Episodic Memory Loss: When Alzheimer's Disease Is Not the Answer.

A 60-year-old man presented to a Neurology Clinic specialized in cognitive disorders to evaluate memory complaints. A comprehensive neuropsychological examination detected an isolated and severe hippocampal memory deficit. Laboratory tests, brain magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) tests, including Alzheimer's disease (AD) biomarkers, did not show remarkable results. Due to family history of cognitive impairment, we extended the study to non-Alzheimer monogenic mutations (Next Generation Sequencing) detecting a pathogenic variant of the progranulin (PGRN) gene (c.1414-1 G > T) which has been previously associated with the same phenotype. These results should be considered in patients with an Alzheimer-like presentation, negative AD biomarkers' results, and family history of dementia.

Cell-Type Specificity of Mosaic Chromosome 1q Gain Resolved by snRNA-seq in a Case of Epilepsy With Hyaline Protoplasmic Astrocytopathy.

Objectives: Mosaic gain of chromosome 1q (chr1q) has been associated with malformation of cortical development (MCD) and epilepsy. Hyaline protoplasmic astrocytopathy (HPA) is a rare neuropathologic finding seen in cases of epilepsy with MCD. The cell-type specificity of mosaic chr1q gain in the brain and the molecular signatures of HPA are unknown. Methods: We present the case of a child with pharmacoresistant epilepsy who underwent epileptic focus resections at age 3 and 5 years and was found to have mosaic chr1q gain and HPA. We performed single-nuclei RNA sequencing (snRNA-seq) of brain tissue from the second resection. Results: snRNA-seq showed increased expression of chr1q genes specifically in subsets of neurons and astrocytes. Differentially expressed genes associated with inferred chr1q gain included AKT3 and genes associated with cell adhesion or migration. A subpopulation of astrocytes demonstrated marked enrichment for synapse-associated transcripts, possibly linked to the astrocytic inclusions observed in HPA. Discussion: snRNA-seq may be used to infer the cell-type specificity of mosaic chromosomal copy number changes and identify associated gene expression alterations, which in the case of chr1q gain may involve aberrations in cell migration. Future studies using spatial profiling could yield further insights on the molecular signatures of HPA.

A pilot study of virtual reality for inpatients with opioid use disorder.

BACKGROUND AND OBJECTIVES: While inpatient withdrawal management/acute stabilization can improve outcomes for individuals with opioid use disorder (OUD), patients often leave treatment early due to mood, tension, and cravings associated with opioid withdrawal. The aim of this study was to evaluate the feasibility and preliminary effectiveness of a novel virtual reality (VR) based intervention; 3D Therapy Thrive (3DTT). METHODS: Subjects with OUD (N = 32) were recruited from a community acute stabilization program and received up to two sessions of 3DTT. They completed questionnaires related to their overall satisfaction with the experience and side effects; as well as those related to mood, tension, and cravings. RESULTS: There were no reported side effects and the majority of subjects (94%) reported high satisfaction with the experience. Out of 62 patients approached, 33 patients agreed to participate (53%) 33 patients completed one, and 17 of these patients (52%) completed both sessions of 3DTT, with 19 participants (58%) completing their treatment protocols. Compared to baseline, 3DTT participants reported significant reductions in depression, tension, and cravings (p's < 0.001). DISCUSSION AND CONCLUSIONS: This pilot study supports the feasibility and preliminary effectiveness of 3DTT for improving outcomes for inpatients with OUD. Future randomized controlled trials are necessary to evaluate the efficacy of 3DTT for improving retention, reducing cravings, and improving mood and tension. SCIENTIFIC SIGNIFICANCE: This is the first study to evaluate the feasibility of a psychologically informed VR intervention in inpatients with OUD.

Cell type specificity of mosaic chromosome 1q gain resolved by snRNA-seq in a case of epilepsy with hyaline protoplasmic astrocytopathy.

Introduction: Mosaic gain of chromosome 1q (chr1q) has been associated with malformation of cortical development (MCD) and epilepsy. Hyaline protoplasmic astrocytopathy (HPA) is a rare neuropathological finding seen in cases of epilepsy with MCD. The cell-type specificity of mosaic chr1q gain in the brain and the molecular signatures of HPA are unknown. Methods: We present a child with pharmacoresistant epilepsy who underwent epileptic focus resections at age 3 and 5 years and was found to have mosaic chr1q gain and HPA. We performed single-nuclei RNA-sequencing (snRNA-seq) of brain tissue from the second resection. Results: snRNA-seq showed increased expression of chr1q genes specifically in subsets of neurons and astrocytes. Differentially expressed genes associated with inferred chr1q gain included AKT3 and genes associated with cell adhesion or migration. A subpopulation of astrocytes demonstrated marked enrichment for synapse-associated transcripts, possibly linked to the astrocytic inclusions observed in HPA. Discussion: snRNA-seq may be used to infer the cell type-specificity of mosaic chromosomal copy number changes and identify associated gene expression alterations, which in the case of chr1q gain may involve aberrations in cell migration. Future studies using spatial profiling could yield further insights on the molecular signatures of HPA.

Design, Recruitment, and Implementation of Research Interventions Among Youth Experiencing Homelessness: A Systematic Review.

Transitional age youth experiencing homelessness (TAY-EH) represent an underserved and understudied population. While an increasing number of empirical interventions have sought to address the high burden of psychopathology in this population, findings remain mixed regarding intervention effectiveness. In this systematic review of behavioral health interventions for TAY-EH, we sought to examine the structural framework in which these interventions take place and how these structures include or exclude certain populations of youth. We also examined implementation practices to identify how interventions involving youth and community stakeholders effectively engage these populations. Based on PRISMA guidelines, searches of Medline, PsycInfo, Embase, Cochrane Central, Web of Science, and ClinicalTrials.gov databases were conducted, including English language literature published before October 2022. Eligible studies reported on interventions for adolescent or young adult populations ages 13-25 years experiencing homelessness. The initial search yielded 3850 citations; 353 underwent full text review and 48 met inclusion criteria, of which there were 33 unique studies. Studies revealed a need for greater geographic distribution of empirically based interventions, as well as interventions targeting TAY-EH in rural settings. Studies varied greatly regarding their operationalizations of homelessness and their method of intervention implementation, but generally indicated a need for increased direct-street outreach in participant recruitment and improved incorporation of youth feedback into intervention design. To our knowledge, this is the first systematic review to examine the representation of various groups of TAY-EH in the literature on substance use and mental health interventions. Further intervention research engaging youth from various geographic locations and youth experiencing different forms of homelessness is needed to better address the behavioral health needs of a variety of TAY-EH.

Alterations in Lysosomal, Glial and Neurodegenerative Biomarkers in Patients with Sporadic and Genetic Forms of Frontotemporal Dementia.

Background: Frontotemporal dementia (FTD) is the most common cause of early-onset dementia with 10-20% of cases caused by mutations in one of three genes: GRN, C9orf72, or MAPT. To effectively develop therapeutics for FTD, the identification and characterization of biomarkers to understand disease pathogenesis and evaluate the impact of specific therapeutic strategies on the target biology as well as the underlying disease pathology are essential. Moreover, tracking the longitudinal changes of these biomarkers throughout disease progression is crucial to discern their correlation with clinical manifestations for potential prognostic usage. Methods: We conducted a comprehensive investigation of biomarkers indicative of lysosomal biology, glial cell activation, synaptic and neuronal health in cerebrospinal fluid (CSF) and plasma from non-carrier controls, sporadic FTD (symptomatic non-carriers) and symptomatic carriers of mutations in GRN, C9orf72, or MAPT, as well as asymptomatic GRN mutation carriers. We also assessed the longitudinal changes of biomarkers in GRN mutation carriers. Furthermore, we examined biomarker levels in disease impacted brain regions including middle temporal gyrus (MTG) and superior frontal gyrus (SFG) and disease-unaffected inferior occipital gyrus (IOG) from sporadic FTD and symptomatic GRN carriers. Results: We confirmed glucosylsphingosine (GlcSph), a lysosomal biomarker regulated by progranulin, was elevated in the plasma from GRN mutation carriers, both symptomatic and asymptomatic. GlcSph and other lysosomal biomarkers such as ganglioside GM2 and globoside GB3 were increased in the disease affected SFG and MTG regions from sporadic FTD and symptomatic GRN mutation carriers, but not in the IOG, compared to the same brain regions from controls. The glial biomarkers GFAP in plasma and YKL40 in CSF were elevated in asymptomatic GRN carriers, and all symptomatic groups, except the symptomatic C9orf72 mutation group. YKL40 was also increased in SFG and MTG regions from sporadic FTD and symptomatic GRN mutation carriers. Neuronal injury and degeneration biomarkers NfL in CSF and plasma, and UCHL1 in CSF were elevated in patients with all forms of FTD. Synaptic biomarkers NPTXR, NPTX1/2, and VGF were reduced in CSF from patients with all forms of FTD, with the most pronounced reductions observed in symptomatic MAPT mutation carriers. Furthermore, we demonstrated plasma NfL was significantly positively correlated with disease severity as measured by CDR+NACC FTLD SB in genetic forms of FTD and CSF NPTXR was significantly negatively correlated with CDR+NACC FTLD SB in symptomatic GRN and MAPT mutation carriers. Conclusions: In conclusion, our comprehensive investigation replicated alterations in biofluid biomarkers indicative of lysosomal function, glial activation, synaptic and neuronal health across sporadic and genetic forms of FTD and unveiled novel insights into the dysregulation of these biomarkers within brain tissues from patients with GRN mutations. The observed correlations between biomarkers and disease severity open promising avenues for prognostic applications and for indicators of drug efficacy in clinical trials. Our data also implicated a complicated relationship between biofluid and tissue biomarker changes and future investigations should delve into the mechanistic underpinnings of these biomarkers, which will serve as a foundation for the development of targeted therapeutics for FTD.

Treating Executive Function in Youth With Attention Deficit Hyperactivity Disorder: A Review of Pharmacological and Non-Pharmacological Interventions.

INTRODUCTION: Executive function (EF) deficits are common in youth with ADHD and pose significant functional impairments. The extent and effect of interventions addressing EF in youth with ADHD remain unclear. METHODS: We conducted a systematic literature review using PRISMA guidelines. Included studies were randomized controlled trials of interventions to treat EF in youth with ADHD. RESULTS: Our search returned 136 studies representing 11,443 study participants. We identified six intervention categories: nonstimulant pharmacological (N = 3,576 participants), neurological (N = 1,935), psychological (N = 2,387), digital (N = 2,416), physiological (N = 680), and combination (N = 366). The bulk of the evidence supported pharmacological interventions as most effective in mitigating EF, followed by psychological and digital interventions. CONCLUSION: A breadth of treatments exists for EF in youth with ADHD. Pharmacological, psychotherapeutic, and digital interventions had the most favorable, replicable outcomes. A lack of outcome standardization across studies limited treatment comparison. More data on the persistence of intervention effects are necessary.

Diagnosing major depressive disorder and substance use disorder using the electronic health record: A preliminary validation study.

Background: One mechanism to examine if major depressive disorder (MDD) is related to the development of substance use disorder (SUD) is by leveraging naturalistic data available in the electronic health record (EHR). Rules for data extraction and variable construction linked to psychometrics validating their use are needed to extract data accurately. Objective: We propose and validate a methodologic framework for using EHR variables to identify patients with MDD and non-nicotine SUD. Methods: Proxy diagnoses and index dates of MDD and/or SUD were established using billing codes, problem lists, patient-reported outcome measures, and prescriptions. Manual chart reviews were conducted for the 1-year period surrounding each index date to determine (1) if proxy diagnoses were supported by chart notes and (2) if the index dates accurately captured disorder onset. Results: The results demonstrated 100% positive predictive value for proxy diagnoses of MDD. The proxy diagnoses for SUD exhibited strong agreement (Cohen's kappa of 0.84) compared to manual chart review and 92% sensitivity, specificity, positive predictive value, and negative predictive value. Sixteen percent of patients showed inaccurate SUD index dates generated by EHR extraction with discrepancies of over 6 months compared to SUD onset identified through chart review. Conclusions: Our methodology was very effective in identifying patients with MDD with or without SUD and moderately effective in identifying SUD onset date. These findings support the use of EHR data to make proxy diagnoses of MDD with or without SUD.

Complement Factor I Gene Variant as a Treatable Cause of Recurrent Aseptic Neutrophilic Meningitis: A Case Report.

Mutations in the complement factor I (CFI) gene have previously been identified as causes of recurrent CNS inflammation. We present a case of a 26-year-old man with 18 episodes of recurrent meningitis, who had a variant in CFI(c.859G>A,p.Gly287Arg) not previously associated with neurologic manifestations. He achieved remission with canakinumab, a human monoclonal antibody targeted at interleukin-1 beta.

A Manualized Behavioral Therapy Intervention for Youth with Autism Spectrum Disorder and Substance Use Disorder.

Research highlights the increasing overlap of autism spectrum disorder and substance use disorders in young people. However, no behavioral treatments exist addressing this comorbidity despite great need. A team of clinicians developed an integrated behavioral protocol addressing substance use in youth with autism spectrum disorder. The multidisciplinary team developed 12 youth, 7 parent, and 3 joint modules based on established evidence-based therapies shown to have effectiveness separately addressing autism spectrum and substance use. Two cases are discussed to illuminate this integrated intervention. Adaptations to the protocol were made during feedback from patients and their parents. Further research is needed to determine the effectiveness of this preliminary protocol.

Examining the clinical correlates of conduct disorder in youth with bipolar disorder.

BACKGROUND: Conduct Disorder (CD) is highly comorbid with Bipolar Disorder (BP) and this comorbidity is associated with high morbidity and dysfunction. We sought to better understand the clinical characteristics and familiality of comorbid BP + CD by examining children with BP with and without co-morbid CD. METHODS: 357 subjects with BP were derived from two independent datasets of youth with and without BP. All subjects were evaluated with structured diagnostic interviews, the Child Behavior Checklist (CBCL), and neuropsychological testing. We stratified the sample of subjects with BP by the presence or absence of CD and compared the two groups on measures of psychopathology, school functioning, and neurocognitive functioning. First-degree relatives of subjects with BP +/- CD were compared on rates of psychopathology in relatives. RESULTS: Subjects with BP + CD compared to BP without CD had significantly more impaired scores on the CBCL Aggressive Behavior (p < 0.001), Attention Problems (p = 0.002), Rule-Breaking Behavior (p < 0.001), Social Problems (p < 0.001), Withdrawn/Depressed clinical scales (p = 0.005), the Externalizing Problems (p < 0.001), and Total Problems composite scales(p < 0.001). Subjects with BP + CD had significantly higher rates of oppositional defiant disorder (ODD) (p = 0.002), any SUD (p < 0.001), and cigarette smoking (p = 0.001). First-degree relatives of subjects with BP + CD had significantly higher rates of CD/ODD/ASPD and cigarette smoking compared to first-degree relatives of subjects without CD. LIMITATIONS: The generalization of our findings was limited due to a largely homogeneous sample and no CD only comparison group. CONCLUSIONS: Given the deleterious outcomes associated with comorbid BP + CD, further efforts in identification and treatment are necessary.

Exploring Limited English Proficiency in the Clinical Outcomes of Pediatric Burn Patients.

INTRODUCTION: Limited English proficiency (LEP) is linked to lower health care access and worse clinical outcomes. This study aims to explore the potential role of LEP on clinical outcomes of pediatric burn patients. METHODS: We conducted a single-institution retrospective study of burn patients presenting at a tertiary pediatric burn referral program between January 2016 and December 2020. Patient demographics, burn mechanism, severity, interventions, and primary patient language were abstracted from the electronic health record. Clinical outcomes (length of stay [LOS], clinic follow-up, and 30-day readmission) of patients with LEP were compared to patients with English as primary language (EPL). RESULTS: Thirty-five (4.2%) patients with LEP were identified of 840 total patients. On univariate analysis, there was no difference in mean total body surface area (6.5% versus 6.1%), report of physical abuse (2.9% versus 8.9%), or need for grafting (14.3% versus 15.0%) comparing patients with LEP to those with EPL. Patients with LEP were more likely to have a scald burn (68.6% versus 48.9%, P = 0.025) and less likely to have a flame/fire burn (20.0% versus 37.6%, P = 0.047). On multivariate analysis, there was no difference between patients with LEP compared to patients with EPL for LOS (2.9 versus 3.5 d), 30-day readmissions (5.6% versus 5.7%), or clinic follow-up (80.6% versus 75.0%). In patients with >10% total body surface area, patients with LEP had a longer emergency department LOS (277 min versus 145 min, P = 0.06) but no difference in outcome measures. CONCLUSIONS: Pediatric patients with LEP were not found to have worse burn outcomes compared to EPL patients in our patient sample. However, a true association is difficult to determine given the small sample size of LEP patients and the potential underestimation of language discordancy as recorded in the electronic medical record. Further research is needed to better explore the role of primary language and health communication as a social determinant of health in pediatric burn patients.

A systematic review of virtual reality therapies for substance use disorders: Impact on secondary treatment outcomes.

BACKGROUND AND OBJECTIVES: Virtual reality (VR) therapy may be an effective tool in treating urges and cravings in substance use disorder (SUD). Given the high co-occurrence of difficulties with mood, anxiety, and emotional dysregulation with SUD, this review sought to examine the extant literature on the efficacy of VR for SUD in improving these secondary treatment outcomes. METHODS: A systematic literature review was conducted following PRISMA guidelines in PubMed, PsychInfo, and Embase. Studies were included if they utilized immersive VR, were conducted with individuals with substance use disorder/dependence/misuse, and included measures of mood, anxiety, depression, emotional dysregulation, or retention in treatment. RESULTS: Seven articles met our inclusion criteria. Five studies were conducted on patients using nicotine and utilized a cue-exposure intervention. VR was effective at reducing substance use and cravings in the majority of studies. Results on the efficacy of VR for improving mood, anxiety, and emotional regulation were mixed. Work examining retention in treatment was limited. DISCUSSION AND CONCLUSIONS: VR for SUD has the potential to improve mood and anxiety symptoms as well as retention in treatment for patients with SUD, particularly if the therapy targets these psychological symptoms. Future studies examining components of VR for SUD in individuals with drug use disorders, as well as examinations of targeted interventions for associated mood, emotional dysregulation, and retention in treatment, are necessary. SCIENTIFIC SIGNIFICANCE: This is the first systematic review of the impact of VR on mood, anxiety, and emotional dysregulation for individuals with substance use.

Structural evaluation of child physical abuse in trauma: Social determinants of health at the population level.

PURPOSE: Child physical abuse (CPA) is closely linked to social factors like insurance status with limited evaluation at a structural population-level. This study evaluates the role of social determinants of health within the built environment on CPA. METHODS: A single-institution retrospective review of pediatric trauma patients was conducted between January 2016 and December 2020. Patient address was geocoded to the census-tract level. Socioeconomic metrics, including poverty rate, supermarket access and Social Vulnerability Index (SVI) were estimated from the Food Access Research Atlas. Univariate and multivariable regression analyses were conducted to compare demographics and outcomes. RESULTS: Of 3,540 patients, 317 (9.0%) had concern for physical abuse reported in the registry. CPA patients were younger (7.5 vs 9.6 years, p<0.0001) and more often Black (37.0%, N = 117 vs 23.5%, N = 753; p<0.0001). CPA had higher injury severity scores (ISS) (7.9 vs 5.8, p<0.0001) and longer length of stay (5.3 vs 2.9 days, p<0.0001). CPA had higher Medicaid (73.0%, N = 232 vs 53.8%, N = 1748, p<0.0001) and SVI (0.65 vs 0.59, p<0.0001) with lower median income ($52,100 vs $56,100, p<0.0001) and more low-food access tracts (59.6% vs 53.6%, p = 0.06). Combined low-income and low-food access populations showed widened disparities (40.0% vs 28.9%, p = 0.0002). On multivariate analysis, CPA was associated with poverty (OR 2.3, 95% CI [0.979, 3.60], p = 0.0006), low-access Black share (OR 3.3, 95% CI [1.18, 5.47], p = 0.002) and urban designation (OR 1.5, 95% CI [1.13, 1.87], p = 0.004). CONCLUSION: The built-environment and population-level social determinants of health are related to child physical abuse and should influence advocacy and prevention. LEVEL OF EVIDENCE: Level III. TYPE OF STUDY: Retrospective.

Are adolescents and young adults in substance use disorder treatment as engaged in the research recruitment process as those in general behavioral health treatment?

BACKGROUND AND OBJECTIVE: While prior research suggests that individuals with substance use disorders (SUD) are generally more difficult to engage in research, little is known about the research engagement of adolescents and young adults (AYA) in SUD treatment as it compares to peers seen in general behavioral health settings. This study aimed to systematically compare engagement in virtual research recruitment between AYA in SUD treatment and AYA in behavioral health (BH) treatment. METHODS: Study staff contacted patients ages 16-30 at three outpatient clinics to recruit them for a naturalistic longitudinal online study. Staff documented whether patients answered the phone, expressed interest in the study, answered questions regarding eligibility, and enrolled in the study. RESULTS: Overall, 18% (n = 117) of those contacted by phone enrolled in the study. The rate of AYA reached did not significantly differ between those in SUD treatment (51%) and those in BH treatment (55%). Among those who were reached, those in SUD and BH treatment did not significantly differ (all p > 0.05) in rates of being interested in the study (SUD: 58%; BH: 49%), completing the phone screen (SUD: 46%; BH: 41%) or enrolling in the study (SUD: 33%; BH: 35%). CONCLUSIONS: Overall, we found that engaging AYA in SUD treatment in virtual naturalistic longitudinal research was no more difficult than engaging AYA seen in general behavioral health settings. Future research should examine generalizability of engagement in naturalistic research to other study designs and explore the continuity of this effect into study retention and completion.

Social determinants of health in pediatric scald burns: Is food access an issue?

BACKGROUND: Burn injury risk, severity, and outcomes have been associated with socioeconomic status. Limited data exist to evaluate health access-related influences at a structural population level. This study evaluated factors at the Census-tract level, specifically evaluating food access and social vulnerability in pediatric scald burns. METHODS: A single-institution retrospective review using the trauma registry and electronic medical record was conducted of pediatric burns between 2016 and 2020. Home address was coded to the Census-tract level and bulk analyzed. Socioeconomic metrics of the home environment were evaluated from publicly available databases, the United States Food and Drug Administration Food Access Research Atlas, and the Centers for Disease Control's Social Vulnerability Index. RESULTS: There were 840 patients that met inclusion criteria (49.8% scald, N = 418). The mean total body surface area for scalds was 6.6% with an age of 10.2 years; 76% (n = 317) of scalds had Medicaid, and 15% (n = 63) were due to hot noodles. Scalds occurred more in females (45.7%, N = 191 vs 28.0%, N = 118; P < .0001), non-White race (62.7%, N = 262 vs 29.1%, N = 123; P < .0001), and low-income and low-food access populations (39.8%, N = 147 vs 30.4%, N = 116; P = .007). Low-food access Black populations showed increased scald injury (18% [interquartile range 6-35] vs 10% [interquartile range 4-25]), whereas all other populations showed no association. The patients with scalds had a higher overall social vulnerability index (0.67 vs 0.62, P = .008). CONCLUSION: Often related to poverty, health access, and health equity, population-level social determinants of health like social vulnerability and food access have significant impact on health care and should influence health outreach and systems improvement.

Microvascular anatomy suggests varying aerobic activity levels in the adipose tissues of diving tetrapods.

Adipose tissue has many important functions including metabolic energy storage, endocrine functions, thermoregulation and structural support. Given these varied functions, the microvascular characteristics within the tissue will have important roles in determining rates/limits of exchange of nutrients, waste, gases and molecular signaling molecules between adipose tissue and blood. Studies on skeletal muscle have suggested that tissues with higher aerobic capacity contain higher microvascular density (MVD) with lower diffusion distances (DD) than less aerobically active tissues. However, little is known about MVD in adipose tissue of most vertebrates; therefore, we measured microvascular characteristics (MVD, DD, diameter and branching) and cell size to explore the comparative aerobic activity in the adipose tissue across diving tetrapods, a group of animals facing additional physiological and metabolic stresses associated with diving. Adipose tissues of 33 animals were examined, including seabirds, sea turtles, pinnipeds, baleen whales and toothed whales. MVD and DD varied significantly (P < 0.001) among the groups, with seabirds generally having high MVD, low DD and small adipocytes. These characteristics suggest that microvessel arrangement in short duration divers (seabirds) reflects rapid lipid turnover, compared to longer duration divers (beaked whales) which have relatively lower MVD and greater DD, perhaps reflecting the requirement for tissue with lower metabolic activity, minimizing energetic costs during diving. Across all groups, predictable scaling patterns in MVD and DD such as those observed in skeletal muscle did not emerge, likely reflecting the fact that unlike skeletal muscle, adipose tissue performs many different functions in marine organisms, often within the same tissue compartment.

Can low-carbohydrate diets be recommended for reducing cardiovascular risk?

PURPOSE OF REVIEW: This review provides a rationale for implementing carbohydrate restriction as a dietary therapy to improve biomarkers of cardiovascular health and suggests that this will require a paradigm shift away from what is currently promulgated as a 'heart-healthy' diet. RECENT FINDINGS: Type 2 diabetes mellitus (T2DM), metabolic syndrome, and related co-morbidities are major risk factors for cardiovascular disease (CVD). Ideally, then, a diet intended to support cardiovascular health should be one that improves or reverses these underlying risk factors. Carbohydrate restriction is effective for this purpose as well as for favorably impacting atherogenic dyslipidemia. Recent consensus reports from select national organizations have endorsed low-carbohydrate diets for improving glycemia and cardiovascular risk. Reluctance among public health organizations and some clinicians to more widely promote this therapeutic nutritional approach is driven primarily by the increase in serum low-density lipoprotein cholesterol (LDL-C) observed in a proportion of individuals who adopt a low-carbohydrate diet. Here we explore the rationale for using carbohydrate restriction to improve cardiovascular health by way of favorably impacting T2DM and insulin resistance, and why this salutary effect outweighs the potential adverse effects of an increase in serum LDL-C. SUMMARY: Carbohydrate restriction is a logical foundation for a dietary intervention intended to reduce CVD risk, particularly among individuals with T2DM or metabolic syndrome.

Cardiovascular Considerations for Stimulant Class Medications.

The cardiovascular (CV) impact of stimulants has been examined for decades, with investigations ranging from small sample targeted studies of heart rate (HR) and blood pressure (BP), to large scale epidemiologic investigations. The preponderance of evidence is reassuring, albeit generally based on healthy samples using variable methodology, excluding those at theoretic high risk (eg, comorbid cardiac illness). Screening for theoretically vulnerable patients are recommended, as well as monitoring for CV symptoms and BP/HR, with shared inquiry/further evaluation if concerned. Future investigations to support the identification of risk are needed, while attention to stimulant-associated CV risk is an opportunity for clinicians to engage in general CV risk identification and intervention.

The Impact of Pharmacotherapy of Childhood-Onset Psychiatric Disorders on the Development of Substance Use Disorders.

Background and Objective: Child- and adolescent-onset psychopathology is known to increase the risk for developing substance use and substance use disorders (SUDs). While pharmacotherapy is effective in treating pediatric psychiatric disorders, the impact of medication on the ultimate risk to develop SUDs in these youth remains unclear. Methods: We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) systematic review of peer-reviewed literature published on PubMed through November 2021, examining pharmacological treatments of psychiatric disorders in adolescents and young adults and their effect on substance use, misuse, and use disorder development. Results: Our search terms yielded 21 studies examining the impact of pharmacotherapy and later SUD in attention-deficit/hyperactivity disorder (ADHD), two studies on Major Depressive Disorder, and three studies on psychotic disorders. The majority of these studies reported reductions in SUD (N = 14 sides) followed by no effects (N = 10) and enhanced rates of SUD (N = 2). Studies in ADHD also reported that earlier-onset and longer-duration treatment was associated with the largest risk reduction for later SUD. Conclusions: Overall, pharmacological treatments for psychiatric disorders appear to mitigate the development of SUD, especially when treatment is initiated early and for longer durations. More studies on the development of SUD linked to the effects of psychotherapy alone and in combination with medication, medication initiation and duration, adequacy of treatment, non-ADHD disorders, and psychiatric comorbidity are necessary.