Genetic addiction risk and psychological profiling analyses for preaddiction severity index

Since 1990, when our laboratory published the association of th

Future newborns with opioid-induced neonatal abstinence syndrome (NAS) could be assessed with the genetic addiction risk severity (GARS) test and potentially treated using precision amino-acid enkephalinase inhibition therapy (KB220) as a frontline modality instead of potent opioids

In this nonsystematic review and opinion, including articles primarily selected from PubMed, we examine the pharmacological and nonpharmacological treatments of neonatal abstinence syndrome (NAS) in order to craft a reasonable opinion to help forge a paradigm shift in the treatment and prevention of primarily opioid-induced NAS. Newborns of individuals who use illicit and licit substances during pregnancy are at risk for withdrawal, also known as NAS. In the US, the reported prevalence of NAS has increased from 4.0 per 1000 hospital births in 2010 to 7.3 per 1000 hospital births in 2017, which is an 82% increase. The management of NAS is varied and involves a combination of nonpharmacologic and pharmacologic therapy. The preferred first-line pharmacological treatment for NAS is opioid therapy, specifically morphine, and the goal is the short-term improvement in NAS symptomatology. Nonpharmacological therapies are individualized and typically focus on general care measures, the newborn-parent/caregiver relationship, the environment, and feeding. When used appropriately, nonpharmacologic therapies can help newborns with NAS avoid or reduce the amount of pharmacologic therapy required and the length of hospitalization. In addition, genetic polymorphisms of the catechol-o-methyltransferase (COMT) and mu-opioid receptor (OPRM1) genes appear to affect the length of stay and the need for pharmacotherapy in newborns with prenatal opioid exposure. Therefore, based on this extensive literature and additional research, this team of coauthors suggests that, in the future, in addition to the current nonpharmacological therapies, patients with opioid-induced NAS should undergo genetic assessment (i.e., the genetic addiction risk severity (GARS) test), which can subsequently be used to guide DNA-directed precision amino-acid enkephalinase inhibition (KB220) therapy as a frontline modality instead of potent opioids

Statistical validation of risk alleles in Genetic Addiction Risk Severity (GARS) test: Early identification of risk for Alcohol Use Disorder (AUD) in 74,566 case-control subjects

Since 1990, when our laboratory published the association of the DRD2 Taq A1 allele and severe alcoholism i

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

Substance use disorders and behavioral addictions during the COVID-19 pandemic and COVID-19-related restrictions

COVID-19 was first identified in Wuhan, China in December of 2019 and appeared in the United States 1 month later. Between the onset of the pandemic and January 13, 2021, over 92 million people have tested positive for the virus and over 1.9 million people have died globally. Virtually every country in the world has been impacted by this virus. Beginning in March 2020, many U.S. state governments enforced a quarantine to respond to the growing health crisis. Citizens were required to remain at home; schools, restaurants, and non-essential businesses were forced to close, and large gatherings were prohibited. Americans\u27 lives were transformed in a span of days as daily routines were interrupted and people were shuttered indoors. Mounting fear and unpredictability coupled with widespread unemployment and social isolation escalated anxiety and impacted the mental health of millions across the globe. Most (53%) U.S. adults reported that the coronavirus outbreak has had a negative impact on their mental health, including inducing or exacerbating use of alcohol, drugs, gambling and overeating as coping mechanisms. In this paper, we will examine substance use and addictive behaviors that have been used to manage the stress and uncertainty wrought by the COVID-19 pandemic. We review the changing treatment landscape as therapy pivoted online and telemedicine became the norm

Hatching the behavioral addiction egg: Reward Deficiency Solution System (RDSS)™ as a function of dopaminergic neurogenetics and brain functional connectivity linking all addictions under a common rubric

Abstract Background Following the first association between the dopamine D2 receptor gene polymorphism and severe alcoholism, there has been an explosion of research reports in the psychiatric and behavioral addiction literature and neurogenetics. With this increased knowledge, the field has been rife with controversy. Moreover, with the advent of Whole Genome-Wide Studies (GWAS) and Whole Exome Sequencing (WES), along with Functional Genome Convergence, the multiple-candidate gene approach still has merit and is considered by many as the most prudent approach. However, it is the combination of these two approaches that will ultimately define real, genetic allelic relationships, in terms of both risk and etiology. Since 1996, our laboratory has coined the umbrella term Reward Deficiency Syndrome (RDS) to explain the common neurochemical and genetic mechanisms involved with both substance and non-substance, addictive behaviors. Methods This is a selective review of peer-reviewed papers primary listed in Pubmed and Medline. Results A review of the available evidence indicates the importance of dopaminergic pathways and resting-state, functional connectivity of brain reward circuits. Discussion Importantly, the proposal is that the real phenotype is RDS and impairments in the brain's reward cascade, either genetically or environmentally (epigenetically) induced, influence both substance and non-substance, addictive behaviors. Understanding shared common mechanisms will ultimately lead to better diagnosis, treatment and prevention of relapse. While, at this juncture, we cannot as yet state that we have “hatched the behavioral addiction egg”, we are beginning to ask the correct questions and through an intense global effort will hopefully find a way of “redeeming joy” and permitting homo sapiens live a life, free of addiction and pain

Association of Air Pollution with Increased Incidence of Ventricular Tachyarrhythmias Recorded by Implanted Cardioverter Defibrillators

Epidemiologic studies have demonstrated a consistent link between sudden cardiac deaths and particulate air pollution. We used implanted cardioverter defibrillator (ICD) records of ventricular tachyarrhythmias to assess the role of air pollution as a trigger of these potentially life-threatening events. The study cohort consisted of 203 cardiac patients with ICD devices in the Boston metropolitan area who were followed for an average of 3.1 years between 1995 and 2002. Fine particle mass and gaseous air pollution plus temperature and relative humidity were measured on almost all days, and black carbon, sulfate, and particle number on a subset of days. Date, time, and intracardiac electrograms of ICD-detected arrhythmias were downloaded at the patients’ regular follow-up visits (about every 3 months). Ventricular tachyarrhythmias were identified by electrophysiologist review. Risk of ventricular arrhythmias associated with air pollution was estimated with logistic regression, adjusting for season, temperature, relative humidity, day of the week, patient, and a recent prior arrhythmia. We found increased risks of ventricular arrhythmias associated with 2-day mean exposure for all air pollutants considered, although these associations were not statistically significant. We found statistically significant associations between air pollution and ventricular arrhythmias for episodes within 3 days of a previous arrhythmia. The associations of ventricular tachyarrhythmias with fine particle mass, carbon monoxide, nitrogen dioxide, and black carbon suggest a link with motor vehicle pollutants. The associations with sulfate suggest a link with stationary fossil fuel combustion sources

A comparison of regional and general anesthesia in patients undergoing carotid endarterectomy

AbstractPurpose: The optimal anesthetic for use during carotid endarterectomy is controversial. Advocates of regional anesthesia suggest that it may reduce the incidence of perioperative complications in addition to decreasing operative time and hospital costs. To determine whether the anesthetic method correlated with the outcome of the operation, a retrospective review of 3975 carotid operations performed over a 32-year period was performed.Methods: The records of all patients who underwent carotid endarterectomy at our institution from 1962 to 1994 were retrospectively reviewed. Operations performed with the patient under regional anesthesia were compared with those performed with the patient under general anesthesia with respect to preoperative risk factors and perioperative complications.Results: Regional anesthesia was used in 3382 operations (85.1%). There were no significant differences in the age, gender ratio, or the rates of concomitant medical illnesses between the two patient populations. The frequency of perioperative stroke in the series was 2.2%; that of myocardial infarction, 1.7%; and that of perioperative death, 1.5%. There were no statistically significant differences in the frequency of perioperative stroke, myocardial infarction, or death on the basis of anesthetic technique. A trend toward higher frequencies of perioperative stroke (3.2% vs 2.0%) and perioperative death (2.0% vs 1.4%) in the general anesthesia group was noted. In examining operative indications, however, there was a significant increase in the percentage of patients receiving general anesthesia who had sustained preoperative strokes when compared with the regional anesthesia patients (36.1% vs 26.4%; p < 0.01). There was also a statistically significant higher frequency of contralateral total occlusion in the general anesthesia group (21.8% vs 15.4%; p = 0.001). The trend toward increased perioperative strokes in the general anesthesia group may be explicable either by the above differences in the patient populations or by actual differences based on anesthetic technique that favor regional anesthesia.Conclusions: In a retrospective review of a large series of carotid operations, regional anesthesia was shown to be applicable to the vast majority of patients with good clinical outcome. Although the advantages over general anesthesia are perhaps small, the versatility and safety of the technique is sufficient reason for vascular surgeons to include it in their armamentarium of surgical skills. Considering that carotid endarterectomy is a procedure in which complication rates are exceedingly low, a rigidly controlled, prospective randomized trial may be required to accurately assess these differences. (J Vasc Surg 1996;24;946-56.

PATHOS: A Brief Screening Application for Assessing Sexual Addiction

Sexual addiction is estimated to afflict up to 3% to 6% of the population. However, many clinicians lack clear criteria for detecting potential cases. Objectives: The present studies were conducted to assess the effectiveness of a brief sexual addiction screening instrument (ie, PATHOS Questionnaire) to correctly classify patients being treated for sex addiction and healthy volunteers. Methods: In study 1, a 6-item questionnaire, which utilizes the mnemonic PATHOS, was examined in regard to sensitivity and specificity using a sample combining patients being treated for sex addiction and healthy volunteers (970 men/80.2% patients; 938 women/63.8% patients). In study 2, a cross-validation sample of 672 men (93% patients) and 241 women (35.3% patients) completed the PATHOS screener. Results: Results of receiver operating characteristics analyses in study 1 demonstrated that the PATHOS captured 92.6% of the area under the curve and achieved 88.3% sensitivity and 81.6% specificity for classifying the male sample (n = 963) as patients and healthy subjects using a cutoff score of 3. Similarly, the PATHOS captured 90.2% of the area under the curve and, with a cutoff of 3, achieved 80.9% sensitivity and 87.2% specificity for the female sample (n = 808). In study 2, results of receiver operating characteristics analyses indicated that the PATHOS captured 85.1% of the area under the curve, with sensitivity of 70.7% and specificity of 86.9% for men (cutoff of 3). For women, the PATHOS captured 80.9% of the area under the curve and achieved 69.7% sensitivity and 85.1% specificity with the cutoff of 3. Conclusions: These studies provide support for the use of the PATHOS as a screening instrument to detect potential sexual addiction cases in clinical settings