of homologous and complementary hybridization.

Molecular recognition of DNA quadruplex structures is envisioned to be a strategy for regulating gene expression at the transcriptional level and for in situ analysis of telomere structure and function. The recognition of DNA quadruplexes by peptide nucleic acid (PNA) oligomers is presented here, with a focus on comparing complementary, heteroduplex-forming and homologous, heteroquadruplex-forming PNAs. Surface plasmon resonance and optical spectroscopy experiments demonstrated that the efficacy of a recognition mode depended strongly on the target. Homologous PNA readily invades a quadruplex derived from the promoter regulatory region found upstream of the MYC proto-oncogene to form a heteroquadruplex at high potassium concentration mimicking the intracellular environment, whereas complementary PNA exhibits virtually no hybridization. In contrast, complementary PNA is superior to the homologous in hybridizing to a quadruplex modeled on the human telomere sequence. The results are discussed in terms of the different structural morphologies of the quadruplex targets and the implications for in vivo recognition of quadruplexes by PNAs.

[A project to improve psychiatric nursing station air quality].

BACKGROUND: Ambient air at the psychiatric nursing station in our hospital had been notably poor for an extensive period of time. CO2 levels at the station averaged 1211 ppm during August, 2009 and a specialist team estimated a CO2 abnormality ratio of 32%. Analysis identified key issues in three problem areas, including (1) ENVIRONMENT: air at the station was not refreshed and electronic equipment was in constant operation; (2) Staff: the station had a high staff-to-space ratio and staffs lacked practical knowledge on indoor air quality maintenance; and (3) Policy: the hospital had no guidelines addressing indoor air quality maintenance. PURPOSE: The purpose of this project was to reduce ambient CO2 levels at the hospital's acute psychiatric ward in order to create a high-quality working environment for all staff. The short-term goal was to reduce the CO2 abnormality ratio from 32% to 10%. Long-term goals were to maintain an ambient CO2 level in the ward below 1000ppm and further reduce the abnormality ratio to 0%. METHODS: To address environment-related issues, we increased the number of indoor plants and turned certain computers off at night. To address staff-related issues, we rearranged staff activity space and educated staff on how to maintain indoor air quality. To address the policy-related issue, we drafted proposed hospital guidelines on indoor air quality maintenance. RESULTS: Post-intervention measurements made in October, 2011 found significantly improved ambient air quality, with CO2 levels at 997ppm and a CO2 abnormality ratio of 0%. CONCLUSIONS: Results demonstrate that improvement measures implemented can effectively improve the quality of ambient air at psychiatric nursing stations. A post-intervention survey further found that staffs were both more satisfied with ward air quality and perceived a friendlier ward work environment.

Endothelial activation and fibrotic changes are impeded by laminar flow-induced CHK1-SENP2 activity through mechanisms distinct from endothelial-to-mesenchymal cell transition.

Background: The deSUMOylase sentrin-specific isopeptidase 2 (SENP2) plays a crucial role in atheroprotection. However, the phosphorylation of SENP2 at T368 under disturbed flow (D-flow) conditions hinders its nuclear function and promotes endothelial cell (EC) activation. SUMOylation has been implicated in D-flow-induced endothelial-to-mesenchymal transition (endoMT), but the precise role of SENP2 in counteracting this process remains unclear. Method: We developed a phospho-specific SENP2 S344 antibody and generated knock-in (KI) mice with a phospho-site mutation of SENP2 S344A using CRISPR/Cas9 technology. We then investigated the effects of SENP2 S344 phosphorylation under two distinct flow patterns and during hypercholesteremia (HC)-mediated EC activation. Result: Our findings demonstrate that laminar flow (L-flow) induces phosphorylation of SENP2 at S344 through the activation of checkpoint kinase 1 (CHK1), leading to the inhibition of ERK5 and p53 SUMOylation and subsequent suppression of EC activation. We observed a significant increase in lipid-laden lesions in both the aortic arch (under D-flow) and descending aorta (under L-flow) of female hypercholesterolemic SENP2 S344A KI mice. In male hypercholesterolemic SENP2 S344A KI mice, larger lipid-laden lesions were only observed in the aortic arch area, suggesting a weaker HC-mediated atherogenesis in male mice compared to females. Ionizing radiation (IR) reduced CHK1 expression and SENP2 S344 phosphorylation, attenuating the pro-atherosclerotic effects observed in female SENP2 S344A KI mice after bone marrow transplantation (BMT), particularly in L-flow areas. The phospho-site mutation SENP2 S344A upregulates processes associated with EC activation, including inflammation, migration, and proliferation. Additionally, fibrotic changes and up-regulated expression of EC marker genes were observed. Apoptosis was augmented in ECs derived from the lungs of SENP2 S344A KI mice, primarily through the inhibition of ERK5-mediated expression of DNA damage-induced apoptosis suppressor (DDIAS). Summary: In this study, we have revealed a novel mechanism underlying the suppressive effects of L-flow on EC inflammation, migration, proliferation, apoptosis, and fibrotic changes through promoting CHK1-induced SENP2 S344 phosphorylation. The phospho-site mutation SENP2 S344A responds to L-flow through a distinct mechanism, which involves the upregulation of both mesenchymal and EC marker genes.

Psychometric testing of the Chinese evidence-based practice scales.

AIM: This article is a report of the psychometric testing of the Chinese version of Evidence-Based Practice Implementation and Beliefs, and Barriers to, and Facilitators of Research Utilization scales. BACKGROUND: Investigations into the effect of evidence-based practice on clinical care could be facilitated by instruments for measuring the levels of evidence-based practice implementation; the strength of beliefs in evidence-based practice; the barriers to, and the facilitators of research utilization. An English version of the scales measuring the above constructs has been tested whereas the Chinese one has not. DESIGN: Instrument development. METHODS: Psychometric analyses of the four evidence-based scales were conducted on a sample of 361 nurses from a medical centre in Taiwan. Both the internal consistency and squared multiple correlation coefficients were used to examine reliability. The validity testing for the four scales was estimated by examining their construct and concurrent validity. Data were collected between December 2008-January 2009. FINDINGS: Internal consistencies exist for the Chinese Evidence-Based Practice Implementation, Beliefs, and Barriers to, and Facilitator of Research Utilization scales (≥0·85); some were greater than 0·9, which may indicate redundancy in items. Construct validity of the four scales was supported by hypotheses testing. Concurrent validity of the four scales was supported by known-group analysis, in which experienced nursing researchers had higher scores compared with clinical nurses. CONCLUSION: These scales may have value in discrimination between implementation of EBP and perception of barriers to, and facilitators of research utilization among nurses with different education levels, research experiences or working years in clinical setting.

The effect of an intervention combining self-efficacy theory and pedometers on promoting physical activity among adolescents.

AIM: To study the effect of an intervention combining self-efficacy theory and pedometers on promoting physical activity among adolescents. BACKGROUND: The beneficial effects of regular physical activity on health in youths are well-documented. However, adolescence is found to be the age of greatest decline in physical activity participation. Physical activity participation among girls was generally less frequent and less intense than boys. Therefore, there is a strong need for effective interventions that can help promote physical activity in this population. DESIGN: An experimental design. METHODS: Two classes of female junior college students (mean age = 16) were randomly sampled from a total of four classes and, of those, one each was randomly assigned to either the intervention (n = 46) or the control group (n = 48). Self-efficacy was used as a core theoretical foundation of the intervention design, and pedometers were provided to the students in the intervention group. Distances between each domestic scenic spot were illustrated graphically in a walking log for students to mark the extent of their walking or running. Students in the control group participated in a usual physical education programme. The primary outcome was a change in the number of aerobic steps. The secondary outcomes were changes in cardiopulmonary endurance and exercise self-efficacy. RESULTS: At 12-week follow-up, the mean change in aerobic steps was 371 steps and 108 steps in the intervention and control group, respectively. The difference in mean change between the two groups was 467 steps. Effects of the intervention on changes of cardiopulmonary endurance and perceived exercise self-efficacy scores were not found. CONCLUSIONS: Among adolescent girls, a 12-week intervention designed on the theoretical foundation of self-efficacy theory and provision of pedometers was found to have an effect on increasing their physical activity. The intervention, using graphs of domestic scenic spots to represent the distance of walking or running as monitored by pedometers, might enhance motivation regarding physical activity. RELEVANCE TO CLINICAL PRACTICE: It is important for health professionals, including school health nurses, involved in the care of adolescent health, to design and provide a physical activity intervention combining self-efficacy theory and provision of pedometer to promote physical activity.

Association of Risk of Incident Venous Thromboembolism With Atopic Dermatitis and Treatment With Janus Kinase Inhibitors: A Systematic Review and Meta-analysis.

Importance: The risk of venous thromboembolism (VTE) among patients with atopic dermatitis (AD), especially when receiving treatment with Janus kinase (JAK) inhibitors, is unclear. Objective: To determine the association of AD with incident VTE and evaluate the risk of incident VTE among patients with AD who were receiving treatment with JAK inhibitors. Data Sources: The MEDLINE, Embase, Cochrane Library, and Web of Science databases were searched with no restrictions on language nor geographic locations from their respective inception to February 5, 2022. Study Selection: Cohort studies examining the association of AD with incident VTE and randomized clinical trials (RCTs) reporting VTE events in participants with AD receiving JAK inhibitors were included. Around 0.7% of initially identified articles met the selection criteria. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed. The risk of bias of included cohort studies and RCTs was assessed by the Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool 2, respectively. A random-effects model meta-analysis was conducted to calculate the pooled hazard ratio (HR) and risk difference for incident VTE. Main Outcomes and Measures: The HRs for incident VTE associated with AD and risk difference for incident VTE between participants with AD who were receiving treatment with JAK inhibitors and controls receiving placebo or dupilumab. Results: Two cohort studies and 15 RCTs with a total of 466 993 participants were included. The meta-analysis found no significant association of AD with incident VTE (HR, 0.95; 95% CI 0.62-1.45; incidence rate of VTE, 0.23 events/100 patient-years). Overall, 3 of 5722 patients with AD (0.05%) who were receiving treatment with JAK inhibitors experienced VTE compared with 1 of 3065 patients with AD (0.03%) receiving placebo or dupilumab (Mantel-Haenszel risk difference, 0; 95% CI, 0-0). The incidence rate of VTE was 0.15 and 0.12 events per 100 patient-years in participants with AD receiving JAK inhibitors and placebo, respectively. The findings were similar in 4 unique JAK inhibitors (abrocitinib, baricitinib, upadacitinib, and SHR0302). Conclusions and Relevance: The results of this systematic review and meta-analysis suggest that the currently available evidence does not detect an increased risk of VTE associated with AD or treatment with JAK inhibitors. These findings may provide a reference for clinicians in prescribing JAK inhibitors for patients with AD.

Increased Joint Space Narrowing After Arthroscopic Partial Meniscectomy: Data From the Osteoarthritis Initiative.

BACKGROUND: Arthroscopic partial meniscectomy (APM) is widely performed and remains an important therapeutic option for patients with a meniscal tear. However, it is debated whether or not APM accelerates the progression of osteoarthritis (OA) in the long term. PURPOSE/HYPOTHESIS: The purpose was to compare the progression of OA measured by the change in tibiofemoral joint space width (JSW)-a quantitative measure of OA radiographic severity-across 3 groups with a midterm follow-up: (1) patients undergoing APM; (2) those with a meniscal tear treated nonoperatively; and (3) those without a tear. We hypothesized that the reduction in JSW would be greatest in patients undergoing APM and least in those patients without a tear. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Using the Osteoarthritis Initiative cohort, a total of 144 patients were identified that underwent APM with at least 12 months of follow up and without previous knee surgery. Those with a meniscal tear who did not have APM (n = 144) and those without a tear (n = 144) were matched to patients who had APM by sex, age, Kellgren-Lawrence (KL) grade, and follow up time. Participants underwent magnetic resonance imaging at baseline. Knee radiographs to assess JSW were collected annually or biannually. The change in minimum medial compartment JSW was calculated using a validated automated method. A piecewise linear mixed effects model was constructed to examine the relationship between JSW decline over time and treatment group-adjusting for age, body mass index, smoking status, KL grade, and baseline JSW. RESULTS: All groups had comparable baseline JSW-ranging from 4.33 mm to 4.38 mm. The APM group had a rate of JSW decline of -0.083 mm/mo in the first 12 months and -0.014 mm/mo between 12 and 72 months. The rate of JSW decline in the APM group was approximately 27 times greater in the first 12 months than that in the nonsurgical group (-0.003 mm/mo) and 5 times greater than that in the no tear group (-0.015 mm/mo); however, there was no significant difference between groups for 12 to 72 months (nonsurgical group: -0.009 mm/mo; no tear group: -0.010 mm/mo). The adjusted JSW in the APM group was 4.38 mm at baseline and decreased to 2.57 mm at 72 months; the JSW in the nonsurgical group declined from 4.31 mm to 3.73 mm, and in the no tear group it declined from 4.33 mm to 3.54 mm. There was a statistically significant difference in JSW change between baseline and 72 months for the APM group compared with the other groups (P < .001), but not between the nonsurgical and no tear groups (P = .12). CONCLUSION: In the first postoperative year, APM results in a faster rate of joint space narrowing compared with knees undergoing nonsurgical management of meniscal tears. Thereafter, there are comparable rates of OA progression regardless of the chosen management. APM results in a persistent decrease in JSW over at least 72 months. An untreated meniscal tear does not contribute to radiographic progression-assessed by JSW-as compared with an intact meniscus.

Association of Psoriasis With Incident Venous Thromboembolism and Peripheral Vascular Disease: A Systematic Review and Meta-analysis.

IMPORTANCE: Psoriasis, venous thromboembolism (VTE), and peripheral vascular disease (PVD) share similar mechanisms involving chronic inflammation. However, the associations between psoriasis and VTE or PVD are unclear. OBJECTIVE: To determine the association of psoriasis with incident VTE and PVD. DATA SOURCES: MEDLINE, Embase, Cochrane Library, Web of Science, and Cumulative Index to Nursing and Allied Health Literature were systematically searched for relevant publications from their respective inception through May 21, 2021. No restrictions on language or geographic locations were imposed. STUDY SELECTION: Two authors independently selected cohort studies that investigated the risk for incident VTE or PVD in patients with psoriasis. Any discrepancy was resolved through discussion with 2 senior authors until reaching consensus. Only 13 initially identified studies met the selection criteria for qualitative review, and only 9 of these for quantitative analysis. DATA EXTRACTION AND SYNTHESIS: The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline was followed. Two authors independently extracted data and assessed the risk of bias of included studies by using the Newcastle-Ottawa Scale. Disagreements were resolved by discussion with 2 other authors. A random-effects model meta-analysis was conducted to calculate the pooled hazard ratios (HRs) with the corresponding confidence intervals for incident VTE and PVD. Subgroup analyses based on arthritis status, psoriasis severity, sex, and geographic location were also performed. MAIN OUTCOMES AND MEASURES: Hazard ratios for incident VTE and PVD associated with psoriasis. RESULTS: A total of 13 cohort studies with 12 435 982 participants were included. The meta-analysis demonstrated a significantly increased risk for incident VTE (pooled HR, 1.26; 95% CI, 1.08-1.48) and PVD (pooled HR, 1.27; 95% CI, 1.16-1.40) among patients with psoriasis. Subgroup analyses illustrated increased risk for incident VTE among participants with psoriatic arthritis (pooled HR, 1.24; 95% CI, 1.01-1.53), women (pooled HR, 1.89; 95% CI, 1.36-2.61), and those in Asia (pooled HR, 2.02; 95% CI, 1.42-2.88) and Europe (pooled HR, 1.28; 95% CI, 1.06-1.53). CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis found an increased risk for incident VTE and PVD among patients with psoriatic disease. Typical presentations of VTE or PVD should not be overlooked in patients with psoriasis. Risk factors, such as obesity, physical inactivity, smoking, and varicose veins, should be identified and treated in patients with psoriasis, and medications like hormone-related therapies should be prescribed with caution.

MAGI1 inhibits interferon signaling to promote influenza A infection.

We have shown that membrane-associated guanylate kinase with inverted domain structure-1 (MAGI1), a scaffold protein with six PSD95/DiscLarge/ZO-1 (PDZ) domains, is involved in the regulation of endothelial cell (EC) activation and atherogenesis in mice. In addition to causing acute respiratory disease, influenza A virus (IAV) infection plays an important role in atherogenesis and triggers acute coronary syndromes and fatal myocardial infarction. Therefore, the aim of this study is to investigate the function and regulation of MAGI1 in IAV-induced EC activation. Whereas, EC infection by IAV increases MAGI1 expression, MAGI1 depletion suppresses IAV infection, suggesting that the induction of MAGI1 may promote IAV infection. Treatment of ECs with oxidized low-density lipoprotein (OxLDL) increases MAGI1 expression and IAV infection, suggesting that MAGI1 is part of the mechanistic link between serum lipid levels and patient prognosis following IAV infection. Our microarray studies suggest that MAGI1-depleted ECs increase protein expression and signaling networks involve in interferon (IFN) production. Specifically, infection of MAGI1-null ECs with IAV upregulates expression of signal transducer and activator of transcription 1 (STAT1), interferon b1 (IFNb1), myxovirus resistance protein 1 (MX1) and 2'-5'-oligoadenylate synthetase 2 (OAS2), and activate STAT5. By contrast, MAGI1 overexpression inhibits Ifnb1 mRNA and MX1 expression, again supporting the pro-viral response mediated by MAGI1. MAGI1 depletion induces the expression of MX1 and virus suppression. The data suggests that IAV suppression by MAGI1 depletion may, in part, be due to MX1 induction. Lastly, interferon regulatory factor 3 (IRF3) translocates to the nucleus in the absence of IRF3 phosphorylation, and IRF3 SUMOylation is abolished in MAGI1-depleted ECs. The data suggests that MAGI1 inhibits IRF3 activation by maintaining IRF3 SUMOylation. In summary, IAV infection occurs in ECs in a MAGI1 expression-dependent manner by inhibiting anti-viral responses including STATs and IRF3 activation and subsequent MX1 induction, and MAGI1 plays a role in EC activation, and in upregulating a pro-viral response. Therefore, the inhibition of MAGI1 is a potential therapeutic target for IAV-induced cardiovascular disease.

Radiation therapy induces immunosenescence mediated by p90RSK.

Radiation therapy (RT) to the chest increases the patients' risk of cardiovascular disease (CVD). A complete understanding of the mechanisms by which RT induces CVD could lead to specific preventive, therapeutic approaches. It is becoming evident that both genotoxic chemotherapy agents and radiation induce mitochondrial dysfunction and cellular senescence. Notably, one of the common phenotypes observed in cancer survivors is accelerated senescence, and immunosenescence is closely related to both cancer risk and CVD development. Therefore, suppression of immunosenescence can be an ideal target to prevent cancer treatment-induced CVD. However, the mechanism(s) by which cancer treatments induce immunosenescence are incompletely characterized. We isolated peripheral blood mononuclear cells (PBMCs) before and 3 months after RT from 16 thoracic cancer patients. We characterized human immune cell lineages and markers of senescence, DNA damage response (DDR), efferocytosis, and determinants of clonal hematopoiesis of indeterminant potential (CHIP), using mass cytometry (CyTOF). We found that the frequency of the B cell subtype was decreased after RT. Unsupervised clustering of the CyTOF data identified 138 functional subsets of PBMCs. Compared with baseline, RT increased TBX21 (T-bet) expression in the largest B cell subset of Ki67-/DNMT3a+naïve B cells, and T-bet expression was correlated with phosphorylation of p90RSK expression. CD38 expression was also increased in naïve B cells (CD27-) and CD8+ effector memory CD45RA T cells (TEMRA). In vitro, we found the critical role of p90RSK activation in upregulating (1) CD38+/T-bet+ memory and naïve B, and myeloid cells, (2) senescence-associated ß-gal staining, and (3) mitochondrial reactive oxygen species (ROS) after ionizing radiation (IR). These data suggest the crucial role of p90RSK activation in immunosenescence. The critical role of p90RSK activation in immune cells and T-bet induction in upregulating atherosclerosis formation has been reported. Furthermore, T-bet directly binds to the CD38 promoter region and upregulates CD38 expression. Since both T-bet and CD38 play a significant role in the process of immunosenescence, our data provide a cellular and molecular mechanism that links RT-induced p90RSK activation and the immunosenescence with T-bet and CD38 induction observed in thoracic cancer patients treated by RT and suggests that targeting the p90RSK/T-bet/CD38 pathway could play a role in preventing the radiation-associated CVD and improving cancer prognosis by inhibiting immunosenescence.

Associations Between Unhealthy Weight-Loss Strategies and Depressive Symptoms.

INTRODUCTION: There appears to be a link between weight loss and improved mental health, but less is known about how using unhealthy weight-loss strategies impacts the odds of reporting depression. METHODS: This study includes respondents from the National Health and Nutrition Examination Survey from 2005 to 2014 who attempted to lose weight over the past year. Analysis occurred in 2017. Multivariable logistic regression was used to describe associations between all weight-loss strategies, including those grouped as unhealthy (smoking, vomiting, laxatives, skipping meals, and using diet pills), and the adjusted odds of depression (Patient Health Questionnaire-9 score ≥10). The model was then stratified by BMI, sex, race, and antidepressant use to compare the effect of using at least one unhealthy weight-loss strategy and depression within certain populations. RESULTS: The sample included 6,765 respondents (weighted n=59.2 million, 95% CI=55.5, 62.9 million). Of these respondents, 18.0% (n=1,270) reported using at least one unhealthy weight-loss strategy. In unadjusted analysis, unhealthy weight-loss strategies were generally associated with higher incidence and odds of reporting depression. In multivariable analysis, using at least one unhealthy weight-loss strategy was significantly associated with odds of reporting depression (AOR=1.47, 95% CI=1.14, 1.91, p<0.01). When the model was stratified, this effect was statistically significant among respondents with class I or II obsesity (AOR=2.20, 95% CI=1.56, 3.10, p<0.01); female respondents (AOR=1.46, 95% CI=1.06, 2.00, p=0.02); and respondents who did not use an antidepressant (AOR=1.57, 95% CI=1.14, 2.15, p=0.01). CONCLUSIONS: Unhealthy weight-loss strategies are associated with increased odds of depression. This may inform screening practices and public health messaging.

A systematic review of silver-releasing dressings in the management of infected chronic wounds.

AIM: This paper is a systematic review with the objective of determining the effectiveness of silver-releasing dressing in the management of infected chronic wounds. BACKGROUND: Chronic wounds exhibit increased bacterial burdens which not only result in a negative physical impact on patients, impairing their quality of life, but also increase treatment costs. Silver dressings are wound products designed to control and inhibit infection and provide a wound environment conducive to healing. However, there is limited evidence on their effectiveness in doing so. METHODS: A systematic review of literature from 1950-May 2007 was conducted using the PubMed, CINAHL, Cochrane, MEDLINE, British Nursing Index, EBSCO Host, OCLC, Proquest and PsychInfo databases. The review included randomised or non-randomised control trials, published in English or non-English, of silver-releasing dressings in infected chronic wounds. RESULTS: Of the over 1957 potentially releasing studies examined, 14 pertinent articles involving 1285 participants were identified. Almost all the participants reported one or more statistically significant outcomes. The main points to emerge from this review of studies are that silver-releasing dressings show positive effects on infected chronic wounds. The quality of the trials was limited by the potential for bias associated with inadequate concealment, no detailed description of the outcome measurement and no reported intention-to-treat analysis. Moreover, problems existed in some studies with confounding factors. CONCLUSION: The review clearly highlights the need for well-designed, methodologically standardised outcome measurement research into the effectiveness of silver-releasing dressings. It also points to the need for a comprehensive assessment of wound bed status in further studies. RELEVANCE TO CLINICAL PRACTICE: This review strengthens the case for the use of silver dressings when managing infected chronic wounds. They appear more effective and are tolerated well by patients. However, their use should be accompanied by a comprehensive wound assessment.

Using self-efficacy theory to develop interventions that help older people overcome psychological barriers to physical activity: a discussion paper.

BACKGROUND: Only a fifth of older people undertake a level of physical activity sufficient to lead to health benefit. Misconceptions about the ageing process and beliefs about the costs and benefits of exercise in late life may result in unnecessary self-imposed activity restriction. Thus, adhering to a physical activity can be difficult particularly when the benefits of exercise are often not immediate. Many of the barriers to engaging in physical activity among older people are attitudinal. It is therefore important to take account of the non-physical aspects of physical activity intervention programmes, such as increasing confidence. Self-efficacy is a widely applied theory used to understand health behaviour and facilitate behavioural modification, such as the increase of physical activity. AIM: This paper aims to examine the ways in which self-efficacy theory might be used in intervention programmes designed to overcome psychological barriers for increasing physical activity among older people. CONCLUSION: A number of studies have demonstrated that exercise self-efficacy is strongly associated with the amount of physical activity undertaken. Evidence from some trials supports the view that incorporating the theory of self-efficacy into the design of a physical activity intervention is beneficial. Physical activity interventions aimed at improving the self perception of exercise self-efficacy can have positive effects on confidence and the ability to initiate and maintain physical activity behaviour. There are a number of ways for nurses to facilitate older people to draw on the four information sources of self-efficacy: performance accomplishments, vicarious learning, verbal encouragement, and physiological and affective states. Research challenges that future studies need to address include the generalisability of exercise setting, the role of age as an effect modifier, and the need for more explicit reporting of how self-efficacy is operationalised in interventions.