Prison or treatment? Gender, racial, and ethnic inequities in mental health care utilization and criminal justice history among incarcerated persons with borderline and antisocial personality disorders.

OBJECTIVE: Borderline and antisocial personality disorders are characterized by pervasive psychosocial impairment, disproportionate criminal justice involvement, and high mental health care utilization. Although some evidence suggests that systemic bias may contribute to demographic inequities in criminal justice and mental health care among persons experiencing these mental health conditions, no research to date has explicitly examined such differences. HYPOTHESES: Women and White persons would be more likely to endorse internalizing symptoms and have a more extensive history of mental health service utilization, whereas men, persons from minoritized racial groups, and persons identifying as Hispanic/Latino would be more likely to endorse externalizing symptoms and have more extensive histories of involvement with the criminal justice system. METHOD: This study examined gender, racial, and ethnic differences in symptom presentation, criminal justice history, and mental health care utilization in a sample of 314 adults with comorbid borderline and antisocial personality disorders enrolled in prison-based substance use treatment programs in the United States. RESULTS: Results suggested that men with these personality disorders were more likely to have early extensive criminal justice involvement, whereas women and White people had more extensive mental health treatment histories. Women were also more likely to endorse a range of internalizing symptoms, and White and non-Hispanic participants were more likely to endorse a history of reckless behavior. Notably, however, many associations-particularly, racial differences in symptom presentation and mental health utilization history and gender differences in symptom presentation-did not persist after we controlled for preincarceration employment and educational attainment. CONCLUSION: Results highlight a range of gender, racial, and ethnic inequities in criminal justice involvement and mental health utilization among this high-risk high-need population. Findings attest to the likely impact of societal, structural, and systemic factors on trajectories of persons affected by this comorbidity. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Honokiol hexafluoro confers reversal of neuropathological markers of HIV infection in a murine SCID model.

Cognitive impairment remains a persistent challenge in people living with HIV (PWLH) despite antiretroviral therapy (ART) due to ART's inability to eliminate brain HIV. HIV-induced cognitive dysfunction results from immune dysregulation, ongoing neuroinflammation, and the continuous virus presence, collectively contributing to cognitive deficits. Therefore, adjunctive therapies are needed to reduce cerebral HIV reservoirs, mitigate neuroinflammation, and impede cognitive dysfunction progression. Our study focused on Honokiol, known for its anti-inflammatory and neuroprotective properties, in an experimental mouse model simulating HIV-induced cognitive dysfunction. Using Honokiol Hexafluoro (HH), a synthetic analogue, we comprehensively evaluated its potential to ameliorate cognitive dysfunction and cerebral pathology in HIV-associated cognitive dysfunction. Our findings showed that HH treatment effectively reversed HIV-induced cognitive dysfunction, concurrently suppressing astrocyte activation, restoring neuronal dendritic arborization, and reducing microglial activation. Furthermore, HH remodeled the metabolic profile of HIV-infected human monocyte-derived macrophages, resulting in decreased activation and the promotion of a quiescent state in vitro.

The mediating role of social support in associations between childhood adversity, military sexual trauma, and homelessness in a nationally representative sample of US veterans.

Among veterans, availability of social support and histories of military sexual trauma (MST) and/or adverse childhood experiences (ACEs) are particularly salient correlates of homelessness. Using path analyses, we investigated whether social support (i.e., interpersonal social support and community integration) would at least partially account for the relationships of MST and ACEs with any lifetime homelessness in a large, nationally representative sample of veterans (N = 4069, 9.8% female). Interpersonal social support and community integration partially explained the relationship between ACEs and any lifetime homelessness. However, they did not mediate the relationship between MST and any lifetime homelessness. Female veterans also reported higher trauma rates and lower perceived social support than male counterparts during correlational analyses. These results reinforce existing literature on the importance of research and interventions tailored to veterans with low social support and integration. Results have potential to inform interventions and policy for veterans experiencing and/or at risk for homelessness.

Diagnosis and Management of 2 Cases of Spontaneous Septostomy: Monochorionic/Dichorionic Hybrid Twin Gestation and Dichorionic Triamniotic Triplet Gestation.

INTRODUCTION: Spontaneous septostomy is a rare complication of multiple gestations. Related complications include cord entanglement and preterm delivery. Limited data exist to guide the management of these high-risk patients. The majority of spontaneous septostomy cases have been reported in monochorionic diamniotic twins. We present 2 cases of spontaneous septostomy occurring in a monochorionic/dichorionic hybrid twin gestation (chorionicity transitions from dichorionicity to monochorionicity within the placenta) and in a dichorionic triamniotic triplet gestation. CASE PRESENTATION: Case 1 was a monochorionic/dichorionic hybrid twin gestation with a septostomy complicated by fetal parts of one twin protruding into the co-twin's sac as well as symptomatic polyhydramnios. Fetal magnetic resonance imaging confirmed the septostomy. Case 2 was a dichorionic triamniotic triplet gestation with septostomy and cord entanglement. Both patients were managed akin to a pseudo-monoamniotic gestation with serial ultrasound surveillance and eventual inpatient admission for heightened fetal monitoring. Case 1 underwent elective scheduled cesarean delivery at 33 weeks, and case 2 underwent emergent cesarean delivery for fetal heart rate decelerations at 28 weeks. CONCLUSION: With a high degree of clinical suspicion, spontaneous septostomy can be diagnosed in uncommon settings such as hybrid twin gestations and higher order multiples. Management of such patients is individualized and may include a combination of heightened outpatient and inpatient surveillance.

Veteran Cultural Competence Training: Initial Effectiveness and National-Level Implementation.

OBJECTIVE: Because service professionals often lack cultural competence in working with veterans, veterans often perceive such professionals as "not understanding." The authors developed, evaluated, and implemented Veteran Cultural Competence Training (VCCT), combining educational and experiential components in an in-person training focused on building awareness, knowledge, and skills to better work with veterans. METHODS: Study 1 was a type 1 effectiveness-implementation hybrid trial examining VCCT effectiveness in a sample of social service professionals (N=41) compared with a matched comparison group (N=41) via the Multicultural Counseling Self-Efficacy Scale-Veteran Form (MCSE-V) instrument. In study 2, the authors used the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework to conduct a type 2 effectiveness-implementation hybrid trial and implemented VCCT with an expanded population (N=312) during eight training sessions in three U.S. states. RESULTS: Results from study 1 indicated that VCCT significantly increased self-efficacy of trainees in veteran cultural competence compared with the matched group (p<0.001). In study 2, the RE-AIM framework highlighted the importance of building coalitions and utilizing implementation facilitation to maintain fidelity. The within-group effectiveness of VCCT was statistically significant and maintained across settings and professions (p<0.001), and trainees were satisfied with VCCT. Maintenance analysis revealed expansion of VCCT after implementation in terms of the number of training sessions (N=9), regions hosting the training (N=5), staff hired (N=13), and trainee applications (N=1,018). CONCLUSIONS: VCCT effectively increases self-efficacy in veteran cultural competence. Gains appeared across different professions, demographic characteristics, and locations. Participation in VCCT may increase professionals' competence in understanding veteran culture, thereby potentially improving veteran services.

A practical risk calculator for suicidal behavior among transitioning U.S. Army soldiers: results from the Study to Assess Risk and Resilience in Servicemembers-Longitudinal Study (STARRS-LS).

BACKGROUND: Risk of suicide-related behaviors is elevated among military personnel transitioning to civilian life. An earlier report showed that high-risk U.S. Army soldiers could be identified shortly before this transition with a machine learning model that included predictors from administrative systems, self-report surveys, and geospatial data. Based on this result, a Veterans Affairs and Army initiative was launched to evaluate a suicide-prevention intervention for high-risk transitioning soldiers. To make targeting practical, though, a streamlined model and risk calculator were needed that used only a short series of self-report survey questions. METHODS: We revised the original model in a sample of n = 8335 observations from the Study to Assess Risk and Resilience in Servicemembers-Longitudinal Study (STARRS-LS) who participated in one of three Army STARRS 2011-2014 baseline surveys while in service and in one or more subsequent panel surveys (LS1: 2016-2018, LS2: 2018-2019) after leaving service. We trained ensemble machine learning models with constrained numbers of item-level survey predictors in a 70% training sample. The outcome was self-reported post-transition suicide attempts (SA). The models were validated in the 30% test sample. RESULTS: Twelve-month post-transition SA prevalence was 1.0% (s.e. = 0.1). The best constrained model, with only 17 predictors, had a test sample ROC-AUC of 0.85 (s.e. = 0.03). The 10-30% of respondents with the highest predicted risk included 44.9-92.5% of 12-month SAs. CONCLUSIONS: An accurate SA risk calculator based on a short self-report survey can target transitioning soldiers shortly before leaving service for intervention to prevent post-transition SA.

TCF3 haploinsufficiency defined by immune, clinical, gene-dosage, and murine studies.

BACKGROUND: TCF3 is a transcription factor contributing to early lymphocyte differentiation. Germline monoallelic dominant negative and biallelic loss-of-function (LOF) null TCF3 mutations cause a fully penetrant severe immunodeficiency. We identified 8 individuals from 7 unrelated families with monoallelic LOF TCF3 variants presenting with immunodeficiency with incomplete clinical penetrance. OBJECTIVE: We sought to define TCF3 haploinsufficiency (HI) biology and its association with immunodeficiency. METHODS: Patient clinical data and blood samples were analyzed. Flow cytometry, Western blot analysis, plasmablast differentiation, immunoglobulin secretion, and transcriptional activity studies were conducted on individuals carrying TCF3 variants. Mice with a heterozygous Tcf3 deletion were analyzed for lymphocyte development and phenotyping. RESULTS: Individuals carrying monoallelic LOF TCF3 variants showed B-cell defects (eg, reduced total, class-switched memory, and/or plasmablasts) and reduced serum immunoglobulin levels; most but not all presented with recurrent but nonsevere infections. These TCF3 LOF variants were either not transcribed or translated, resulting in reduced wild-type TCF3 protein expression, strongly suggesting HI pathophysiology for the disease. Targeted RNA sequencing analysis of T-cell blasts from TCF3-null, dominant negative, or HI individuals clustered away from healthy donors, implying that 2 WT copies of TCF3 are needed to sustain a tightly regulated TCF3 gene-dosage effect. Murine TCF3 HI resulted in a reduction of circulating B cells but overall normal humoral immune responses. CONCLUSION: Monoallelic LOF TCF3 mutations cause a gene-dosage-dependent reduction in wild-type protein expression, B-cell defects, and a dysregulated transcriptome, resulting in immunodeficiency. Tcf3+/- mice partially recapitulate the human phenotype, underscoring the differences between TCF3 in humans and mice.

Supporting servicemembers and veterans during their transition to civilian life using certified sponsors: A three-arm randomized controlled trial.

Transitioning servicemembers and veterans (TSMVs) face difficulties throughout their reintegration to civilian life, including challenges with employment, poor social connection, and elevated risk for suicide. To meet the needs of this high-risk population, national initiatives have leveraged community-based interventions. Authors conducted a three-arm randomized controlled trial (n = 200) to evaluate two community-based interventions. The first, Team Red, White, and Blue (RWB), connects TSMVs to their community through physical/social activities. The second, Expiration Term of Service Sponsorship Program (ETS-SP) provides one-on-one certified sponsors to TSMVs who provide support during the reintegration process. TSMVs were assessed at baseline, 3, 6, and 12 months. The primary hypothesis was not supported as reintegration difficulties and social support were not significantly different for participants randomly assigned to the two community-based interventions (Arm-2/RWB and Arm-3/RWB + ETS-SP), when the data from the separate arms were collapsed and combined, compared to the waitlist. The results did support the secondary hypothesis as Arm-3/RWB + ETS-SP had less reintegration difficulties over 12 months and initially had more social support compared to Arm-2/RWB, which suggest that augmenting interventions with sponsors outperforms participation in community-based interventions alone. Overall, the results show some limitations of the studied community-based interventions, as implemented and researched within this study. The authors identified factors that may have contributed to the null findings for the primary hypothesis, which can be addressed in future studies, such as addressing the unique needs of TSMVs, enrolling TSMVs into interventions prior to military discharge, measuring and improving participation levels, and providing stepped-care interventions based on risk levels. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Situational stress and suicide attempt behavior in Army soldiers and veterans: Insights from the Army Study to Assess Risk and Resilience in Servicemembers-Longitudinal Study.

INTRODUCTION: Prevention of suicide-related behaviors is considered a top clinical priority within the Departments of Veterans Affairs and Defense. Despite previous literature attesting to the likely importance of situational stress as a key correlate of acute changes in suicide risk, longitudinal research into associations between situational stress and suicide-related outcomes among military personnel has been relatively limited. METHODS: The current study examined associations between situational stress, recent suicide attempt, and future suicide attempt using data from 14,508 Army soldiers and recently discharged veterans enrolled in the Army Study to Assess Risk and Resilience in Servicemembers-Longitudinal Studies (STARRS-LS). RESULTS: Recent situational stress was more common among recently discharged veterans (vs. soldiers), those with a recent suicide attempt (vs. those without), and those with a subsequent suicide attempt (vs. those without). Job loss was more closely associated with suicide attempts among soldiers, whereas financial crisis, police contact, and death, illness, or injury of close others were more closely associated with suicide attempts among recently discharged veterans. CONCLUSION: Findings further highlight situational stress as a salient risk factor for suicide-related outcomes among military personnel, particularly among recently discharged veterans. Implications for screening and treatment of at-risk military personnel are discussed.

COVID-19 Adenoviral Vector Vaccination Elicits a Robust Memory B Cell Response with the Capacity to Recognize Omicron BA.2 and BA.5 Variants.

Following the COVID-19 pandemic, novel vaccines have successfully reduced severe disease and death. Despite eliciting lower antibody responses, adenoviral vector vaccines are nearly as effective as mRNA vaccines. Therefore, protection against severe disease may be mediated by immune memory cells. We here evaluated plasma antibody and memory B cells (Bmem) targeting the SARS-CoV-2 Spike receptor-binding domain (RBD) elicited by the adenoviral vector vaccine ChAdOx1 (AstraZeneca), their capacity to bind Omicron subvariants, and compared this to the response to mRNA BNT162b2 (Pfizer-BioNTech) vaccination. Whole blood was sampled from 31 healthy adults pre-vaccination and 4 weeks after dose one and dose two of ChAdOx1. Neutralizing antibodies (NAb) against SARS-CoV-2 were quantified at each time point. Recombinant RBDs of the Wuhan-Hu-1 (WH1), Delta, BA.2, and BA.5 variants were produced for ELISA-based quantification of plasma IgG and incorporated separately into fluorescent tetramers for flow cytometric identification of RBD-specific Bmem. NAb and RBD-specific IgG levels were over eight times lower following ChAdOx1 vaccination than BNT162b2. In ChAdOx1-vaccinated individuals, median plasma IgG recognition of BA.2 and BA.5 as a proportion of WH1-specific IgG was 26% and 17%, respectively. All donors generated resting RBD-specific Bmem, which were boosted after the second dose of ChAdOx1 and were similar in number to those produced by BNT162b2. The second dose of ChAdOx1 boosted Bmem that recognized VoC, and 37% and 39% of WH1-specific Bmem recognized BA.2 and BA.5, respectively. These data uncover mechanisms by which ChAdOx1 elicits immune memory to confer effective protection against severe COVID-19.

Understanding changes in aggression among U.S. army soldiers: The role of trauma exposure during deployment.

Aggression is one of the leading concerns reported by United States service members and veterans. Trauma and posttraumatic stress disorder (PTSD) symptoms have emerged as key drivers of aggression. Research to date, however, has largely overlooked the effect of aggression on increasing risk of trauma exposure and subsequent PTSD. The current study addresses this gap by examining whether (a) pre-deployment aggression predicts trauma exposure on deployment and post-deployment PTSD, (b) trauma exposure on deployment and post-deployment PTSD predict post-deployment aggression, and (c) trauma exposure on deployment and post-deployment PTSD symptoms explain changes in aggressive behavior from pre-to post-deployment. Data from the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) Pre/Post Deployment Study (PPDS) on nationally representative sample of 8558 Active-duty Army soldiers were analyzed. Results revealed positive correlations between pre-deployment aggression (assessed via items from the Joint Mental Health Advisory Team 7), trauma exposure on deployment (assessed via items from the Deployment Stress Scale), post-deployment PTSD symptoms (assessed via items from the civilian PTSD Checklist and PTSD Checklist for DSM-5), and post-deployment aggression. Further, pre-deployment aggression predicted trauma exposure on deployment and post-deployment PTSD; trauma exposure on deployment and post-deployment PTSD predicted post-deployment aggression; and changes in aggression from pre-to post-deployment were partially mediated by trauma exposure on deployment and post-deployment PTSD symptoms. Collectively, these findings highlight the utility of identifying and addressing pre-deployment aggression in mitigating trauma exposure and later psychopathology.

Combined immunodeficiency and impaired PI3K signaling in a patient with biallelic LCP2 variants.

BACKGROUND: Inborn errors affecting components of the T-cell receptor signaling cascade cause combined immunodeficiency with various degrees of severity. Recently, homozygous variants in LCP2 were reported to cause pediatric onset of severe combined immunodeficiency with neutrophil, platelet, and T- and B-cell defects. OBJECTIVE: We sought to unravel the genetic cause of combined immunodeficiency and early-onset immune dysregulation in a 26-year-old man who presented with specific antibody deficiency, autoimmunity, and inflammatory bowel disease since early childhood. METHODS: The patient was subjected to whole-exome sequencing of genomic DNA and examination of blood neutrophils, platelets, and T and B cells. Expression levels of the Src homology domain 2-containing leukocyte protein of 76 kDa (SLP76) and tonic and ligand-induced PI3K signaling were evaluated by flow-cytometric detection of phosphorylated ribosomal protein S6 in B and T cells. RESULTS: Compound heterozygous missense variants were identified in LCP2, affecting the proline-rich repeat domain of SLP76 (p.P190R and p.R204W). The patient's total B- and T-cell numbers were within the normal range, as was platelet function. However, neutrophil function, numbers of unswitched and class-switched memory B cells, and serum IgA were decreased. Moreover, intracellular SLP76 protein levels were reduced in the patient's B cells, CD4+ and CD8+ T cells, and natural killer cells. Tonic and ligand-induced levels of phosphorylated ribosomal protein S6 and ligand-induced phosphorylated PLCγ1 were decreased in the patient's B cells and CD4+ and CD8+ T cells. CONCLUSIONS: Biallelic variants in LCP2 impair neutrophil function and T-cell and B-cell antigen-receptor signaling and can cause combined immunodeficiency with early-onset immune dysregulation, even in the absence of platelet defects.

Military experiences, connection to military identity, and time since military discharge as predictors of United States veteran suicide risk.

Veterans navigating the military-to-civilian transition appear at elevated risk for suicide. However, research on the transition-suicide association often fails to consider co-occurring risk factors. The independent association of time since military discharge and suicide among veterans therefore remains unclear. Data from 1,495 post-Vietnam community veterans provided estimates of suicide risk, military-based stressful experiences, connection to military identity, and recency of military discharge. Hierarchical regression analyses examined independent, incremental utility of factors associated with suicide risk after controlling for quality of life, age, and duration of military service among the total veteran sample and a subsample discharged from military service within five years prior. The resulting model explained 41% of variance in suicide risk in the total veteran sample and 51% of variance in suicide risk in the recently discharged subsample. Recency of discharge, combat exposure, moral injury, poor quality of life, and poor psychological wellness showed statistically significant, independent associations with suicide risk, whereas connection to military identity did not show significant, independent associations. Results highlight the salience of the military-to-civilian transition as an independent risk factor for veteran suicide even after controlling for military-based stressful experiences, military identity, quality of life, age, and service duration.

Personality Disorder Diagnosis Among Justice-Involved Veterans: An Investigation of VA Using Veterans.

ABSTRACT: Justice-involved veterans are more likely to experience myriad mental health sequelae. Nonetheless, examination of personality psychopathology among justice-involved veterans remains limited, with studies focused on males within correctional settings. We examined Department of Veterans Affairs (VA) electronic medical records for 1,534,108 (12.28% justice-involved) male and 127,230 (8.79% justice-involved) female veterans. Male and female veterans accessing VA justice-related services were both approximately three times more likely to have a personality disorder diagnosis relative to those with no history of using justice-related services. This effect persisted after accounting for VA use (both overall and mental health), age, race, and ethnicity. Augmenting and tailoring VA justice-related services to facilitate access to evidence-based psychotherapy for personality psychopathology may promote optimal recovery and rehabilitation among these veterans.

An open trial of VA CONNECT: Caring for Our Nation's Needs Electronically during the COVID-19 Transition.

The COVID-19 pandemic impacted emotional well-being due to safety concerns, grief, employment impacts, and social interaction limitations. Face-to-face mental health treatment restrictions were especially impactful to veterans who often gain social enrichment from Veterans Health Administration (VHA) care. We present results from a novel group-based telehealth intervention, VA Caring for Our Nation's Needs Electronically during the COVID-19 Transition (VA CONNECT), which integrates skills training and social support to develop a COVID-19 Safety & Resilience Plan. Veterans (n â€‹= â€‹29) experiencing COVID-related stress participated in an open trial of this 10-session, manualized group VHA telehealth intervention. We examined whether COVID-19-related stress, adjustment disorder symptoms, and loneliness decreased, and coping strategy use increased after participation in VA CONNECT. Between baseline and two-month follow-up, participants reported a significant reduction in perceived stress and adjustment disorder symptoms, and an increase in planning coping skills use. Significant changes were not observed in loneliness or other specific coping strategies. Findings may support the utility of VA CONNECT as an intervention for pandemic-related stress and improving certain coping skills. Future research should explore group-based telehealth interventions like VA CONNECT with other populations within and outside of the VA, which have value during major disruptions to face-to-face mental healthcare access.

Shewanella oneidensis MR-1 respires CdSe quantum dots for photocatalytic hydrogen evolution.

Living bio-nano systems for artificial photosynthesis are of growing interest. Typically, these systems use photoinduced charge transfer to provide electrons for microbial metabolic processes, yielding a biosynthetic solar fuel. Here, we demonstrate an entirely different approach to constructing a living bio-nano system, in which electrogenic bacteria respire semiconductor nanoparticles to support nanoparticle photocatalysis. Semiconductor nanocrystals are highly active and robust photocatalysts for hydrogen (H2) evolution, but their use is hindered by the oxidative side of the reaction. In this system, Shewanella oneidensis MR-1 provides electrons to a CdSe nanocrystalline photocatalyst, enabling visible light-driven H2 production. Unlike microbial electrolysis cells, this system requires no external potential. Illuminating this system at 530 nm yields continuous H2 generation for 168 h, which can be lengthened further by replenishing bacterial nutrients.

Dialectical behavior therapy for justice-involved veterans: Changes in treatment targets in a small, pre-post design clinical trial.

[Correction Notice: An Erratum for this article was reported online in Psychological Services on Jul 13 2023 (see record 2023-89801-001). In the article, the title was incorrect and should have been "Dialectical Behavior Therapy for Justice-Involved Veterans: Changes in Treatment Targets in a Small, Pre-Post Design Clinical Trial." This error did not impact the results or conclusions. All versions of this article have been corrected.] Dialectical Behavior Therapy for Justice-Involved Veterans (DBT-J; Edwards, Dichiara, Epshteyn, et al., 2022) was recently developed as an integrative psychotherapy + case management intervention to address the range of complex criminogenic, mental health, substance use, and case management needs commonly faced by justice-involved veterans. Research to date suggests delivery of DBT-J to be both acceptable and feasible (Edwards, Dichiara, Epshteyn, et al., 2022). However, data on therapeutic change experienced by DBT-J participants has been limited. The present study represents an initial investigation into longitudinal changes in criminogenic risk, psychological distress, substance use, case management needs, and quality of life experienced by 20 justice-involved veterans across their course of DBT-J participation. Results reflected notable improvements across treatment targets from pre- to posttreatment; these gains were largely maintained at 1-month follow-up. Such findings attest to the potential utility of DBT-J and to the need for continued research into the efficacy of this intervention. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The Rapidly Expanding Genetic Spectrum of Common Variable Immunodeficiency-Like Disorders.

The understanding of common variable immunodeficiency disorders (CVID) is in evolution. CVID was previously a diagnosis of exclusion. New diagnostic criteria have allowed the disorder to be identified with greater precision. With the advent of next-generation sequencing (NGS), it has become apparent that an increasing number of patients with a CVID phenotype have a causative genetic variant. If a pathogenic variant is identified, these patients are removed from the overarching diagnosis of CVID and are deemed to have a CVID-like disorder. In populations where consanguinity is more prevalent, the majority of patients with severe primary hypogammaglobulinemia will have an underlying inborn error of immunity, usually an early-onset autosomal recessive disorder. In nonconsanguineous societies, pathogenic variants are identified in approximately 20% to 30% of patients. These are often autosomal dominant mutations with variable penetrance and expressivity. To add to the complexity of CVID and CVID-like disorders, some genetic variants such as those in TNFSF13B (transmembrane activator calcium modulator cyclophilin ligand interactor) predispose to, or enhance, disease severity. These variants are not causative but can have epistatic (synergistic) interactions with more deleterious mutations to worsen disease severity. This review is a description of the current understanding of genes associated with CVID and CVID-like disorders. This information will assist clinicians in interpreting NGS reports when investigating the genetic basis of disease in patients with a CVID phenotype.

Botanical inhibitors of SARS-CoV-2 viral entry: a phylogenetic perspective.

Throughout the SARS-CoV-2 pandemic, the use of botanical dietary supplements in the United States has increased, yet their safety and efficacy against COVID-19 remains underexplored. The Quave Natural Product Library is a phylogenetically diverse collection of botanical and fungal natural product extracts including popular supplement ingredients. Evaluation of 1867 extracts and 18 compounds for virus spike protein binding to host cell ACE2 receptors in a SARS-CoV-2 pseudotyped virus system identified 310 extracts derived from 188 species across 76 families (3 fungi, 73 plants) that exhibited ≥ 50% viral entry inhibition activity at 20 µg/mL. Extracts exhibiting mammalian cytotoxicity > 15% and those containing cardiotoxic cardiac glycosides were eliminated. Three extracts were selected for further testing against four pseudotyped variants and infectious SARS-CoV-2 and were then further chemically characterized, revealing the potent (EC50 < 5 µg/mL) antiviral activity of Solidago altissima L. (Asteraceae) flowers and Pteridium aquilinum (L.) Kuhn (Dennstaedtiaceae) rhizomes.