Osteoarthritis year in review 2022: Genetics, genomics and epigenetics.

This "year in review" provides a summary of the research findings on the topic of genetics, genomics and epigenetics for osteoarthritis (OA) between Mar 2021-Apr 2022. A search routine of the literature in PubMed for the keyword, osteoarthritis, together with topics on genetics, genomics, epigenetics, polymorphism, Deoxyribonucleic acid (DNA) methylation, noncoding RNA, lncRNA, proteomics, and single cell RNA sequencing, returned key research articles and relevant reviews. Following filtering of duplicates across search routines, 695 unique research articles and 112 reviews were identified. We manually curated these articles and selected 90 as references for this review. However, we were unable to refer to all these articles, and only used selected articles to highlight key outcomes and trends. The trend in genetics is on the meta-analysis of existing cohorts with comparable genetic and phenotype characterization of OA; in particular, clear definition of sub phenotypes to enhance the genetic power. Further, many researchers are realizing the power of big data and multi-omics approaches to gain molecular insights for OA, and this has opened innovative approaches to include transcriptomics and epigenetics data as quantitative trait loci (QTLs). Given that most of the genetic loci for OA are not located within coding regions of genes, implying the impact is likely to be on gene regulation, epigenetics is a hot topic, and there is a surge in studies relating to the role of miRNA and long non-coding RNA on cartilage biology and pathology. The findings are exciting and new insights are provided in this review to summarize a year of research and the road map to capture all new innovations to achieve the desired goal in OA prevention and treatment.

Fibrotic-like changes in degenerate human intervertebral discs revealed by quantitative proteomic analysis.

OBJECTIVE: Intervertebral disc degeneration (IDD) can lead to symptomatic conditions including sciatica and back pain. The purpose of this study is to understand the extracellular matrix (ECM) changes in disc biology through comparative proteomic analysis of degenerated and non-degenerated human intervertebral disc (IVD) tissues of different ages. DESIGN: Seven non-degenerated (11-46 years of age) and seven degenerated (16-53 years of age) annulus fibrosus (AF) and nucleus pulposus (NP) samples were used. Proteins were extracted using guanidine hydrochloride, separated from large proteoglycans (PGs) by caesium chloride (CsCl) density gradient ultracentrifugation, and identified using liquid chromatography (LC) coupled with tandem mass spectrometry (MS/MS). For quantitative comparison, proteins were labeled with iTRAQ reagents. Collagen fibrils in the NP were assessed using scanning electron microscopy (SEM). RESULTS: In the AF, quantitative analysis revealed increased levels of HTRA1, COMP and CILP in degeneration when compared with samples from older individuals. Fibronectin showed increment with age and degeneration. In the NP, more CILP and CILP2 were present in degenerated samples of younger individuals. Reduced protein solubility was observed in degenerated and older non-degenerated samples correlated with an accumulation of type I collagen in the insoluble fibers. Characterization of collagen fibrils in the NP revealed smaller mean fibril diameters and decreased porosity in the degenerated samples. CONCLUSIONS: Our study identified distinct matrix changes associated with aging and degeneration in the intervertebral discs (IVDs). The nature of the ECM changes, together with observed decreased in solubility and changes in fibril diameter is consistent with a fibrotic-like environment.

An integrative review of experiences of patients with rheumatoid arthritis.

AIM: To provide an overview of evidence on the experiences and needs of adults living with rheumatoid arthritis (RA). BACKGROUND: Many research have studied the impact of RA on one's quality of life, but no reviews have examined the overall experiences of patients living with RA. METHODS: An integrative review was performed to synthesize the experiences and/or needs of adult patients with RA based on articles retrieved from databases of CINAHL, Scopus, PubMed, PsycINFO and Web of Science, and published between January 2003 and March 2014 in English. RESULTS: A total of 38 studies were reviewed. RA has adverse effects on patients' quality of life due to its negative impacts in their physical and psychosocial aspects of health. Patients with RA cope with these impacts using various methods and are frequent users of healthcare services. However, few studies have evaluated patients' further needs in coping or the effectiveness of their coping mechanisms, and patients' experiences with health care. CONCLUSION: This review provides evidence for healthcare professionals to gain a better understanding of RA patients' experiences and needs. Future studies can explore interventions that will enhance the quality of current healthcare practices and ultimately improve patients' quality of life. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Establishing a positive healthcare professional-patient relationship is crucial and healthcare professionals are in a position to provide greater informational and emotional support to patients. Policy makers and healthcare organizations need to look into ways to enhance the healthcare services to better suit RA patients' needs.

An outbreak of refrigerant-induced acute hepatitis in Hong Kong.

We report a cluster of acute hepatitis in five air-conditioning maintenance workers following accidental exposure to 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123). They presented to us with complaints of feverishness, generalised malaise, and epigastric discomfort. Their blood biochemistry tests were compatible with acute hepatitis. Viral hepatitis serology, tests for autoimmune hepatitis, and analyses for drugs and alcohol consumption were all negative. No focal hepatic lesion was detected by ultrasound imaging. Percutaneous liver biopsy samples were taken from two of them. The patients were managed with supportive treatment. All had spontaneous, but slow, recovery. Their liver function tests returned to normal after 4 months and their outcomes were favourable. Physicians should be aware of this occupational disease entity.

A meta-analysis on dose-response relationship between night shift work and the risk of breast cancer.

This study aimed to conduct a systematic review to sum up evidence of the associations between different aspects of night shift work and female breast cancer using a dose-response meta-analysis approach. We systematicly searched all cohort and case-control studies published in English on MEDLINE, Embase, PSYCInfo, APC Journal Club and Global Health, from January 1971 to May 2013. We extracted effect measures (relative risk, RR; odd ratio, OR; or hazard ratio, HR) from individual studies to generate pooled results using meta-analysis approaches. A log-linear dose-response regression model was used to evaluate the relationship between various indicators of exposure to night shift work and breast cancer risk. Downs and Black scale was applied to assess the methodological quality of included studies. Ten studies were included in the meta-analysis. A pooled adjusted relative risk for the association between 'ever exposed to night shift work' and breast cancer was 1.19 [95% confidence interval (CI) 1.05-1.35]. Further meta-analyses on dose-response relationship showed that every 5-year increase of exposure to night shift work would correspondingly enhance the risk of breast cancer of the female by 3% (pooled RR = 1.03, 95% CI 1.01-1.05; Pheterogeneity < 0.001). Our meta-analysis also suggested that an increase in 500-night shifts would result in a 13% (RR = 1.13, 95% CI 1.07-1.21; Pheterogeneity = 0.06) increase in breast cancer risk. This systematic review updated the evidence that a positive dose-response relationship is likely to present for breast cancer with increasing years of employment and cumulative shifts involved in the work.

Cognitive predictors for five-year conversion to dementia in community-dwelling Chinese older adults.

BACKGROUND: This study evaluates which cognitive measure is best for predicting incident dementia in a population-based random sample of Chinese older adults without dementia over a five-year period. METHODS: A total of 787 community-dwelling Chinese older adults without dementia in Hong Kong were assessed at baseline (T0), at two years (T1), and at five years (T2). RESULTS: The annual conversion rate to dementia was 1.6% and 6.3% for baseline normal participants and baseline mild cognitive impairment (MCI) participants, respectively. The Cantonese version of Mini-mental State Examination (CMMSE) scores declined significantly over time. In participants who progressed to dementia, Category Verbal Fluency Test (CVFT) scores dropped significantly from T0 to T1. A 1-SD drop of either CMMSE or CVFT in two years predicted dementia at five years with 91.5% sensitivity and 62.0% specificity. A stable CMMSE and CVFT at two years predicted a 91% chance of not progressing to clinical dementia at five years. CONCLUSION: In this community sample of Chinese older adults, a decline in cognitive screening tests in short term (two years) offered useful information in predicting dementia conversion over a longer period.

Reward System in Late-Life Depression: a Cross-Sectional Case-Control Study.

OBJECTIVE: Anhedonia, commonly defined as a reduced ability to feel pleasure, is a core clinical symptom of late-life depression (LLD). Deficits in reward processing are hypothesised to be associated with anhedonia. We examined differences in reward sensitivity between patients with LLD and healthy controls and explored the associations between LLD-related symptomatology, global cognition, and the reward system. METHODS: The reward responsiveness of 63 patients with LLD and 58 healthy controls aged ≥60 years was assessed using the probabilistic reward learning task with an asymmetric reward schedule. RESULTS: Compared with healthy controls, patients with LLD displayed lower response bias and reward learning. Global cognition of all participants was positively correlated with response bias. In patients with LLD, anhedonia severity explained impaired reward learning. CONCLUSION: A deficit in reward processing is implicated in patients with LLD. Our findings suggest that executive dysfunction and anhedonia contribute to lower sensitivity to reward learning in patients with LLD.

DNA methylation age in paired tumor and adjacent normal breast tissue in Chinese women with breast cancer.

BACKGROUND: Few studies have examined epigenetic age acceleration (AA), the difference between DNA methylation (DNAm) predicted age and chronological age, in relation to somatic genomic features in paired cancer and normal tissue, with less work done in non-European populations. In this study, we aimed to examine DNAm age and its associations with breast cancer risk factors, subtypes, somatic genomic profiles including mutation and copy number alterations and other aging markers in breast tissue of Chinese breast cancer (BC) patients from Hong Kong. METHODS: We performed genome-wide DNA methylation profiling of 196 tumor and 188 paired adjacent normal tissue collected from Chinese BC patients in Hong Kong (HKBC) using Illumina MethylationEPIC array. The DNAm age was calculated using Horvath's pan-tissue clock model. Somatic genomic features were based on data from RNA sequencing (RNASeq), whole-exome sequencing (WES), and whole-genome sequencing (WGS). Pearson's correlation (r), Kruskal-Wallis test, and regression models were used to estimate associations of DNAm AA with somatic features and breast cancer risk factors. RESULTS: DNAm age showed a stronger correlation with chronological age in normal (Pearson r = 0.78, P < 2.2e-16) than in tumor tissue (Pearson r = 0.31, P = 7.8e-06). Although overall DNAm age or AA did not vary significantly by tissue within the same individual, luminal A tumors exhibited increased DNAm AA (P = 0.004) while HER2-enriched/basal-like tumors exhibited markedly lower DNAm AA (P = < .0001) compared with paired normal tissue. Consistent with the subtype association, tumor DNAm AA was positively correlated with ESR1 (Pearson r = 0.39, P = 6.3e-06) and PGR (Pearson r = 0.36, P = 2.4e-05) gene expression. In line with this, we found that increasing DNAm AA was associated with higher body mass index (P = 0.039) and earlier age at menarche (P = 0.035), factors that are related to cumulative exposure to estrogen. In contrast, variables indicating extensive genomic instability, such as TP53 somatic mutations, high tumor mutation/copy number alteration burden, and homologous repair deficiency were associated with lower DNAm AA. CONCLUSIONS: Our findings provide additional insights into the complexity of breast tissue aging that is associated with the interaction of hormonal, genomic, and epigenetic mechanisms in an East Asian population.

Clinical and molecular characterization of diffuse large B-cell lymphomas with 13q14.3 deletion.

BACKGROUND: Deletions at 13q14.3 are common in chronic lymphocytic leukemia and are also present in diffuse large B-cell lymphomas (DLBCL) but never in immunodeficiency-related DLBCL. To characterize DLBCL with 13q14.3 deletions, we combined genome-wide DNA profiling, gene expression and clinical data in a large DLBCL series treated with rituximab, cyclophosphamide, doxorubicine, vincristine and prednisone repeated every 21 days (R-CHOP21). PATIENTS AND METHODS: Affymetrix GeneChip Human Mapping 250K NspI and U133 plus 2.0 gene were used. MicroRNA (miRNA) expression was studied were by real-time PCR. Median follow-up of patients was 4.9 years. RESULTS: Deletions at 13q14.3, comprising DLEU2/MIR15A/MIR16, occurred in 22/166 (13%) cases. The deletion was wider, including also RB1, in 19/22 cases. Samples with del(13q14.3) had concomitant specific aberrations. No reduced MIR15A/MIR16 expression was observed, but 172 transcripts were significantly differential expressed. Among the deregulated genes, there were RB1 and FAS, both commonly deleted at genomic level. No differences in outcome were observed in patients treated with R-CHOP21. CONCLUSIONS: Cases with 13q14.3 deletions appear as group of DLBCL characterized by common genetic and biologic features. Deletions at 13q14.3 might contribute to DLBCL pathogenesis by two mechanisms: deregulating the cell cycle control mainly due RB1 loss and contributing to immune escape, due to FAS down-regulation.

Comparison of empirical continuous positive airway pressure (CPAP) treatment versus initial portable sleep monitoring followed by CPAP treatment for patients with suspected obstructive sleep apnoea.

BACKGROUND: Polysomnography is labour-intensive for diagnosing obstructive sleep apnoea (OSA). We compared two algorithms for initiating continuous positive airway pressure (CPAP) treatment for patients with suspected OSA. METHODS: Symptomatic OSA patients were randomised into either algorithm I or II. Algorithm I consisted of an empirical CPAP trial whereas algorithm II utilised an Apnea Risk Evaluation System, a wireless device applied on the forehead, for establishing a diagnosis before a CPAP trial for 3 weeks. Primary outcome was success of CPAP trial, defined as CPAP usage > 4 h/night and willingness to continue CPAP. Subjective usefulness of CPAP, accuracy of Apnea Risk Evaluation System versus polysomnography and CPAP adherence at 6 months were secondary end-points. RESULTS: Altogether 138 patients in algorithm I and 110 patients in algorithm II completed the CPAP trial. There were no significant differences between these algorithms with respect to the primary end-point. The sensitivity and specificity of algorithm I versus II as a diagnostic test for OSA were 0.3, 0.8 versus 0.31, 1.00 respectively. In predicting CPAP adherence at 6 months, the likelihood ratio positive for algorithms I and II was 2.7 and 5.27 respectively. The mean (SE) time taken from the first consultation to the end of CPAP trial in algorithm I and algorithm II was 60 (2) and 98 (5) days, respectively, P < 0.01. CONCLUSION: An ambulatory approach with portable sleep monitoring for diagnosing OSA before a CPAP trial can identify more patients who would adhere to CPAP at 6 months than empirical CPAP treatment alone.

Hopes and fears regarding care robots: Content analysis of newspapers in East Asia and Western Europe, 2001-2020.

Background: As a type of welfare technology, care robotics is now widely seen as a potential aide to rehabilitation, increasing independence and enhancing the wellbeing of people with disabilities and older adults. Research into and development of care robots have both been vigorously promoted in North America, Europe and Asia, and the competition for technological advancement in robotics is becoming fierce. AI ethics and policy guidelines are being established. However, there are still differences in attitudes and perceptions, as well as national policies regarding this type of welfare technology. Moreover, despite the anticipated usefulness, it is believed that progress has been slow in the diffusion of care robots. Purpose: In order to explore how public discourses support technological innovation, such as care robots, while preparing society for potential risks and impact, we sought to ascertain whether public discourse on care robots varies from region to region. For example, what are the hopes and promises associated with care robots and what are the concerns? Methods: To address these questions, this article explored how care robots have been portrayed in five major broadsheet newspapers in five jurisdictions in Asia and Europe (France, Great Britain, Hong Kong SAR, Ireland and Japan). We obtained 545 articles for the period between January 2001 and September 2020, more than half of which originated in Japan. A thematic analysis was conducted of these articles written in four languages (Chinese, English, French and Japanese). Results: Positive and negative narratives were teased out, alongside other key prominent themes identified, such as Japan as the land of robots, the pandemic, and the impact of robots on the economy. As the number of robot-related articles grew from the year 2012 onwards, narratives became more nuanced in European newspapers, but not in Asian ones. Furthermore, recent articles began to address the social and relational impact of care robots, while providing concrete examples of improvements in the quality of life for users. Further careful examination will be necessary in the future in order to establish the impact of robotics use in rehabilitation for people with disabilities, older adults, their carers and society at large.

Associations between Preserved Foods and Breast Cancer Risk in Hong Kong Chinese Women.

Preserved food such as cured foods may contain nitrate and nitrite that may contribute to the breast cancer development. Evidence on the associations between these preserved food intakes and risk of breast cancer is sparse. This study aimed to examine the associations between preserved foods (i.e., cured meat, pickled vegetables, canned meat, and canned fruit/vegetables) and breast cancer risk in Hong Kong Chinese women. A total of 1,307 breast cancer cases and 1,050 age-matched controls were recruited from three hospitals during November 2011 through January 2018. We used a standardized questionnaire to collect information on dietary factors, including preserved foods. Unconditional multiple logistic regression was performed to calculate the adjusted odds ratio (AOR) of breast cancer in relation to preserved food with adjustment of potential confounders. We further performed stratified analysis according to the breast cancer biology subtypes. We found that cured meat consumption was significantly associated with the risk of breast cancer [AOR, 1.32; 95% confidence interval 95% (CI), 1.06-1.64]. Compared with no cured meat consumption, cured meat intake ≥ once per week was associated with an AOR of 2.66 (95% CI, 1.38-5.35). Women with canned fruit/vegetable ≥ consumption once per week had a higher risk of breast cancer (OR, 1.19; 95% CI, 1.00-1.41), particularly for the HER2-positive subtypes, but it became borderline after adjustment of confounders. Our study reveals a positive association between consumption of cured meat and breast cancer risk in Chinese population. Cured meat intake might be a potential novel risk factor for breast cancer but this would have to be confirmed by large prospective cohort studies. PREVENTION RELEVANCE: The main finding of this case-control study, an association between cured meat intake and a higher risk of breast cancer in Hong Kong Chinese women, contributes to the growing evidence for population-level health benefits of reducing cured meat consumption.

Stromal gene signatures in large-B-cell lymphomas.

BACKGROUND: The addition of rituximab to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), or R-CHOP, has significantly improved the survival of patients with diffuse large-B-cell lymphoma. Whether gene-expression signatures correlate with survival after treatment of diffuse large-B-cell lymphoma is unclear. METHODS: We profiled gene expression in pretreatment biopsy specimens from 181 patients with diffuse large-B-cell lymphoma who received CHOP and 233 patients with this disease who received R-CHOP. A multivariate gene-expression-based survival-predictor model derived from a training group was tested in a validation group. RESULTS: A multivariate model created from three gene-expression signatures--termed "germinal-center B-cell," "stromal-1," and "stromal-2"--predicted survival both in patients who received CHOP and patients who received R-CHOP. The prognostically favorable stromal-1 signature reflected extracellular-matrix deposition and histiocytic infiltration. By contrast, the prognostically unfavorable stromal-2 signature reflected tumor blood-vessel density. CONCLUSIONS: Survival after treatment of diffuse large-B-cell lymphoma is influenced by differences in immune cells, fibrosis, and angiogenesis in the tumor microenvironment.

Suicidal Risk in Older Patients with Depression During COVID-19 Pandemic: a Case-Control Study.

OBJECTIVES: To compare older adults with late-life depression (LLD) and healthy controls in terms of suicidal ideation during the COVID-19 pandemic, and to determine predictors of suicidal ideation. METHODS: Between March and April 2020, old adults diagnosed with major depressive disorder (single or recurrent episode) as defined by the DSM-5 were recruited from psychiatric clinics or inpatient wards, whereas 31 healthy older adults without a history of depression or other psychiatric illnesses were recruited from voluntary organisations or elderly community centres. Their depressive symptoms, perceived severity of the pandemic, perceived time spent on receiving related information, perceived health, levels of loneliness, perceived coping efficacy, suicidal ideation, and the level of symptomatic responses to a specific traumatic stressor in the past week were assessed. RESULTS: In total, 21 men and 43 women aged 61 to 89 years were interviewed through telephone by trained research assistants. Of them, 33 were older adults with LLD (cases) and 31 were healthy older adults (controls). Older people with LLD had a higher level of suicidal ideation than healthy controls, after controlling for the level of depression and medical comorbidity (F (1, 59) = 5.72, p = 0.020). Regression analyses showed that coping efficacy and loneliness accounted for a significant portion of the variance in suicidal ideation, and loneliness significantly predicted the level of stress. Mediation analyses reveal an indirect effect between group and suicidal ideation through coping efficacy (Z = 2.43, p = 0.015). CONCLUSIONS: Older people with LLD are at increased suicidal risk and require timely mental health support. Coping efficacy and loneliness are important predictors for suicidal ideation and stress.

Mindfulness-Based Cognitive Therapy for Late-Life Depression: a Randomised Controlled Trial.

BACKGROUND: Rumination and overgeneral autobiographical memory are dysfunctional cognitions commonly found in older adults with depression. The theoretical underpinnings of mindfulness-based cognitive therapy (MBCT) address the ruminative tendencies and the non-specific retrieval of autobiographical memories. This study aims to examine the efficacy and cognitive mechanisms of MBCT in older adults with active depressive symptoms. METHODS: 57 older adults (mean age, 70 years) with normal cognition and mild to moderate depressive symptoms were randomly allocated to either the MBCT group or the active control group for 8 weeks. The MBCT group consisted of eight 2-hour weekly sessions and a 7-hour full-day retreat, with different themes for each class, guided mindfulness exercises, feedback and discussion, homework review, and psychoeducation. The active control group comprised a 1-hour physical exercise and a standardised health education of the specific theme with group discussion (eg fall prevention, chronic pain). Participants were assessed before and after the 8-week intervention for four outcome measures: the Hamilton Depression Rating Scale (HAMD), the Ruminative Response Scale (RRS), the Autobiographical Memory Test (AMT), and the Mindful Attention Awareness Scale (MAAS). RESULTS: There was a significant reduction in severity of depressive symptoms (HAMD score) in both the MBCT group (F(1, 27) = 35.9, p < 0.001, η2 = 0.57) and the active control group (F(1, 28) = 9.29, p < 0.01, η2 = 0.24), but only the MBCT group showed substantial improvements in autobiographical memory specificity (AMT score), rumination (RRS score), and mindfulness (MAAS score). CONCLUSION: Although both MBCT and active control programme decrease the severity of depressive symptoms in older adults, only MBCT improves AMS, rumination, and mindfulness. Our findings provide empirical support for the theoretical underpinnings of MBCT. Older adults with more severe depression and more severe dysfunctional cognition may benefit more from the specific therapeutic effects of MBCT.

Cognitive Stimulation for Persons with Dementia: a Systematic Review and Meta-Analysis.

OBJECTIVE: We aim to provide an up-to-date systematic review and meta-analysis of the effects of cognitive stimulation (CS) on cognition, depressive symptoms, and quality of life in persons with dementia. Factors affecting the treatment effect were examined. METHODS: A literature search was performed on databases of MEDLINE, EMBASE, PsycINFO, CINAHL Plus, and Cochrane Library up to 7 March 2019. Only randomised controlled trials investigating the effects of CS in persons with dementia were included. The outcome measures were cognitive function, depressive symptoms, and quality of life. RESULTS: 20 randomised controlled trials with a total of 1251 participants (intervention group: 674; control group: 577) were included for meta-analysis. Most participants had mild to moderate dementia. CS had a significant positive small-to-moderate effect on cognition (Hedges's g = 0.313, p < 0.001). Heterogeneity of CS was low to moderate (Q=30.5854, df=19, p < 0.05, I2 = 37.877%). Inconclusive results were found for depressive symptoms and quality of life. CONCLUSION: CS has a significant positive effect on cognitive function, but its effect on depressive symptoms and quality of life was inconclusive. Future studies with more robust methodology establishing evidence of its efficacy are required.