Infant Behaviors, Prenatal Cocaine Exposure, and Adult Intelligence.

Importance: Linking prenatal drug exposures to both infant behavior and adult cognitive outcomes may improve early interventions. Objective: To assess whether neonatal physical, neurobehavioral, and infant cognitive measures mediate the association between prenatal cocaine exposure (PCE) and adult perceptual reasoning IQ. Design, Setting, and Participants: This study used data from a longitudinal, prospective birth cohort study with follow-up from 1994 to 2018 until offspring were 21 years post partum. A total of 384 (196 PCE and 188 not exposed to cocaine [NCE]) infants and mothers were screened for cocaine or polydrug use. Structural equation modeling was performed from June to November 2023. Exposures: Prenatal exposures to cocaine, alcohol, marijuana, and tobacco assessed through urine and meconium analyses and maternal self-report. Main Outcomes and Measures: Head circumference, neurobehavioral assessment, Bayley Scales of Infant Development, Fagan Test of Infant Intelligence score, Wechsler Perceptual Reasoning IQ, Home Observation for Measurement of the Environment (HOME) score, and blood lead level. Results: Among the 384 mothers in the study, the mean (SD) age at delivery was 27.7 (5.3) years (range, 18-41 years), 375 of 383 received public assistance (97.9%) and 336 were unmarried (87.5%). Birth head circumference (standardized estimate for specific path association, -0.05, SE = 0.02; P = .02) and 1-year Bayley Mental Development Index (MDI) (standardized estimate for total of the specific path association, -0.05, SE = 0.02; P = .03) mediated the association of PCE with Wechsler Perceptual Reasoning IQ, controlling for HOME score and other substance exposures. Abnormal results on the neurobehavioral assessment were associated with birth head circumference (ß = -0.20, SE = 0.08; P = .01). Bayley Psychomotor Index (ß = 0.39, SE = 0.05; P < .001) and Fagan Test of Infant Intelligence score (ß = 0.16, SE = 0.06; P = .01) at 6.5 months correlated with MDI at 12 months. Conclusions and Relevance: In this cohort study, a negative association of PCE with adult perceptual reasoning IQ was mediated by early physical and behavioral differences, after controlling for other drug and environmental factors. Development of infant behavioral assessments to identify sequelae of prenatal teratogens early in life may improve long-term outcomes and public health awareness.

Drugs of abuse hijack a mesolimbic pathway that processes homeostatic need.

Drugs of abuse are thought to promote addiction in part by "hijacking" brain reward systems, but the underlying mechanisms remain undefined. Using whole-brain FOS mapping and in vivo single-neuron calcium imaging, we found that drugs of abuse augment dopaminoceptive ensemble activity in the nucleus accumbens (NAc) and disorganize overlapping ensemble responses to natural rewards in a cell type-specific manner. Combining FOS-Seq, CRISPR-perturbation, and single-nucleus RNA sequencing, we identified Rheb as a molecular substrate that regulates cell type-specific signal transduction in NAc while enabling drugs to suppress natural reward consumption. Mapping NAc-projecting regions activated by drugs of abuse revealed input-specific effects on natural reward consumption. These findings characterize the dynamic, molecular and circuit basis of a common reward pathway, wherein drugs of abuse interfere with the fulfillment of innate needs.

Granulomatosis with polyangiitis or its mimic? A case report.

Differentiation between granulomatosis with polyangiitis (GPA) limited to the upper airways and cocaine-induced midline destructive lesion (CIMDL) may be particularly difficult because of their common histopathologic features and antineutrophil cytoplasmic antibody (ANCA) profiles. We herein present a case involving a young woman with an initial diagnosis of GPA based on upper and lower airway manifestations and constitutional symptoms, histopathologic evidence of granulomas, a positive cytoplasmic ANCA indirect immunofluorescent test result, and proteinase 3 positivity by enzyme-linked immunosorbent assay (ELISA). CIMDL was confirmed based on the appearance of a hard palate perforation, positivity for methylecgonine on urine toxicology, a positive perinuclear ANCA indirect immunofluorescent test result, and subsequent human neutrophil elastase (HNE) ANCA positivity by ELISA. Finally, based on the coexistence of CIMDL, constitutional symptoms, and lower airway manifestations, the diagnosis was modified to cocaine-induced GPA mimic. Urine toxicology for cocaine and HNE ELISA are indicated in young patients with GPA who develop limited airway disease to check for the presence of CIMDL and cocaine-/levamisole-induced ANCA-associated vasculitis. Continued abstinence from cocaine is the first-choice therapy for both CIMDL and cocaine-induced GPA mimic.

Alterações sistêmicas e bucais em pacientes usuários de cocaína: uma revisão integrativa da literatura / Cambios sistémicos y orales em pacientes consumidores de cocaína: una revisión bibliográfica integradora / Systemic and oral changes in cocaína-using patients: an integrative literature review

Introdução: A utilização de cocaína é bastante associada ao surgimento de algumas manifestações sistêmicas e também de algumas alterações orais. Objetivo: Identificaras alterações sistêmicas e bucais mais comuns a pacientes usuários de cocaína. Metodologia: Trata-se de uma revisão sistemática da literatura, considerando artigos com texto completo, com restrição de idioma em Português ou Inglês e que tenham sido publicados entre os anos de 2017 a 2022. Usou-se as bases de dados LiLaCS, MedLine e BBO, por via portal Biblioteca Virtual de Saúde, e SciELO. Os artigos excluídosf oram aqueles que não apresentaram relação explícita do uso de cocaína com alguma manifestação sistêmica e/ou bucal. Resultados: Após o processo de triagem,10 artigos foram salvos para serem analisados e 111 foram descartados por não atenderem aos critérios de inclusão. Dos 10 artigosselecionados,40% deles (n=4) trouxeram informações identificando possíveis riscos de desenvolvimento de doenças cardiovasculares sofridas pelos usuários de cocaína, 10%(n=1) identificou problemas cognitivos associados ao uso da cocaína,30% dos artigos (n=3) mostrou as alterações bucais associadas à utilização abusiva de cocaína. Conclusões: Houve a predominância de algumas manifestações sistêmicas e bucais nos indivíduos usuários de cocaína, como doenças cardiovasculares, xerostomia, perfurações no palato, etc. A partir disso, há algumas alterações sistêmicas e bucais provocadas por esse uso. Mediante o risco considerável, faz-se necessário que o Cirurgião-Dentista se atualize sobre essas alterações em pacientes usuários de cocaína visando promover um trabalho transdisciplinare multiprofissional para atender adequadamente às suas necessidades (AU).

Introduction: The use of cocaine is closely associated with the appearance of some systemic manifestations and also some oral alterations.Objective: To identify the most common systemic and oral alterations in cocaine-using patients.Methodology:This is a systematic review of the literature, considering full-text articles, with a language restriction of "Portuguese" or "English" and published between 2017 and 2022. We used the LiLaCS, MedLine and BBO databases, via the Virtual Health Library (VHL) portal, and SciELO.The articles excluded were those that did not explicitly relate cocaine use to some systemic and/or oral manifestation.Results: After the screening process, 10 articles were saved for analysis and 111 were discarded because they did not meet the inclusion criteria. Of the 10 articles selected, 40% (n=4) provided information identifying possible risks of developing cardiovascular diseases suffered by cocaine users, 10% (n=1)identified cognitive problems associated with cocaine use, 30% of the articles (n=3) showed oral alterations associated with cocaine abuse.Conclusions: There has been a predominance of some systemic and oral manifestations in cocaine users, such as cardiovascular diseases, xerostomia, perforations in the palate, etc. Based on this, there are some systemic and oral alterations caused by this use. Given the considerable risk, it is necessary for dentists to be up-to-date on these alterations in cocaine-using patients in order to promote transdisciplinary and multi-professional work to adequately meet their needs (AU).

Introducción: El consumo de cocaína está estrechamente asociado a la aparición de algunas manifestaciones sistémicas y también de algunas alteraciones orales. Objetivo:Identificar las alteraciones sistémicas y bucales más frecuentes en los consumidores de cocaína. Metodología: Se trata de una revisión sistemática de la literatura, considerando artículos a texto completo, con restricción de idioma en "portugués" o "inglés" y publicados entre 2017 y 2022. Se utilizaron las bases de datos LiLaCS, MedLine y BBO, a través del portal Biblioteca Virtual en Salud (BVS) y SciELO. Los artículos excluidos fueron aquellos que no mostraban una relación explícita entre el consumo de cocaína y alguna manifestación sistémica y/o oral. Resultados: Tras el proceso de cribado, se guardaron10 artículos para el análisis y se descartaron 111 por no cumplir los criterios de inclusión. De los 10 artículos seleccionados, el 40% (n=4) proporcionaba información que identificaba posibles riesgos de desarrollar enfermedades cardiovasculares sufridaspor consumidores de cocaína, el 10% (n=1) identificaba problemas cognitivos asociados al consumo de cocaína, el 30% de los artículos (n=3) mostraban alteraciones orales asociadas al abuso de cocaína.Conclusiones:Ha habido un predominio de algunas manifestaciones sistémicas y orales en los consumidores de cocaína, como enfermedades cardiovasculares, xerostomía, perforaciones en el paladar, etc. De acuerdo con esto, existen algunas alteraciones sistémicas y orales causadas por este uso. Dado el considerable riesgo, es necesario que los odontólogos estén al día sobre estas alteraciones en los pacientes consumidores de cocaína, con el fin de promover el trabajo transdisciplinar y multiprofesional para atender adecuadamente sus necesidades (AU).

Trans-generational effects of parental exposure to drugs of abuse on offspring memory functions.

Recent evidence reported that parental-derived phenotypes can be passed on to the next generations. Within the inheritance of epigenetic characteristics allowing the transmission of information related to the ancestral environment to the offspring, the specific case of the trans-generational effects of parental drug addiction has been extensively studied. Drug addiction is a chronic disorder resulting from complex interactions among environmental, genetic, and drug-related factors. Repeated exposures to drugs induce epigenetic changes in the reward circuitry that in turn mediate enduring changes in brain function. Addictive drugs can exert their effects trans-generally and influence the offspring of addicted parents. Although there is growing evidence that shows a wide range of behavioral, physiological, and molecular phenotypes in inter-, multi-, and trans-generational studies, transmitted phenotypes often vary widely even within similar protocols. Given the breadth of literature findings, in the present review, we restricted our investigation to learning and memory performances, as examples of the offspring's complex behavioral outcomes following parental exposure to drugs of abuse, including morphine, cocaine, cannabinoids, nicotine, heroin, and alcohol.

Cocaine-Induced Plasma Cell Orificial "Dermatomucositis": A More Accurate Descriptive Term for a Clearly Dermatological Entity.

ABSTRACT: Although the involvement of the nasal passages and nasal septum in cocaine users has been known for decades, a new presentation affecting the nostrils and upper lip with an inflamed appearance has recently been documented. The authors who identified this presentation termed it "cocaine-related plasma cell mucositis" due to the abundance of plasma cells in the infiltrate. In this article, we present a second case and emphasize the dermal involvement of the lip, leading us to consider the condition as a genuine dermatomucositis.

Relationship Between Sexual Abuse and Substance Use Among Students from Caribbean Colombian.

Sexual abuse is a public health problem due to its negative impact on physical and mental health. This study aimed to determine the association between sexual abuse and the use of psychoactive substances among high-school adolescents in Colombia. A cross-sectional analytical study was designed in which tenth and eleventh-grade students were included. Overall, a history of sexual abuse was explored with the Trauma Symptom Checklist, and lifetime substance use was assessed with the United States Centers for Disease Control Youth Risk Behavior Questionnaire. The prevalence of sexual abuse was 17.4%, lifetime alcohol use was 77.4%, cigarette 22.4%, cannabis 11.6%, cocaine 2.7%, and other substances 5.1%. History of sexual abuse was associated with alcohol use (OR = 1.59, 95% CI 1.10-2.30), cigarette (OR = 2.08, 95% CI 1.51-2.85), cannabis (OR = 2.43, 95% CI 1.66-3.56), cocaine (OR = 2.51, 95% CI 1.25-5.04) and use of other substances (OR = 2.33, 95% CI 1.31-4.13). The history of sexual abuse is related to the use of substances in high school adolescents in the Caribbean Region of Colombia. More studies are needed to identify the impact of sexual abuse on short-term and lifelong mental health.

Epidemiology studies on effects of lithium salts in pregnancy are confounded by the inability to control for other potentially teratogenic factors.

INTRODUCTION: In bipolar women who took lithium during pregnancy, several epidemiology studies have reported small increases in a rare fetal cardiac defect termed Ebstein's anomaly. METHODS: Behavioral, environmental, and lifestyle-associated risk factors associated with bipolar disorder and health insurance status were determined from an Internet search. The search was conducted from October 1, 2023, through October 14, 2023. The search terms employed included the following: bipolar, bipolar disorder, mood disorders, pregnancy, congenital heart defects, Ebstein's anomaly, diabetes, hypertension, Medicaid, Medicaid patients, alcohol use, cigarette smoking, marijuana, cocaine, methamphetamine, narcotics, nutrition, diet, obesity, body mass index, environment, environmental exposures, poverty, socioeconomic status, divorce, unemployment, and income. No quotes, special fields, truncations, etc., were used in the searches. No filters of any kind were used in the searches. RESULTS: Women who remain on lithium in the United States throughout their pregnancy are likely to be experiencing mania symptoms and/or suicidal ideation refractory to other drugs. Pregnant women administered the highest doses of lithium salts would be expected to have been insufficiently responsive to lower doses. Any small increases in the retrospectively determined risk of fetal cardiac anomalies in bipolar women taking lithium salts cannot be disentangled from potential developmental effects resulting from very high rates of cigarette smoking, poor diet, alcohol abuse, ingestion of illegal drugs like cocaine or opioids, marijuana smoking, obesity, and poverty. CONCLUSIONS: The small risks in fetal cardiac abnormalities reported in the epidemiology literature do not establish a causal association for lithium salts and Ebstein's anomaly.

GPR55 is expressed in glutamate neurons and functionally modulates drug taking and seeking in rats and mice.

G protein-coupled receptor 55 (GPR55) has been thought to be a putative cannabinoid receptor. However, little is known about its functional role in cannabinoid action and substance use disorders. Here we report that GPR55 is predominantly found in glutamate neurons in the brain, and its activation reduces self-administration of cocaine and nicotine in rats and mice. Using RNAscope in situ hybridization, GPR55 mRNA was identified in cortical vesicular glutamate transporter 1 (VgluT1)-positive and subcortical VgluT2-positive glutamate neurons, with no detection in midbrain dopamine (DA) neurons. Immunohistochemistry detected a GPR55-like signal in both wildtype and GPR55-knockout mice, suggesting non-specific staining. However, analysis using a fluorescent CB1/GPR55 ligand (T1117) in CB1-knockout mice confirmed GPR55 binding in glutamate neurons, not in midbrain DA neurons. Systemic administration of the GPR55 agonist O-1602 didnt impact ∆9-THC-induced analgesia, hypothermia and catalepsy, but significantly mitigated cocaine-enhanced brain-stimulation reward caused by optogenetic activation of midbrain DA neurons. O-1602 alone failed to alter extracellar DA, but elevated extracellular glutamate, in the nucleus accumbens. In addition, O-1602 also demonstrated inhibitory effects on cocaine or nicotine self-administration under low fixed-ratio and/or progressive-ratio reinforcement schedules in rats and wildtype mice, with no such effects observed in GPR55-knockout mice. Together, these findings suggest that GPR55 activation may functionally modulate drug-taking and drug-seeking behavior possibly via a glutamate-dependent mechanism, and therefore, GPR55 deserves further study as a new therapeutic target for treating substance use disorders.

Cocaine use and head and neck cancer risk: A pooled analysis in the International Head and Neck Cancer Epidemiology Consortium.

BACKGROUND: Cocaine is an illegal recreational drug used worldwide, yet little is known about whether cocaine inhalation (smoking/snorting) increases the risk of head and neck cancer (HNC). METHODS: The analyses were conducted by pooling data from three case-control studies with 1639 cases and 2506 controls from the International Head and Neck Cancer Epidemiology Consortium. Epidemiologic data, including cocaine use histories, were obtained in face-to-face interviews. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using hierarchical logistic regression models. RESULTS: Controlling for cumulative tobacco and alcohol use, we observed a weak positive association between cocaine use and HNC (ORever vs. never = 1.35, 95% CI: 0.96, 1.90). In stratified analysis, while we did not detect associations among never tobacco or alcohol users due to the limited sample size, the association with cocaine use was observed among tobacco users and alcohol drinkers. ORs for ever and high cumulative use (>18 times) versus never use were 1.40 (95% CI: 0.98, 2.00) and 1.66 (95% CI: 1.03, 2.69) among tobacco users, and 1.34 (95% CI: 0.93, 1.92) and 1.59 (95% CI: 1.00, 2.51) among alcohol drinkers, respectively. CONCLUSION: In this pooled analysis, we observed a weak positive association between cocaine inhalation and HNC risk. Our findings provide preliminary evidence of the potential carcinogenic effect of cocaine on HNC. Because of study limitations, including limited number of cocaine users, confounding, and heterogeneity across studies, future investigations will require larger studies with more detailed information on cocaine use history.

Evaluation of an Oral Fluid Collection Device and a Solid-Phase Extraction Method for the Determination of Coca Leaf Alkaloids by Gas Chromatography-Mass Spectrometry.

Some South American countries have ancient traditions that may pose legal problems, such as the consumption of coca leaves, as this can provide positive results for cocaine use after the analysis of biological samples. For this reason, it is necessary to find specific markers that help differentiate legal from illegal consumption, such as tropacocaine, cinnamoylcocaine, and especially hygrine and cuscohygrine. In this work, two techniques for collecting biological samples are compared: the Quantisal® Oral Fluid collection device and passive drooling. Once the samples were collected, they were subjected to solid-phase extraction for subsequent injection into GC-MS. Different validation parameters included in international guides have been studied to evaluate whether the proposed method is valid for the defined purpose, placing special emphasis on the study of the matrix effect and little value on GC-MS analyses. With respect to this parameter, an increase in the signal was found for CUS and t-CIN, but it was not significant for the rest of the substances studied. The recoveries have varied significantly depending on the way of working, being higher when working with standardized areas. After carrying out work with the oral fluid samples collected from laboratory volunteers, the method was applied to two real samples. The results obtained support the need for further research to overcome certain limitations presented by the device.

A 42-Year-Old Woman With Rapidly Expanding White Matter Lesions: From the National Multiple Sclerosis Society Case Conference Proceedings.

A 42-year-old woman and active cocaine user complained of subacutely worsening blurred vision and imbalance. Examination of the brain MRI showed rapidly expanding white matter lesions. Brain biopsy was consistent with inflammatory demyelination. Given an unusual presentation and a history of cocaine use, a broad differential diagnosis was considered including neurologic toxidromes.

Retrospective Case Series of Cocaine-Associated Plasma Cell Orificial Mucositis.

Importance: Plasma cell orificial mucositis (PCOM) associated with cocaine use is an emerging, rare condition that has become a concern in Spain in recent years. Limited knowledge exists regarding this novel condition. Objectives: To delineate the clinicopathologic characteristics of this emerging entity and establish a novel approach in the differential diagnosis of cocaine-associated lesions. Design, Setting, and Participants: A descriptive, retrospective, multicenter case series of 10 patients diagnosed with cocaine-associated PCOM was conducted in Spain from April 2020 to March 2023. Main Outcomes and Measures: Patient demographic, clinical, histopathologic, and treatment data were collected. Results: A total of 10 patients (6 [60%] male; median [range] age, 45.5 [36-66] years) presenting with exudative ulcerated plaques were identified for this study. The lesions had raised and erythematous edges over the nostril and a median (range) evolution time of 9 (2-24) months. Septal or palate perforations were observed in 4 (40%) of the patients. Biopsies revealed a dense inflammatory infiltrate of plasma cells in the dermis without atypia and with eosinophils. All patients reported recent cocaine use. Three urine tests detected cocaine but found no presence of amphetamines or opiates. Six patients improved with corticosteroid therapy. Up to 60% of patients were lost to follow-up. Conclusions and Relevance: This case series describes the clinicopathologic characteristics of PCOM, an emerging entity associated with cocaine use in Spain, and demonstrates a novel approach in the differential diagnosis of cocaine-associated lesions. To date, cocaine-associated skin lesions have been reported as neutrophilic dermatoses and vasculitis. The appearance of a plasma cell infiltrate changes what has been described in the medical literature so far. PCOM is a benign condition of unknown cause characterized by a proliferative polyclonal plasma cell infiltrate. A comprehensive differential diagnosis workup is required to reach this exclusionary diagnosis. Several irritants have been documented in cases of PCOM, and a hypersensitivity mechanism has been proposed. Since the initial report of cocaine-associated PCOM in Spain, its incidence has experienced a surge in the country. The cause of this phenomenon may be attributed to newly unidentified adulterants. The administration of corticosteroids and discontinuation of cocaine use are the sole treatments that have demonstrated efficacy. Clinicians should be vigilant regarding this emerging condition and conduct inquiries into cocaine use. Additional research is required to clarify the pathophysiology of this emerging condition.

Prenatal cocaine exposure and its influence on pediatric epigenetic clocks and epigenetic scores in humans.

The investigation of the effects of prenatal cocaine exposure (PCE) on offspring has been inconsistent, with few studies investigating biological outcomes in humans. We profiled genome-wide DNA methylation (DNAm) of umbilical cord blood (UCB) from newborns with (n = 35) and without (n = 47) PCE. We used DNAm data to (1) assess pediatric epigenetic clocks at birth and (2) to estimate epigenetic scores (ES) for lifetime disorders. We generated gestational epigenetic age estimates (DNAmGA) based on Knight and Bohlin epigenetic clocks. We also investigated the association between DNAmGA and UCB serum brain-derived neurotrophic factor (BDNF) levels. Considering the large-scale DNAm data availability and existing evidence regarding PCE as a risk for health problems later in life, we generated ES for tobacco smoking, psychosis, autism, diabetes, and obesity. A gene ontology (GO) analysis on the CpGs included in the ES with group differences was performed. PCE was associated with lower DNAmGA in newborns, and this effect remained significant when controlling for potential confounders, such as blood cell type composition predicted by DNAm and obstetric data. DNAmGA was negatively correlated with BDNF levels in the serum of UCB. Higher tobacco smoking, psychosis, and diabetes ES were found in the PCE group. The GO analysis revealed GABAergic synapses as a potential pathway altered by PCE. Our findings of decelerated DNAmGA and ES for adverse phenotypes associated with PCE, suggest that the effects of gestational cocaine exposure on the epigenetic landscape of human newborns are detectable at birth.

Cocaine-use disorder and childhood maltreatment are associated with the activation of neutrophils and increased inflammation.

BACKGROUND: Cocaine-use disorder (CUD) has been associated with early life adversity and activated cellular immune responses. Women are most vulnerable to complications from chronic substance disorders, generally presenting an intense feeling of abstinence and consuming significant drug amounts. Here, we investigated neutrophil functional activities in CUD, including the formation of neutrophil extracellular traps (NETs) and related intracellular signalling. We also investigated the role of early life stress in inflammatory profiles. METHODS: Blood samples, clinical data, and history of childhood abuse or neglect were collected at the onset of detoxification treatment of 41 female individuals with CUD and 31 healthy controls (HCs). Plasma cytokines, neutrophil phagocytosis, NETs, intracellular reactive oxygen species (ROS) generation, and phosphorylated protein kinase B (Akt) and mitogen-activated protein kinases (MAPK)s were assessed by flow cytometry. RESULTS: CUD subjects had higher scores of childhood trauma than controls. Increased plasma cytokines (TNF-α, IL-1ß, IL-6, IL-8, IL-12, and IL-10), neutrophil phagocytosis, and production of NETs were reported in CUD subjects as compared to HC. Neutrophils of CUD subjects also produced high levels of intracellular ROS and had more activated Akt and MAPKs (p38/ERK), which are essential signalling pathways involved in cell survival and NETs production. Childhood trauma scores were significantly associated with neutrophil activation and peripheral inflammation. CONCLUSION: Our study reinforces that smoked cocaine and early life stress activate neutrophils in an inflammatory environment.

Elevated homocysteine levels may moderate and mediate the association between HIV and cognitive impairment among middle-aged and older adults in an underserved population in Baltimore, Maryland.

Background: In the antiretroviral therapy (ART) era, HIV-associated neurocognitive disorders (HAND) remain a considerable challenge for people with HIV, yet not all such disorders can be attributed to HIV alone. This study aimed to: (1) identify factors influencing neurocognitive impairment (NCI) utilizing the NIH Toolbox Cognition Battery (NIHTB-CB) as per the revised research criteria for HAND; (2) ascertain the moderating role of high homocysteine levels in the association between NCI and HIV; and (3) assess the mediating effect of elevated homocysteine levels on this association.Methods: We analyzed data from 788 adults (≥45 years) participating in a study on HIV-related comorbidities in underserved Baltimore communities, using NIHTB-CB to gauge neurocognitive performance. Special attention was given to results from the Dimensional Change Card Sort (DCCS) test within the executive function domain during causal mediation analysis.Results: Overall, HIV was not associated with NCI presence. However, HIV was associated with NCI among individuals with homocysteine >14 µmol/L. Furthermore, HIV was both directly and indirectly associated with NCI in DCCS test scores. Notably, the mediating role of elevated homocysteine in DCCS scores was only observable among individuals who had never used cocaine or had used it for ≤ 10 years, suggesting that extended cocaine use may have a substantial influence on cognitive performance.Conclusions: The findings from this study suggest elevated homocysteine levels may moderate and mediate the association between HIV and neurocognitive impairment.

Novel partial reduction of the humanized anti-cocaine mAb h2E2 for selective cysteine labeling.

Monoclonal antibodies are utilized for treating many diseases and disorders, as well as for basic research and development. Covalent labeling of mAbs is important for various antibody applications and creating antibody drug conjugates. Labeling at reactive lysine residues using lysine selective reagents is useful, but is non-selective and can interfere with antigen binding and interactions of the Fc antibody region. In this work, using an anti-cocaine mAb (h2E2), we utilized triphenylphosphine-3,3',3″-trisulfonic acid (TPPTS), and demonstrated for the first time reduction of disulfides in an antibody by TPPTS. More importantly, this reduction was very reproducible, limited, and selective, and permitted selective labeling of the antibody with a cysteine reactive fluorescent reagent, resulting in labeling of a few specific cysteines. Similar results were obtained using TCEP-agarose reduction. We demonstrated that both of these selective partial reduction methods gave rise to approximately two labels per mAb, mostly by selective reduction of the heavy chain to light chain disulfide bond, as demonstrated by non-reducing SDS-PAGE protein band analysis. Thus, convenient, reproducible, and selective mAb disulfide reduction was achieved under mild conditions. These labeled, partially reduced mAbs were characterized by differential scanning fluorimetry (DSF), detecting the incorporated fluorescein instead of an exogenously added dye, and for antigen (cocaine) binding by isothermal titration calorimetry (ITC). Both the structure and antigen binding of the mAb was maintained. This novel selective reduction and labeling is generally relevant to modification of antibodies and to future development of conjugated mAbs for experimental and therapeutic purposes.

Mismatch of Biological and Social Time in Cocaine-Addicted Men.

INTRODUCTION: Chronotype describes a person's preferential activity pattern during a 24-hour period, which may not be in line with their social lifestyle. A mismatch between biological and social time is known as "social jetlag," which has negative effects on wellbeing. Cocaine influences a person's activity levels, but very little is known about possible changes in chronotype of patients with cocaine use disorder (CUD). Here, we aimed to shed light on self-reported changes in chronotype in patients with CUD and the clinical implications. METHODS: A total of 90 men from the local community were recruited; about half of the sample met the criteria for CUD, while the other half were healthy without a personal history of substance use disorder. Participants completed the Munich Chronotype Questionnaire along with questionnaires about mental health, daily fatigue, and drug/alcohol use. RESULTS: Half of the CUD patients fell into the category of late chronotype - a significantly larger proportion than their healthy peers. Late "night owls" tended to have started using cocaine at an earlier age than other chronotypes; a finding that was not observed with tobacco, cannabis, or alcohol. Drug use severity in CUD patients did not differ across chronotypes. CUD patients (52%) did not have a preferred time of day to use cocaine. The mismatch between social and biological time was significantly greater in CUD patients and unrelated to drug use or mental health status. CONCLUSION: CUD appears to be associated with disruptions in chronotype which are, contrary to a widely held view, not reflected by using patterns or addiction severity.

Relationships Between Prenatal Cocaine Exposure, Cannabis-Use Onset and Emotional and Related Characteristics in Young/Emerging Adults.

Background: Exposure to substances in utero may have significant early-life consequences. Less is known about the effects in emerging adulthood, particularly regarding patterns of substance use and related characteristics.Objectives: In this study, we recruited emerging adults, followed since birth, who had been prenatally exposed, or not, to cocaine. Individuals reported on their cannabis, alcohol, and tobacco use, and measures of impulsivity, anhedonia, emotional regulation, and mental health were obtained. Comparisons were made between emerging adults with prenatal cocaine exposure and those without. Correlations were performed between psychological measures and substance use, and regression analyses were conducted to determine potential pathways by which such measures may relate to prenatal exposure or substance use.Results: Individuals with prenatal cocaine exposure (vs. those without) used cannabis at younger ages, reported greater cannabis-use severity, and demonstrated higher impulsivity, state anxiety, and alexithymia. Earlier age of onset of cannabis use was associated with higher impulsivity, state anxiety, alexithymia, and social and physical anhedonia. Cannabis-use age-of-onset mediated the relationship between prenatal cocaine-exposure status and state anxiety and between prenatal cocaine-exposure status and cannabis-use severity in emerging adulthood but not relationships between prenatal cocaine-exposure status and impulsivity or alexithymia in emerging adulthood. Findings suggest that adults with prenatal cocaine exposure may use cannabis at younger ages, which may relate to increased anxiety and more severe use.Conclusions: These findings suggest both mechanisms and possible intervention targets to improve mental health in emerging adults with prenatal cocaine exposure.

Targeting cravings in substance addiction with transcranial direct current stimulation: insights from a meta-analysis of sham-controlled trials.

Addiction is a substantial health concern; craving-the core symptom of addiction-is strongly associated with relapse. Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that reduces cravings by altering cortical excitability and connectivity in brain regions. This systematic review and meta-analysis was conducted (following the PRISMA guidelines) to evaluate the efficacy of tDCS in reducing cravings for substances. Our analysis included 43 randomized, sham-controlled trials involving 1,095 and 913 participants receiving tDCS and sham stimulation, respectively. We analyzed the changes in craving scores and found that tDCS led to a moderate reduction in cravings compared with the sham effects. This effect was particularly pronounced when bilateral stimulation was used, the anodal electrode was placed on the right dorsolateral prefrontal cortex, current intensities ranged from 1.5 to 2 mA, stimulation sessions lasted 20 minutes, and the electrodes size was ≥35 cm². Notably, tDCS effectively reduced cravings for opioids, methamphetamine, cocaine, and tobacco but not for alcohol or cannabis. Our findings indicate tDCS as a promising, noninvasive, and low-risk intervention for reducing cravings for opioids, methamphetamine, cocaine, and tobacco. Additional studies are warranted to refine stimulation parameters and evaluate the long-term efficacy of tDCS in managing substance cravings.