Osteoarthriris year in review 2023: genetics, genomics, and epigenetics.

OBJECTIVE: To elucidate the scientific advances made in the last 12 months within the realm of osteoarthritis genetics, genomics, and epigenetics. This review paper highlights major research publications that enhance our current understanding of the role of genetics, genomics, and epigenetics in osteoarthritis. METHODS: A systematic literature search was conducted on pubmed.ncbi.nlm.nih.gov on "March 17, 2023", using the following keywords: "osteoarthritis" in combination with any of these terms: "genetic(s)", "mutation(s)", "genomic(s)", "epigenetic(s)", "DNA methylation", "noncoding RNA", "lncRNA", "circular RNA", "microRNA", "transcriptomic(s)", "RNA sequencing", "single cell RNA sequencing", or "single nucleus RNA sequencing". The selection comprised original research articles published in the English language between the OARSI congresses of 2022 and 2023. RESULTS: A total of 2178 research articles were identified, which subsequently reduced to 67 unique articles relevant to the field. Current trends in osteoarthritis genetics research involve meta-analyses of various cohorts to explore the impact of gene variants on osteoarthritis-related outcomes, such as pain. Early developmental changes within the joint were also found to influence osteoarthritis through genetic variations. Researchers also prioritize testing the mechanisms and functions of miRNAs, circRNAs, and lncRNAs. Potential drug targets began to emerge; however, independent validation studies are lacking. Single cell RNA sequencing studies revealed unique immune cell populations in the knee; however, no study reported single nucleus RNA sequencing analysis. CONCLUSIONS: This review focused on recent advances in the above-mentioned themes within the field of osteoarthritis. These advances improve our understanding of the disease's complexity and guide us toward functional assessments of genetic/epigenetic outcomes and toward their translational and clinical applications.

Organisational values of National Health Service trusts in England: semantic analysis and relation to performance indicators.

BACKGROUND: Organisational values are widely assumed to have positive effects on performance and staff. National Health Service (NHS) trusts in England have accordingly chosen their own organisational values. However, there has been no survey of the values adopted, and there is little evidence that the choice of values per se has consequences for outcomes. We comprehensively described trusts' organisational values, using natural language processing to identify common themes. We tested whether the choice of themes was associated with outcomes for patients and staff. METHODS: We collected data on trusts' values (from their websites), performance (Summary Hospital-level Mortality Indicator (SHMI) statistics, Care Quality Commission (CQC) ratings), sickness absence rates (SAR) and staff opinions (NHS Staff Survey responses). We first characterised values based on lexical properties then progressed to semantic analysis, using Google's Universal Sentence Encoder, to transform values to high-dimensional embeddings, and k-means clustering of embeddings to semantically cluster values into 12 common themes. We tested for associations between trusts' use of these themes and outcomes. RESULTS: Organisational values were obtained for 221 of 228 NHS trusts, with 985 values in total (480 unique). Semantic clustering identified themes including 'care', 'value respect' and 'togetherness'. There was no significant association between themes and SHMI or CQC ratings. However, themes predicted trusts' SAR (p=0.001, R2=0.159), with use of 'care', 'value respect', 'aspirational' and 'people' all significant predictors of increased sickness absence; themes also predicted staff opinions on 'Equality, diversity and inclusion' (p=0.011, R2=0.116), but with 'supportive' and 'openness' predicting more negative responses. CONCLUSION: A trust's adoption of individualised organisational values does not seem to make a positive difference to its patients or staff. These findings should give NHS managers pause for thought, challenging them to reconsider their reliance on value-defining initiatives, and to seek evidence that a focus on values has measurable benefits on outcomes.

Health, Lifestyle, and Psycho-Social Determinants of Poor Sleep Quality During the Early Phase of the COVID-19 Pandemic: A Focus on UK Older Adults Deemed Clinically Extremely Vulnerable.

Background: Several studies have assessed the impact of COVID-19-related lockdowns on sleep quality across global populations. However, no study to date has specifically assessed at-risk populations, particularly those at highest risk of complications from coronavirus infection deemed "clinically-extremely-vulnerable-(COVID-19CEV)" (as defined by Public Health England). Methods: In this cross-sectional study, we surveyed 5,558 adults aged ≥50 years (of whom 523 met criteria for COVID-19CEV) during the first pandemic wave that resulted in a nationwide-lockdown (April-June 2020) with assessments of sleep quality (an adapted sleep scale that captured multiple sleep indices before and during the lockdown), health/medical, lifestyle, psychosocial and socio-demographic factors. We examined associations between these variables and sleep quality; and explored interactions of COVID-19CEV status with significant predictors of poor sleep, to identify potential moderating factors. Results: Thirty-seven percent of participants reported poor sleep quality which was associated with younger age, female sex and multimorbidity. Significant associations with poor sleep included health/medical factors: COVID-19CEV status, higher BMI, arthritis, pulmonary disease, and mental health disorders; and the following lifestyle and psychosocial factors: living alone, higher alcohol consumption, an unhealthy diet and higher depressive and anxiety symptoms. Moderators of the negative relationship between COVID-19CEV status and good sleep quality were marital status, loneliness, anxiety and diet. Within this subgroup, less anxious and less lonely males, as well as females with healthier diets, reported better sleep. Conclusions: Sleep quality in older adults was compromised during the sudden unprecedented nation-wide lockdown due to distinct modifiable factors. An important contribution of our study is the assessment of a "clinically-extremely-vulnerable" population and the sex differences identified within this group. Male and female older adults deemed COVID-19CEV may benefit from targeted mental health and dietary interventions, respectively. This work extends the available evidence on the notable impact of lack of social interactions during the COVID-19 pandemic on sleep, and provides recommendations toward areas for future work, including research into vulnerability factors impacting sleep disruption and COVID-19-related complications. Study results may inform tailored interventions targeted at modifiable risk factors to promote optimal sleep; additionally, providing empirical data to support health policy development in this area.

Hypopharyngeal pepsin and Sep70 as diagnostic markers of laryngopharyngeal reflux: preliminary study.

INTRODUCTION: The management of laryngopharyngeal reflux (LPR) has been challenging. Hypopharyngeal multichannel intraluminal impedance (HMII) has shown to increase the sensitivity in diagnosing LPR. The objective of this study is to investigate the potential use of pepsin and Sep70 as diagnostic tools for detection of LPR in combination with HMII. MATERIALS AND METHODS: Tissue samples of hypopharynx, distal esophagus, and gastric cardia were collected from patients with LPR symptoms regardless of gastroesophageal reflux (GERD) diagnosis and underwent HMII to detect LPR and high esophageal reflux (HER: reflux 2 cm distal to upper esophageal sphincter) events. Patients were classified into two groups based on the presence of abnormal proximal exposure (APE), which was defined as LPR ≥1/day and/or HER ≥5/day: (1) positive-APE and (2) negative-APE. Patients with typical GERD symptoms without LPR symptoms who did not undergo HMII were used as a "control" GERD group. Protein was isolated from tissue samples and Western blot analysis of pepsin and Sep70 was performed. Pepsinogen was used as a control to differentiate pepsin from pepsinogen. Relative quantitation was performed using Image Studio Lite Software with normalization against the internal actin of each blot. RESULTS: From October 2012 to September 2013, 55 patients underwent HMII. Of 55, 20 patients underwent biopsies from hypopharynx (17 positive-APE and 3 negative-APE). Ten patients with typical GERD symptoms were identified from tissue bank as a "control" GERD group. Pepsin was detected in distal esophagus and hypopharynx in all groups without significant difference among groups. However, Sep70 in distal esophagus and hypopharynx was significantly depleted in the positive-APE group compared to the other groups (p = 0.032 and 0.002, respectively). CONCLUSION: Depletion of Sep70 with the presence of pepsin in the hypopharynx may indicate cellular injury in laryngopharynx due to constant proximal reflux. However, the normative data for these markers have to be validated.