Climate change and healthy ageing: An assessment of the impact of climate hazards on older people.

Background: Climate change not only directly impacts older people's longevity but also healthy ageing, which is the process of maintaining physical and mental capacities while optimising functional abilities. The urgency to address both population ageing and climate change necessitates a rethink and assessment of the impact of climate change on older people. This includes identifying what can be done to anticipate, mitigate and adapt to climate change and engage older persons. Methods: A review of climate change and healthy ageing forms the basis of evidence in this report. We developed a comprehensive search to assess current literature, combining terms related to ageing and climate change across four major data sets and assessing articles published up to the end of 2021. Results: We summarised the current and future impact of climate change on older people and developed a framework identifying climate change impacts on older persons, recognising social and environmental determinants of healthy ageing. Major hazards and some key exposure pathways include extreme temperatures, wildfire, drought, flooding, storm and sea level rise, air quality, climate-sensitive infectious diseases, food and water insecurities, health and social care system displacement, migration, and relocation. Strategies to address climate change require interventions to improve systems and infrastructure to reduce vulnerability and increase resilience. As a heterogeneous group, older people's perceptions of climate change should be integrated into climate activism. Increasing climate change literacy among older people and enabling them to promote intergenerational dialogue will drive the development and implementation of equitable solutions. Pathways may operate via direct or indirect exposures, requiring longitudinal studies that enable assessment of exposures and outcomes at multiple time points, and analyses of cumulative impacts of hazards across the life course. Conclusions: The lack of systematic reviews and primary research on the impact of most climate hazards, except for heat, on older people is apparent. Future research should include outcomes beyond mortality and morbidity and assess how older people interact with their environment by focusing on their capacities and optimising abilities for being and doing what they value.

Mental health and psychosocial interventions in the context of climate change: a scoping review.

The evidence on the impacts of climate change on mental health and wellbeing is growing rapidly. The objective of this scoping review is to understand the extent and type of existing mental health and psychosocial interventions aimed at addressing the mental health and psychosocial impacts of climate change. A scoping review methodology was followed. MEDLINE, PsycINFO, and Web of Science databases were searched from inception to May 2022. Comprehensive gray literature search, including expert consultation, was conducted to identify interventions for which peer-reviewed academic literature may not yet be available. Data on intervention type, setting, climate stressor, mental health outcome, evaluation, and any other available details were extracted, and results were summarized narratively. Academic literature search identified 16 records and gray literature search identified a further 24 records. Altogether, 37 unique interventions or packages of interventions were identified. The interventions act at the levels of microsystem, mesosystem, exosystem, and macrosystem through diverse mechanisms. While most interventions have not been formally evaluated, promising preliminary results support interventions in low- and middle-income-country settings disproportionately affected by climate disasters. Interventions from multidisciplinary fields are emerging to reduce psychological distress and enhance mental health and wellbeing in the context of climate change. This scoping review details existing evidence on the interventions and summarizes intervention gaps and lessons learned to inform continued intervention development and scale-up interventions.

A systematic review on the effectiveness of dialectical behavior therapy for improving mood symptoms in bipolar disorders.

BACKGROUND: Evidence-based psychotherapies available to treat patients with bipolar disorders (BD) are limited. Dialectical behavior therapy (DBT) may target several common symptoms of BD. We conducted a systematic review on the efficacy of DBT for mood symptoms in patients with BD. The systematic search used key words related to DBT and BD in Medline, Embase, PsycInfo, CINAHL, and Cochrane Library databases from 1980 to April 1st, 2022. We included studies that enrolled patients with a BD I or II diagnosis (DSM or ICD), age 12 and older who received a DBT-based intervention. Studies reviewed were clinical trials including observational studies that reported at least one outcome related to BD mood symptoms or severity. We did not exclude based upon psychiatric or physical co-morbidity. RESULTS: We screened 848 abstracts and reviewed 28 full texts; 10 publications with 11 studies met our pre-determined eligibility criteria. All but one were feasibility pilot studies and most included participants in all mood states except for mania. The studies provided preliminary evidence suggesting these interventions may be effective for improving several core symptoms of BD. Overall, all the studies consistently supported that DBT-based interventions are feasible and acceptable for patients with BD. CONCLUSION: DBT may be an effective treatment for BD; however, the confidence in this conclusion is limited by the small sample sizes, heterogeneity, and high risk of bias in all published trials. Larger well-designed RCTs are now required to establish the effectiveness of DBT in BD.

Competitive Reactions during Ethanol Chain Elongation Were Temporarily Suppressed by Increasing Hydrogen Partial Pressure through Methanogenesis Inhibition.

Organic waste streams can be converted into high-value platform chemicals such as medium-chain carboxylic acids (MCCAs) using mixed microbial communities via chain elongation. However, the heterogeneity of waste streams and the use of complex microbial communities can lead to undesirable reactions, thus decreasing process efficiency. We explored suppressing excessive ethanol oxidation to acetate (EEO) by increasing the hydrogen partial pressure (PH2) through hydrogenotrophic methanogenesis inhibition by periodically adding 2-bromoethanesulfonate (2-BES) to an MCCA-producing bioreactor to reach 10 mM of 2-BES upon addition. The bioreactor was fed with pretreated food waste and brewery waste containing high concentrations of short-chain carboxylic acids and ethanol, respectively. While 2-BES addition initially reduced EEO, some methanogens (Methanobrevibacter spp.) persisted and resistant populations were selected over time. Besides changing the methanogenic community structure, adding 2-BES also changed the bacterial community structure due to its impact on PH2. While we demonstrated that PH2 could be manipulated using 2-BES to control EEO, methods that do not require the addition of a chemical inhibitor should be explored to maintain optimum PH2 for long-term suppression of EEO.

Bipolar disorders in Nigeria: a mixed-methods study of patients, family caregivers, clinicians, and the community members' perspectives.

BACKGROUND: Bipolar Disorders (BDs) are chronic mental health disorders that often result in functional impairment and contribute significantly to the disability-adjusted life years (DALY). BDs are historically under-researched compared to other mental health disorders, especially in Sub-Saharan Africa and Nigeria. DESIGN: We adopted a mixed-methods design. Study 1 examined the public knowledge of BDs in relation to sociodemographic outcomes using quantitative data whilst Study 2 qualitatively assessed the lived experiences of patients with BDs, clinicians, and family caregivers. METHODS: In Study 1, a non-clinical sample of n = 575 participants responded to a compact questionnaire that examined their knowledge of BDs and how they relate to certain sociodemographic variables. One-way ANOVA was used to analyse quantitative data. Study 2 interviewed N = 15 participants (n = 5 patients with BDs; n = 7 clinicians; n = 3 family caregivers). These semi-structured interviews were audio-recorded, transcribed, and thematically analysed. RESULTS: In Study 1, findings showed no statistically significant differences, suggesting low awareness of BDs, especially among vulnerable populations such as young people and older adults. However, there was a trajectory in increased knowledge of BDs among participants between the ages of 25-44 years and part-time workers compared to other ages and employment statuses. In Study 2, qualitative findings showed that BDs are perceived to be genetically and psycho-socially induced by specific lived experiences of patients and their family caregivers. Although psychotropic medications and psychotherapy are available treatment options in Nigeria, cultural and religious beliefs were significant barriers to treatment uptake. CONCLUSIONS: This study provides insight into knowledge and beliefs about BDs, including the lived experiences of patients with BDs, their caregivers and clinicians in Nigeria. It highlights the need for further studies assessing Nigeria's feasibility and acceptability of culturally adapted psychosocial interventions for patients with BDs.

Climate emergency, young people and mental health: time for justice and health professional action.

Climate change is driving a public mental health crisis that disproportionately, and unjustly, affects the world's young people. Despite the growing evidence for harm to the next generation, the medical community has largely been hesitant to take the next step and act on the evidence. We propose that the medical community has a responsibility to do more.Drawing from our interdisciplinary experience in paediatrics and psychiatry, we call for our profession to take the 'leap' beyond the walls of our clinics and laboratories, and take a courageous stance on the topic of climate change. We argue that the medical profession must adopt a broader conception of health and its determinants-or a 'social lens'-if it is to move beyond rhetoric to action.Viewing climate change as a clear determinant of mental health opens up potential avenues of action, both as individual clinicians and as a profession as a whole. We offer the beginnings of a framework for action in the context of climate change and youth mental health, before calling for our profession to re-examine its role - and its very purpose - to better address the climate crisis.

Efficacy and acceptability of pharmacotherapy for comorbid anxiety symptoms in bipolar disorder: A systematic review and meta-analysis.

OBJECTIVE: Anxiety symptoms are highly prevalent among individuals with bipolar disorder (BD) but there is little guidance on pharmacotherapy for these symptoms. The objective of this systematic review and meta-analysis was to evaluate the available evidence for pharmacotherapy of comorbid anxiety symptoms in BD. METHODS: Completed randomized clinical trials (RCTs) of medications for BD published prior to December 2020 were identified through a systematic search of MEDLINE, Embase, PsycInfo, Web of Science, clinicaltrials.gov, and the ISRCTN. Data from RCTs measuring anxiety symptoms at baseline and endpoint and all-cause discontinuation were pooled to compare the efficacy and acceptability of medications with control conditions. RESULTS: Thirty-seven RCTs met our inclusion criteria; 13 placebo-controlled RCTs with 2175 participants had sufficient data to be included in the meta-analysis assessing anxiety symptoms. Compared with placebo, the overall effect size of medications (primarily atypical antipsychotics) on anxiety symptoms was small with a standardized mean difference (SMD) = -0.22 (95% CI: -0.34 to -0.11). Study heterogeneity was low (I2  = 26%). The acceptability of these medications was comparable with placebo with odds ratio of discontinuation from all causes = 0.98 (95% CI: 0.91-1.06). CONCLUSION: There is limited evidence for a small anxiolytic effect and good acceptability of pharmacotherapy (primarily atypical antipsychotics) in the treatment of comorbid anxiety symptoms in BD. These results highlight the need for further research on medications other than atypical antipsychotics.

Depression, Anxiety, and Other Mental Disorders in Patients With Cancer in Low- and Lower-Middle-Income Countries: A Systematic Review and Meta-Analysis.

PURPOSE: Cancer is a growing public health issue in low- and lower-middle-income countries (LLMICs), but the mental health consequences in this setting have not been well-characterized. We aimed to systematically evaluate the available literature on the prevalence, associates, and treatment of mental disorders in patients with cancer in LLMICs. METHODS: We systematically searched Medline, PsycINFO, EMBASE, and CINAHL. We performed a random effects meta-analysis to determine the pooled prevalence of major depression or anxiety disorders in this population, defined by Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases criteria. We qualitatively reviewed studies that examined the prevalence of depressive or anxiety disorders defined by self-report tools, the prevalence of other mental disorders, associated factors of depressive and anxiety symptoms, and the treatment of mental disorders in this population. RESULTS: Forty studies spanning a 15-year period were included in the review. The pooled prevalence defined by Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases criteria was 21% for major depression (95% CI, 15 to 28) and 18% for anxiety disorders (95% CI, 8 to 30). Depressive and anxiety symptoms were most frequently associated with advanced disease and low levels of education. Among the four studies evaluating treatment, three evaluated the effectiveness of psychotherapy and one evaluated a yoga program. CONCLUSION: The prevalence of depression and anxiety in patients with cancer generally appears higher in LLMICs than in upper-income countries. Our findings demonstrate the existence of a significant and underappreciated disease burden. We suggest that clinicians remain vigilant to psychiatric symptoms. Improved screening and treatment are likely to improve quality of life and reduce both morbidity and mortality.

Suicidality in patients with bipolar depression: Findings from a lower middle-income country.

The prevalence and risk factors of suicidal ideation in bipolar depression in low- and middle-income countries (LMICs) are poorly understood. This study is a secondary, cross-sectional analysis of a randomized controlled trial from Pakistan, a lower middle-income country. Participants included psychiatric outpatients aged 18 to 65 with a known diagnosis of bipolar disorder and currently in a depressive episode. Suicidality was assessed using the suicide item of the 17-item Hamilton Depression Rating Scale (HAM-D) and levels of severity were categorized as absent, mild/moderate, or severe. Biometric data and biomarkers were obtained. Descriptive statistics were used to describe prevalence and logistic regression applied to establish correlates to suicidal ideation. Among the 266 participants, 67% indicated suicidality of any level and 16% endorsed severe suicidality. Lower body mass index (BMI) (OR = 0.93, 95% CI = 0.88-0.98), higher HAM-D score (OR = 1.29, 95% CI = 1.16-1.43), lower C-reactive protein (CRP) level (OR = 0.53, 95% CI = 0.40-0.70), and increased number of inpatient hospitalizations (OR = 1.16, 95% CI = 1.03-1.31) were identified as significant predictors of suicidality in the fully adjusted regression model. Our findings add to the limited literature on suicidality in bipolar disorder in the LMIC context and suggest roles of biological variables such as BMI and CRP level in predicting suicidal ideation and potentially suicidal behaviours in bipolar depression.

Cannabis Use and Prospective Long-Term Association with Anxiety: A Systematic Review and Meta-Analysis of Longitudinal Studies: Usage du cannabis et association prospective à long terme avec l'anxiété: une revue systématique et une méta-analyse d'études longitudinales.

OBJECTIVES: Cannabis use is proposed as a risk factor for psychosis and is associated with depressive disorders. However, the relationship between recreational cannabis use and its longitudinal implications on anxiety conditions is less studied. The aim of this investigation is to systematically evaluate published literature and perform a meta-analysis of the data. METHODS: A systematic search was performed of MEDLINE, Embase, and PsychINFO from inception to May 31, 2020, in addition to a hand search. Longitudinal studies that evaluated the relationship of cannabis use and development of anxiety were included. Where applicable, adjusted odds ratios (ORs) were extracted, pooled, and evaluated using random-effects meta-analysis. RESULTS: After screening of unique abstracts (n = 6835), the final evaluation included 24 studies, of which 10 reported ORs that were analyzed quantitatively. Cannabis use was significantly associated with increased odds of developing any anxiety conditions (OR = 1.25; 95% CI, 1.01 to 1.54). Cannabis use was not significantly associated with developing generalized anxiety disorder, panic disorder, or social anxiety disorder. Review of studies not reporting OR revealed mixed results but are suggestive of a link between cannabis use and increased rates/severity of anxiety. CONCLUSIONS: Published evidence suggests that cannabis use is likely associated with increased risk of anxiety in the long term but variability of study designs precludes declaration of a causal relationship. Awareness of this association is of relevance for both clinical practice and mental health policy implementation.

Discovery of pyridine tetrahydroisoquinoline thiohydantoin derivatives with low blood-brain barrier penetration as the androgen receptor antagonists.

Prostate cancer (PC) is the most diagnosed type of malignancy in men and the major frequently cause of cancer-related death worldwide. The androgen receptor (AR) has become a promising drug target for the treatment of PC. Here, we reported the design, optimization and evaluation of pyridine tetrahydroisoquinoline thiohydantoin derivatives with improved activity and safety as potent AR antagonists. The most promising compound 42f exhibited potent inhibitory activity on AR and strongly blocked AR nuclear translocation. Moreover, 42f displayed promising in vitro antitumor activity toward AR-dependent prostate cancer cell lines (LNCaP) and also demonstrated therapeutic effects in LNCaP xenograft tumor model in mice (TGI: 79%) with no apparent toxicity observed in vivo. More importantly, 42f showed negligible penetration of the brain-blood barrier (BBB) compared with enzalutamide. These results provide a foundation for the development of a new class of androgen receptor antagonists for potential therapeutics against PC with lower seizurogenic risk for patients.

COVID-19: Implications for bipolar disorder clinical care and research.

The COVID-19 pandemic has posed significant challenges to health care globally, and individuals with bipolar disorder are likely disproportionally affected. Based on review of literature and collective clinical experience, we discuss that without special intervention, individuals with bipolar disorder will experience poorer physical and mental health outcomes due to interplay of patient, provider and societal factors. Some risk factors associated with bipolar disorder, including irregular social rhythms, risk-taking behaviours, substantial medical comorbidities, and prevalent substance use, may be compounded by lockdowns, social isolation and decrease in preventive and maintenance care. We further discuss implications for clinical research of bipolar disorders during the pandemic. Finally, we propose mitigation strategies on working with individuals with bipolar disorder in a clinical and research context, focusing on digital medicine strategies to improve quality of and accessibility to service.

A validated UPLC-MS/MS method for determination of tebipenem in human plasma and its application to a pharmacokinetic study in healthy volunteers.

A rapid and sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for determining tebipenem (TBPM) in human plasma. Plasma samples were prepared following a single-step protein precipitation method using acetonitrile and 3-morpholinopropanesulfonic acid (MOPS, pH 7.0, 50 mM) which equal volume of plasma samples were added for stabilizing the analyte. Separation was achieved using an ACQUITY UPLC BEH C18 (1.7 µm, 2.1 × 50 mm) column. A repeated gradient program was employed for reducing the carryover effect, and the total chromatographic run time was 3.0 min. Method validation results showed TBPM was linear in its analytical range i.e. between 0.1-20 µg/mL (r2>0.99), and the lower limit of quantification (LLOQ) was 0.1 µg/mL. The intra-run and inter-run precision (coefficient of variation, CV) was within 3.81%, and the accuracy (relative error, RE) was within ± 8.56%. The carryover was restricted below 8.1%. Matrix effects were minimal, and recovery of TBPM was 90.19-95.74%. The stability of TBPM in plasma sample stored at room temperature (25 °C) for 4 h, at -20 °C for 3 days, at -80 °C for 30 days, five freeze-thaw cycles at -80 °C and processed samples at auto sampler vials (8 °C) for 24 h were within 91.11-106.33%. Finally, the validated method was successfully applied to a pharmacokinetic study of TBPM in healthy volunteers after oral administration of tebipenem pivoxil (TBPM-PI).

Exploring the tetrahydroisoquinoline thiohydantoin scaffold blockade the androgen receptor as potent anti-prostate cancer agents.

Prostate cancer (PC) is a major cause of cancer-related male death in worldwide and the identification of new and improved potent anti-PC molecules is constantly required. A novel scaffold of tetrahydroisoquinoline thiohydantoin was rationally designed based on the enzalutamide structures and our pre-work, leading to the discovery of a series of new antiproliferative compounds. Several new analogues displayed improved androgen receptor (AR) antagonistic activity, while maintaining the higher selective toxicity toward LNCaP cells (AR-rich) versus DU145 cells (AR-deficient) compared to enzalutamide. In fact, compound 55 exhibited promising in vitro antitumor activity by impairing AR unclear translocation. More importantly, 55 showed better pharmacokinetic properties compared to the compound 1 reported in our pre-work. These results demonstrate a step towards the development of novel and improved AR antagonists.

The effect of fenofibric acid on the pharmacokinetics and pharmacodynamics of warfarin in rats.

1. Case reports have shown that coadministration of fenofibric acid (FA) could increase bleeding risks of warfarin, but the mechanisms remained unknown. We therefore investigated the pharmacokinetic and pharmacodynamic interaction between warfarin and FA in rats. 2. Rats received warfarin alone (2 mg/kg) or coadministered with FA (100 mg/kg). FA significantly increased the exposure to warfarin, and decreased that to 7-hydroxywarfarin in rats nearly by two-fold, meanwhile increased Cmax and prolonged t1/2 of warfarin. Anticoagulant activity significantly increased, with prothrombin time (PT) up to 199 ± 33 s in coadministered group (approximately ten-fold compared with rats received warfarin alone). Incubation experiments illustrated FA inhibited CYP2C6 and CYP3A1/2 with the IC50 values of 6.98 and 16.14 µM, and inhibited the metabolism of warfarin (Ki value of 2.21 µM). Meanwhile, FA decreased the plasma protein binding of warfarin in vitro. 3. Our data suggested that the altered pharmacokinetics and pharmacodynamics of warfarin in rats was primarily attributed to the inhibition of metabolism. Anticoagulant activity monitoring or warfarin dose lowering needs to be considered when patients are coadministered with FA.

Coping strategies used by traumatic spinal cord injury patients in Sri Lanka: a focus group study.

PURPOSE: Psychosocial consequences of traumatic spinal cord injury (SCI) have been well documented in Western populations, but there is no published literature on such incidence in the Sri Lankan population. The purpose of this study was to explore the psychosocial impact of SCI in a Sri Lankan population and to examine this population's coping mechanisms. METHODS: Participants were recruited purposively at the Ragama Rheumatology and Rehabilitation Hospital, the sole rehabilitation facility for SCI patients in Sri Lanka. Focus groups were conducted with 23 consenting individuals. Interview transcripts were analysed using descriptive thematic analysis. RESULTS: Four domains of life impact, three types of active coping strategies and four types of external supports were identified. Decreased ambulation and burden on family life were significant concerns for male and female participants alike. Religious practices were reported most frequently as active coping strategies, followed by positive reframing and goal-setting. Reported external supports included guided physiotherapy, informational workshops, social support and peer networks. CONCLUSION: Rehabilitation efforts for Sri Lankan SCI patients should be sensitive to psychosocial concerns in addition to physical concerns in order to help patients re-integrate into their family lives and community. Furthermore, religious practices should be respected as possible aids to rehabilitation. Implications for Rehabilitation Rehabilitative efforts should be conscientious of patients' psychosocial well-being in addition to their physical well-being. Hospital-based rehabilitative efforts for traumatic spinal cord injury patients should promote functional independence and community re-integration. Spiritual and/or religious practices should be respected as ways by which traumatic spinal cord injury patients may confront personal challenges that arise following injury.

Methylene-Functionalize Saponite: A New Type of Organoclay with CH(2) Groups Substituting for Bridging Oxygen Centers in the Tetrahedral Sheet.

The synthesis of saponite in the presence of bis(triethoxysilyl)methane (BTESM) as an organosilicon reagent results in the replacement of up to 33.3 % of the oxygen atoms in the tetrahedral sheet by bridging methylene groups. The methylene-functionalized saponites represent a new form of covalently-bonded organoclay that truly is isomorphic with purely inorganic saponite made under equivalent reaction conditions from sodium silicate as the silicon source. The isoelectronic and isolobal relationship between methylene and bridging oxygen centers is essential for methylene saponite formation. Bridging ethylene groups are not incorporated into the Kagome net of the basal surfaces due to a mismatch in bridging group size. The textural properties of the methylene saponites are similar to those for purely inorganic magnesium saponite made under equivalent synthetic conditions in the absence of BTESM. Layer stacking disorders afford large surface areas (~550 to 650 m(2)/g), making the methylene saponites attractive candidates for use as adsorbents and functional fillers for polymer composites.