Seizing the moment: The opportunity and relevance of the California Conservation Genomics Project to state and federal conservation policy.

Conservation science and environmental regulation are sibling constructs of the latter half of the 20th century, part of a more general awakening to humanity's effect on the natural world in the wake of 2 world wars. Efforts to understand the evolution of biodiversity using the models of population genetics and the data derived from DNA sequencing, paired with legal and political mandates to protect biodiversity through novel laws, regulations, and conventions arose concurrently. The extremely rapid rate of development of new molecular tools to document and compare genetic identities, and the global goal of prioritizing species and habitats for protection are separate enterprises that have benefited from each other, ultimately leading to improved outcomes for each. In this article, we explore how the California Conservation Genomics Project has, and should, contribute to ongoing and future conservation implementation, and how it serves as a model for other geopolitical regions and taxon-oriented conservation efforts. One of our primary conclusions is that conservation genomics can now be applied, at scale, to inform decision-makers and identify regions and their contained species that are most resilient, and most in need of conservation interventions.

Landscape Genomics to Enable Conservation Actions: The California Conservation Genomics Project.

The California Conservation Genomics Project (CCGP) is a unique, critically important step forward in the use of comprehensive landscape genetic data to modernize natural resource management at a regional scale. We describe the CCGP, including all aspects of project administration, data collection, current progress, and future challenges. The CCGP will generate, analyze, and curate a single high-quality reference genome and 100-150 resequenced genomes for each of 153 species projects (representing 235 individual species) that span the ecological and phylogenetic breadth of California's marine, freshwater, and terrestrial ecosystems. The resulting portfolio of roughly 20 000 resequenced genomes will be analyzed with identical informatic and landscape genomic pipelines, providing a comprehensive overview of hotspots of within-species genomic diversity, potential and realized corridors connecting these hotspots, regions of reduced diversity requiring genetic rescue, and the distribution of variation critical for rapid climate adaptation. After 2 years of concerted effort, full funding ($12M USD) has been secured, species identified, and funds distributed to 68 laboratories and 114 investigators drawn from all 10 University of California campuses. The remaining phases of the CCGP include completion of data collection and analyses, and delivery of the resulting genomic data and inferences to state and federal regulatory agencies to help stabilize species declines. The aspirational goals of the CCGP are to identify geographic regions that are critical to long-term preservation of California biodiversity, prioritize those regions based on defensible genomic criteria, and provide foundational knowledge that informs management strategies at both the individual species and ecosystem levels.

Putative COVID- 19 Induction of Reward Deficiency Syndrome (RDS) and Associated Behavioral Addictions with Potential Concomitant Dopamine Depletion: Is COVID-19 Social Distancing a Double Edged Sword?

BACKGROUND: The overwhelming fatalities of the global COVID-19 Pandemic will have daunting epigenetic sequala that can translate into an array of mental health issues, including panic, phobia, health anxiety, sleep disturbances to dissociative like symptoms including suicide. Method: We searched PUBMED for articles listed using the search terms "COVID 19 Pandemic", COVID19 and genes," "stress and COVID 19", Stress and Social distancing: Results: Long-term social distancing may be neurologically harmful, the consequence of epigenetic insults to the gene encoding the primary receptor for SARS-CoV2, and COVID 19. The gene is Angiotensin I Converting-Enzyme 2 (ACE2). According to the multi-experiment matrix (MEM), the gene exhibiting the most statistically significant co-expression link to ACE2 is Dopa Decarboxylase (DDC). DDC is a crucial enzyme that participates in the synthesis of both dopamine and serotonin. SARS-CoV2-induced downregulation of ACE2 expression might reduce dopamine and serotonin synthesis, causing hypodopaminergia. Discussion: Indeed, added to the known reduced dopamine function during periods of stress, including social distancing the consequence being both genetic and epigenetic vulnerability to all Reward Deficiency Syndrome (RDS) addictive behaviors. Stress seen in PTSD can generate downstream alterations in immune functions by reducing methylation levels of immune-related genes. Conclusion: Mitigation of these effects by identifying subjects at risk and promoting dopaminergic homeostasis to help regulate stress-relative hypodopaminergia, attenuate fears, and prevent subsequent unwanted drug and non-drug RDS type addictive behaviors seems prudent.

Adapting Urban Water Systems to Manage Scarcity in the 21st Century: The Case of Los Angeles.

Acute water shortages for large metropolitan regions are likely to become more frequent as climate changes impact historic precipitation levels and urban population grows. California and Los Angeles County have just experienced a severe four year drought followed by a year of high precipitation, and likely drought conditions again in Southern California. We show how the embedded preferences for distant sources, and their local manifestations, have created and/or exacerbated fluctuations in local water availability and suboptimal management. As a socio technical system, water management in the Los Angeles metropolitan region has created a kind of scarcity lock-in in years of low rainfall. We come to this through a decade of coupled research examining landscapes and water use, the development of the complex institutional water management infrastructure, hydrology and a systems network model. Such integrated research is a model for other regions to unpack and understand the actual water resources of a metropolitan region, how it is managed and potential ability to become more water self reliant if the institutions collaborate and manage the resource both parsimoniously, but also in an integrated and conjunctive manner. The Los Angeles County metropolitan region, we find, could transition to a nearly water self sufficient system.

A Systematic, Intensive Statistical Investigation of Data from the Comprehensive Analysis of Reported Drugs (CARD) for Compliance and Illicit Opioid Abstinence in Substance Addiction Treatment with Buprenorphine/naloxone.

BACKGROUND: Buprenorphine and naloxone (bup/nal), a combination partial mu receptor agonist and low-dose delta mu antagonist, is presently recommended and used to treat opioid-use disorder. However, a literature review revealed a paucity of research involving data from urine drug tests that looked at compliance and abstinence in one sample. METHOD: Statistical analysis of data from the Comprehensive Analysis of Reported Drugs (CARD) was used to assess compliance and abstinence during treatment in a large cohort of bup/nal patients attending chemical-dependency programs from eastern USA in 2010 and 2011. RESULTS: Part 1: Bup/nal was present in 93.4% of first (n = 1,282; p <.0001) and 92.4% of last (n = 1,268; p <.0001) urine samples. Concomitantly, unreported illicit drugs were present in 47.7% (n = 655, p =.0261) of samples. Patients who were compliant to the bup/nal prescription were more likely than noncompliant patients to be abstinent during treatment (p =.0012; odds ratio = 1.69 with 95% confidence interval (1.210, 2.354). Part 2: An analysis of all samples collected in 2011 revealed a significant improvement in both compliance (p < 2.2 × 10-16) and abstinence (p < 2.2 × 10-16) during treatment. Conclusion/Importance: While significant use of illicit opioids during treatment with bup/nal is present, improvements in abstinence and high compliance during maintenance-assisted therapy programs may ameliorate fears of diversion in comprehensive programs. Expanded clinical datasets, the treatment modality, location, and year of sampling are important covariates, for further studies. The potential for long-term antireward effects from bup/nal use requires consideration in future investigations.

Implementation of an automated beach water quality nowcast system at ten California oceanic beaches.

Fecal indicator bacteria like Escherichia coli and entercococci are monitored at beaches around the world to reduce incidence of recreational waterborne illness. Measurements are usually made weekly, but FIB concentrations can exhibit extreme variability, fluctuating at shorter periods. The result is that water quality has likely changed by the time data are provided to beachgoers. Here, we present an automated water quality prediction system (called the nowcast system) that is capable of providing daily predictions of water quality for numerous beaches. We created nowcast models for 10 California beaches using weather, oceanographic, and other environmental variables as input to tuned regression models to predict if FIB concentrations were above single sample water quality standards. Rainfall was used as a variable in nearly every model. The models were calibrated and validated using historical data. Subsequently, models were implemented during the 2017 swim season in collaboration with local beach managers. During the 2017 swim season, the median sensitivity of the nowcast models was 0.5 compared to 0 for the current method of using day-to-week old measurements to make beach posting decisions. Model specificity was also high (median of 0.87). During the implementation phase, nowcast models provided an average of 140 additional days per beach of updated water quality information to managers when water quality measurements were not made. The work presented herein emphasizes that a one-size-fits all approach to nowcast modeling, even when beaches are in close proximity, is infeasible. Flexibility in modeling approaches and adaptive responses to modeling and data challenges are required when implementing nowcast models for beach management.

Granger causality reveals a dominant role of memory circuit in chronic opioid dependence.

Resting-state magnetic resonance imaging has uncovered abnormal functional connectivity in heroin-dependent individuals (HDIs). However, it remains unclear how brain regions implicated in addictions are related in baseline state without conditioned cues in heroin dependent individuals during opioid maintenance treatment (HDIs-OMT). Previous connectivity analysis assessed the strength of correlated activity between brain regions but lacked the ability to infer directional neural interactions. In the current study, we employed Granger causality analysis to investigate directional causal influences among the brain circuits in HDIs-OMT and non-opioid users. The results revealed a weaker effective connectivity between the caudate nucleus implicated in mediating the reward circuit and other brain regions and also a weaker connectivity between the anterior cingulate cortex and medial prefrontal cortex implicated in mediating inhibitory control. Conversely, HDIs-OMT exhibited stronger effective connectivity between the hippocampus and amygdala implicated in mediating learning-memory, and the anterior cingulate cortex involved in mediating inhibitory control while the putamen mediated learned habits, suggesting that the hippocampus and amygdala may propel the memory circuit to override the control circuit and drive the learned habit in HDIs-OMT. Alterations in learning-memory and inhibitory control may contribute jointly and form a basis for relapse risk even after a period of heroin abstinence. Sustained neural effect of opioid dependence on methadone maintenance including hyperactivation in the memory circuit and impairment in the control circuit support the role of the memory circuitry in relapse and may help redefine targets for treatment.

Preclinical evidence for the addiction potential of highly palatable foods: Current developments related to maternal influence.

It is well established that obesity has reached pandemic proportions. Over the last four decades the prevalence of obesity and morbid obesity have risen substantially in both men and women worldwide. Although there are many causative factors leading to excessive weight gain including genetics and sedentary lifestyle, the transformation of the food environment has undoubtedly contributed to the dangerously high rates of obesity. The current food landscape is inundated with food engineered to contain artificially high levels of sugar and fat. Overconsumption of these types of food overrides the homeostatic mechanisms, which under normal circumstances regulate appetite and body mass, leading to hedonic eating. Evidence from the animal literature has illustrated nutrition-influenced perturbations that occur within the mesolimbic dopamine pathway, as well as maladaptive behavioral responses that result from chronic ingestion of highly palatable foods. These neurobehavioral adaptations are similar to what is observed in drugs of abuse. Recent evidence also supports that maternal exposure to these foods is capable of provoking neurobehavioral alterations in offspring. Therefore the purpose of this review is to summarize the current developments on the addictive potential of highly palatable foods, as well as illuminate the impact of maternal hyperphagia and obesity on the reward-related neurocircuitry and addiction-like behaviors in the offspring.

A REVIEW OF KETAMINE ABUSE AND DIVERSION.

Ketamine was discovered in the 1960s and released for public use in 1970. Originally developed as a safer alternative to phencyclidine, ketamine is primarily used in clinical settings for analgesia and sedation. In recent years, other uses have been developed, including pain management and treatment of asthma and depression. Clinical use of ketamine causes dissociation and emergence delirium. These effects have led to recreational abuse. Although death from direct pharmacologic effects appears rare, the disinhibition and altered sensory perceptions caused by ketamine puts users at risk of environmental harm. Ketamine has also been implicated in nonconsensual sexual intercourse. Data continue to build that chronic ketamine use may lead to morbidity. Impairment of memory and persistent dissociative, depressive, and delusional thinking has also been reported with long-term use. Lower urinary tract symptoms, including cystitis have been described. Gastric and hepatic pathology have also been noted, including abnormal liver function tests, choledochal cysts and dilations of the common bile duct. S-ketamine, an enantiomer in racemic ketamine, has been shown to be hepatotoxic in vitro. Abstinence from ketamine may reduce the adverse effects of chronic use and is considered the mainstay of treatment. Specialized urine drug testing may be required to detect use, as not all point of care urine drug screens include ketamine.

Should the United States Government Repeal Restrictions on Buprenorphine/Naloxone Treatment?

Attention must be focused on needed changes to the current United States law that restricts physicians who prescribe buprenorphine for the detoxification or treatment of Opioid Use Disorder, to accepting no more than 100 patients. The current system does not provide comprehensive treatment as defined by the American Society of Addiction Medicine (ASAM) criteria. In addition, it suffers from both fragmentation and stigma and will require a significant change to comply with ASAM's call for integrated delivery of comprehensive addiction treatment. This commentary calls for the development and implementation of "best practice," by recommending caution in lifting the 100 patient limit until substantial achievement of this goal occurs. The authors call for an increase to 200 in the patient limit to be restricted to those physicians who are Board Certified in Addiction Medicine by the American Board of Addiction Medicine (ABAM) or in Addiction Psychiatry by the American Board of Psychiatry and Neurology (ABPN), or other responsible medical organizations. Any additional restriction lifting should follow a systemic evolution that rewards and documents competency. Such a system would involve the integration of treatment, treatment systems, and recovery with prescription medication. In addition, it should monitor emotional blunting, treatment progress and initiation of genetic addiction risk testing.

Predicting subsequent relapse by drug-related cue-induced brain activation in heroin addiction: an event-related functional magnetic resonance imaging study.

Abnormal salience attribution is implicated in heroin addiction. Previously, combining functional magnetic resonance imaging (fMRI) and a drug cue-reactivity task, we demonstrated abnormal patterns of subjective response and brain reactivity in heroin-dependent individuals. However, whether the changes in cue-induced brain response were related to relapse was unknown. In a prospective study, we recruited 49 heroin-dependent patients under methadone maintenance treatment, a gold standard treatment (average daily dose 41.8 ± 16.0 mg), and 20 healthy subjects to perform the heroin cue-reactivity task during fMRI. The patients' subjective craving was evaluated. They participated in a follow-up assessment for 3 months, during which heroin use was assessed and relapse was confirmed by self-reported relapse or urine toxicology. Differences between relapsers and non-relapsers were analyzed with respect to the results from heroin-cue responses. Compared with healthy subjects, relapsers and non-relapsers commonly demonstrated significantly increased brain responses during the processing of heroin cues in the mesolimbic system, prefrontal regions and visuospatial-attention regions. However, compared with non-relapsers, relapsers demonstrated significantly greater cue-induced craving and the brain response mainly in the bilateral nucleus accumbens/subcallosal cortex and cerebellum. Although the cue-induced heroin craving was low in absolute measures, the change in craving positively correlated with the activation of the nucleus accumbens/subcallosal cortex among the patients. These findings suggest that in treatment-seeking heroin-dependent individuals, greater cue-induced craving and greater specific regional activations might be related to reward/craving and memory retrieval processes. These responses may predict relapse and represent important targets for the development of new treatment for heroin addiction.

Food consumption and weight gain after cessation of chronic amphetamine administration.

Cessation of drug use often coincides with increased food consumption and weight gain in recovering addicts. However, it is not known whether this phenomenon (particularly the weight gain) is uniquely human, or whether it represents a consequence of drug cessation common across species. To address this issue, rats (n = 10/group) were given systemic injections of D-amphetamine (3 mg/kg) or an equal volume of saline vehicle for 9 consecutive days. Beginning 2 days after the final injection, rats were given free access to a highly palatable food mixture (consisting of sugar and butter) along with their standard chow diet, and food consumption and body weight were measured every 48 h for 30 days. Consistent with clinical observations, amphetamine-treated rats showed a greater increase in body weight over the course of the 30 days relative to vehicle-treated rats. Surprisingly, there was no difference in highly palatable food consumption between amphetamine- and vehicle-treated groups, but the amphetamine-treated group consumed significantly more standard chow than the control group. The finding that a history of chronic amphetamine exposure increases food consumption is consistent with previous work in humans showing that withdrawal from drugs of abuse is associated with overeating and weight gain. The current findings may reflect amphetamine-induced sensitization of mechanisms involved in reward motivation, suggesting that weight gain following drug cessation in humans could be due to similar mechanisms.

Brief educational intervention to improve medical student competence in managing patients exposed to secondhand smoke.

BACKGROUND: Secondhand smoke (SHS) exposure may lead to the development of various diseases and conditions. One way to reduce SHS exposure is to screen for it within each primary care examination so that appropriate counseling can be directed to affected individuals. There has been little attention to improving medical education about SHS exposure and screening. The goal of this study was to develop an SHS-related educational intervention for medical students, with the purpose of improving knowledge regarding consequences of SHS exposure, and increasing intent to screen patients for exposure. METHODS: Medical students (N = 405) were given a measure assessing their knowledge of SHS exposure and intent to screen. Two groups of students served as controls (i.e., a posttest-only group and a pre/posttest group), and one group participated in the SHS education intervention. A factorial analysis with repeated measures and chi-square analyses were used to assess the differences between the groups to determine the impact of the SHS education intervention (ie, online lectures and a standardized patient interaction) on knowledge and intent to screen. RESULTS: Results of pretesting demonstrated that medical students had little knowledge of SHS exposure, averaging scores between 63% and 69% on the examination. One control group was reassessed a year later with no educational intervention. They did not demonstrate a significant change in their pre- to posttest scores, although the vast majority (∼95%) reported intending to screen future patients. Students who participated in the SHS educational intervention significantly improved their scores from pre- to posttest (P <.001), and 100% also reported intending to screen future patients. CONCLUSIONS: This study suggests that brief education regarding the consequences of SHS exposure may improve medical students' knowledge and increase intent to screen. Future research should assess the long-term impact of educational programs on improved clinical care.

A Narrative Review of Current and Emerging Trends in the Treatment of Alcohol Use Disorder.

Alcohol use disorder (AUD) is a significant contributor to morbidity and mortality in the United States. It contributes to over 140,000 annual deaths, to over 200 related diseases and health conditions globally, and accounts for 5.1% of the global disease burden. Despite its substantial impact, AUD remains undertreated, marked by a scarcity of approved medications. This paper explores the current treatment landscape and novel strategies for both alcohol withdrawal syndrome and AUD. Promising results, including the use of psychedelics alongside psychotherapy, noninvasive neural-circuit-based interventions, phosphodiesterase-4 inhibitors, and GLP-1 receptor agonists, have emerged from recent studies. While these advancements show potential, further research is crucial for a comprehensive understanding of their effectiveness. The clear shortage of approved medications and other treatment modalities underscores the pressing need for ongoing research.

Chronic Methylphenidate Effects on Brain Gene Expression: An Exploratory Review.

Methylphenidate (MP) is a psychostimulant commonly prescribed for individuals with attention deficit hyperactivity disorder (ADHD) but it is also taken with and without a prescription for performance enhancement. Prior research has characterized the effects of MP on behavior, cognition, and neurochemistry. This exploratory review covers the uses of MP and examined the effects of MP on gene expression in the brain following exposure. Overall, MP causes a wide-spread potentiation of genes, in a region-specific manner; consequently, inducing neuronal alterations, such as synaptic plasticity and transmission, resulting in observed behaviors and affects. Monoamine neurotransmitters and post-synaptic density protein genes generally had a potentiating effect in gene expression after exposure to MP.

Treatments for Cannabis Use Disorder across the Lifespan: A Systematic Review.

Cannabis use disorder (CUD) is a growing public health concern, with rising prevalence and significant impact on individuals across age groups. This systematic review examines 24 studies investigating pharmacological and non-pharmacological interventions for CUD among adolescents (up to 17), young adults (18-24), and older adults (25-65). Database searches were conducted for randomized controlled trials of CUD interventions reporting outcomes such as cannabis use, abstinence, withdrawal symptoms, and treatment retention. For adolescents, interventions such as contingent rewards and family engagement have shown promise, while young adults benefit from technology-based platforms and peer support. In older adults, pharmacological adjuncts combined with counseling have shown promise in enhancing treatment outcomes. However, optimal treatment combinations remain uncertain, highlighting the need for further research. Addressing CUD requires tailored interventions that acknowledge developmental stages and challenges across the lifespan. Although promising interventions exist, further comparative effectiveness research is needed to delineate the most efficacious approaches.

Exercise Influences the Brain's Metabolic Response to Chronic Cocaine Exposure in Male Rats.

Cocaine use is associated with negative health outcomes: cocaine use disorders, speedballing, and overdose deaths. Currently, treatments for cocaine use disorders and overdose are non-existent when compared to opioid use disorders, and current standard cocaine use disorder treatments have high dropout and recidivism rates. Physical exercise has been shown to attenuate addiction behavior as well as modulate brain activity. This study examined the differential effects of chronic cocaine use between exercised and sedentary rats. The effects of exercise on brain glucose metabolism (BGluM) following chronic cocaine exposure were assessed using Positron Emission Tomography (PET) and [18F]-Fluorodeoxyglucose (FDG). Compared to sedentary animals, exercise decreased metabolism in the SIBF primary somatosensory cortex. Activation occurred in the amygdalopiriform and piriform cortex, trigeminothalamic tract, rhinal and perirhinal cortex, and visual cortex. BGluM changes may help ameliorate various aspects of cocaine abuse and reinstatement. Further investigation is needed into the underlying neuronal circuits involved in BGluM changes and their association with addiction behaviors.

Addressing cortex dysregulation in youth through brain health check coaching and prophylactic brain development.

The Carter Center has estimated that the addiction crisis in the United States (US), if continues to worsen at the same rate, may cost the country approximately 16 trillion dollars by 2030. In recent years, the well-being of youth has been compromised by not only the coronavirus disease 2019 pandemic but also the alarming global opioid crisis, particularly in the US. Each year, deadly opioid drugs claim hundreds of thousands of lives, contributing to an ever-rising death toll. In addition, maternal usage of opioids and other drugs during pregnancy could compromise the neurodevelopment of children. A high rate of DNA polymorphic antecedents compounds the occurrence of epigenetic insults involving methylation of specific essential genes related to normal brain function. These genetic antecedent insults affect healthy DNA and mRNA transcription, leading to a loss of proteins required for normal brain development and function in youth. Myelination in the frontal cortex, a process known to extend until the late 20s, delays the development of proficient executive function and decision-making abilities. Understanding this delay in brain development, along with the presence of potential high-risk antecedent polymorphic variants or alleles and generational epigenetics, provides a clear rationale for embracing the Brain Research Commission's suggestion to mimic fitness programs with an adaptable brain health check (BHC). Implementing the BHC within the educational systems in the US and other countries could serve as an effective initiative for proactive therapies aimed at reducing juvenile mental health problems and eventually criminal activities, addiction, and other behaviors associated with reward deficiency syndrome.