A randomized controlled trial of a behavioral activation intervention to increase engagement with life and wellbeing in older adults.

INTRODUCTION: Engagement with life is central to ageing well. There is currently a lack of flexible programs for promoting engagement that tailor to the unique interests, capacities, and life circumstances of individuals. We designed and evaluated a new program for promoting engagement with later life based on principles of behavioral activation. METHODS: A total of 135 adults aged 65 and older who scored at or below the median on the Life Engagement Test were randomly assigned to either a 6-week behavioral activation program (n = 69); or a 6-week well-being program based on brief positive psychology interventions (the active control; n = 66). Participants completed assessments at baseline, 1-week follow-up and 3-month follow-up. The primary outcome was engagement with life, and secondary outcome measures included social network characteristics, measures of mental health, well-being, and psychological and self-regulatory resources. RESULTS: Participants in both conditions showed improvements in engagement with life post-intervention that were sustained at 3-months. Post-intervention improvements in both conditions were observed across most secondary outcomes; however, for several outcomes, participants with more limited functional and cognitive resources benefitted from participation in the positive psychology (active control) condition, but not the treatment condition. CONCLUSION: Similar levels of improvement in engagement with life and well-being were evident for participants who completed a behavioral activation-focused intervention, compared with participants who completed a positive psychology focused intervention. The positive psychology approach may confer greater benefits for emotional well-being among those with poorer functional and cognitive abilities.

Health Care Needs of Individuals with Parkinson's Disease Living in Eastern North Carolina: Insights for Multidisciplinary Care and Telemedicine.

Parkinson's disease (PD) is a complex condition, and individuals living in rural areas often face challenges accessing the specialized care they require. To better understand the specific healthcare needs of individuals with PD in Eastern North Carolina (ENC), the present study investigated three key areas: access to a multidisciplinary care team, access to PD-specific resources, and access to resources for establishing telemedicine services. Participants were recruited through email invitations to Parkinson's Foundation members and the distribution of postcards in the region, and 106 individuals with PD in ENC completed the online survey. Only 28.3% of respondents reported access to an interdisciplinary care team, with approximately 50% stating that their healthcare provider had not informed them of the availability of such a team. Nevertheless, the quality of care received was generally perceived as high, and 41.5% of participants were part of a PD support group. Approximately half of the respondents expressed a willingness to have telemedicine appointments with a movement disorder specialist. These findings offer valuable insights for healthcare providers and policymakers in rural areas to better understand the needs of people with PD. Several strategies, including community building and increased access to telemedicine, are recommended to address these needs.

Self-Compassion, Stressor Exposure, and Negative Affect: A Daily Diary Study of Older Adults.

OBJECTIVES: Self-compassion has been identified as a psychological resource for aging well. To date, self-compassion among older adults has typically been conceptualized as a trait variable. This study examined whether day-to-day (state) variability in self-compassion was associated with negative affective reactivity to daily stressors. METHODS: Daily diary assessment methods were used to examine the potential moderating role of between- and within-person self-compassion on the relationship between daily stressors and negative affect. A community-based sample of 107 older adults aged 65+ completed questionnaires once daily over 14 days. RESULTS: Multilevel modeling revealed that 37% of the variance in self-compassion occurred within persons. Daily self-compassion moderated the relationship between daily stressor exposure and daily negative affect. On days with greater stressor exposure than usual, older adults showed less negative affective reactivity on days when self-compassion was higher, compared with days when self-compassion was lower. No moderating effects were observed for between-person (trait) self-compassion. DISCUSSION: These findings suggest that self-compassion in older adults should be conceptualized as both state and trait variables and that state self-compassion may be protective in the stress-reactivity pathway. Future research should investigate whether brief self-compassion interventions might help older adults to avoid or downregulate negative emotions in response to stressors.

Engage! a pilot study of a brief behavioural activation program to promote engagement and well-being in older adults.

Previous research has indicated the suitability of behavioural activation (BA) as an intervention for reducing depression in older adults. However, little research has investigated the potential of BA to increase active engagement and well-being in older adults. The current pilot study sought to investigate the usefulness and acceptability of BA to promote well-being in a group of non-clinical older adults. Participants (N = 18) aged between 65 and 86 (M = 77.82, SD = 5.59) who were retired and living independently in the community were provided a 6-week BA program predominantly delivered online. Treatment retention, self-ratings, and participants' compliance to treatment principles indicate preliminary feasibility for the use of BA as an approach for increasing active engagement in older adult populations. Participants also provided feedback on their experiences with the program post-intervention via individual structured interviews. Thematic analysis of these data revealed that participants found the program to be beneficial in terms of increased self-awareness and social engagement, and provided several recommendations for improving acceptability of the program and workbook. The unexpected events relating to the first wave of the novel coronavirus (COVID-19) led to necessary adaptations to delivery modalities, and provided the researchers with an opportunity to investigate the use of a structured well-being program on a high-risk population during a pandemic. Our findings support the proposition that BA is a suitable intervention for increasing engagement and well-being in older adults, provide insight into adapting programs for older adults, and suggest next steps for testing intervention efficacy.

Enhancing Pain Management for Open Inguinal Hernia Repair With a Novel Long-Acting Bupivacaine Drug Device (Xaracoll®) in Multimodal Pain Control: A Quality Improvement Initiative to Reduce Post-Operative Opioid Prescribing.

Background Xaracoll® is a Food and Drug Administration (FDA) approved Type 1 Bovine collagen-based bupivacaine hydrochloride (HCl) implant developed to provide postoperative pain management for up to 24 hours after open inguinal hernia repair in adults. This retrospective review examined the efficacy of Xaracoll® in the management of postoperative pain compared to injectable Bupivacaine. Methods This retrospective study examines 54 patients who underwent unilateral open inguinal hernia repair by a single surgeon over three years. The control group consisted of 36 patients who received injectable Bupivacaine as the local anesthetic. Eighteen patients received the Xaracoll® drug device intra-operatively following the FDA-approved manufacturer's guidelines. Intra-operative analgesics administered and quantified by oral morphine equivalents (OME), opioid administration for pain control postoperatively, opioid prescriptions upon discharge, postoperative pain scores, and turnaround time (TAT) were compared. Results The use of Xaracoll® in inguinal hernia repair is associated with a decrease in the rate of opioid administration in the post-anesthesia care unit (PACU) (22.2% vs. 52.8%; p = 0.043). In addition, patients requiring opioids in the outpatient setting needed significantly less OME in the Xaracoll® group compared to the control group (52.50 vs. 136.15; p < .001). Conclusion This study demonstrates compelling evidence that Xaracoll® is a useful analgesia adjuvant for inguinal hernia repair, significantly reducing the need for opioids in the PACU and decreasing doses of opioid medications upon discharge. Xaracoll® is effective in minimizing postoperative pain and opioid medication dosages upon discharge as part of a multimodal approach to pain and improving patient experience. Further research is warranted to evaluate Xaracoll®'s role in pain control in the PACU and on discharge.

Unraveling the molecular interactions between α7 nicotinic receptor and a RIC3 variant associated with backward speech.

Recent work putatively linked a rare genetic variant of the chaperone Resistant to Inhibitors of acetylcholinesterase (RIC3) (NM_024557.4:c.262G > A, NP_078833.3:p.G88R) to a unique ability to speak backwards, a language skill that is associated with exceptional working memory capacity. RIC3 is important for the folding, maturation, and functional expression of α7 nicotinic acetylcholine receptors (nAChR). We compared and contrasted the effects of RIC3G88R on assembly, cell surface expression, and function of human α7 receptors using fluorescent protein tagged α7 nAChR and Förster resonance energy transfer (FRET) microscopy imaging in combination with functional assays and 125I-α-bungarotoxin binding. As expected, the wild-type RIC3 protein was found to increase both cell surface and functional expression of α7 receptors. In contrast, the variant form of RIC3 decreased both. FRET analysis showed that RICG88R increased the interactions between RIC3 and α7 protein in the endoplasmic reticulum. These results provide interesting and novel data to show that a RIC3 variant alters the interaction of RIC3 and α7, which translates to decreased cell surface and functional expression of α7 nAChR.

Fatty acid elongation regulates mitochondrial ß-oxidation and cell viability in prostate cancer by controlling malonyl-CoA levels.

Recently, the fatty acid elongation enzyme ELOVL5 was identified as a critical pro-metastatic factor in prostate cancer, required for cell growth and mitochondrial homeostasis. The fatty acid elongation reaction catalyzed by ELOVL5 utilizes malonyl-CoA as the carbon donor. Here, we demonstrate that ELOVL5 knockdown causes malonyl-CoA accumulation. Malonyl-CoA is a cellular substrate that can inhibit fatty acid ß-oxidation in the mitochondria through allosteric inhibition of carnitine palmitoyltransferase 1A (CPT1A), the enzyme that controls the rate-limiting step of the long chain fatty acid ß-oxidation cycle. We hypothesized that changes in malonyl-CoA abundance following ELOVL5 knockdown could influence mitochondrial ß-oxidation rates in prostate cancer cells, and regulate cell viability. Accordingly, we find that ELOVL5 knockdown is associated with decreased mitochondrial ß-oxidation in prostate cancer cells. Combining ELOVL5 knockdown with FASN inhibition to increase malonyl-CoA abundance endogenously enhances the effect of ELOVL5 knockdown on prostate cancer cell viability, while preventing malonyl-CoA production rescues the cells from the effect of ELOVL5 knockdown. Our findings indicate an additional role for fatty acid elongation, in the control of malonyl-CoA homeostasis, alongside its established role in the production of long-chain fatty acid species, to explain the importance of fatty acid elongation for cell viability.

Complications and Healthcare Costs Associated With the First Year Following Colostomy and Ileostomy Formation: A Retrospective Study.

PURPOSE: The purpose of this study was to evaluate clinical and economic outcomes during the first year following ostomy formation. DESIGN: Single-center retrospective audit. SUBJECTS AND SETTING: The sample comprised 200 patients who underwent surgery leading to ileostomy or colostomy at a large English National Health Service (NHS) Trust. METHODS: Clinical complications, medicine prescriptions, and interactions with healthcare services were reported over 12 months postsurgery, and interactions with the NHS were matched to the closest NHS unit cost to determine mean patient cost. RESULTS: The most common ostomy-related surgical site complications were high output (35.0%; n = 70), followed by moderate/severe peristomal skin complications (24.5%; n = 49) and bleeding (23.5%; n = 47). Ostomy management-related complications included general difficulties with ostomy management (50.0%; n = 100) and leakage-related mild peristomal skin issues (48.5%; n = 97). Clinical complication rates were highest in the first quarter following ostomy formation, except parastomal hernia, which increased in incidence over time. Ileostomy patients more frequently experienced high output, acute renal failure, and ostomy management-related complications and had increased length of inpatient admission. However, healthcare resource use was high in both groups, with a median of 13 inpatient admission days and 12 outpatient contacts overall within the first year. Mean cost per patient was £20,444.60 (US $26,018.41); 90.5% of these costs were attributed to ostomy-related factors. CONCLUSIONS: Patients are likely to experience at least one clinical complication following intestinal ostomy formation and have multiple interactions with the NHS. While a number of complications are more frequent in patients with ileostomies, both groups experienced considerable costs within the first year following surgery associated with ostomy management and recovery.

Sexually Transmitted Infections and the Risk of Reinfection Within 12 Months: A Population-Based Cohort.

BACKGROUND: Chlamydia, gonorrhea, and syphilis are common sexually transmitted infections that disproportionately affect specific groups in New Zealand (NZ). Predictors of reinfection are not well studied in NZ but could inform public health strategies to decrease sexually transmitted infection (STI) incidence. METHODS: New Zealand-wide chlamydia, gonorrhea, and syphilis cases during 2019 were identified using nationally collected data. Cases were followed-up to identify reinfection with the same STI within 12 months of initial infections. Logistic regression models were used to identify predictors for each STI reinfection. RESULTS: Determinants identified for increased odds of chlamydia reinfection were age groups 16-19 and 20-24 years, females, Maori and Pacific peoples, cases in the Northern region, and cases with at least one test before the initial infection. Age 40 years and older was associated with lower odds of gonorrhea reinfection, as was being of Asian ethnicity, living in Midland or Southern regions, and reporting heterosexual behavior. Region was the only statistically significant predictor for syphilis reinfection, with higher odds of reinfection for people living in the Central region. CONCLUSIONS: Our findings reflect disproportionate STI rates for some groups in NZ, with younger age groups, Maori and Pacific peoples, men who have sex with men, and people living in the Northern region experiencing higher odds of reinfection. Groups identified with higher odds for reinfection require increased access to culturally responsive health services to treat, understand, and prevent possible reinfection. Changes to current public health strategies could include culturally specific behavioral counseling, and improvements to and adherence to effective contract tracing.

Ozone-enabled fatty acid discovery reveals unexpected diversity in the human lipidome.

Fatty acid isomers are responsible for an under-reported lipidome diversity across all kingdoms of life. Isomers of unsaturated fatty acids are often masked in contemporary analysis by incomplete separation and the absence of sufficiently diagnostic methods for structure elucidation. Here, we introduce a comprehensive workflow, to discover unsaturated fatty acids through coupling liquid chromatography and mass spectrometry with gas-phase ozonolysis of double bonds. The workflow encompasses semi-automated data analysis and enables de novo identification in complex media including human plasma, cancer cell lines and vernix caseosa. The targeted analysis including ozonolysis enables structural assignment over a dynamic range of five orders of magnitude, even in instances of incomplete chromatographic separation. Thereby we expand the number of identified plasma fatty acids two-fold, including non-methylene-interrupted fatty acids. Detection, without prior knowledge, allows discovery of non-canonical double bond positions. Changes in relative isomer abundances reflect underlying perturbations in lipid metabolism.

Barriers to activity engagement in older adulthood: Results of a community survey.

OBJECTIVES: Losses that occur with age can create barriers to meaningful activity engagement, a crucial aspect of ageing well. Research on this topic is frequently qualitative, with few studies accessing large community samples. This study (a) assessed the frequency specific personal and environmental barriers (such as poor health and limited transport access), identified by older adults in previous research, were endorsed; (b) used latent class analysis (LCA) to identify population subgroups based on combinations of these barriers, and (c) examined associations of subgroups with purpose in life and quality of life. METHODS: Four hundred and thirty-two randomly selected Australian adults aged 65+ years (average age 76.7, 58% female) completed a telephone survey. They were asked whether certain barriers affected engagement and provided data on sense of purpose and quality of life. RESULTS: Physical health/mobility were the most frequently reported barriers, followed by sensory difficulties, financial limitations, and caring responsibilities. The LCA revealed up to three subgroups/classes of participants according to the barriers endorsed. Class 1 had low endorsement of all barriers, including physical health. The majority of Class 2 endorsed physical health barriers and other barriers more frequently than Class 1. Class 3 were comparable to Class 2, but also frequently endorsed community access barriers. Class 1 were younger and reported a greater sense of purpose and higher quality of life. CONCLUSIONS: Physical health/mobility barriers to engagement are those most frequently endorsed by older adults. These barriers may increase vulnerability to, or exacerbate the impact of additional barriers, such as sensory difficulties, access to transport and lack of finances.

A behavioural activation intervention to increase engagement with life and wellbeing in older adults: Study protocol for a randomised controlled trial.

BACKGROUND: Meaningful activity engagement is a critical element of ageing well. Interventions designed to increase activity engagement tend to be activity-specific and do not always meet the needs of older adults with diverse interests and capacities. Behavioural activation (BA) provides a promising person-centred framework for promoting engagement in valued activities. This study will examine the effectiveness of a behavioural activation-based intervention for promoting engagement with life and wellbeing among older adults. METHOD: Participants will be randomly allocated to one of two conditions (BA intervention, Active Control) and take part in a six-week intervention that consists of one-on-one weekly sessions of up to one hour to be administered either via telephone or online video conferencing with a trained facilitator. This study will recruit 120 + participants aged 65 + who score at or below the median on a test of life engagement. Participants will complete questionnaires of primary and secondary measures both pre-program, one-week and three months post-program. Participants will also complete a daily diary questionnaire during the fourth and fifth weeks of the intervention. The primary outcome measure is the Life Engagement Test, and secondary outcome measures include assessments of subjective wellbeing, psychological wellbeing, mental health, self-reported health, social engagement, loneliness and life satisfaction. DISCUSSION: The outcomes from this study will provide evidence as to whether a BA based approach represents an effective method for promoting engagement with life and wellbeing among older community-dwelling adults. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (Reg no. ACTRN 12621001192875). Trial retrospectively registered 6th September, 2021.

UCS Chaperone Folding of the Myosin Head: A Function That Evolved before Animals and Fungi Diverged from a Common Ancestor More than a Billion Years Ago.

The folding of the myosin head often requires a UCS (Unc45, Cro1, She4) domain-containing chaperone. Worms, flies, and fungi have just a single UCS protein. Vertebrates have two; one (Unc45A) which functions primarily in non-muscle cells and another (Unc45B) that is essential for establishing and maintaining the contractile apparatus of cardiac and skeletal muscles. The domain structure of these proteins suggests that the UCS function evolved before animals and fungi diverged from a common ancestor more than a billion years ago. UCS proteins of metazoans and apicomplexan parasites possess a tetratricopeptide repeat (TPR), a domain for direct binding of the Hsp70/Hsp90 chaperones. This, however, is absent in the UCS proteins of fungi and largely nonessential for the UCS protein function in Caenorhabditis elegans and zebrafish. The latter part of this review focusses on the TPR-deficient UCS proteins of fungi. While these are reasonably well studied in yeasts, there is little precise information as to how they might engage in interactions with the Hsp70/Hsp90 chaperones or might assist in myosin operations during the hyphal growth of filamentous fungi.

Monounsaturated Fatty Acids: Key Regulators of Cell Viability and Intracellular Signaling in Cancer.

Cancer cells feature increased macromolecular biosynthesis to support the formation of new organelles and membranes for cell division. In particular, lipids are key macromolecules that comprise cellular membrane components, substrates for energy generation and mediators of inter- and intracellular signaling. The emergence of more sensitive and accurate technology for profiling the "lipidome" of cancer cells has led to unprecedented leaps in understanding the complexity of cancer metabolism, but also highlighted promising therapeutic vulnerabilities. Notably, fatty acids, as lipid building blocks, are critical players in all stages of cancer development and progression and the importance of fatty acid desaturation and its impact on cancer cell biology has been well established. Recent years have seen the reports of new mechanistic insights into the role of monounsaturated fatty acids (MUFA) in cancer, as regulators of cell death and lipid-related cellular signaling. This commentary aims to highlight these diverse roles of MUFAs in cancer cells which may yield new directions for therapeutic interventions involving these important fatty acids.

Vitreous cytokine levels following the administration of a single 0.19 mg fluocinolone acetonide (ILUVIEN®) implant in patients with refractory diabetic macular edema (DME)-results from the ILUVIT study.

PURPOSE: To investigate the changes in vitreous inflammatory and angiogenic cytokine levels, primarily interleukin-(IL)-6, following intravitreal injection of the 0.19 mg fluocinolone acetonide (FAc, ILUVIEN®) implant in patients with diabetic macular edema. METHODS: A single-center phase IV study involving 12 patients' eyes with diabetic macular edema. Vitreous fluid samples were obtained prior to intravitreal injection of the fluocinolone acetonide implant and then again over a 6-month period. Vitreous samples were examined using a cytometric bead array to measure IL-6, IL-8, IP-10, MCP-1, VEGF, and CD54. PIGF and PEDF were measured using an enzyme-linked immunosorbent assay. Changes in the cytokine and chemokine expression patterns were analyzed. Clinical parameters such as BCVA and center point thickness (CPT) were also examined. RESULTS: There were mean reductions in all parameters between baseline and month 6. Significant changes (p < 0.05 versus baseline) were observed in the expression of IL-6, IP-10, MCP-1, and CD54 following the administration of fluocinolone acetonide implant. VEGF and PIGF increased at month 1 before declining at month 6, though this trend was not significant. CPT decreased rapidly between screening and the first follow-up visit, and this decrease was sustained. BCVA remained relatively stable throughout. CONCLUSION: This study demonstrated changes in vitreous inflammatory and angiogenic cytokine levels following intravitreal injection of the FAc implant in patients with diabetic macular edema. Data show that the fluocinolone acetonide implant led to rapid and sustained reductions of some inflammatory cytokines with improvement of the overall clinical picture.

Investigation of SARS-CoV-2 Transmission Associated With a Large Indoor Convention - New York City, November-December 2021.

During November 19-21, 2021, an indoor convention (event) in New York City (NYC), was attended by approximately 53,000 persons from 52 U.S. jurisdictions and 30 foreign countries. In-person registration for the event began on November 18, 2021. The venue was equipped with high efficiency particulate air (HEPA) filtration, and attendees were required to wear a mask indoors and have documented receipt of at least 1 dose of a COVID-19 vaccine.* On December 2, 2021, the Minnesota Department of Health reported the first case of community-acquired COVID-19 in the United States caused by the SARS-CoV-2 B.1.1.529 (Omicron) variant in a person who had attended the event (1). CDC collaborated with state and local health departments to assess event-associated COVID-19 cases and potential exposures among U.S.-based attendees using data from COVID-19 surveillance systems and an anonymous online attendee survey. Among 34,541 attendees with available contact information, surveillance data identified test results for 4,560, including 119 (2.6%) persons from 16 jurisdictions with positive SARS-CoV-2 test results. Most (4,041 [95.2%]), survey respondents reported always wearing a mask while indoors at the event. Compared with test-negative respondents, test-positive respondents were more likely to report attending bars, karaoke, or nightclubs, and eating or drinking indoors near others for at least 15 minutes. Among 4,560 attendees who received testing, evidence of widespread transmission during the event was not identified. Genomic sequencing of 20 specimens identified the SARS-CoV-2 B.1.617.2 (Delta) variant (AY.25 and AY.103 sublineages) in 15 (75%) cases, and the Omicron variant (BA.1 sublineage) in five (25%) cases. These findings reinforce the importance of implementing multiple, simultaneous prevention measures, such as ensuring up-to-date vaccination, mask use, physical distancing, and improved ventilation in limiting SARS-CoV-2 transmission, during large, indoor events.†.

Nests of dividing neuroblasts sustain interneuron production for the developing human brain.

The human cortex contains inhibitory interneurons derived from the medial ganglionic eminence (MGE), a germinal zone in the embryonic ventral forebrain. How this germinal zone generates sufficient interneurons for the human brain remains unclear. We found that the human MGE (hMGE) contains nests of proliferative neuroblasts with ultrastructural and transcriptomic features that distinguish them from other progenitors in the hMGE. When dissociated hMGE cells are transplanted into the neonatal mouse brain, they reform into nests containing proliferating neuroblasts that generate young neurons that migrate extensively into the mouse forebrain and mature into different subtypes of functional interneurons. Together, these results indicate that the nest organization and sustained proliferation of neuroblasts in the hMGE provide a mechanism for the extended production of interneurons for the human forebrain.

Patient reported experiences and treatment outcomes of orthodontic patients treated within secondary care settings in the South West of England during the COVID-19 pandemic.

OBJECTIVE: To assess the impact of the temporary cessation of orthodontic services on patients undergoing treatment during the COVID-19 pandemic. DESIGN: Two-phase multicentre service evaluation. SETTING: Secondary care orthodontic departments in the South West of England. MATERIALS AND METHODS: Phase 1 - Patient-Reported Experience Measure questionnaire (PREM). The questionnaire was distributed to patients who had undergone orthodontic treatment during the COVID-19 pandemic once services had resumed. Phase 2 - assessment of treatment outcomes, specifically with the Peer Assessment Rating (PAR) Index. A total of 280 PAR scores were obtained from a cohort of patients treated before and during the pandemic. RESULTS: A total of 711 PREM questionnaires were completed. Participants generally felt relaxed when visiting secondary care settings, orthodontic departments and whilst wearing orthodontic appliances during the pandemic. Nearly 40% of participants were concerned that the pandemic would impact on their treatment, particularly treatment length. Treatment outcomes revealed that patients treated before and during the pandemic experienced percentage PAR score reductions of 83.9% and 80.6%, respectively. Patients receiving treatment during the pandemic experienced longer treatment durations of 126 days. CONCLUSION: During the pandemic, low levels of anxiety were reported with respect to receiving orthodontic treatment in secondary care settings. Irrespective of the pandemic, a high standard of orthodontic treatment was provided. However, patient concerns regarding treatment length were justified.