Adverse childhood experiences (ACEs), resilience, and outcomes in older adulthood: A scoping review.

BACKGROUND: Previous research has demonstrated a dose-response relationship between exposure to adverse childhood experiences (ACEs) and adverse outcomes in adulthood. Despite widely known associations, previous reviews have primarily focused on outcomes in younger and middle-aged adults exposed to ACEs to the exclusion of older adults and do not consider the potential role of resilience for understanding outcomes in older adulthood. OBJECTIVE: The present scoping review aimed to examine the extent and nature of existing literature on the influence of ACEs and resilience on the cognitive, physical, mental, and social health outcomes among older adults. METHODS: We conducted a search of five electronic databases (CINAHL, MEDLINE, PsycINFO, AgeLine, Scopus) using the following keywords: adversity, resilience, aging, and older adults. We limited our inclusion criteria to works published in English or French after 1998 as Felitti et al. published the first study describing ACEs in this year. RESULTS: Of the 4926 studies screened, 27 studies met the inclusion criteria. Overall, results from the included studies indicated that exposure to adversity during childhood was associated with worse outcomes in older adulthood. Additionally, we found that resilience and resiliency-related factors (e.g., problem-focused coping strategies) mitigated or reduced harms associated with ACEs to improve outcomes in older adulthood. CONCLUSIONS: Exposure to ACEs is associated with reduced functioning in later adulthood. Findings from this review indicate a need for further exploration into the role of ACEs, and the potential effects of resilience, on health outcomes in older adults to develop better individual- and population-level interventions for this group.

Group Psychological Treatment Preferences of Individuals Living With Chronic Disease: Brief Report of a Saskatchewan-Based Cross-Sectional Survey.

Given that individuals with chronic diseases comorbid with psychological distress experience worse clinical outcomes than those without psychological distress, treatment of the psychological sequalae that accompanies chronic diseases is of utmost importance. Thus, the present study aimed to examine group treatment preferences among adults living with chronic disease in Saskatchewan, Canada. An online survey regarding group treatment preferences was administered to 207 participants living with chronic disease comorbid with psychological distress. The most often reported treatment scenario was virtual sessions (45%) lasting 1 h (51%) and occurring every other week (45%) in the evening (63%) for 3 to4 months (40%). Preferences included a medium group (48%), a relatively closed group nature (ie, only occasional new members; 44%), and group leadership including at least 1 professional living with chronic disease (54%). Future-oriented (81%), supportive (83%), skill-based (95%), and group discussions (78%) were desired treatment characteristics among participants. Survey results showed clear preferences on treatment content and session logistics. Slight variations exist by gender and age, but a consensus can be identified and act as a preliminary treatment plan. This study contributes to the body of literature on psychological treatment preferences for individuals living with chronic disease by outlining the preferred format and composition of groups according to those with lived experience. Group-based psychological treatment for chronic disease patients should account for these preferences to improve its acceptability and usefulness among patients.

A controlled method for the identification of forensic traces from clandestine grave fill.

Deceased human remains are often buried as a forensic countermeasure or method of disposal by homicide perpetrators. Owing to this, the excavation of clandestine grave sites is a task that forensic crime scene teams may only encounter a few times a year. Not all crime scene units have specialised teams for this task, and even those that do, may not have specific protocols for the optimal recovery of forensic traces retained within grave fill as procedures such as sieving require optimisation for the specific soil conditions of the jurisdiction. This study aimed to define the optimal sieving conditions for a sandy environment when searching for minute traces of paint, glass, hair and fibres. Furthermore, this study justifies the practice of retaining grave fill and examining it under controlled laboratory conditions, rather than in-situ adjacent to the grave site. The results demonstrate that using sieve mesh sizes as fine as 0.1 mm can recover up to 82% of the deposited traces and almost all paint, hair and glass traces. The processing of grave fill in the laboratory lead to increased yield of forensic evidence, which on a case-basis may warrant the increased time needed. These findings merit consideration for clandestine grave crime scenes where evidence is scarce or the case is likely to become cold.

Designing a virtual course for essential care partners (ECPs) in long-term care (LTC): a pre-implementation study.

Objectives: We describe our co-design process aimed at supporting the reintegration of essential care partners into long-term care homes during the COVID-19 pandemic.Methods: More specifically, using a co-design process, we describe the pre-design, generative, and evaluative phases of developing a virtual infection prevention and control course for essential care partners at our partnering long-term care home. For the evaluative phase, we also provide an overview of our findings from interviews conducted with essential care partners on the expected barriers and facilitators associated with this virtual course.Results: Results from these interviews indicated that the virtual course was viewed as comprehensive, detailed, engaging, refreshing, and reliable, and that its successful implementation would require appropriate resources and support to ensure its sustainability and sustainment. Findings from this study provide guidance for the post-design phase of our co-design process.Conclusion: Our careful documentation of our co-design process also facilitates its replication for other technological interventions and in different healthcare settings. Limitations of the present study and implications for co-designing in the context of emergent public health emergencies are explored in the discussion.

The Art of Hormone Replacement Therapy (HRT) in Menopause Management.

Hormone replacement therapy (HRT) is considered the gold standard for management of vasomotor and vaginal symptoms of menopause. Vasomotor symptoms of menopause may include hot flashes and diaphoresis that vary in intensity and duration. Other symptoms of menopause can include vaginal atrophy and dryness, leading to dyspareunia and increased risk of infection. These symptoms can be impactful on a woman's life and HRT has data to support its efficacy, however, HRT carries significant risks that are generally well known, including risk of stroke, cardiovascular disease, breast cancer, and venous thromboembolism. These risks were most well characterized by several landmark trials published in the early 2000s. There are several nuances to prescribing HRT that can make doing so complex. These include consideration of cyclic vs continuous administration and of tapering therapy. Additionally, estrogen is available in a variety of dosage forms including injections and transdermal formulations. However, for women with an intact uterus, estrogen will need to be combined with progestin or bazedoxifene (a selective estrogen receptor modulator - SERM), both once daily oral formulations, in order to minimize malignancy risk. Though product preference and considerations of dosing may vary depending on practitioner preference, this brief report aims to clarify some nuances to prescribing or recommending HRT.

Improving Family Presence in Long-Term Care during the COVID-19 Pandemic.

Family caregivers play a vital role in supporting the physical and mental health of long-term care (LTC) residents. Due to LTC visitor restrictions during the COVID-19 pandemic, residents (as well as family caregivers) showed significant adverse health outcomes due to a lack of family presence. To respond to these outcomes, eight implementation science teams led research projects in conjunction with Canadian LTC homes to promote the implementation of interventions to improve family presence. Overall, technological and virtual innovations, increased funding to the sector and partnerships with family caregivers were deemed effective methods to promote stronger family presence within LTC.

Behavioural and dopaminergic signatures of resilience.

Chronic stress can have lasting adverse consequences in some individuals, yet others are resilient to the same stressor1,2. Susceptible and resilient individuals exhibit differences in the intrinsic properties of mesolimbic dopamine (DA) neurons after the stressful experience is over3-8. However, the causal links between DA, behaviour during stress and individual differences in resilience are unknown. Here we recorded behaviour in mice simultaneously with DA neuron activity in projections to the nucleus accumbens (NAc) (which signals reward9-12) and the tail striatum (TS) (which signals threat13-16) during social defeat. Supervised and unsupervised behavioural quantification revealed that during stress, resilient and susceptible mice use different behavioural strategies and have distinct activity patterns in DA terminals in the NAc (but not the TS). Neurally, resilient mice have greater activity near the aggressor, including at the onset of fighting back. Conversely, susceptible mice have greater activity at the offset of attacks and onset of fleeing. We also performed optogenetic stimulation of NAc-projecting DA neurons in open loop (randomly timed) during defeat or timed to specific behaviours using real-time behavioural classification. Both open-loop and fighting-back-timed activation promoted resilience and reorganized behaviour during defeat towards resilience-associated patterns. Together, these data provide a link between DA neural activity, resilience and resilience-associated behaviour during the experience of stress.

Assisted versus referred pharmacy smoking interventions for patients with thoracic malignancies or pulmonary nodules.

BACKGROUND: Tobacco use is the foremost preventable cause of death, disease, and disability in the United States. Continued tobacco use in malignant disease contributes to treatment failure and disease progression. Pharmacists are pivotal to tobacco cessation counseling, management, and follow up. METHODS: This retrospective, observational, single-center, cohort study of ambulatory cancer patients was designed to assess the impact of assisted versus "Ask, Advise, Refer" (AAR) pharmacy-driven smoking cessation interventions on patient-reported quit rates at 30- and 90-days. Those included were currently smoking or recently quit adults with a thoracic malignancy or nodule. Those in the assisted intervention were offered nicotine replacement therapy (NRT) for free according to a personalized quit plan. After July 1, 2020, patients were enrolled in the AAR intervention, whereby participants were referred to obtain NRT through insurance or external resources. Both clinical interventions were provided as standard of care. RESULTS: 129 participants were included (assisted n = 83; AAR n = 46) with baseline characteristics evenly matched. After excluding those unable to be reached at 30-days, 30 (44.8%) in the assisted intervention quit smoking versus 11 (27.5%) in the AAR intervention, p = 0.08. Lung cancer patients were more likely to report quitting at 30-days in the assisted intervention, 16 (64.0%) versus 5 (29.4%) in the AAR intervention, p = 0.03. After excluding those unable to be reached at 90-days, 30 (45.5%) in the assisted intervention quit versus 11 (35.5%) in the AAR intervention, p = 0.35. CONCLUSIONS: Pharmacy-led smoking cessation initiatives that include providing NRT are especially impactful on smoking cessation in lung cancer patients.

A systematic review of integrative medicine for opioid withdrawal.

INTRODUCTION: The United States has been battling an opioid epidemic for decades. As substance use disorders have grown, so too has investigation into treatment options, including integrative medicine approaches, for managing opioid withdrawal symptoms (OWS). OBJECTIVES: This systematic review sought to assess the use of integrative medicine approaches for the alleviation of OWS in patients dependent on opioids and to summarize the available data. METHODS: The authors searched using synonyms for opioids, substance use disorder, and integrative medicine and standardized searches in Embase, PubMed, and Cochrane Library. We also hand searched references for systematic reviews. This review did not include articles that could not be obtained as full-text publications via interlibrary loan. The review also excluded studies with interventions involving acupuncture because multiple systematic reviews on this approach already exist. In addition, we also excluded studies of therapy for opioid maintenance. We evaluated studies for inclusion based on the Jadad criteria. We compared opioid withdrawal outcomes of the studies to determine the efficacy of integrative medicine approaches. RESULTS: The authors identified a total of 382 unique publications initially for possible inclusion through systematic searches. After applying inclusion and exclusion criteria, five studies met Jadad criteria. The authors identified an additional two studies for inclusion via hand searching. A total of seven studies included interventions consisting of passionflower, weinicom, fu-yuan pellet, jinniu capsules, tai-kang-ning, dynorphin, and l-tetrahydropalmatine. Analyzing the articles was difficult given the varied scoring methods they used to quantify opioid withdrawal symptoms and the small sample sizes in the trials. Most showed evidence that supported integrative medicine approaches for OWS, although the strength of evidence was limited because of sample sizes. CONCLUSIONS: This review found evidence of multiple integrative medicine approaches for opioid withdrawal symptoms. Well-designed randomized controlled trials should assess the efficacy of integrative medicine for improvement in OWS.

Neofusicoccum caryigenum, a new species causing leaf dieback disease of pecan (Carya illinoinensis).

Neofusicoccum species are endophytes and pathogens of woody hosts and members of the Botryosphaeriaceae. Leaf dieback is a new disease resulting in death of compound leaves and extensive defoliation of pecan trees (Carya illinoinensis) throughout the southeastern United States. Currently, the disease is consistently most severe on trees that are not managed with fungicides for pecan scab. Preliminary observations of the fungus isolated from symptomatic leaves indicated that it was a member of the genus Neofusicoccum. Our objectives were to confirm that this is the causal organism of leaf dieback disease of pecan and to determine whether this disease is caused by a new or previously described species of Neofusicoccum. Morphological observations of pure cultures, conidiomata, conidiogenous cells, and conidia were consistent with members of the genus Neofusicoccum. Using Koch's postulates, we established that Neofusicoccum sp. isolated from symptomatic leaves caused the disease. We sequenced the internal transcribed spacer of the rDNA (ITS), elongation factor 1-α (EF1-α), the second largest subunit of RNA polymerase II (RPB2), and ß-tubulin (TUB2) of 11 isolates collected from Georgia and Texas. Phylogenetic and network analyses of these sequences combined with publicly available sequences of 40 members of the N. parvum-N. ribis species complex and the outgroup N. australe revealed that this fungus is a member of the species complex but is genetically distinct from previously described species. We determined that leaf dieback of pecan is caused by a novel species, named herein N. caryigenum.

Mechanisms Underlying the Anti-Suicidal Treatment Potential of Buprenorphine.

Death by suicide is a global epidemic with over 800 K suicidal deaths worlwide in 2012. Suicide is the 10th leading cause of death among Americans and more than 44 K people died by suicide in 2019 in the United States. Patients with chronic pain, including, but not limited to, those with substance use disorders, are particularly vulnerable. Chronic pain patients have twice the risk of death by suicide compared to those without pain, and 50% of chronic pain patients report that they have considered suicide at some point due to their pain. The kappa opioid system is implicated in negative mood states including dysphoria, depression, and anxiety, and recent evidence shows that chronic pain increases the function of this system in limbic brain regions important for affect and motivation. Additionally, dynorphin, the endogenous ligand that activates the kappa opioid receptor is increased in the caudate putamen of human suicide victims. A potential treatment for reducing suicidal ideation and suicidal attempts is buprenorphine. Buprenorphine, a partial mu opioid agonist with kappa opioid antagonist properties, reduced suicidal ideation in chronic pain patients with and without an opioid use disorder. This review will highlight the clinical and preclinical evidence to support the use of buprenorphine in mitigating pain-induced negative affective states and suicidal thoughts, where these effects are at least partially mediated via its kappa antagonist properties.

A Cell Segmentation/Tracking Tool Based on Machine Learning.

The ability to gain quantifiable, single-cell data from time-lapse microscopy images is dependent upon cell segmentation and tracking. Here, we present a detailed protocol for obtaining quality time-lapse movies and introduce a method to identify (segment) and track cells based on machine learning techniques (Fiji's Trainable Weka Segmentation) and custom, open-source Python scripts. To provide a hands-on experience, we provide datasets obtained using the aforementioned protocol.

Increased Cocaine Motivation Is Associated with Degraded Spatial and Temporal Representations in IL-NAc Neurons.

Craving for cocaine progressively increases in cocaine users during drug-free periods, contributing to relapse. The projection from the infralimbic cortex to the nucleus accumbens shell (IL-NAc) is thought to inhibit cocaine seeking. However, it is not known whether and how IL-NAc neurons contribute to the increased motivation associated with a drug-free period. We first performed cellular resolution imaging of IL-NAc neurons in rats during a drug-seeking test. This revealed neurons with spatial selectivity within the cocaine-associated context, a decrease in activity around the time of cocaine seeking, and an inverse relationship between cocaine-seeking activity and subsequent cocaine motivation. All these properties were reduced by a drug-free period. Next, we transiently activated this projection, which resulted in reduced drug seeking, regardless of the drug-free period. Taken together, this suggests that altered IL-NAc activity after a drug-free period may enhance cocaine motivation without fundamentally altering the projection's ability to inhibit drug seeking.

One month of cocaine abstinence potentiates rapid dopamine signaling in the nucleus accumbens core.

Cocaine addiction is a chronic relapsing disorder that is difficult to treat in part because addicts relapse even after extended periods of abstinence. Given the importance of the mesolimbic dopamine (DA) system in drug addiction, we sought to characterize cocaine abstinence induced changes in rapid DA signaling in the nucleus accumbens (NAc). Here, rats were trained to self-administer cocaine for 14 consecutive days, then divided into two groups. Day 1 rats (D1; n = 7) underwent 24 h of abstinence; Day 30 rats (D30; n = 7) underwent one month of abstinence. After abstinence, all rats underwent a single extinction session. Immediately after, rats were deeply anesthetized and fast scan cyclic voltammetry (FSCV) was used to measure DA release and uptake dynamics in the NAc core before and following a single cocaine injection. We show that one month of cocaine abstinence potentiates the peak concentration of electrically evoked DA in the NAc core following an acute injection of cocaine. This potentiation is not related to alterations in DA uptake parameters, which are unchanged following abstinence, but may reflect alterations in release. These results further support the abundance of literature showing that cocaine abstinence induces neuroplasticity in brain areas implicated in drug reward and relapse. The present findings also demonstrate critical differences between abstinence-induced neuroadaptations in DA signaling and those caused by drug exposure itself.

Reward and choice encoding in terminals of midbrain dopamine neurons depends on striatal target.

Dopaminergic (DA) neurons in the midbrain provide rich topographic innervation of the striatum and are central to learning and to generating actions. Despite the importance of this DA innervation, it remains unclear whether and how DA neurons are specialized on the basis of the location of their striatal target. Thus, we sought to compare the function of subpopulations of DA neurons that target distinct striatal subregions in the context of an instrumental reversal learning task. We identified key differences in the encoding of reward and choice in dopamine terminals in dorsal versus ventral striatum: DA terminals in ventral striatum responded more strongly to reward consumption and reward-predicting cues, whereas DA terminals in dorsomedial striatum responded more strongly to contralateral choices. In both cases the terminals encoded a reward prediction error. Our results suggest that the DA modulation of the striatum is spatially organized to support the specialized function of the targeted subregion.

Construction of Training Sets for Valid Calibration of in Vivo Cyclic Voltammetric Data by Principal Component Analysis.

Principal component regression, a multivariate calibration technique, is an invaluable tool for the analysis of voltammetric data collected in vivo with acutely implanted microelectrodes. This method utilizes training sets to separate cyclic voltammograms into contributions from multiple electroactive species. The introduction of chronically implanted microelectrodes permits longitudinal measurements at the same electrode and brain location over multiple recordings. The reliability of these measurements depends on a consistent calibration methodology. One published approach has been the use of training sets built with data from separate electrodes and animals to evaluate neurochemical signals in multiple subjects. Alternatively, responses to unpredicted rewards have been used to generate calibration data. This study addresses these approaches using voltammetric data from three different experiments in freely moving rats obtained with acutely implanted microelectrodes. The findings demonstrate critical issues arising from the misuse of principal component regression that result in significant underestimates of concentrations and improper statistical model validation that, in turn, can lead to inaccurate data interpretation. Therefore, the calibration methodology for chronically implanted microelectrodes needs to be revisited and improved before measurements can be considered reliable.

Dynamics of rapid dopamine release in the nucleus accumbens during goal-directed behaviors for cocaine versus natural rewards.

Electrophysiological studies show that distinct subsets of nucleus accumbens (NAc) neurons differentially encode information about goal-directed behaviors for intravenous cocaine versus natural (food/water) rewards. Further, NAc rapid dopamine signaling occurs on a timescale similar to phasic cell firing during cocaine and natural reward-seeking behaviors. However, it is not known whether dopamine signaling is reinforcer specific (i.e., is released during responding for only one type of reinforcer) within discrete NAc locations, similar to neural firing dynamics. Here, fast-scan cyclic voltammetry (FSCV) was used to measure rapid dopamine release during multiple schedules involving sucrose reward and cocaine self-administration (n = 8 rats) and, in a separate group of rats (n = 6), during a sucrose/food multiple schedule. During the sucrose/cocaine multiple schedule, dopamine increased within seconds of operant responding for both reinforcers. Although dopamine release was not reinforcer specific, more subtle differences were observed in peak dopamine concentration [DA] across reinforcer conditions. Specifically, peak [DA] was higher during the first phase of the multiple schedule, regardless of reinforcer type. Further, the time to reach peak [DA] was delayed during cocaine-responding compared to sucrose. During the sucrose/food multiple schedule, increases in dopamine release were also observed relative to operant responding for both natural rewards. However, peak [DA] was higher relative to responding for sucrose than food, regardless of reinforcer order. Overall, the results reveal the dynamics of rapid dopamine signaling in discrete locations in the NAc across reward conditions, and provide novel insight into the functional role of this system in reward-seeking behaviors.

Repeated methamphetamine administration differentially alters fos expression in caudate-putamen patch and matrix compartments and nucleus accumbens.

BACKGROUND: The repeated administration of psychostimulant drugs produces a persistent and long-lasting increase ("sensitization") in their psychomotor effects, which is thought to be due to changes in the neural circuitry that mediate these behaviors. One index of neuronal activation used to identify brain regions altered by repeated exposure to drugs involves their ability to induce immediate early genes, such as c-fos. Numerous reports have demonstrated that past drug experience alters the ability of drugs to induce c-fos in the striatum, but very few have examined Fos protein expression in the two major compartments in the striatum--the so-called patch/striosome and matrix. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we used immunohistochemistry to investigate the effects of pretreatment with methamphetamine on the ability of a subsequent methamphetamine challenge to induce Fos protein expression in the patch and matrix compartments of the dorsolateral and dorsomedial caudate-putamen and in the ventral striatum (nucleus accumbens). Animals pretreated with methamphetamine developed robust psychomotor sensitization. A methamphetamine challenge increased the number of Fos-positive cells in all areas of the dorsal and ventral striatum. However, methamphetamine challenge induced Fos expression in more cells in the patch than in the matrix compartment in the dorsolateral and dorsomedial caudate-putamen. Furthermore, past experience with methamphetamine increased the number of methamphetamine-induced Fos positive cells in the patch compartment of the dorsal caudate putamen, but not in the matrix or in the core or shell of the nucleus accumbens. CONCLUSIONS/SIGNIFICANCE: These data suggest that drug-induced alterations in the patch compartment of the dorsal caudate-putamen may preferentially contribute to some of the enduring changes in brain activity and behavior produced by repeated treatment with methamphetamine.

Cocaine abstinence alters nucleus accumbens firing dynamics during goal-directed behaviors for cocaine and sucrose.

Distinct subsets of nucleus accumbens (NAc) neurons differentially encode goal-directed behaviors for natural vs. drug rewards [R. M. Carelli et al. (2000)The Journal of Neuroscience, 20, 4255-4266], and the encoding of cocaine-seeking is altered following cocaine abstinence [J. A. Hollander & R. M. Carelli (2007) The Journal of Neuroscience, 27, 3535-3539]. Here, electrophysiological recording procedures were used to determine if the selective encoding of natural vs. cocaine reward by NAc neurons is: (i) maintained when the natural reinforcer is a highly palatable sweet tastant and (ii) altered by cocaine abstinence. Rats (n = 14) were trained on a multiple schedule of sucrose reinforcement and cocaine self-administration (2-3 weeks) and NAc activity was recorded during the task before and after 30 days of cocaine abstinence. Of 130 cells recorded before abstinence, 82 (63%) displayed patterned discharges (increases or decreases in firing rate, termed phasic activity) relative to operant responding for sucrose or cocaine. As in previous reports, the majority of those cells displayed nonoverlapping patterns of activity during responding for sucrose vs. cocaine. Specifically, only 17 (21%) showed similar patterns of activity (i.e. overlapping activity) across the two reinforcer conditions. After abstinence, this pattern was largely maintained, 23 of 70 phasic cells (33%) were overlapping. However, cocaine abstinence altered the overall percentage of selectively active neurons across reinforcer conditions. Specifically, significantly more neurons became selectively activated during cocaine-directed behaviors than during sucrose-directed behaviors. The results indicate that, although the selective encoding of cocaine and natural rewards is maintained even with a highly palatable substance, 30 days of cocaine abstinence dynamically alters the overall population encoding of natural and drug rewards by NAc neurons.