Novel OX40 and 4-1BB Derived Spacers Enhance CD30 CAR Activity and Safety in CD30 Positive Lymphoma Models.

The chimeric antigen receptor (CAR) derived from the CD30 specific murine antibody, HRS-3, has produced promising clinical efficacy with a favorable safety profile in the treatment of relapsed or refractory CD30-positive lymphomas. However, persistence of the autologous CAR T cells was brief, and many patients relapsed a year after treatment. The lack of persistence may be attributed to the use of a wildtype IgG1 spacer that can associate with Fc receptors. We first identified the cysteine rich domain (CRD) 5 of CD30 as the primary binding epitope of HRS-3 and armed with this insight, attempted to improve the HRS-3 CAR functionality with a panel of novel spacer designs. We demonstrate that HRS-3 CARs with OX40 and 4-1BB derived spacers exhibited similar anti-tumor efficacy, circumvented interactions with Fc receptors and secreted lower levels of cytokines in vitro than a CAR employing the IgG1 spacer. Humanization of the HRS-3 scFv coupled with the 4-1BB spacer preserved potent on-target, on-tumor efficacy, and on-target, off-tumor safety. In a lymphoma mouse model of high tumor burden, T cells expressing a humanized HRS-3 CD30.CARs with the 4-1BB spacer potently killed tumors with low levels of circulating inflammatory cytokines, providing a promising candidate for future clinical development in the treatment of CD30-positive malignancies.

PRL1 and PRL3 promote macropinocytosis via its lipid phosphatase activity.

PRL1 and PRL3, members of the protein tyrosine phosphatase family, have been associated with cancer metastasis and poor prognosis. Despite extensive research on their protein phosphatase activity, their potential role as lipid phosphatases remains elusive. Methods: We conducted comprehensive investigations to elucidate the lipid phosphatase activity of PRL1 and PRL3 using a combination of cellular assays, biochemical analyses, and protein interactome profiling. Functional studies were performed to delineate the impact of PRL1/3 on macropinocytosis and its implications in cancer biology. Results: Our study has identified PRL1 and PRL3 as lipid phosphatases that interact with phosphoinositide (PIP) lipids, converting PI(3,4)P2 and PI(3,5)P2 into PI(3)P on the cellular membranes. These enzymatic activities of PRLs promote the formation of membrane ruffles, membrane blebbing and subsequent macropinocytosis, facilitating nutrient extraction, cell migration, and invasion, thereby contributing to tumor development. These enzymatic activities of PRLs promote the formation of membrane ruffles, membrane blebbing and subsequent macropinocytosis. Additionally, we found a correlation between PRL1/3 expression and glioma development, suggesting their involvement in glioma progression. Conclusions: Combining with the knowledge that PRLs have been identified to be involved in mTOR, EGFR and autophagy, here we concluded the physiological role of PRL1/3 in orchestrating the nutrient sensing, absorbing and recycling via regulating macropinocytosis through its lipid phosphatase activity. This mechanism could be exploited by tumor cells facing a nutrient-depleted microenvironment, highlighting the potential therapeutic significance of targeting PRL1/3-mediated macropinocytosis in cancer treatment.

Caregivers' experiences in helping individuals with severe and enduring mental health challenges integrate into the community: A qualitative descriptive study in Singapore.

WHAT IS KNOWN ABOUT THE SUBJECT: Individuals with severe and enduring mental health challenges continued to consume mental health services for an average of 13 years as they needed multiple acute psychiatric admissions due to the challenges they experienced in their everyday activities. As caregivers of individuals with severe and enduring mental health challenges, they often bear the brunt of caregiving through their assistance with activities of daily living (ADL), providing emotional support and ensuring medication compliance for their loved ones. When caring for their loved ones, caregivers often reported psychological stress, social isolation and emotional exhaustion due to stressors such as uncertainty of the future, the lack of support from professional services and the isolation from their own social network and support mechanism. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE: Insights from this study revealed that caregivers for individuals with severe and enduring mental health challenges went through a lonely and exhausting journey fraught with psychological, physical, social and financial challenges, echoing the caregiving needs and the prevalence of the caregiver burden. WHAT ARE THE IMPLICATIONS FOR PRACTICE: Insights shared by the caregivers demonstrated the need for a centralised point of contact to navigate Singapore's fragmented mental healthcare sector. Peer-support groups should be further promoted because they offer the benefits of information exchange, mutual support and a sense of empowerment and hopefulness, which may help ease the caregiver burden. Life skills training, such as teaching how to communicate empathetically with family members, resolve conflicts using open communication, maintain a structured daily routine and solve pragmatic problems in daily life, is more critical for individuals with severe and enduring mental health challenges. This will help them learn how to manage their well-being, live independently, and stabilise their conditions. Lastly, public awareness campaigns should honour caregivers by highlighting their strength, resilience, and dedication. The state can provide financial assistance in the form of tax relief for their income per annum or caregiver allowance to alleviate the financial stress that caregivers are facing. ABSTRACT: Introduction The progressive deinstitutionalisation of mental healthcare has increasingly shifted care responsibilities from healthcare professionals to family caregivers for individuals with severe mental illness. Caregivers must balance many obligations, which often compromise their overall health and well-being, while helping their loved ones integrate into the community. Aim To identify and understand caregivers' needs and challenges as they help individuals with severe and enduring mental health challenges integrate into the community. Methods This study used a descriptive qualitative approach to explore the experiences and challenges of caregivers for individuals with severe and enduring mental health challenges when integrating back into the community. A semi-structured guide was used during the video-conferencing interviews conducted between December 2021 and November 2022. This study was reported according to the 32-item Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist. Findings Fourteen caregivers were individually interviewed by the primary author. Most caregivers were female, with an average of 15 years of experience caring for their loved ones. Using Braun and Clark's six-phase thematic framework, we inductively generate the themes and subthemes from the data. The two themes were (i) challenges (whose subthemes included personal challenges in caregiving, the lack of awareness, and stigma and employment) and (ii) support (whose subthemes included the importance of socialisation for individuals with mental health conditions, existing avenues of support and potential areas for support). Discussion Our findings informed the contemporary needs of caregivers caring for individuals with severe and enduring mental health challenges integrating into the community. Like the global challenges for people with mental health issues, psychosocial support and other supplementary support are still common themes in mental health settings. The findings further specifically highlighted the importance of accessible points of contact as resources and employment-enabling and sustaining initiatives to help manage caregivers' emotional and system challenges, which addresses the gaps identified in the findings. Caregivers' peer-support groups, life skills training and public mental health awareness are also necessitated by the caregivers' voices. Implications for Practice Priority areas include having a centralised point of contact within the community for caregivers. Government or not-for-profit organisations can take the lead by initiating employment-enabling initiatives for individuals with severe and enduring mental health challenges and their caregivers.

Advancing equitable access to digital mental health in the Asia-Pacific region in the context of the COVID-19 pandemic and beyond: A modified Delphi consensus study.

The COVID-19 pandemic had an unprecedented impact on global mental health and well-being, including across the Asia-Pacific. Efforts to mitigate virus spread led to far-reaching disruption in the delivery of health and social services. In response, there was a rapid shift to the use of digital mental health (DMH) approaches. Though these technologies helped to improve access to care for many, there was also substantial risk of access barriers leading to increased inequities in access to mental health care, particularly among at-risk and equity-deserving populations. The objective of this study was to conduct a needs assessment and identify priorities related to equitable DMH access among at-risk and equity-deserving populations in the Asia Pacific region during the first year of the COVID-19 pandemic. The study consisted of a modified Delphi consensus methodology including two rounds of online surveys and online consultations with stakeholders from across the region. Study participants included policy makers, clinicians and service providers, and people with lived experience of mental health conditions. Results demonstrate that vulnerabilities to negative mental health impacts and access barriers were compounded during the pandemic. Access barriers included a lack of linguistically and culturally appropriate DMH options, low mental health literacy and poor access to technological infrastructure and devices, low levels of awareness and trust of DMH options, and lack of policies and guidelines to support effective and equitable delivery of DMH. Recommendations to improve equitable access include ensuring that diverse people with lived experience are engaged in research, co-design and policy development, the development and implementation of evidence-based and equity-informed guidelines and frameworks, clear communication about DMH evidence and availability, and the integration of DMH into broader health systems. Study results can inform the development and implementation of equitable DMH as its use becomes more widespread across health systems.

Overexpression of an Engineered SerpinB9 Enhances Allogeneic T-Cell Persistence and Efficacy.

Allogeneic chimeric antigen receptor (CAR)-expressing T cells offer many advantages over autologous therapies, but their benefits are curtailed by graft-versus-host disease (GvHD) and elimination by recipient immune cells. Moreover, just as with autologous therapies, allogeneic CAR T cells are susceptible to activation-induced cell death (AICD) caused by chronic antigen exposure (CAE). Granzyme B (GzmB) and Fas/FasL-initiated, caspase-mediated apoptosis are key mechanisms of T-cell death caused by T/NK cell-mediated allorejection or CAE. We explored a protective strategy of engineering CAR T cells to overexpress variants of the GzmB-specific serine protease inhibitor, SerpinB9 (SB9), to improve allogeneic T-cell persistence and antitumor efficacy. We showed that the overexpression of an SB9 variant with broadened caspase specificity, SB9(CAS), not only significantly reduced rejection of allogeneic CAR T cells, but also increased their resistance to AICD and enabled them to thrive better under CAE, thus improving allogeneic T-cell persistence and antitumor activity in vitro and in vivo. In addition, while SB9(CAS)-overexpression improved the efficacy of allogeneic CAR T-cell therapy by conferring protection to cell death, we did not observe any autonomous growth and the engineered CAR T cells were still susceptible to an inducible suicide switch. Hence, SB9(CAS)-overexpression is a promising strategy that can strengthen current development of cell therapies, broadening their applications to address unmet medical needs.

The network structures of mental and behavioral problems among children and adolescents in China using propensity score matching: A comparison between one-child and multi-child families based on a nationwide survey.

BACKGROUND: Exploring networks of mental and behavioral problems in children and adolescents may identify differences between one-child and multi-child families. This study compared the network structures of mental and behavioral problems in children and adolescents in one-child families versus multi-child families based on a nationwide survey. METHODS: Propensity score matching (PSM) was used to match children and adolescents from one-child families with those from multi-child families. Mental and behavioral problems were assessed using the Achenbach's Child Behavior Checklist (CBCL) with eight syndromal subscales. In the network analysis, strength centrality index was used to estimate central symptoms, and case-dropping bootstrap method was used to assess network stability. RESULTS: The study included 39,648 children and adolescents (19,824 from one-child families and 19,824 from multi-child families). Children and adolescents from multi-child families exhibited different network structure and higher global strength compared to those from one-child families. In one-child families, the most central symptoms were "Social problems", "Anxious/depressed" and "Withdrawn/depressed", while in multi-child families, the most central symptoms were "Social problems", "Rule-breaking behavior" and "Anxious/depressed". CONCLUSION: Differences in mental and behavioral problems among children and adolescents between one-child and multi-child families were found. To address these problems, interventions targeting "Social problems" and "Anxious/depressed" symptoms should be developed for children and adolescents in both one-child and multi-child families, while other interventions targeting "Withdrawn/depressed" and "Rule-breaking behavior" symptoms could be useful for those in one-child and multi-child families, respectively.

Prevalence and network structure of depression, insomnia and suicidality among mental health professionals who recovered from COVID-19: a national survey in China.

Psychiatric syndromes are common following recovery from Coronavirus Disease 2019 (COVID-19) infection. This study investigated the prevalence and the network structure of depression, insomnia, and suicidality among mental health professionals (MHPs) who recovered from COVID-19. Depression and insomnia were assessed with the Patient Health Questionnaire (PHQ-9) and Insomnia Severity Index questionnaire (ISI7) respectively. Suicidality items comprising suicidal ideation, suicidal plan and suicidal attempt were evaluated with binary response (no/yes) items. Network analyses with Ising model were conducted to identify the central symptoms of the network and their links to suicidality. A total of 9858 COVID-19 survivors were enrolled in a survey of MHPs. The prevalence of depression and insomnia were 47.10% (95% confidence interval (CI) = 46.09-48.06%) and 36.2% (95%CI = 35.35-37.21%), respectively, while the overall prevalence of suicidality was 7.8% (95%CI = 7.31-8.37%). The key central nodes included "Distress caused by the sleep difficulties" (ISI7) (EI = 1.34), "Interference with daytime functioning" (ISI5) (EI = 1.08), and "Sleep dissatisfaction" (ISI4) (EI = 0.74). "Fatigue" (PHQ4) (Bridge EI = 1.98), "Distress caused by sleep difficulties" (ISI7) (Bridge EI = 1.71), and "Motor Disturbances" (PHQ8) (Bridge EI = 1.67) were important bridge symptoms. The flow network indicated that the edge between the nodes of "Suicidality" (SU) and "Guilt" (PHQ6) showed the strongest connection (Edge Weight= 1.17, followed by "Suicidality" (SU) - "Sad mood" (PHQ2) (Edge Weight = 0.68)). The network analysis results suggest that insomnia symptoms play a critical role in the activation of the insomnia-depression-suicidality network model of COVID-19 survivors, while suicidality is more susceptible to the influence of depressive symptoms. These findings may have implications for developing prevention and intervention strategies for mental health conditions following recovery from COVID-19.

Incidence and Predictors for Recurrence of Ventricular Arrhythmia Presenting During Acute Myocarditis: A Multicenter Study.

BACKGROUND: Management of acute myocarditis (AM) patients experiencing ventricular arrhythmia (VA) during acute illness is controversial, especially regarding early implantable cardioverter-defibrillator (ICD) implantation. OBJECTIVES: The purpose of this study was to evaluate the prevalence of and find predictors for long-term sustained VA recurrence and overall mortality among AM patients with VA. METHODS: This was a multicenter retrospective analysis of AM patients (verified by cardiac magnetic resonance imaging or myocardial biopsy) with documented VA during the acute illness ("initial VA"). Patients with history of myocardial infarction, heart failure, or VA were excluded. The study endpoint was a composite of sustained VA and overall mortality during follow-up. RESULTS: The study included 69 AM patients with initial VA: sustained monomorphic ventricular tachycardia (MMVT) (n = 25), sustained polymorphic ventricular tachycardia (VT)/ventricular fibrillation (n = 13), and nonsustained VT (n = 31). Age was 44 ± 13 years, and 23 of 69 (33.3%) were women. During median follow-up of 5.5 years, 27 of 69 (39%) patients reached the composite endpoint including sustained VA (n = 24) and death (n = 11). Initial MMVT, predischarge left ventricular dysfunction (left ventricular ejection fraction <50%), and anteroseptal delayed enhancement on cardiac magnetic resonance imaging were significantly associated with the composite endpoint. On multivariable analysis, initial MMVT (HR: 5.17; 95% CI: 1.81-14.6; P = 0.001) and predischarge LV dysfunction (HR: 4.57; 95% CI: 1.83-11.5; P = 0.005) were independently associated with the composite endpoint. Using these 2 predictors, we could delineate subgroups with low (∼4%), medium (∼42%), and high (∼82%) 10-year incidence of composite endpoint. CONCLUSIONS: AM patients presenting with VA have high incidence of sustained VA recurrence and mortality posthospitalization. Initial MMVT and predischarge LV dysfunction are independently associated with VA recurrence and mortality. Implantable cardioverter-defibrillator implantation may be considered in such high-risk patients.

Compensatory growth and recovery of cartilage cytoarchitecture after transient cell death in fetal mouse limbs.

A major question in developmental and regenerative biology is how organ size and architecture are controlled by progenitor cells. While limb bones exhibit catch-up growth (recovery of a normal growth trajectory after transient developmental perturbation), it is unclear how this emerges from the behaviour of chondroprogenitors, the cells sustaining the cartilage anlagen that are progressively replaced by bone. Here we show that transient sparse cell death in the mouse fetal cartilage is repaired postnatally, via a two-step process. During injury, progression of chondroprogenitors towards more differentiated states is delayed, leading to altered cartilage cytoarchitecture and impaired bone growth. Then, once cell death is over, chondroprogenitor differentiation is accelerated and cartilage structure recovered, including partial rescue of bone growth. At the molecular level, ectopic activation of mTORC1 correlates with, and is necessary for, part of the recovery, revealing a specific candidate to be explored during normal growth and in future therapies.

Use of patient-reported experience and outcome measures within the colorectal cancer care continuum: a scoping review.

OBJECTIVE: Patient-reported outcome measures (PROM) are frequently adopted to evaluate colorectal cancer (CRC) care, but the use of patient-reported experience measures (PREM) appears to be underdeveloped and not widely validated. This scoping review aims to understand the contexts for deployment of PREMs in CRC care, reliability of measures, gaps in current use of PREMs, and how PREMs are associated with PROMs when deployed together. METHODS: Four scientific databases (PubMed, CINAHL, PsycINFO, Scopus) were systematically searched from January 2011 to December 2023. Observational or interventional studies involving quantitative or mixed methodology with samples consisting CRC patients undergoing screening, treatment, or cancer surveillance and utilizing at least one PREM as an exposure or outcome were included. RESULTS: The initial search resulted in 10,400 records. Only 13 relevant studies (consisting of 17,105 participants) met the eligibility criteria. Utilization of PREMs was heterogenous across our sample and the CRC care continuum, and about half of the studies (53.8%) evaluated the relationship between PREMs and PROMs. PREM usage across the CRC care continuum largely focused on treatment/survivorship. Better care experience was positively associated with improved patient-reported outcomes. CONCLUSIONS: Future work in CRC PREM development should focus on (1) establishing validated measures that aim to either capture disease/treatment-specific granularity or capitalize on applicability across care settings, (2) localizing novel or existing PREMs to consider different cultural contexts in healthcare, and (3) benchmarking associations between PREMs, PROMs, and other outcomes of interest. IMPLICATIONS FOR CANCER SURVIVORS: Individuals progressing through the CRC care continuum often undergo a multitude of procedures from detection and diagnosis to treatment and surveillance. The establishment of validated PREMs specific to CRC would help to benchmark and further improve the quality of care received-which should translate to better patient-reported outcomes-and serve as process indicators for institutions and providers to maintain rigorous health service delivery standard for CRC survivors.

Management of advanced prostate cancer in the Asia-Pacific region: Summary of the Asia-Pacific Advanced Prostate Cancer Consensus Conference 2023.

AIM: The aim of the third Asia-Pacific Advanced Prostate Cancer Consensus Conference (APAC APCCC 2023) was to discuss the application in the Asia-Pacific (APAC) region of consensus statements from the 4th Advanced Prostate Cancer Consensus Conference (APCCC 2022). METHODS: The one-day meeting in July 2023 brought together 27 experts from 14 APAC countries. The meeting covered five topics: (1) Intermediate- and high-risk and locally advanced prostate cancer; (2) Management of newly diagnosed metastatic hormone-sensitive prostate cancer; (3) Management of non-metastatic castration-resistant prostate cancer; (4) Homologous recombination repair mutation testing; (5) Management of metastatic castration-resistant prostate cancer. Pre- and post-symposium polling gathered APAC-specific responses to APCCC consensus questions and insights on current practices and challenges in the APAC region. RESULTS: APAC APCCC highlights APAC-specific considerations in an evolving landscape of diagnostic technologies and treatment innovations for advanced prostate cancer. While new technologies are available in the region, cost and reimbursement continue to influence practice significantly. Individual patient considerations, including the impact of chemophobia on Asian patients, also influence decision-making. CONCLUSION: The use of next-generation imaging, genetic testing, and new treatment combinations is increasing the complexity and duration of prostate cancer management. Familiarity with new diagnostic and treatment options is growing in the APAC region. Insights highlight the continued importance of a multidisciplinary approach that includes nuclear medicine, genetic counseling, and quality-of-life expertise. The APAC APCCC meeting provides an important opportunity to share practice and identify APAC-specific issues and considerations in areas of low evidence where clinical experience is growing.

Predictive value of donor kidney quality assessment and risk quantification scores on 5-year outcomes of deceased donor kidney transplantation.

BACKGROUND: Due to the excess demand for deceased donor kidneys, risk quantification scores were developed to help with kidney allocation. The kidney donor risk index (KDRI) is used in the US kidney allocation system. We currently use expanded criteria (UNOS) and Remuzzi scoring for allocation of deceased donor kidneys and the utility of KDRI in our cohort is unknown. We aim to evaluate the association of KDRI with relation to 5 year graft and patient survival. METHODS: Retrospective cohort study of 225 adults who received a deceased donor kidney transplant between 1 Nov 2005 and 30 June 2014. Patients were followed up for 5 years or until graft-loss or death. Implant biopsies of donor kidneys were done and the Remuzzi score was calculated. RESULTS: The median age was 48 (IQR 42, 52.5) years and 50.7% were male. KDRI-USA, KDRI-THAI, and KDRI-AUST were found to have no correlation with 5 year graft survival. Donor characteristics which define an expanded criteria donor kidney, not associated with 5 year graft survival are age (p = 0.58), terminal creatinine (p = 0.71) and history of hypertension (p = 0.35). Donor cerebrovascular accident (CVA) as a cause of death (p = 0.02) and Remuzzi score were associated with graft survival at 5 years, with 75.8% with Remuzzi score ≤ 3 vs 24.2% with Remuzzi score of > 3 achieving 5 year graft survival (p = 0.001). CONCLUSION: The association of KDRI with graft and patient survival was not demonstrated in our cohort. Histological assessment of the transplant kidney remains the best method of predicting long-term survival during donor selection.

The network structures of depressive and insomnia symptoms among cancer patients using propensity score matching: Findings from the Health and Retirement Study (HRS).

OBJECTIVE: Both depression and insomnia are found to be more prevalent in cancer patients compared to the general population. This study compared the network structures of depression and insomnia among cancer patients versus cancer-free participants (controls hereafter). METHOD: The 8-item Center for Epidemiological Studies Depression Scale (CESD-8) and the 4-item Jenkins Sleep Scale (JSS-4) were used to measure depressive and insomnia symptoms, respectively. Propensity score matching (PSM) was used to construct the control group using data from the Health and Retirement Study (HRS). In total, a sample consisting of 2216 cancer patients and 2216 controls was constructed. Central (influential) and bridge symptoms were estimated using the expected influence (EI) and bridge expected influence (bridge EI), respectively. Network stability was assessed using the case-dropping bootstrap method. RESULT: The prevalence of depression (CESD-8 total score ≥ 4) in cancer patients was significantly higher compared to the control group (28.56 % vs. 24.73 %; P = 0.004). Cancer patients also had more severe depressive symptoms relative to controls, but there was no significant group difference for insomnia symptoms. The network structures of depressive and insomnia symptoms were comparable between cancer patients and controls. "Felt sadness" (EI: 6.866 in cancer patients; EI: 5.861 in controls), "Felt unhappy" (EI: 6.371 in cancer patients; EI: 5.720 in controls) and "Felt depressed" (EI: 6.003 in cancer patients; EI: 5.880 in controls) emerged as the key central symptoms, and "Felt tired in morning" (bridge EI: 1.870 in cancer patients; EI: 1.266 in controls) and "Everything was an effort" (bridge EI: 1.046 in cancer patients; EI: 0.921 in controls) were the key bridge symptoms across both groups. CONCLUSION: Although cancer patients had more frequent and severe depressive symptoms compared to controls, no significant difference was observed in the network structure or strength of the depressive and insomnia symptoms. Consequently, psychosocial interventions for treating depression and insomnia in the general population could be equally applicable for cancer patients who experience depression and insomnia.

Target-mediated drug disposition model for drugs with N > 2 binding sites that bind to a target with one binding site.

The paper extended the TMDD model to drugs with more than two (N > 2) identical binding sites (N-to-one TMDD). The quasi-steady-state (N-to-one QSS), quasi-equilibrium (N-to-one QE), irreversible binding (N-to-one IB), and Michaelis-Menten (N-to-one MM) approximations of the model were derived. To illustrate properties of new equations and approximations, N = 4 case was investigated numerically. Using simulations, the N-to-one QSS approximation was compared with the full N-to-one TMDD model. As expected, and similarly to the standard TMDD for monoclonal antibodies (mAb), N-to-one QSS predictions were nearly identical to N-to-one TMDD predictions, except for times of fast changes following initiation of dosing, when equilibrium has not yet been reached. Predictions for mAbs with soluble targets (slow elimination of the complex) were simulated from the full 4-to-one TMDD model and were fitted to the 4-to-one TMDD model and to its QSS approximation. It was demonstrated that the 4-to-one QSS model provided nearly identical description of not only the observed (simulated) total drug and total target concentrations, but also unobserved concentrations of the free drug, free target, and drug-target complexes. For mAb with a membrane-bound target, the 4-to-one MM approximation adequately described the data. The 4-to-one QSS approximation converged 8 times faster than the full 4-to-one TMDD.

A Delphi consensus on clinical features, diagnosis and treatment of major depressive disorder patients with anhedonia amongst psychiatrists in the Asia-Pacific.

Background: Anhedonia, a core diagnostic feature for major depressive disorder (MDD), is defined as the loss of pleasure and interest in daily activities. Its prevalence in MDD patients vary from 35 to 70%. Anhedonia in MDD negatively impacts functioning and is associated with treatment resistance and poorer prognosis for various clinical outcomes. Owing to its complexity, there remains considerable heterogeneity in the conceptualization, diagnosis and clinical management of anhedonia in MDD. Methods: This modified Delphi panel was conducted to elicit expert opinion and establish consensus on concepts relating to clinical features, diagnosis and treatment of MDD with anhedonia (MDDwA) amongst psychiatrists in the Asia-Pacific region. Seven themes were covered. A three-stage process was adopted for consensus generation (two online survey rounds, followed by a moderated consensus meeting). Statements were developed based on a literature review and input from a steering committee of six regional experts. The panel included 12 psychiatrists practicing in Australia, China, Hong Kong, Japan, South Korea and Taiwan with ≥5 years of specialist clinical experience, including assessment or management of patients with MDDwA. Results: Overall, consensus was achieved (median ≥8) on 89/103 statements (86%). About half of the statements (55/103, 53%) achieved consensus in Round 1, and 29/36 modified statements achieved consensus in Round 2. At the moderated consensus meeting, five modified statements were discussed by the steering committee and consensus was achieved on all statements (5/5). The findings highlighted a lack of clear and practical methods in clinical practice for assessing anhedonia in MDD patients and limited physician awareness of anhedonia in Asia-Pacific. Conclusion: Insights from this Delphi consensus provide a reference point for psychiatrists in Asia-Pacific to optimize their strategies for personalized diagnosis and management of patients with MDDwA. Identification of distinct and clinically relevant subtypes in MDD may be valuable for guiding personalized diagnosis and management approaches, including type-specific therapies.

The evolving role of social media in enhancing quality of life: a global perspective across 10 countries.

BACKGROUND: Excessive or inappropriate use of social media has been linked to disruptions in regular work, well-being, mental health, and overall reduction of quality of life. However, a limited number of studies documenting the impact of social media on health-related quality of life (HRQoL) are available globally. AIM: This study aimed to explore the perceived social media needs and their impact on the quality of life among the adult population of various selected countries. METHODOLOGY: A cross-sectional, quantitative design and analytical study utilized an online survey disseminated from November to December 2021. RESULTS: A total of 6689 respondents from ten countries participated in the study. The largest number of respondents was from Malaysia (23.9%), followed by Bangladesh (15.5%), Georgia (14.8%), and Turkey (12.2%). The prevalence of social media users was over 90% in Austria, Georgia, Myanmar, Nigeria, and the Philippines. The majority of social media users were from the 18-24 age group. Multiple regression analysis showed that higher education level was positively correlated with all four domains of WHOQoL. In addition, the psychological health domain of quality of life was positively associated in all countries. Predictors among Social Media Needs, Affective Needs (ß = -0.07), and Social Integrative Needs (ß = 0.09) were significantly associated with psychological health. CONCLUSION: The study illuminates the positive correlation between higher education levels and improved life quality among social media users, highlighting an opportunity for policymakers to craft education-focused initiatives that enhance well-being. The findings call for strategic interventions to safeguard the mental health of the global social media populace, particularly those at educational and health disadvantages.

The Brain Economy: Advancing Brain Science to Better Understand the Modern Economy.

The coming years are likely to be turbulent due to a myriad of factors or polycrisis, including an escalation in climate extremes, emerging public health threats, weak productivity, increases in global economic instability and further weakening in the integrity of global democracy. These formidable challenges are not exogenous to the economy but are in some cases generated by the system itself. They can be overcome, but only with far-reaching changes to global economics. Our current socio-economic paradigm is insufficient for addressing these complex challenges, let alone sustaining human development, well-being and happiness. To support the flourishing of the global population in the age of polycrisis, we need a novel, person-centred and collective paradigm. The brain economy leverages insights from neuroscience to provide a novel way of centralising the human contribution to the economy, how the economy in turn shapes our lives and positive feedbacks between the two. The brain economy is primarily based on Brain Capital, an economic asset integrating brain health and brain skills, the social, emotional, and the diversity of cognitive brain resources of individuals and communities. People with healthy brains are essential to navigate increasingly complex systems. Policies and investments that improve brain health and hence citizens' cognitive functions and boost brain performance can increase productivity, stimulate greater creativity and economic dynamism, utilise often underdeveloped intellectual resources, afford social cohesion, and create a more resilient, adaptable and sustainability-engaged population.

Pain trajectories and their associations with cognition among older adults: a 10-year cohort study from network perspective.

BACKGROUND: Few studies have examined the associations between pain trajectories and cognitive function in older adults. This study explored the associations between pain trajectories and different cognitive domains in older adults from a network perspective. METHODS: Data on pain trajectories were derived from the Health and Retirement Study between 2010 and 2020 using latent class growth analyses. Measurements of key cognition domains, including memory, attention, calculation, orientation and language, were included. Linear regression and network analysis were performed to evaluate the associations between different pain trajectories and cognition. RESULTS: A total of 9,551 older adults were included in this study and three trajectories of pain were identified. After controlling for the covariates, persistent severe pain trajectory was associated with poorer overall cognition, memory and calculation ability when compared to mild or non-persistent pain trajectory. In the pain and cognition network model, memory (expected influence (EI) = 0.62), language (EI = 0.58) and calculation (EI = 0.41) were the most central domains. CONCLUSIONS: Pain trajectories appeared stable over time among older adults in this study. Severity of persistent pain was an important risk factor for poor cognition, especially in relation to memory and calculation domains. Interventions targeting memory, language and calculation domains might be useful in addressing cognitive decline in older adults with persistent pain.

Corrigendum: Smartphone-delivered multicomponent lifestyle medicine intervention for improving mental health in a nonclinical population: a randomized controlled trial.

[This corrects the article DOI: 10.3389/fpubh.2023.1231981.].