Advances in Pain Medicine: a Review of New Technologies.

PURPOSE OF REVIEW: This narrative review highlights the interventional musculoskeletal techniques that have evolved in recent years. RECENT FINDINGS: The recent progress in pain medicine technologies presented here represents the ideal treatment of the pain patient which is to provide personalized care. Advances in pain physiology research and pain management technologies support each other concurrently. As new technologies give rise to new perspectives and understanding of pain, new research inspires the development of new technologies.

Validation of a clinical and genetic model for predicting severe COVID-19

Using nested case-control data from the Lifelines COVID-19 cohort, we undertook a validation study of a clinical and genetic model to predict the risk of severe COVID-19 in people with confirmed COVID-19 and in people with confirmed or self-reported COVID-19. The model performed well in terms of discrimination of cases and controls for all ages (area under the receiver operating characteristic curve [AUC] = 0.680 for confirmed COVID-19 and AUC = 0.689 for confirmed and self-reported COVID-19) and in the age group in which the model was developed (50 years and older; AUC = 0.658 for confirmed COVID-19 and AUC= 0.651 for confirmed and self-reported COVID-19). There was no evidence of over- or under-dispersion of risk scores but there was evidence of overall over-estimation of risk in all analyses (all P < 0.0001). In the light of large numbers of people worldwide remaining unvaccinated and continuing uncertainty regarding vaccine efficacy over time and against variants of concern, identification of people at high risk of severe COVID-19 may encourage the uptake of vaccinations (including boosters) and the use of non-pharmaceutical inventions.

Genetic associations with severe COVID-19

Identification of host genetic factors that predispose individuals to severe COVID-19 is important, not only for understanding the disease and guiding the development of treatments, but also for risk prediction when combined to form a polygenic risk score (PRS). Using population controls, Pairo-Castineira et al. identified 12 SNPs (a panel of 8 SNPs and a panel of 6 SNPs, with two SNPs in both panels) associated with severe COVID-19. Using controls with asymptomatic or mild COVID-19, we were able to replicate the association with severe COVID-19 for only three of their SNPs and found marginal evidence for an association for one other. When combined as an 8-SNP PRS and a 6-SNP PRS, we found no evidence of association with severe COVID-19. The difference in our results and the results of Pairo-Castineira et al. might be the choice of controls: population controls vs controls with asymptomatic or mild COVID-19.

Development and validation of a clinical and genetic model for predicting risk of severe COVID-19

Age, sex, and comorbidities are known risk factors for severe COVID-19 but are frequently considered independently and without accurate knowledge of the magnitude of their effects on risk. Single-nucleotide polymorphisms (SNPs) associated with risk of severe COVID-19 have appeared in the literature, but their application in predictive risk testing has not been validated. Reliance on age and sex alone to determine risk of severe COVID-19 will fail to accurately quantify risk. Here, we report the development and validation of a clinical and genetic model to predict risk of severe COVID-19 using confirmed SARS-CoV-2 positive participants from the UK Biobank. Our new model out-performed an age and sex model and had excellent discrimination and was well calibrated in the validation dataset. We also report validation studies of our prototype model and polygenic risk scores based on 8-SNP and 6-SNP panels identified in the literature. Accurate prediction of individual risk will be important in regions where vaccines are not widely available or where people refuse or are disqualified from vaccination, especially given uncertainty about the extent of infection transmission among vaccinated people and the emergence of SARS-CoV-2 variants of concern.

An integrated clinical and genetic model for predicting risk of severe COVID-19

BackgroundAge and gender are often the only considerations in determining risk of severe COVID-19. There is an urgent need for accurate prediction of the risk of severe COVID-19 for use in workplaces and healthcare settings, and for individual risk management. MethodsClinical risk factors and a panel of 64 single-nucleotide polymorphisms were identified from published data. We used logistic regression to develop a model for severe COVID-19 in 1,582 UK Biobank participants aged 50 years and over who tested positive for the SARS-CoV-2 virus: 1,018 with severe disease and 564 without severe disease. Model discrimination was assessed using the area under the receiver operating characteristic curve (AUC). ResultsA model incorporating the SNP score and clinical risk factors (AUC=0.786) had 111% better discrimination of disease severity than a model with just age and gender (AUC=0.635). The effects of age and gender are attenuated by the other risk factors, suggesting that it is those risk factors - not age and gender - that confer risk of severe disease. In the whole UK Biobank, most are at low or only slightly elevated risk, but one- third are at two-fold or more increased risk. ConclusionsWe have developed a model that enables accurate prediction of severe COVID-19. Continuing to rely on age and gender alone to determine risk of severe COVID-19 will unnecessarily classify healthy older people as being at high risk and will fail to accurately quantify the increased risk for younger people with comorbidities.

COVID-19 containment in the Caribbean: the experience of Small Island Developing States

BackgroundSmall island developing states (SIDS) have limited absolute resources for responding to national disasters, including health emergencies. Since the first confirmed case of COVID-19 in the Caribbean on 1st March 2020, non-pharmaceutical interventions (NPIs) have been widely used to control the resulting COVID-19 outbreak. We document the variety of government measures introduced across the Caribbean and explore their impact on aspects of outbreak control. MethodsDrawing on publically available information, we present confirmed cases and confirmed deaths to describe the extent of the Caribbean outbreak. We document the range of outbreak containment measures implemented by national Governments, focussing on measures to control movement and gatherings. We explore the temporal association of containment measures with the start of the outbreak in each country, and with aggregated information on human movement, using smartphone positioning data. We include a set of comparator countries to provide an international context. ResultsAs of 25th May, the Caribbean reported 18,755 confirmed cases and 631 deaths. There have been broad similarities but also variation in the number, the type, the intensity, and particularly the timing of the NPIs introduced across the Caribbean. On average, Caribbean governments began controlling movement into countries 27 days before their first confirmed case and 23 days before comparator countries. Controls on movement within country were introduced 9 days after the first case and 36 days before comparators. Controls on gatherings were implemented 1 day before the first confirmed case and 30 days before comparators. Confirmed case growth rates and numbers of deaths have remained low across much the Caribbean. Stringent Caribbean curfews and stay-at-home orders coincided with large reductions in community mobility, regularly above 60%, and higher than most international comparator countries. ConclusionStringent controls to limit movement, and specifically the early timing of those controls has had an important impact on containing the spread of COVID-19 across much of the Caribbean. Very early controls to limit movement into countries may well be particularly effective for small island developing states. With much of the region economically reliant on international tourism, and with steps to open borders now being considered, it is critical that the region draws on a solid evidence-base to balance the competing demands of economics and public health.

Disorder in convergent floral nanostructures enhances signalling to bees.

Diverse forms of nanoscale architecture generate structural colour and perform signalling functions within and between species. Structural colour is the result of the interference of light from approximately regular periodic structures; some structural disorder is, however, inevitable in biological organisms. Is this disorder functional and subject to evolutionary selection, or is it simply an unavoidable outcome of biological developmental processes? Here we show that disordered nanostructures enable flowers to produce visual signals that are salient to bees. These disordered nanostructures (identified in most major lineages of angiosperms) have distinct anatomies but convergent optical properties; they all produce angle-dependent scattered light, predominantly at short wavelengths (ultraviolet and blue). We manufactured artificial flowers with nanoscale structures that possessed tailored levels of disorder in order to investigate how foraging bumblebees respond to this optical effect. We conclude that floral nanostructures have evolved, on multiple independent occasions, an effective degree of relative spatial disorder that generates a photonic signature that is highly salient to insect pollinators.

Effect of a Randomized Controlled Trial Walking Program on Walking, Stress, Depressive Symptoms and Cardiovascular Biomarkers in Elderly Korean Immigrants

PURPOSE: Despite well-known benefits of walking on cardiovascular health, no structured walking exercise program has been formally tested on elderly Korean immigrants (EKIs). This pilot randomized controlled trial study assessed the effect of a walking program on walking behavior (pedometer steps count), stress (cortisol), depressive symptoms (CESD-10), and cardiovascular disease biomarkers (hs-CRP and fibrinogen) via venipuncture in EKIs. METHODS: Seventy EKIs recruited from a Korean community were randomly assigned to a 12-week walking group or control group in a 3:2 ratio. The working program included a pedometer, buddy, monthly coffee card, weekly call for goal setting, and physical activity consultation. Walking group EKIs maintained the Centers for Disease Control and Prevention recommended exercise guidelines and good mental health status over 12 weeks. RESULTS: There was no significant difference in the outcomes between control and walking groups. CONCLUSION: Social networking with Koreans in the senior center and church from a well-established Korean community might have positive effects on mental health.

Prevalence of Stress Urinary Incontinence in Women with Multiple Sclerosis / 대한배뇨장애요실금학회지

PURPOSE: The purpose of this study was to determine the prevalence of stress urinary incontinence (SUI) in women with multiple sclerosis (MS) and to what degree these women are bothered by their SUI, since there is a paucity of literature regarding the nature of SUI in this unique population of women. METHODS: We conducted a prospective Institutional Review Board approved study. Women scheduled for outpatient follow-up appointments at a dedicated MS center were asked to complete a questionnaire regarding urinary incontinence. Urgency urinary incontinence (UUI) and SUI were defined as an answer of slightly, moderately or greatly to the Urogenital Distress Inventory (UDI-6) question #2 and question #3, respectively. Impact of SUI on physical activity was determined by Incontinence Impact Questionnaire (IIQ-7) question #2. RESULTS: A total of 55.9% (80/143) women had SUI, 70.6% (101/143) women had UUI, and 44.8% (64/143) women had mixed urinary incontinence. The mean age was 45.8 years old (range, 20 to 72 years). Women with SUI were significantly older (mean, 47.2 vs. 41.9; P=0.023) and there was a trend towards a greater body mass index (mean, 29.3 vs. 26.5; P=0.057). Women with SUI had significantly higher IIQ-7 scores compared to women without SUI (P<0.001). Impact of urinary incontinence on physical activity was also found to be significantly greater in women with SUI (mean IIQ-7 question #2, 0.96 vs. 0.35; P<0.001). CONCLUSIONS: The prevalence of SUI in women with MS is 55.9% and the presence of SUI has a significant impact on their quality of life. A comprehensive urologic evaluation of a woman with MS should include assessment of SUI.

Etv5, an ETS transcription factor, is expressed in granulosa and cumulus cells and serves as a transcriptional regulator of the cyclooxygenase-2.

Etv4, Etv1, and Etv5 are members of Etv4 subfamily of E26 transformation-specific (Ets) transcription factors that are known to influence a host of biological processes. We previously showed that Etv5, expressed in Sertoli cells, plays a crucial role in maintaining spermatogonial stem cell niche in the mouse testis. However, it is not yet known whether Etv4 family members are expressed in the ovary or play any role in ovarian functions. Here, we show that Etv5 and Etv4 are expressed in mouse ovaries in granulosa and cumulus cells during folliculogenesis. Both Etv5 and Etv4 mRNAs are also detected in cumulus-oocyte complexes (COCs) and denuded oocytes. Notably, Etv4 is highly expressed in the cumulus cells of ovulated COCs at 16-h post-human chorionic gonadotropin. Cyclooxygenase-2 (PTGS2), a rate-limiting enzyme for prostaglandin synthesis, is critical for oocyte maturation and ovulation. Since several putative Ets-binding sites are present in the PTGS2 promoter, we examined whether Etv5 influences Ptgs2 transcriptional activity. Indeed, we found that addition of Etv5 increases the transcriptional activity of the 3.2-kb mouse Ptgs2 promoter by 2.5-fold in luciferase reporter assays. Collectively, the results show that Etv4 and Etv5 are expressed in granulosa and cumulus cells during folliculogenesis and ovulation, suggesting that they influence cellular events in the ovary by regulating downstream genes such as Ptgs2.

Developing novel treatments for mood disorders: accelerating discovery.

This review was generated from discussions by the Pharmacologic and Somatic Treatments Section of the National Institute of Mental Health Strategic Plan for Mood Disorders Committee on advancing novel pharmacologic and somatic treatments for mood disorders. The opening section of the article summarizes in broad strokes, current pharmacologic treatments, and new directions in the field. Thereafter the topics focus on specific research initiatives that could advance the current therapeutics for mood disorders including new basic and clinical research in vivo human imaging procedures, somatic therapeutics, and the vast new area of pharmacogenetics. New scientific and technical opportunities exist today based on advances in basic neuroscience, opportunities in clinical testing, industry interest in advancing central nervous system therapeutics, and on active consumer advocacy groups. The question of how to bring all of these positive forces together to accelerate discovery in mood disorder thera-peutics is the topic of this article.