Integrating wearables and modelling for monitoring rehabilitation following total knee joint replacement.

BACKGROUND AND OBJECTIVE: Wearable inertial devices integrated with modelling and cloud computing have been widely adopted in the sports sector, however, their use in the health and medical field has yet to be fully realised. To date, there have been no reported studies concerning the use of wearables as a surrogate tool to monitor knee joint loading during recovery following a total knee joint replacement. The objective of this study is to firstly evaluate if peak tibial acceleration from wearables during gait is a good surrogate metric for computer modelling predicted functional knee loading; and secondly evaluate if traditional clinical patient related outcomes measures are consistent with wearable predictions. METHODS: Following ethical approval, four healthy participants were used to establish the relationship between computer modelling predicted knee joint loading and wearable measured tibial acceleration. Following this, ten patients who had total knee joint replacements were then followed during their 6-week rehabilitation. Gait analysis, wearable acceleration, computer models of knee joint loading, and patient related outcomes measures including the Oxford knee score and range of motion were recorded. RESULTS: A linear correlation (R2 of 0.7-0.97) was observed between peak tibial acceleration (from wearables) and musculoskeletal model predicted knee joint loading during gait in healthy participants first. Whilst patient related outcome measures (Oxford knee score and patient range of motion) were observed to improve consistently during rehabilitation, this was not consistent with all patient's tibial acceleration. Only those patients that exhibited increasing peak tibial acceleration over 6-weeks rehabilitation were positively correlated with the Oxford knee score (R2 of 0.51 to 0.97). Wearable predicted tibial acceleration revealed three patients with a consistent knee loading, five patients with improving knee loading, and two patients with declining knee loading during recovery. Hence, 20% of patients did not present with satisfactory joint loading following total knee joint replacement and this was not detected with current patient related outcome measures. CONCLUSIONS: The use of inertial measurement units or wearables in this study provided additional insight into patients who were not exhibiting functional improvements in joint loading, and offers clinicians an 'off-site' early warning metric to identify potential complications during recovery and provide the opportunity for early intervention. This study has important implications for improving patient outcomes, equity, and for those who live in rural regions.

Subjective wellbeing and emotion regulation strategies: How are they associated with student engagement in online learning during Covid-19?

BACKGROUND: The COVID-19 pandemic has brought unprecedented challenges to the world, creating significant impact on people's lives and subjective wellbeing. While previous studies have shown that students' wellbeing and how they manage their emotions are critical to students' learning, less research has considered their specific impacts on student engagement in online learning. AIMS: The aim of this study is to examine how students' subjective wellbeing and emotion regulation strategies (viz cognitive reappraisal and expressive suppression) are associated with student engagement in online learning during the pandemic. SAMPLE: A total of 965 students from a university in China participated in the study. METHODS: The data were collected online during the COVID-19 from March to July 2020, which included measures of wellbeing, emotion regulation strategie, and online learning engagement. RESULTS: Structural equation modelling results showed that wellbeing was positively associated with both the use of reappraisal and suppression. Moreover, mediation analysis showed that reappraisal partially mediated the relationship between wellbeing and all types of online learning engagement (including cognitive, emotional and behavioural engagements). Conversely, suppression was found to have a small mediating effect between wellbeing and behavioural engagement of online learning only. No such effect was found on cognitive and emotional engagements. CONCLUSIONS: The findings provide evidence on the positive relationship between wellbeing and both the strategies of suppression and reappraisal during the pandemic. However, only reappraisal has positive impact on learning, suggesting the importance of effective regulation strategies on students' online engagement. Theoretical and practical implications of the findings are discussed.

Dietary Patterns and Intrinsic Capacity in Community-Dwelling Older Adults: A Cross-Sectional Study.

OBJECTIVES: Few studies have investigated the link between diet and intrinsic capacity (IC), and the potential sex difference in such association. This study examined the association between dietary patterns and IC and its sub-domains in Chinese community-dwelling older adults. DESIGN: Cross-sectional analysis using baseline data from the MrOs and MsOs study. SETTING: Community. PARTICIPANTS: Chinese community-dwelling older adults aged ≥65 years in Hong Kong. MEASUREMENTS: Dietary intake was assessed using a validated food frequency questionnaire and priori and posteriori dietary pattern scores were generated. IC including measures of cognitive, locomotor, vitality, sensory and psychological domains was assessed. Multiple logistic regression was performed to examine the associations between dietary pattern scores and the likelihood of greater IC and sub-domain scores with adjustment for sociodemographic and lifestyle factors. RESULTS: Data of 3730 participants (aged 72.2±5.0 years, 50.4% men) was available. In men, higher Diet Quality Index-International (DQI-I) and Okinawan diet scores, and lower "meat-fish" pattern scores were associated with greater IC. A higher DQI-I score was associated with greater locomotion, whereas higher "snacks-drinks-milk products" pattern score was associated with a greater sensory function. In women, none of the dietary pattern scores was associated with IC. Higher DQI-I score, Mediterranean-DASH Intervention for Neurodegenerative Delay Diet (MIND) score and "vegetables-fruits" pattern score were associated with greater psychological function. CONCLUSION: Various dietary patterns were associated with greater IC and its sub-domains in Chinese community-dwelling older adults, and more associations were observed in men than women. Strategies to improve diet and IC should take sex differences into account.

Interleukin-18 and COVID-19.

Vulnerability to coronavirus disease (COVID)-19 varies due to differences in interferon gamma (IFNγ) immunity. We investigated whether a key modifiable interferon precursor, interleukin-18, was related to COVID-19, overall and by severity, using Mendelian randomisation. We used four established genome-wide significant genetic predictors of interleukin-18 applied to the most recent genome-wide association study of COVID-19 (June 2021) to obtain Mendelian randomisation inverse variance weighted estimates by severity, i.e. any (cases = 112 612, non-cases = 2 474 079), hospitalised (cases = 24 274, non-cases = 2 061 529) and very severe (cases = 8779, non-cases = 1 001 875) COVID-19. To be comprehensive, we also conducted an exploratory analysis for IFNγ and two related cytokines with less well-established genetic predictors, i.e. interleukin-12 and interleukin-23. Genetically predicted interleukin-18 was associated with lower risk of any COVID-19 (odds ratio (OR) 0.96 per standard deviation, 95% confidence interval (0.94-0.99, P-value 0.004)) and of very severe COVID-19 (OR 0.88, 95% CI 0.78-0.999, P-value 0.048). Sensitivity analysis and a more liberal genetic instrument selection gave largely similar results. Few genome-wide significant genetic predictors were available for IFNγ, interleukin-12 or interleukin-23, and no associations with COVID-19 were evident. Interleukin-18 could be a modifiable target to prevent COVID-19 and should be further explored in an experimental design.

Prospective Analysis of Fruit and Vegetable Variety on Health Outcomes in Community-Dwelling Chinese Older Adults.

OBJECTIVES: Evidence on the topic regarding fruit and vegetable (FV) variety and health outcomes among older adults is limited. This study explored the prospective association of fruit variety, vegetable variety and combined FV variety with the risk of sarcopenia, frailty, all-cause and cause-specific mortality in community-dwelling Chinese older adults. DESIGN: Prospective cohort study. SETTING: Community. PARTICIPANTS: Community-dwelling Chinese older adults aged ≥65 years in Hong Kong. MEASUREMENTS: Fruit variety, vegetable variety and combined FV variety at baseline were assessed using a validated food frequency questionnaire and the variety scores were stratified into tertiles. Sarcopenia (Asian Working Group for Sarcopenia 2019), frailty (Cardiovascular Health Study) and all-cause and cause-specific mortality (retrieved from an official database) were assessed at 14-year follow-up. Adjusted binary logistic regression or Cox proportional hazards model were performed to examine the association of fruit variety, vegetable variety and combined FV variety with each health outcome. Data are presented as hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Baseline dietary data of 3992 participants (median age: 72 years (interquartile range: 68-76), 49.9% women) was available. There were 436 and 371 participants who were newly identified as having sarcopenia and frailty respectively, and 1654 all-cause mortality, 367 cardiovascular diseases (CVD) mortality and 534 cancer mortality over 14-year. Tertiles of fruit variety, vegetable variety and combined FV variety were not associated with sarcopenia, frailty, CVD mortality and cancer mortality. Participants in the highest tertile of fruit variety (HR 0.81, 95% CI 0.70-0.95, p-trend 0.010), vegetable variety (HR 0.77, 95% CI 0.67-0.89, p-trend <0.001) and combined FV variety (HR 0.77, 95% CI 0.67-0.89. p-trend <0.001) showed lower risk of all-cause mortality compared with participants in the lowest tertile. CONCLUSION: Among community-dwelling Chinese older adults, FV variety was not associated with sarcopenia, frailty, CVD mortality and cancer mortality over 14-year. Higher fruit variety, vegetable variety and combined FV variety were associated with a lower risk of all-cause mortality. Promoting a wide FV variety might be recommended to benefit the health and longevity of this population.

Predictive Value of the GLIM Criteria in Chinese Community-Dwelling and Institutionalized Older Adults Aged 70 Years and Over.

OBJECTIVES: The Global Leadership Initiative on Malnutrition (GLIM) has recently published criteria for classifying malnutrition. This study investigated the associations between malnutrition and adverse outcomes, and identified which component(s) of the GLIM criteria is/are risk factor(s) of adverse outcomes in Chinese older adults. DESIGN: A prospective cohort study of Chinese older adults in a healthy ageing study. SETTING: Participants' place of residence. PARTICIPANTS: Community-dwelling and institutionalized Chinese older adults aged ≥70 years living in Hong Kong. MEASUREMENTS: Malnutrition at baseline was classified according to selected GLIM criteria. Adverse outcomes including poor self-rated health, functional limitation (Barthel Index), falls, frailty (FRAIL scale), hospitalization and mortality were assessed after a 3-year follow-up. Associations between malnutrition and components of selected GLIM criteria (weight loss, low body mass index (BMI), low muscle mass and disease burden) and each adverse outcome were examined using adjusted binary logistic regression and Cox proportional hazards model. Odds ratio (OR) or hazard ratio (HR) and 95% confidence interval (CI) are presented. RESULTS: Data of 1576 community-dwelling (45.5% female, 78.1±6.5 years) and 427 institutionalized (69.6% female, 85.5±6.4 years) older adults were included at baseline. Among community-dwelling older adults, malnutrition was associated with frailty (n=899, OR: 2.44, 95% CI: 1.05-5.70) and mortality (n=1007, HR: 1.37, 95% CI: 1.12-1.66). No association was found for other outcomes. Among institutionalized older adults, malnutrition was not associated with any outcomes. Low BMI and low muscle mass were risk factors of frailty; while weight loss was a risk factor of mortality in community-dwelling older adults. Weight loss and disease burden were risk factors of mortality among institutionalized older adults. CONCLUSION: The association between malnutrition and frailty and mortality was observed in community but not in institutional settings. Further studies are required to draw more definitive conclusions on the use of GLIM criteria in institutional settings.

Investigating pleiotropic effects of statins on ischemic heart disease in the UK Biobank using Mendelian randomisation.

We examined whether specifically statins, of the major lipid modifiers (statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and ezetimibe) have pleiotropic effects on ischemic heart disease (IHD) via testosterone in men or women. As a validation, we similarly assessed whether a drug that unexpectedly likely increases IHD also operates via testosterone. Using previously published genetic instruments we conducted a sex-specific univariable and multivariable Mendelian randomization study in the UK Biobank, including 179918 men with 25410 IHD cases and 212080 women with 12511 IHD cases. Of these three lipid modifiers, only genetically mimicking the effects of statins in men affected testosterone, which partly mediated effects on IHD. Correspondingly, genetically mimicking effects of anakinra on testosterone and IHD presented a reverse pattern to that for statins. These insights may facilitate the development of new interventions for cardiovascular diseases as well as highlighting the importance of sex-specific explanations, investigations, prevention and treatment.

Effects of transforming growth factor-ß1 on plasminogen activation in stem cells from the apical papilla: role of activating receptor-like kinase 5/Smad2 and mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signalling.

AIM: To study the effects of TGF-ß1 on the plasminogen activation (PA) system of stem cells from the apical papilla (SCAP) and its signalling. METHODOLOGY: SCAP cells were isolated from the apical papilla of immature permanent teeth extracted for orthodontic reasons. They were exposed to various concentration of TGF-ß1 with/without pretreatment and coincubation by SB431542 (ALK/Smad2/3 inhibitor), or U0126 (MEK/ERK inhibitor). MTT assay, Western blotting and enzyme-linked immunosorbent assay (ELISA) were used to detect their effects on cell viability, and the protein expression of plasminogen activator inhibitor-1 (PAI-1), urokinase-type plasminogen activator (uPA), uPA receptor (uPAR) and their secretion. The paired Student's t-test was used for statistical analysis. RESULTS: TGF-ß1 significantly stimulated PAI-1 and soluble uPAR (suPAR) secretion of SCAP cells (P < 0.05), whereas uPA secretion was inhibited. Accordingly, TGF-ß1 induced both PAI-1 and uPAR protein expression of SCAP cells. SB431542 (an ALK5/Smad2/3 inhibitor) pretreatment and coincubation prevented the TGF-ß1-induced PAI-1 and uPAR of SCAP. U0126 attenuated the TGF-ß1-induced expression/secretion of uPAR, but not PAI-1 in SCAP. SB431542 reversed the TGF-ß1-induced decline of uPA. CONCLUSIONS: TGF-ß1 may affect the repair/regeneration activities of SCAP via differential increase or decrease of PAI-1, uPA and uPAR. These effects induced by TGF-ß1 are associated with ALK5/Smad2/3 and MEK/ERK activation. Elucidation the signalling pathways and effects of TGF-ß1 is useful for treatment of immature teeth with open apex by revascularization/revitalization procedures and tissue repair/regeneration.

Rapid muscle volume prediction using anthropometric measurements and population-derived statistical models.

Knowledge of subject-specific muscle volumes may be used as surrogates for evaluating muscle strength and power generated by 'fat-free' muscle mass. This study presents population-based statistical learning approaches for predicting 'fat-free' muscle volume from known anthropometric measurements. Using computed tomography (CT) imaging data to obtain lower-limb muscle volumes from 50 men and women, this study evaluated six statistical learning methods for predicting muscle volumes from anthropometric measurements: (i) stepwise regression, (ii) linear support vector machine (SVM), (iii) 2nd-order polynomial SVM, (iv) linear partial least squares regression (PLSR), (v) quadratic PLSR, and (vi) 3rd-order spline fit PLSR. These techniques have successfully been demonstrated in bioengineering applications and freely available in open-source toolkits. Analysis revealed that separating a general population into sexes and/or cohorts based on adipose level may improve prediction accuracies. The most important measures that statistically influence muscle volume predictions were shank girth, followed by sex and finally leg length, as identified using stepwise regression. SVM learning predicted muscle volume with an accuracy of 85 ± 4% when using linear interpolation, but performed poorly with an accuracy of 59 ± 6% using polynomial interpolation. The simpler linear PLSR exhibited muscle volume prediction accuracy of 87 ± 2%, while quadratic PLSR was slightly reduced at 82 ± 3%. For the spline fit PLSR, high accuracy was observed on the training data set (~ 99%) but over-fitting (a drawback of high-interpolation methods) resulted in erroneous predictions on testing data, and hence, the model was deemed unsuitable. In conclusion, use of linear PLSR models with variables of sex, leg length, and shank girth is a useful tool for predicting 'fat-free' muscle volume.

Relationship between lower lumbar spine shape and patient bone metabolic activity as characterised by 18F NaF bio-markers.

Chronic lower lumbar pain has been associated with elevated bone metabolic activity in the spine. Diagnosis of bone metabolic activity is currently through integrating Positron Emission Tomography (PET) with Sodium Fluoride (18F-NaF) biomarkers. It has been reported that numerous observable pathologies including lumbar fusion, disc abnormalities and scoliosis have often been associated with increased 18F-NaF uptake. The aim of this study was to identify what features of lower lumbar shape most strongly correlate with 18F-NaF uptake. Following a principal component analysis of 23 patients who presented with lumbar pain and underwent 18F-NaF PET-CT, it was revealed that three modes interpreted as (i) sacral tilt, (ii) vertebral disc spacing and (iii) spine size were the three characteristics that described 88.7% of spine shape in our study population. 18F-NaF was described by two modes including 18F-NaF intensity and spatial variation (anterior-inferior to posterior-superior). 18F-NaF was most sensitive to sacral tilt followed by vertebral disc spacing. A predictive model derived from that spine population was able to predict 18F-NaF 'hot-spot' locations with 85 ±â€¯5% accuracy and with 71 ±â€¯3% accuracy for the 18F-NaF magnitude. These results suggest that patients reporting with lower lumbar pain and who present with increased sacral tilt profiles and/or reduced disc spacing are good candidates for further 18F-NaF PET-CT imaging, evidenced by the high association between those shape profiles and 18F-NaF uptake.

Uterine Fibroid Symptom and Health-related Quality of Life Questionnaire: a Chinese translation and validation study.

INTRODUCTION: The Uterine Fibroid Symptom and Health-related Quality of Life (UFS-QOL) questionnaire is a validated tool in English language to assess treatment outcomes for women with fibroids. We performed a Chinese (traditional) translation and cultural adaptation of it and evaluated its reliability, validity, and responsiveness. METHODS: Overall, 223 Chinese women aged ≥18 years with uterine fibroids self-administered the UFS-QOL, Short-Form Health Survey-12, pictorial blood loss assessment chart (PBAC), and a visual analogue scale (VAS) on fibroid-related symptom severity. Demographics and haemoglobin levels were recorded; physical examination and ultrasound for size of fibroids were performed. Half of the women were followed up 6 months later for responsiveness. RESULTS: Cronbach's alpha coefficients ranged from 0.706 to 0.937, demonstrating high internal reliability. The intra-class correlation coefficients to measure test-retest reliability implied excellent stability of symptom scores (0.819, P<0.001), health-related quality of life scores (0.897, P<0.001), and all subscales (range 0.721-0.870, P<0.001). Convergent validity was demonstrated by positive correlations between the findings of various symptom severity assessment tools (PBAC, VAS on fibroid-related symptoms severity) and the symptom severity domain of Chinese UFS-QOL. In addition, there were positive correlations between health-related quality of life scores of Chinese UFS-QOL and the corresponding subscales of the Short-Form Health Survey-12. Responsiveness was shown by reduction of symptom severity scores and improvement of health-related quality of life scores after treatment. CONCLUSIONS: The Chinese version of the UFS-QOL is valid, reliable, and responsive to changes after treatment.

Reporting and guidelines for mendelian randomization analysis: A systematic review of oncological studies.

BACKGROUND: Mendelian randomization (MR) analyses have been increasingly used to seek evidence of causal associations. This systematic review aims at characterizing and evaluating the reporting of MR analyses in oncological studies. METHODS: The PubMed database was searched to identify MR cancer studies until December 31, 2017. Two of the authors independently selected and evaluated reporting quality of the studies. Reporting quality in MR studies before 2016 and in 2016/17 was compared. RESULTS: Cancer studies with MR analyses in 2016 and 2017 accounted for 55.8% of the total number of studies identified. In the 77 eligible articles, 39 (50.6%) did not report subjects' characteristics, 53 (68.8%) did not conduct power estimation, 40 (51.9%) did not state all of the first three MR assumptions (i.e., genetic instrument is associated with exposure, is not associated with confounders, and acts on outcome only through exposure), and 31 (40.3%) did not exclude SNPs that diverged from Hardy-Weinberg equilibrium. More studies estimated power in 2016/2017 than before 2016 (p = 0.028). CONCLUSIONS: Some MR cancer studies did not sufficiently report essential information, posing obstacles for critical appraisal. This study proposes for MR analysis a guideline/checklist for future publications in cancer and other biomedical research.

Parental consanguinity in Hong Kong.

INTRODUCTION: Consanguineous union increases the risk of genetic disorders in offspring. The present study aimed to evaluate the prevalence and characteristics of parental consanguinity in Hong Kong, and its effects on pregnancy, perinatal, and child health outcomes. METHODS: Pregnant women in consanguineous unions attending an obstetrics unit at a public hospital in Hong Kong were retrospectively studied. Their pregnancy, perinatal, and child health outcomes were compared with an ethnicity-matched control group of pregnant women in non-consanguineous unions. RESULTS: The overall prevalence of parental consanguinity was 0.6% (first cousins or closer, 78.4%; beyond first cousins, 21.6%). The majority were ethnic Pakistani (85.0%). Women in consanguineous unions were more likely to have an obstetric history of congenital abnormality (10.5%), unexplained intrauterine fetal demise (4.2%) and unexplained neonatal death (4.6%), or family history of congenital abnormality (4.6%). Offspring of consanguineous parents had significantly higher risk of recessive diseases (odds ratio [OR]=8.70, 95% confidence interval [CI]=1.06-71.36), structural abnormalities (OR=4.55, 95% CI=2.17-9.53) and developmental delay (OR=6.72, 95% CI=1.48-30.63), and significantly higher incidence of autistic spectrum disorder (2.1%; P=0.008). CONCLUSIONS: It is essential that information on the increased risks associated with parental consanguinity is included in genetic counselling for consanguineous couples, so that they can make informed decisions.

Non-surgical treatment of knee osteoarthritis.

Knee osteoarthritis is one of the most common degenerative diseases causing disability in elderly patients. Osteoarthritis is an increasing problem for ageing populations, such as that in Hong Kong. It is important for guidelines to be kept up to date with the best evidence-based osteoarthritis management practices available. The aim of this study was to review the current literature and international guidelines on non-surgical treatments for knee osteoarthritis and compared these with the current guidelines in Hong Kong, which were proposed in 2005. Internationally, exercise programmes for non-surgical management of osteoarthritis have been proven effective, and a pilot programme in Hong Kong for comprehensive non-surgical knee osteoarthritis management has been successful. Long-term studies on the effectiveness of such exercise programmes are required, to inform future changes to guidelines on osteoarthritis management.