The effectiveness of a positive psychological intervention for promoting preschool teachers' well-being and professional competence: EASP intervention program.

The present study investigated the effectiveness of the Early Advancement in Social-Emotional Health and Positivity (EASP) program, a positive psychological intervention promoting preschool teachers' well-being and the motivational aspect of professional competence. Participants were 273 in-service preschool teachers (Mage = 34.56 years, SD = 9.52, range = 22-58; female = 98.90%) who participated in a 2-month randomized controlled trial. Participants were randomly assigned to the intervention group (n = 143) receiving 1) four online workshops, 2) a smartphone app, and 3) an online activity, or to the wait-list control group (n = 130), which received the intervention materials after all the data collection. Participants reported their well-being dimensions, teaching self-efficacy, and autonomous motivation for teaching before and after the intervention. Results from a path analytic model exhibited excellent fit with the data, χ2 = 37.62, df = 33, CFI = .99, TLI = .98, RMSEA = .02 [90% CI = 0.00, 0.05], SRMR = .02. The intervention had direct effects on changes in well-being dimensions, including positivity, outcome, strength, engagement, and resilience (ß = .14 to .26, ps = .00 to .04), and indirect intervention effects on changes in teaching self-efficacy and autonomous motivation for teaching (ß = .14 to .15, ps = .00 to .01). These findings highlighted the potential value of implementing positive psychological interventions in educational settings to promote the well-being and professional competence among preschool teachers.

Genome-wide characterization of circulating metabolic biomarkers.

Genome-wide association analyses using high-throughput metabolomics platforms have led to novel insights into the biology of human metabolism1-7. This detailed knowledge of the genetic determinants of systemic metabolism has been pivotal for uncovering how genetic pathways influence biological mechanisms and complex diseases8-11. Here we present a genome-wide association study for 233 circulating metabolic traits quantified by nuclear magnetic resonance spectroscopy in up to 136,016 participants from 33 cohorts. We identify more than 400 independent loci and assign probable causal genes at two-thirds of these using manual curation of plausible biological candidates. We highlight the importance of sample and participant characteristics that can have significant effects on genetic associations. We use detailed metabolic profiling of lipoprotein- and lipid-associated variants to better characterize how known lipid loci and novel loci affect lipoprotein metabolism at a granular level. We demonstrate the translational utility of comprehensively phenotyped molecular data, characterizing the metabolic associations of intrahepatic cholestasis of pregnancy. Finally, we observe substantial genetic pleiotropy for multiple metabolic pathways and illustrate the importance of careful instrument selection in Mendelian randomization analysis, revealing a putative causal relationship between acetone and hypertension. Our publicly available results provide a foundational resource for the community to examine the role of metabolism across diverse diseases.

Inflammation-induced TRPV4 channels exacerbate blood-brain barrier dysfunction in multiple sclerosis.

BACKGROUND: Blood-brain barrier (BBB) dysfunction and immune cell migration into the central nervous system (CNS) are pathogenic drivers of multiple sclerosis (MS). Ways to reinstate BBB function and subsequently limit neuroinflammation present promising strategies to restrict disease progression. However, to date, the molecular players directing BBB impairment in MS remain poorly understood. One suggested candidate to impact BBB function is the transient receptor potential vanilloid-type 4 ion channel (TRPV4), but its specific role in MS pathogenesis remains unclear. Here, we investigated the role of TRPV4 in BBB dysfunction in MS. MAIN TEXT: In human post-mortem MS brain tissue, we observed a region-specific increase in endothelial TRPV4 expression around mixed active/inactive lesions, which coincided with perivascular microglia enrichment in the same area. Using in vitro models, we identified that microglia-derived tumor necrosis factor-α (TNFα) induced brain endothelial TRPV4 expression. Also, we found that TRPV4 levels influenced brain endothelial barrier formation via expression of the brain endothelial tight junction molecule claudin-5. In contrast, during an inflammatory insult, TRPV4 promoted a pathological endothelial molecular signature, as evidenced by enhanced expression of inflammatory mediators and cell adhesion molecules. Moreover, TRPV4 activity mediated T cell extravasation across the brain endothelium. CONCLUSION: Collectively, our findings suggest a novel role for endothelial TRPV4 in MS, in which enhanced expression contributes to MS pathogenesis by driving BBB dysfunction and immune cell migration.

Can a multicomponent positive psychological intervention promote well-being in parents of young children? A randomized controlled trial study in Hong Kong.

The present research examined the effects of an Early Advancement in Social-Emotional Health and Positivity (EASP) multicomponent positive psychological intervention on parents' well-being in Hong Kong. Participants were parents of young children (N = 120; Mage = 37.19 years, SD = 4.71, range = 24-53; female = 95.00%) who participated in the one-month randomized control trial. Participants were randomly assigned into the intervention (n = 50) and waitlist control groups (n = 70). Parents in the intervention group received two online workshops and an evidence-based smartphone application that targeted four positive psychological skills: (1) mindful parenting, (2) hope, (3) positive reappraisal, and (4) growth mindset. The results of the multivariate regression analysis revealed that the intervention significantly improved various dimensions of participants' positive psychological skills, subjective well-being, and psychological well-being immediately at the conclusion of the program. The findings of this study underscore the importance of the well-being payoffs linked to cultivating positive psychological skills among parents of young children.

Longitudinal association between children's mastery motivation and cognitive school readiness: Executive functioning and social-emotional competence as potential mediators.

This study investigated the direct relationships between kindergarten children's object and social mastery motivation and future cognitive school readiness and the indirect relationships mediated through executive functioning and social-emotional competence in the school context. The participants were 103 Hong Kong kindergarten children (45.6% girls; mean age = 60.4 months) and their teachers. The teachers reported the children's demographic information and object and social mastery motivation at Time 1 (in the middle of the school year). They rated the children's executive functioning, social-emotional competence and cognitive school readiness at Time 2 (at the end of the school year). The results from the path analysis model revealed that the children's object mastery motivation at Time 1, but not their social mastery motivation, directly predicted their cognitive school readiness at Time 2. The indirect relationships between (a) object mastery motivation at Time 1 and cognitive school readiness at Time 2 mediated through executive functioning (indirect effect: ß =.32, SE =.05, p <.001) and (b) social mastery motivation at Time 1 and cognitive school readiness at Time 2 mediated through social-emotional competence (indirect effect: ß =.09, SE =.03, p <.01) were significant. The findings highlight the differential roles of object and social mastery motivation in predicting children's cognitive school readiness and propose children's executive functioning and social-emotional competence as processes mediating the relationships. The results also suggest the desirability of providing kindergarten children with extensive play opportunities and materials to support their mastery motivation and cognitive school readiness.

Association of Arachidonic Acid-Derived Lipid Mediators With Disease Severity in Patients With Relapsing and Progressive Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Excessive activation of certain lipid mediator (LM) pathways plays a role in the complex pathogenesis of multiple sclerosis (MS). However, the relationship between bioactive LMs and different aspects of CNS-related pathophysiologic processes remains largely unknown. Therefore, in this study, we assessed the association of bioactive LMs belonging to the ω-3/ω-6 lipid classes with clinical and biochemical (serum neurofilament light [sNfL] and serum glial fibrillary acidic protein [sGFAP]) parameters and MRI-based brain volumes in patients with MS (PwMS) and healthy controls (HCs). METHODS: A targeted high-performance liquid chromatography-tandem mass spectrometry approach was used on plasma samples of PwMS and HCs of the Project Y cohort, a cross-sectional population-based cohort that contains PwMS all born in 1966 in the Netherlands and age-matched HCs. LMs were compared between PwMS and HCs and were correlated with levels of sNfL, sGFAP, disability (Expanded Disability Status Scale [EDSS]), and brain volumes. Finally, significant correlates were included in a backward multivariate regression model to identify which LMs best related to disability. RESULTS: The study sample consisted of 170 patients with relapsing remitting MS (RRMS), 115 patients with progressive MS (PMS), and 125 HCs. LM profiles of patients with PMS significantly differed from those of patients with RRMS and HCs, particularly patients with PMS showed elevated levels of several arachidonic acid (AA) derivatives. In particular, 15-hydroxyeicosatetraenoic acid (HETE) (r = 0.24, p < 0.001) correlated (average r = 0.2, p < 0.05) with clinical and biochemical parameters such as EDSS and sNfL. In addition, higher 15-HETE levels were related to lower total brain (r = -0.24, p = 0.04) and deep gray matter volumes (r = -0.27, p = 0.02) in patients with PMS and higher lesion volume (r = 0.15, p = 0.03) in all PwMS. DISCUSSION: In PwMS of the same birth year, we show that ω-3 and ω-6 LMs are associated with disability, biochemical parameters (sNfL, GFAP), and MRI measures. Furthermore, our findings indicate that, particularly, in patients with PMS, elevated levels of specific products of the AA pathway, such as 15-HETE, associate with neurodegenerative processes. Our findings highlight the potential relevance of ω-6 LMs in the pathogenesis of MS.

A novel penalized inverse-variance weighted estimator for Mendelian randomization with applications to COVID-19 outcomes.

Mendelian randomization utilizes genetic variants as instrumental variables (IVs) to estimate the causal effect of an exposure variable on an outcome of interest even in the presence of unmeasured confounders. However, the popular inverse-variance weighted (IVW) estimator could be biased in the presence of weak IVs, a common challenge in MR studies. In this article, we develop a novel penalized inverse-variance weighted (pIVW) estimator, which adjusts the original IVW estimator to account for the weak IV issue by using a penalization approach to prevent the denominator of the pIVW estimator from being close to zero. Moreover, we adjust the variance estimation of the pIVW estimator to account for the presence of balanced horizontal pleiotropy. We show that the recently proposed debiased IVW (dIVW) estimator is a special case of our proposed pIVW estimator. We further prove that the pIVW estimator has smaller bias and variance than the dIVW estimator under some regularity conditions. We also conduct extensive simulation studies to demonstrate the performance of the proposed pIVW estimator. Furthermore, we apply the pIVW estimator to estimate the causal effects of five obesity-related exposures on three coronavirus disease 2019 (COVID-19) outcomes. Notably, we find that hypertensive disease is associated with an increased risk of hospitalized COVID-19; and peripheral vascular disease and higher body mass index are associated with increased risks of COVID-19 infection, hospitalized COVID-19, and critically ill COVID-19.

Well-Being Profiles of Pre-service Teachers in Hong Kong: Associations with Teachers' Self-Efficacy During the COVID-19 Pandemic.

The present study aims to (1) identify the profiles of subjective well-being (SWB) and psychological well-being (PWB) in a sample of pre-service teachers during the second wave of the COVID-19 pandemic in Hong Kong, and (2) explore how different profiles are linked with teachers' self-efficacy. Participants were 291 pre-service teachers (Mage = 21.295, SD = 2.812, female = 89.903%) who were invited to complete self-report measures of SWB, PWB, and teachers' self-efficacy. Latent profile analysis with maximum likelihood estimation was conducted to identify well-being profiles that emerged in this sample. The results suggested a 3-class model with a high, moderate, and low well-being group. The findings also revealed that the pre-service teachers' well-being profiles as reflected by SWB and PWB indicators were consistent. Moreover, the pre-service teachers in the higher well-being group reported higher teaching self-efficacy than those in the lower well-being group. Findings highlighted the benefits of supporting pre-service teachers' well-being (i.e., SWB and PWB) to maintain their teachers' self-efficacy during the COVID-19 pandemic when teacher education and practicum are significantly disrupted. Interventions targeting various positive psychological skills (e.g., mindfulness, self-compassion, and positive reappraisal) are warranted. Future investigation is needed to examine the longitudinal relationship between pre-service teachers' well-being and self-efficacy.

Robust association tests for quantitative traits on the X chromosome.

The genome-wide association study is an elementary tool to assess the genetic contribution to complex human traits. However, such association tests are mainly proposed for autosomes, and less attention has been given to methods for identifying loci on the X chromosome due to their distinct biological features. In addition, the existing association tests for quantitative traits on the X chromosome either fail to incorporate the information of males or only detect variance heterogeneity. Therefore, we propose four novel methods, which are denoted as QXcat, QZmax, QMVXcat and QMVZmax. When using these methods, it is assumed that the risk alleles for females and males are the same and that the locus being studied satisfies the generalized genetic model for females. The first two methods are based on comparing the means of the trait value across different genotypes, while the latter two methods test for the difference of both means and variances. All four methods effectively incorporate the information of X chromosome inactivation. Simulation studies demonstrate that the proposed methods control the type I error rates well. Under the simulated scenarios, the proposed methods are generally more powerful than the existing methods. We also apply our proposed methods to data from the Minnesota Center for Twin and Family Research and find 10 single nucleotide polymorphisms that are statistically significantly associated with at least two traits at the significance level of 1 × 10-3.

Prospering in the midst of the COVID-19 pandemic: The effects of PROSPER-based intervention on psychological outcomes among preschool teachers.

The growing concerns regarding the risks of transmitting the COVID-19 virus have intensified the job-related stressors commonly encountered by teachers in various cultural contexts. Evidence shows how the COVID-19 crisis has negatively impacted teachers' mental health outcomes such as stress, depression, and quality of life, which highlights the significance of designing psychological programs to boost teachers' well-being. This study examined the effects of a well-being intervention based on the Positivity, Relationship, Outcomes, Strength, Purpose, Engagement, and Resilience (PROSPER) framework on well-being outcomes among 76 in-service teachers (Mage = 26.05 years, SD = 4.71, range = 20-45; female = 93.4%) in Hong Kong. Participants completed survey measures associated with the seven PROSPER outcomes at baseline and 2-month follow-up. Multivariate regression analysis indicated that there were statistically significant multivariate effects for intervention conditions, Wilks' Lambda F(7, 58) = 4.50, p = .01. Results demonstrated that teachers who were assigned to the intervention condition (n = 36) had significantly higher scores than those in the control condition (n = 40) on positivity (b = 0.41, 95% CI [0.16, 0.65], p = .01), strength (b = 0.62, 95% CI [0.23, 1.01], p = .01), purpose (b = 0.61, 95% CI [0.18, 1.04], p = .01), and resilience (b = 0.57, 95% CI [0.07, 1.07], p = .04). Our findings provide evidence on the mental health benefits of the PROSPER-based psychological intervention program for preschool teachers.

Oncostatin M triggers brain inflammation by compromising blood-brain barrier integrity.

Oncostatin M (OSM) is an IL-6 family member which exerts neuroprotective and remyelination-promoting effects after damage to the central nervous system (CNS). However, the role of OSM in neuro-inflammation is poorly understood. Here, we investigated OSM's role in pathological events important for the neuro-inflammatory disorder multiple sclerosis (MS). We show that OSM receptor (OSMRß) expression is increased on circulating lymphocytes of MS patients, indicating their elevated responsiveness to OSM signalling. In addition, OSM production by activated myeloid cells and astrocytes is increased in MS brain lesions. In experimental autoimmune encephalomyelitis (EAE), a preclinical model of MS, OSMRß-deficient mice exhibit milder clinical symptoms, accompanied by diminished T helper 17 (Th17) cell infiltration into the CNS and reduced BBB leakage. In vitro, OSM reduces BBB integrity by downregulating the junctional molecules claudin-5 and VE-cadherin, while promoting secretion of the Th17-attracting chemokine CCL20 by inflamed BBB-endothelial cells and reactive astrocytes. Using flow cytometric fluorescence resonance energy transfer (FRET) quantification, we found that OSM-induced endothelial CCL20 promotes activation of lymphocyte function-associated antigen 1 (LFA-1) on Th17 cells. Moreover, CCL20 enhances Th17 cell adhesion to OSM-treated inflamed endothelial cells, which is at least in part ICAM-1 mediated. Together, these data identify an OSM-CCL20 axis, in which OSM contributes significantly to BBB impairment during neuro-inflammation by inducing permeability while recruiting Th17 cells via enhanced endothelial CCL20 secretion and integrin activation. Therefore, care should be taken when considering OSM as a therapeutic agent for treatment of neuro-inflammatory diseases such as MS.

Gene-Based Methods for Estimating the Degree of the Skewness of X Chromosome Inactivation.

Skewed X chromosome inactivation (XCI-S) has been reported to be associated with some X-linked diseases, and currently several methods have been proposed to estimate the degree of the XCI-S (denoted as γ) for a single locus. However, no method has been available to estimate γ for genes. Therefore, in this paper, we first propose the point estimate and the penalized point estimate of γ for genes, and then derive its confidence intervals based on the Fieller's and penalized Fieller's methods, respectively. Further, we consider the constraint condition of γ∈[0, 2] and propose the Bayesian methods to obtain the point estimates and the credible intervals of γ, where a truncated normal prior and a uniform prior are respectively used (denoted as GBN and GBU). The simulation results show that the Bayesian methods can avoid the extreme point estimates (0 or 2), the empty sets, the noninformative intervals ([0, 2]) and the discontinuous intervals to occur. GBN performs best in both the point estimation and the interval estimation. Finally, we apply the proposed methods to the Minnesota Center for Twin and Family Research data for their practical use. In summary, in practical applications, we recommend using GBN to estimate γ of genes.

Association of genetic variants related to combined exposure to higher BMI and waist-to-hip ratio on lifelong cardiovascular risk in UK Biobank.

OBJECTIVE: This study examines the individual and combined association of BMI and waist-to-hip ratio (WHR) with CVD risk using genetic scores of the obesity measurements as proxies. DESIGN: A 2 × 2 factorial analysis approach was applied, with participants divided into four groups of lifetime exposure to low BMI and WHR, high BMI, high WHR, and high BMI and WHR based on weighted genetic risk scores. The difference in CVD risk across groups was evaluated using multivariable logistic regression. SETTING: Cohort study. PARTICIPANTS: A total of 408 003 participants were included from the prospective observational UK Biobank study. RESULTS: A total of 58 429 CVD events were recorded. Compared to the low BMI and WHR genetic scores group, higher BMI or higher WHR genetic scores were associated with an increase in CVD risk (high WHR: OR, 1·07; 95 % CI (1·04, 1·10)); high BMI: OR, 1·12; 95 % CI (1·09, 1·16). A weak additive effect on CVD risk was found between BMI and WHR (high BMI and WHR: OR, 1·16; 95 % CI (1·12, 1·19)). Subgroup analysis showed similar patterns between different sex, age (<65, ≥65 years old), smoking status, Townsend deprivation index, fasting glucose level and medication uses, but lower systolic blood pressure was associated with higher CVD risk in obese participants. CONCLUSIONS: High BMI and WHR were associated with increased CVD risk, and their effects are weakly additive. Even though there were overlapping of effect, both BMI and WHR are important in assessing the CVD risk in the general population.

BEXCIS: Bayesian methods for estimating the degree of the skewness of X chromosome inactivation.

BACKGROUND: X chromosome inactivation (XCI) is an epigenetic phenomenon that one of two X chromosomes in females is transcriptionally silenced during early embryonic development. Skewed XCI has been reported to be associated with some X-linked diseases. There have been several methods measuring the degree of the skewness of XCI. However, these methods may still have several limitations. RESULTS: We propose a Bayesian method to obtain the point estimate and the credible interval of the degree of XCI skewing by incorporating its prior information of being between 0 and 2. We consider a normal prior and a uniform prior for it (respectively denoted by BN and BU). We also propose a penalized point estimate based on the penalized Fieller's method and derive the corresponding confidence interval. Simulation results demonstrate that the BN and BU methods can solve the problems of extreme point estimates, noninformative intervals, empty sets and discontinuous intervals. The BN method generally outperforms other methods with the lowest mean squared error in the point estimation, and well controls the coverage probability with the smallest median and the least variation of the interval width in the interval estimation. We apply all the methods to the Graves' disease data and the Minnesota Center for Twin and Family Research data, and find that SNP rs3827440 in the Graves' disease data may undergo skewed XCI towards the allele C. CONCLUSIONS: We recommend the BN method for measuring the degree of the skewness of XCI in practice. The R package BEXCIS is publicly available at https://github.com/Wen-YiYu/BEXCIS .

Risk factors associated with surgical site infections following joint replacement surgery: a narrative review.

BACKGROUND: Surgical site infection following joint replacement surgery is still a significant complication, resulting in repeated surgery, prolonged antibiotic therapy, extended postoperative hospital stay, periprosthetic joint infection, and increased morbidity and mortality. This review discusses the risk factors associated with surgical site infection. RELATED RISK FACTORS: The patient-related factors include sex, age, body mass index (BMI), obesity, nutritional status, comorbidities, primary diagnosis, living habits, and scores of the American Society of Anesthesiologists physical status classification system, etc. Surgery-related factors involve preoperative skin preparation, prolonged duration of surgery, one-stage bilateral joint replacement surgery, blood loss, glove changes, anti-microbial prophylaxis, topical anti-bacterial preparations, wound management, postoperative hematoma, etc. Those risk factors are detailed in the review. CONCLUSION: Preventive measures must be taken from multiple perspectives to reduce the incidence of surgical site infection after joint replacement surgery.

Artificial intelligence in diagnosis of knee osteoarthritis and prediction of arthroplasty outcomes: a review.

BACKGROUND: Artificial intelligence is an emerging technology with rapid growth and increasing applications in orthopaedics. This study aimed to summarize the existing evidence and recent developments of artificial intelligence in diagnosing knee osteoarthritis and predicting outcomes of total knee arthroplasty. METHODS: PubMed and EMBASE databases were searched for articles published in peer-reviewed journals between January 1, 2010 and May 31, 2021. The terms included: 'artificial intelligence', 'machine learning', 'knee', 'osteoarthritis', and 'arthroplasty'. We selected studies focusing on the use of AI in diagnosis of knee osteoarthritis, prediction of the need for total knee arthroplasty, and prediction of outcomes of total knee arthroplasty. Non-English language articles and articles with no English translation were excluded. A reviewer screened the articles for the relevance to the research questions and strength of evidence. RESULTS: Machine learning models demonstrated promising results for automatic grading of knee radiographs and predicting the need for total knee arthroplasty. The artificial intelligence algorithms could predict postoperative outcomes regarding patient-reported outcome measures, patient satisfaction and short-term complications. Important weaknesses of current artificial intelligence algorithms included the lack of external validation, the limitations of inherent biases in clinical data, the requirement of large datasets in training, and significant research gaps in the literature. CONCLUSIONS: Artificial intelligence offers a promising solution to improve detection and management of knee osteoarthritis. Further research to overcome the weaknesses of machine learning models may enhance reliability and allow for future use in routine healthcare settings.

Parental self-efficacy: Examining its mediating and reciprocally predictive roles in supportive emotion socialization.

This longitudinal study examined the associations between child negative affect, parental self-efficacy (PSE), and parents' approaches to the provision of supportive socialization. It also investigated the bidirectionality between PSE, problem-focus socialization, and emotion-focus socialization across two time points separated by one year. Participants were 757 Hong Kong Chinese parents (47.4% fathers) of kindergarten children. At both time 1 and time 2, parents reported their PSE, problem-focus socialization, and emotion-focus socialization. Additionally, parents rated their child's negative affect at time 1. Results from the cross-lagged panel model revealed that, controlling for the effects of school's socioeconomic strata, child gender, parental age, and educational level, PSE at time 1 mediated the indirect links of child negative affect at time 1 with problem-focus (indirect effect: ß = -.02, SE = .02, p < .05) and emotion-focus (indirect effect: ß = -.02, SE = .01, p < .05) socialization at time 2 and that PSE (ß = .10, SE = .06, p < .01) and problem-focus socialization (ß = .15, SE = .03, p < .05) were reciprocally associated with each other. Findings underscored the role of PSE in understanding parental provision of supportive socialization and the co-development of belief about parenting and parenting behaviors.

MRCIP: a robust Mendelian randomization method accounting for correlated and idiosyncratic pleiotropy.

Mendelian randomization (MR) is a powerful instrumental variable (IV) method for estimating the causal effect of an exposure on an outcome of interest even in the presence of unmeasured confounding by using genetic variants as IVs. However, the correlated and idiosyncratic pleiotropy phenomena in the human genome will lead to biased estimation of causal effects if they are not properly accounted for. In this article, we develop a novel MR approach named MRCIP to account for correlated and idiosyncratic pleiotropy simultaneously. We first propose a random-effect model to explicitly model the correlated pleiotropy and then propose a novel weighting scheme to handle the presence of idiosyncratic pleiotropy. The model parameters are estimated by maximizing a weighted likelihood function with our proposed PRW-EM algorithm. Moreover, we can also estimate the degree of the correlated pleiotropy and perform a likelihood ratio test for its presence. Extensive simulation studies show that the proposed MRCIP has improved performance over competing methods. We also illustrate the usefulness of MRCIP on two real datasets. The R package for MRCIP is publicly available at https://github.com/siqixu/MRCIP.

Imaging of knee osteoarthritis: A review of current evidence and clinical guidelines.

BACKGROUND: Knee osteoarthritis (OA) is one of the most common and debilitating degenerative joint diseases worldwide. While radiography is the most commonly used imaging modality, it is associated with drawbacks which newer modalities such as magnetic resonance imaging (MRI) and ultrasound could overcome. Nevertheless, the role of imaging in clinical practice and research in knee OA has not been clearly defined. Furthermore, guidelines on imaging in knee OA from different authoritative bodies have not been compared in previous studies. Therefore, the present review aims to summarise existing evidence and compare guidelines on the use of different imaging modalities in evaluating knee OA. METHODS: This is a narrative review based on a search of published clinical guidelines and the PubMed database for articles published between 1 January 1990 and 31 May 2020. RESULTS: There is no broad consensus on the value of imaging in patients with typical OA presentation. If imaging is required, current evidence and clinical guidelines support the use of radiography and MRI as first- and second-line diagnostic modalities respectively. Since radiographic OA features have limited sensitivity and do not manifest in early stages, MRI is the preferred option for whole-joint evaluation in OA research. Discrepancies exist regarding the use of alternative imaging modalities including ultrasound, computed tomography and nuclear medicine. CONCLUSION: Radiography and MRI are the imaging modalities of choice. Other modalities have their respective advantages, and more research is warranted for the standardisation of image acquisition and interpretation methodology, in order to evaluate their validity, reliability and responsiveness in OA research.

Blood Pressure and Risk of Cardiovascular Disease in UK Biobank: A Mendelian Randomization Study.

This study aims to evaluate the causal association of blood pressure (BP) with cardiovascular diseases (CVDs). Two-sample Mendelian randomization was performed using a large genome-wide association study (n=299 024) and the UK Biobank cohort (n=375 256). We identified 327 and 364 single-nucleotide polymorphisms strongly and independently associated with systolic BP and diastolic BP, respectively, as genetic instruments to assess the causal association of BP with total CVD, CVD mortality, and 14 cardiovascular conditions. Nonlinearity was examined with nonlinear instrumental variable assumptions. Genetically predicted BP was significantly positively associated with total CVD (systolic BP, per 10 mm Hg: odds ratio [OR], 1.32 [95% CI, 1.25-1.40]; diastolic BP, per 5 mm Hg: OR, 1.20 [95% CI, 1.15-1.26]). Similar positive causal associations were observed for 14 cardiovascular conditions including ischemic heart disease (systolic BP, per 10 mm Hg: OR, 1.33 [95% CI, 1.24-1.41]; diastolic BP, per 5 mm Hg: OR, 1.20 [95% CI, 1.14-1.27]) and stroke (systolic BP, per 10 mm Hg: OR, 1.35 [95% CI, 1.24-1.48]; diastolic BP, per 5 mm Hg: OR, 1.20 [95% CI, 1.12-1.28]). Nonlinearity Mendelian randomization test demonstrated linear causal association of BP with these outcomes. Consistent estimates were observed in sensitivity analyses, suggesting robustness of the associations and minimal horizontal pleiotropy. The linear positive causal association of BP and CVD was consistent with previous findings that lower BP is better, thus consolidating clinical knowledge on hypertension management in CVD risk reduction.