Predicting psychological distress in advanced ovarian cancer patients during the COVID-19 pandemic.

PURPOSE: This longitudinal study investigated distress rates in patients with advanced ovarian cancer during the COVID-19 pandemic and examined whether time, illness representations, and coping strategies predicted distress levels. METHODS: UK patients with stage 3 or 4 ovarian cancer were recruited between September 2020 and March 2021. Data were collected at baseline (T0), 2 months (T1), and 4 months (T2) post-enrolment. Validated questionnaires assessed distress (anxiety, depression, PTSD, fear of progression) and predictors (coping strategies and illness perceptions), analysed via multilevel modelling. RESULTS: Seventy-two participants returned a questionnaire at T0, decreasing to 49 by T2. High distress was observed, with over 50% of participants experiencing anxiety and depression consistently. Nearly 60% reported clinical levels of fear of progression at some point. PTSD rates resembled the general population. Although distress levels remained stable over time, some individual variability was observed. Time had minimal effect on distress. Coping strategies and illness perceptions remained stable. Threatening illness perceptions consistently predicted distress, while specific coping strategies such as active coping, acceptance, self-blame, and humour predicted various aspects of distress. Together, these factors explained up to half of the distress variance. CONCLUSION: The findings have implications for routine screening for distress and the inclusion of psychological treatment pathways in advanced ovarian cancer care. Addressing illness representations is crucial, with attention to informational support. Future research should explore the long-term effects of heightened distress and the effectiveness of interventions targeting illness perceptions. This study informs current clinical practice and future pandemic preparedness in cancer care.

Zona incerta mediates early life isoflurane-induced fear memory deficits.

The potential long-term effects of anesthesia on cognitive development, especially in neonates and infants, have raised concerns. However, our understanding of its underlying mechanisms and effective treatments is still limited. In this study, we found that early exposure to isoflurane (ISO) impaired fear memory retrieval, which was reversed by dexmedetomidine (DEX) pre-treatment. Measurement of c-fos expression revealed that ISO exposure significantly increased neuronal activation in the zona incerta (ZI). Fiber photometry recording showed that ZI neurons from ISO mice displayed enhanced calcium activity during retrieval of fear memory compared to the control group, while DEX treatment reduced this enhanced calcium activity. Chemogenetic inhibition of ZI neurons effectively rescued the impairments caused by ISO exposure. These findings suggest that the ZI may play a pivotal role in mediating the cognitive effects of anesthetics, offering a potential therapeutic target for preventing anesthesia-related cognitive impairments.

Being able to think when caught in the maelstrom - how adolescents used mindfulness when facing exams.

PURPOSE: Research indicates that exam anxiety may decline with mindfulness-based interventions but there is a lack of research on adolescents' accounts of the processes involved. We explored high-school students' descriptions of how they perceived and applied mindfulness in managing anxiety-inducing thoughts related to academic performance following an 8-week Mindfulness-Based Stress Reduction (MBSR) course. METHOD: Post-course individual semi-structured interviews with 22 high school students (2 males, mean age 17.8 years) were transcribed verbatim and analysed using reflexive thematic analysis. RESULTS: The analyses identified six themes: (1) Noticing and attending to the attention-binding "maelstrom" of anxious thoughts and feelings (2) Attending to the breath to cope with the maelstrom, (3) "removing" and "getting rid of" anxious thoughts (4) Being able to "think" (5) awareness of more helpful thoughts, and (6) Agency and control. The findings are discussed in light of the Buddhist notion of "unwholesome thoughts" and the distinction between thought suppression and the use of breathing as a benign distraction. We propose that mindfulness encompasses both a receptive, nonjudgmental awareness and an active, intentional redirection of attention. CONCLUSION: Mindfulness training aided participants by enhancing their capacity to disengage from fear-engaging thoughts, thereby maintaining them within their window of tolerance and facilitating cognitive processing.

The emotional states and associated behavioral responses (flexible-adaptive behaviors vs. inflexible-maladaptive behaviors) of cancer patients during the SARS-CoV-2 outbreak: A multi-center cross-sectional study in Italy.

OBJECTIVE: Distress during SARS-CoV-2 outbreak affected also cancer patients' well-being. Aim of this study was to investigate patient' reactions and behavior (flexible-adaptive vs. inflexible-maladaptive) during the SARS-CoV-2 outbreak. METHODS: A cross-sectional survey was designed with a self-report questionnaire, "the ImpACT questionnaire," developed for the study. Regression analysis was performed on data. RESULTS: Four hundred and forty five cancer patients from 17 Italian regions participated in the study. 79.8% of participants were female (mean age of 58 years). 92.6% of participants reported feeling vulnerable to COVID-19 contagion; 75.6% reported helpless, 62.7% sad, 60.4% anxious, and 52.0% anger. Avoidance of thinking about coronavirus is the principal maladaptive behavior that emerged. Participants who reported feeling anxious were more likely to have fear of staff being infected with COVID-19 (OR = 3.01; 95% CI = 1.49-6.30) and to have disrupted sleep due to worry (OR = 2.42; 95% CI = 1.23-4.83). Younger participants reported more anxiety (OR = 0.97; 95% CI = 0.94-1.00); men reported feeling calm more than women (OR = 2.60; 95% CI = 1.27-5.43). CONCLUSIONS: Majority of cancer patients reported serious concerns regarding SARS-CoV-2 infection; reliable information and psychological support must be offers to respond to these needs.

Graded Exposure Therapy for Fear Avoidance Behaviour After Concussion (GET FAB): protocol for a multisite Canadian randomised controlled trial.

INTRODUCTION: Persistent symptoms after mild traumatic brain injury (mTBI) negatively affect daily functioning and quality of life. Fear avoidance behaviour, a coping style in which people avoid or escape from activities or situations that they expect will exacerbate their symptoms, maybe a particularly potent and modifiable risk factor for chronic disability after mTBI. This study will evaluate the efficacy of graded exposure therapy (GET) for reducing persistent symptoms following mTBI, with two primary aims: (1) To determine whether GET is more effective than usual care; (2) to identify for whom GET is the most effective treatment option, by evaluating whether baseline fear avoidance moderates differences between GET and an active comparator (prescribed aerobic exercise). Our findings will guide evidence-based care after mTBI and enable better matching of mTBI patients to treatments. METHODS AND ANALYSIS: We will conduct a multisite randomised controlled trial with three arms. Participants (n=220) will be recruited from concussion clinics and emergency departments in three Canadian provinces and randomly assigned (1:2:2 ratio) to receive enhanced usual care, GET or prescribed aerobic exercise. The outcome assessment will occur remotely 14-18 weeks following baseline assessment, after completing the 12-week treatment phase. The primary outcome will be symptom severity (Rivermead Post-concussion Symptoms Questionnaire). ETHICS AND DISSEMINATION: Informed consent will be obtained from all participants. All study procedures were approved by the local research ethics boards (University of British Columbia Clinical Research Ethics Board, University of Calgary Conjoint Health Research Ethics Board, University Health Network Research Ethics Board-Panel D). Operational approvals were obtained for Vancouver Coastal Health Research Institute and Provincial Health Services Authority. If GET proves effective, we will disseminate the GET treatment manual and present instructional workshops for clinicians. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov #NCT05365776.

Central amygdala CRF+ neurons promote heightened threat reactivity following early life adversity in mice.

Failure to appropriately predict and titrate reactivity to threat is a core feature of fear and anxiety-related disorders and is common following early life adversity (ELA). A population of neurons in the lateral central amygdala (CeAL) expressing corticotropin releasing factor (CRF) have been proposed to be key in processing threat of different intensities to mediate active fear expression. Here, we use in vivo fiber photometry to show that ELA results in sex-specific changes in the activity of CeAL CRF+ neurons, yielding divergent mechanisms underlying the augmented startle in ELA mice, a translationally relevant behavior indicative of heightened threat reactivity and hypervigilance. Further, chemogenic inhibition of CeAL CRF+ neurons selectively diminishes startle and produces a long-lasting suppression of threat reactivity. These findings identify a mechanism for sex-differences in susceptibility for anxiety following ELA and have broad implications for understanding the neural circuitry that encodes and gates the behavioral expression of fear.

Disengagement of somatostatin neurons from lateral septum circuitry by oxytocin and vasopressin restores social-fear extinction and suppresses aggression outbursts in Prader-Willi syndrome model.

Background: Responding to social signals by expressing the correct behavior is not only challenged in autism, but also in diseases with high prevalence of autism, like Prader-Willi Syndrome (PWS). Clinical evidence suggests aberrant pro-social behavior in patients can be regulated by intranasal oxytocin (OXT) or vasopressin (AVP). However, what neuronal mechanisms underlie impaired behavioral responses in a socially-aversive context, and how can they be corrected, remains largely unknown. Methods: Using the Magel2 knocked-out (KO) mouse model of PWS (crossed with CRE-dependent transgenic lines), we devised optogenetic, physiological and pharmacological strategies in a social-fear-conditioning paradigm. Pathway specific roles of OXT and AVP signaling were investigated converging on the lateral septum (LS), a region which receives dense hypothalamic inputs. Results: OXT and AVP signaling promoted inhibitory synaptic transmission in the LS, which failure in Magel2KO mice disinhibited somatostatin (SST) neurons and disrupted social-fear extinction. The source of OXT and AVP deficits mapped specifically in the supraoptic nucleus→LS pathway of Magel2KO mice disrupting social-fear extinction, which could be corrected by optogenetic or pharmacological inhibition of SST-neurons in the LS. Interestingly, LS SST-neurons also gated the expression of aggressive behavior, possibly as part of functional units operating beyond local septal circuits. Conclusions: SST cells in the LS play a crucial role in integration and expression of disrupted neuropeptide signals in autism, thereby altering the balance in expression of safety versus fear. Our results uncover novel mechanisms underlying dysfunction in a socially-aversive context, and provides a new framework for future treatments in autism-spectrum disorders.

Phospholipase C beta 1 in the dentate gyrus gates fear memory formation through regulation of neuronal excitability.

Memory processes rely on a molecular signaling system that balances the interplay between positive and negative modulators. Recent research has focused on identifying memory-regulating genes and their mechanisms. Phospholipase C beta 1 (PLCß1), highly expressed in the hippocampus, reportedly serves as a convergence point for signal transduction through G protein-coupled receptors. However, the detailed role of PLCß1 in memory function has not been elucidated. Here, we demonstrate that PLCß1 in the dentate gyrus functions as a memory suppressor. We reveal that mice lacking PLCß1 in the dentate gyrus exhibit a heightened fear response and impaired memory extinction, and this excessive fear response is repressed by upregulation of PLCß1 through its overexpression or activation using a newly developed optogenetic system. Last, our results demonstrate that PLCß1 overexpression partially inhibits exaggerated fear response caused by traumatic experience. Together, PLCß1 is crucial in regulating contextual fear memory formation and potentially enhancing the resilience to trauma-related conditions.

Fear of cancer progression and the quality of sexual life of female cancer patients in Romania.

Introduction: As cancer survival rates increase, it has become crucial to pay attention to the long-term quality of life of survivors, including sexual functioning. The quality of sexual life and fear of cancer progression are often unmet needs, significantly impacting cancer patients' overall quality of life. In this study, we investigate these factors in Romanian female cancer patients and highlight their relationship with mental health and demographic variables. Methods: This study included 242 Romanian female cancer patients who completed questionnaires assessing sexual functioning (EORTC QLQ-SHQ22), fear of cancer progression (FoP-Q), depression (PHQ-9), and anxiety (GAD-7). We examined these relationships using descriptive, exploratory, and regression analyses. Results: Around 50% of patients reported impairments in sexual satisfaction and pain during sex. Lower sexual satisfaction increased sexual dysfunction, and heightened fear of cancer progression (FCP) were associated with depression, anxiety, younger age, lower education, rural residence, and unmarried status. Discussion: This study reveals a complex interplay between sexual health, fear of cancer progression, and psychological well-being among female cancer survivors in Romania. Addressing sexual concerns, providing psychoeducation, promoting coping with the fear of progression, and utilizing interdisciplinary interventions are essential to improving these patients' overall quality of life. These findings underscore the need for integrated care approaches that consider both physical and psychological dimensions of cancer survivorship.

Fear attenuation collaborations to optimize translation.

Here, we describe the efforts we dedicated to the challenge of modifying entrenched emotionally laden memories. In recent years, through a number of collaborations and using a combination of behavioral, molecular, and computational approaches, we: (a) developed novel approaches to fear attenuation that engage mechanisms that differ from those engaged during extinction (Monfils), (b) examined whether our approaches can generalize to other reinforcers (Lee, Gonzales, Chaudhri, Cofresi, and Monfils), (c) derived principled explanations for the differential outcomes of our approaches (Niv, Gershman, Song, and Monfils), (d) developed better assessment metrics to evaluate outcome success (Shumake and Monfils), (e) identified biomarkers that can explain significant variance in our outcomes of interest (Shumake and Monfils), and (f) developed better basic research assays and translated efforts to the clinic (Smits, Telch, Otto, Shumake, and Monfils). We briefly highlight each of these milestones and conclude with final remarks and extracted principles. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Fear of Falling: Exploring Associated Factors among Elderly Residents in the Rural Communities of Vietnam.

This research aimed to explore factors associated with the fear of falling (FOF) among community-dwelling older adults in Vietnam. A cross-sectional study was conducted in five communes in Soc Son, Hanoi, Vietnam, from March to June 2017. We recruited a total of 487 participants, which provided sufficient data for analysis. The outcome variable was fear of falling. Several covariates, including demographics, medical history, general health status, geriatric syndromes, eye diseases, assessment of fall risk environment, timed up-and-go test, and number of standing up in 30 s, were collected. A multivariable logistic regression model was performed to determine predictors associated with FOF. The results showed that 54.6% of the participants had FOF. Furthermore, the logistic multivariable regression model revealed several factors associated with FOF among participants in the research sites, including polypharmacy status (OR: 1.79; 95%CI 1.07-2.99), higher scores in quality of life according to the EQ-5D-5L index (OR:6.27; 95%CI: 2.77-14.17), and having fallen during the past 12 months (OR:4.4; 95%CI: 2.39-8.11). These findings contribute to a comprehensive understanding of the intricate relationship between FOF and several associated factors, notably polypharmacy status, quality of life, and having a fall during the past 12 months.

Activation of Gs Signaling in Cortical Astrocytes Does Not Influence Formation of a Persistent Contextual Memory Engram.

Formation and retrieval of remote contextual memory depends on cortical engram neurons that are defined during learning. Manipulation of astrocytic Gq and Gi associated G-protein coupled receptor (GPCR) signaling has been shown to affect memory processing, but little is known about the role of cortical astrocytic Gs-GPCR signaling in remote memory acquisition and the functioning of cortical engram neurons. We assessed this by chemogenetic manipulation of astrocytes in the medial prefrontal cortex (mPFC) of male mice, during either encoding or consolidation of a contextual fear memory, while simultaneously labeling cortical engram neurons. We found that stimulation of astrocytic Gs signaling during memory encoding and consolidation did not alter remote memory expression. In line with this, the size of the mPFC engram population and the recall-induced reactivation of these neurons was unaffected. Hence, our data indicate that activation of Gs-GPCR signaling in cortical astrocytes is not sufficient to alter memory performance and functioning of cortical engram neurons.

Fear of progression among colorectal cancer patients: a latent profile analysis.

PURPOSE: Fear of progression (FoP) leads to poor clinical outcomes in colorectal cancer patients. The study aimed to clarify the profiles and influencing factors of FoP among colorectal cancer patients. METHODS: A cross-sectional study was conducted with 409 colorectal cancer patients. Convenience sampling method was used to select colorectal cancer patients hospitalized in a tertiary-level hospital in Nanjing as the survey subjects. General information questionnaire, Fear of Progression Questionnaire-Short Form, Distress Disclosure Index, and Social Support Rating Scale were used to collect the data. Latent profile analysis was used to explore the latent profiles of FoP in colorectal cancer patients. Additionally, the influencing factors of profiles were explored by Univariate Analysis and Binomial Logistic Regression Analysis. RESULTS: Latent profile analysis identified two subgroups of fear of disease progression: the "fear low-risk profile (83%)", and the "severe fear profile (17%)." Patients with low age, low social support utilization, first hospital admission, severe healthcare burden, and preoperative bowel symptoms were prone to severe fear of disease progression. CONCLUSIONS: There is some heterogeneity in the level of postoperative fear of disease progression in colorectal cancer patients. Doctors and nurses should focus on patients with severe fear and take targeted preventive and psychological care for patients' fear of disease progression as early as possible according to the distribution characteristics of different categories.

Divergent effects of chronic continuous and intermittent social defeat stress on emotional behaviors: Impact on phosphorylated CREB and BDNF protein levels in the rat hippocampus.

Chronic psychosocial stress stands as a significant heterogeneous risk factor for psychiatric disorders. The brain's physiological response to such stress varies based on the frequency and intensity of stress episodes. However, whether stress episodes divergently could affect hippocampal cyclic AMP response element-binding protein (CREB)-brain-derived neurotrophic factor (BDNF) signaling remains unclear, a key regulator of psychiatric symptoms. We aimed to assess how two distinct patterns of social defeat stress exposure impact anxiety- and depression-like behaviors, fear, and hippocampal CREB-BDNF signaling in adult male rats. To explore this, adult male Sprague-Dawley rats were subjected to psychosocial stress using a Resident/Intruder paradigm for ten consecutive days (continuous social defeat stress: [CS]) or ten social defeat stress over the course of 21 days (intermittent social defeat stress [IS]). Behavioral tests (including novelty-suppressed feeding test, forced swimming test, and contextually conditioned fear) were conducted. Protein expression levels of phosphorylated CREB and BDNF in the dorsal and ventral hippocampi were examined. CS led to heightened anxiety-like behavior, fear, and increased levels of phosphorylated CREB in both the dorsal and ventral hippocampi. Conversely, IS resulted in increased anxiety-like behavior and behavioral despair alongside decreased levels of phosphorylated CREB and BDNF, particularly in the dorsal hippocampus. These findings indicate that chronic psychosocial stress divergently affects hippocampal CREB-BDNF signaling and emotional regulation depending on the stress episode. Such insights could enhance our understanding of the molecular basis of the heterogeneity of psychiatric disorders and facilitate the development of innovative treatment approaches to patients with psychiatric disorders.

Social interaction-induced fear memory reduction: exploring the influence of dopamine and oxytocin receptors on memory updating.

It has been well established that a consolidated memory can be updated during the plastic state induced by reactivation. This updating process opens the possibility to modify maladaptive memory. In the present study, we evaluated whether fear memory could be updated to less-aversive level by incorporating hedonic information during reactivation. Thus, male rats were fear conditioned and, during retrieval, a female was presented as a social rewarding stimulus. We found that memory reactivation with a female (but not a male) reduces fear expression within-session and in the test, without presenting reinstatement or spontaneous recovery. Interestingly, this intervention impaired extinction. Finally, we demonstrated that this emotional remodeling to eliminate fear expression requires the activation of dopamine and oxytocin receptors during retrieval. Hence, these results shed new lights on the memory updating process and suggests that the exposure to natural rewarding information such as a female during retrieval reduces a previously consolidated fear memory.

Real-world predictors of changes in fear of COVID-19 in the Japanese general population: a large-scale internet-based cohort study with 20,712 participants.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a respiratory infection that considerably impacts both physical and mental health. In particular, the prolonged nature of psychological issues associated with COVID-19 has become a concern. However, evidence based on longitudinal studies investigating the changes in fear of COVID-19 has been limited, posing a public health challenge. METHODS: We investigated the predictors of changes in the Fear of COVID-19 Scale (FCV-19S) scores in the general Japanese population using data from a large-scale internet-based cohort study. RESULTS: We included 20,712 study participants (mean age = 51.1 years, percentage of males = 49.9%). The baseline FCV-19S score for the research participants was 17.0, and one year later, the FCV-19S score decreased to 15.8. The predictors of increase in FCV-19S scores were older age, male sex, COVID-19 requiring oxygen therapy, higher baseline FCV-19S total score, severe psychological distress, never married, worsening subjective health status, a greater number of COVID-19 vaccinations, a history of alcohol dependency, and living with family members. Conversely, the predictors of decrease in FCV-19S scores included habitual alcohol intake, COVID-19 not requiring oxygen therapy and a higher household income. Our study was an internet-based survey focused on residents of Japan, which raises the possibility of selection bias and makes it unclear whether the findings can be extrapolated to other countries and cultures. CONCLUSION: During the observation period, the FCV-19S scores significantly decreased. Severe COVID-19 requiring oxygen therapy within one year of baseline was the most impactful predictor of an increase in FCV-19S score. On the other hand, mild COVID-19 not requiring oxygen therapy was a predictor of a decrease in FCV-19S scores. Therefore, we believe that it is necessary to adopt individualized approaches stratified by the severity of the infection when addressing the fear of COVID-19.

Intra-articular Knee Injection Is Less Painful Than Expected.

BACKGROUND: Intra-articular knee injections (IAKI) are commonly used for diagnostic and therapeutic purposes but may induce anxiety and fear. While existing literature has identified the variance between expected and actual pain levels in various medical procedures, this phenomenon remains unexplored in the context of IAKI. OBJECTIVES: To describe the differences between anticipated and experienced pain recorded during IAKI. METHODS: The study cohort included 50 patients who underwent IAKI by an orthopedic specialist in an outpatient clinic. Patients recruited to the study recorded the anticipated and experienced pain, anxiety index, and factors influencing injection related fear. RESULTS: The study population (n=50) demonstrated a significant difference between the pain expected before the injection (mean Visual Analogue Scale [VAS] score 6.19) and the actual experienced (mean VAS score 2.07, P-value < 0.001). Significant differences between anticipated and experienced VAS scores were demonstrated for both females and males. There was a significant difference between males and females in terms of estimated VAS score. There was no significant difference between males and females in term of the experienced VAS score. The difference (delta) between expected and experienced pain differed significantly between sexes. CONCLUSIONS: These findings emphasize the importance of educating patients about expected pain levels during IAKI. Presenting this quantified information may reassure patients that the procedure is not as painful as expected, which can potentially increase the compliance.

Pain, Fear, Anxiety, and Stress: Relations to the Endogenous Opioid System.

Pain, fear, stress, and anxiety are separate yet interrelated phenomena. Each of these concepts has an extensive individual body of research, with some more recent work focusing on points of conceptual overlap. The role of the endogenous opioid system in each of these phenomena is only beginning to be examined and understood. Research examining the ways in which endogenous opioids (e.g., beta-endorphin; ßE) may mediate the relations among pain, fear, stress, and anxiety is even more nascent. This chapter explores the extant evidence for endogenous opioid activity as an underpinning mechanism of these related constructs, with an emphasis on research examining ßE.

An ultra-short-acting benzodiazepine in thalamic nucleus reuniens undermines fear extinction via intermediation of hippocamposeptal circuits.

Benzodiazepines, commonly used for anxiolytics, hinder conditioned fear extinction, and the underlying circuit mechanisms are unclear. Utilizing remimazolam, an ultra-short-acting benzodiazepine, here we reveal its impact on the thalamic nucleus reuniens (RE) and interconnected hippocamposeptal circuits during fear extinction. Systemic or RE-specific administration of remimazolam impedes fear extinction by reducing RE activation through A type GABA receptors. Remimazolam enhances long-range GABAergic inhibition from lateral septum (LS) to RE, underlying the compromised fear extinction. RE projects to ventral hippocampus (vHPC), which in turn sends projections characterized by feed-forward inhibition to the GABAergic neurons of the LS. This is coupled with long-range GABAergic projections from the LS to RE, collectively constituting an overall positive feedback circuit construct that promotes fear extinction. RE-specific remimazolam negates the facilitation of fear extinction by disrupting this circuit. Thus, remimazolam in RE disrupts fear extinction caused by hippocamposeptal intermediation, offering mechanistic insights for the dilemma of combining anxiolytics with extinction-based exposure therapy.

Dynamic Fear in Fear Appeals: Applying Fear Appeals to Environmental Communication in China.

This study investigates the role of dynamic fear in the effectiveness of communicating health threats (i.e. fear appeals) of ground-level ozone among Chinese citizens. An online survey revealed that fear appeal messages effectively enhance the audience's risk perceptions, efficacy beliefs, and acceptance of the message. Crucially, dynamic fear reduction process positively predicts engagement in protective behaviors (i.e. danger control process) and negatively predicts engagement in fear control processes, such as message denial. Presenting severity before susceptibility resulted in a more positive attitude toward the message recommendation. These findings highlight that communicating health-threats about climate pollution is effective in raising awareness and motivating protective behaviors. Furthermore, our study underscores the importance of dynamic fear, specifically fear reduction, in increasing fear appeals' effectiveness in communicating climate issues from a health perspective.