"Weeding out" violence? Translational perspectives on the neuropsychobiological links between cannabis and aggression.

Recent shifts in societal attitudes towards cannabis have led to a dramatic increase in consumption rates in many Western countries, particularly among young people. This trend has shed light on a significant link between cannabis use disorder (CUD) and pathological reactive aggression, a condition involving disproportionate aggressive and violent reactions to minor provocations. The discourse on the connection between cannabis use and aggression is frequently enmeshed in political and legal discussions, leading to a polarized understanding of the causative relationship between cannabis use and aggression. However, integrative analyses from both human and animal research indicate a complex, bidirectional interplay between cannabis misuse and pathological aggression. On the one hand, emerging research reveals a shared genetic and environmental predisposition for both cannabis use and aggression, suggesting a common underlying biological mechanism. On the other hand, there is evidence that cannabis consumption can lead to violent behaviors while also being used as a self-medication strategy to mitigate the negative emotions associated with pathological reactive aggression. This suggests that the coexistence of pathological aggression and CUD may result from overlapping vulnerabilities, potentially creating a self-perpetuating cycle where each condition exacerbates the other, escalating into externalizing and violent behaviors. This article aims to synthesize existing research on the intricate connections between these issues and propose a theoretical model to explain the neurobiological mechanisms underpinning this complex relationship.

In vivo selection in non-human primates identifies AAV capsids for on-target CSF delivery to spinal cord.

Systemic administration of adeno-associated virus (AAV) vectors for spinal cord gene therapy has challenges including toxicity at high doses and pre-existing immunity that reduces efficacy. Intrathecal (IT) delivery of AAV vectors into cerebral spinal fluid can avoid many issues, although distribution of the vector throughout the spinal cord is limited, and vector entry to the periphery sometimes initiates hepatotoxicity. Here we performed biopanning in non-human primates (NHPs) with an IT injected AAV9 peptide display library. We identified top candidates by sequencing inserts of AAV DNA isolated from whole tissue, nuclei, or nuclei from transgene-expressing cells. These barcoded candidates were pooled with AAV9 and compared for biodistribution and transgene expression in spinal cord and liver of IT injected NHPs. Most candidates displayed increased retention in spinal cord compared with AAV9. Greater spread from the lumbar to the thoracic and cervical regions was observed for several capsids. Furthermore, several capsids displayed decreased biodistribution to the liver compared with AAV9, providing a high on-target/low off-target biodistribution. Finally, we tested top candidates in human spinal cord organoids and found them to outperform AAV9 in efficiency of transgene expression in neurons and astrocytes. These capsids have potential to serve as leading-edge delivery vehicles for spinal cord-directed gene therapies.

The ball's in your court: Trends, causes, outcomes, and costs of patient transfer for pediatric testicular torsion.

BACKGROUND: The transfer of pediatric patients with testicular torsion from community hospitals to pediatric centers can be a time and resource-intensive step toward emergent surgical intervention. OBJECTIVE: We sought to describe trends of patient transfer in our state and compare clinical outcomes and health system costs between patients transferred and treated primarily at a pediatric center. STUDY DESIGN: This retrospective cohort study compared patients aged 1-18 years who presented directly to a pediatric center to those transferred for acute testicular torsion from 2018 to 2023. Exclusion criteria included age <1 year, non-urgent surgery, and admission from clinic. Patient age, BMI, Tanner stage, ASA class, insurance coverage, and presentation time were covariates. Group characteristics and times from symptom onset to initial ED presentation to surgery were compared via two-sided Student's t-tests. Clinical outcomes (orchiectomy, testicular atrophy) were compared via Fisher's exact tests. Costs from transferring hospitals were estimated from costs at our institution, and medical transport costs were extrapolated from contract prices between transport agencies and the pediatric center to compare total episode-of-care cost. RESULTS: A total of 133 cases (37 primaries, 96 transfers) met inclusion criteria. Transfers increased over the study period (67%-75%). There were no significant differences in age, Tanner stage, ASA score, BMI, or time of day of presentation between groups. Median transfer distance was 12 miles (IQR 7-22) and time was 1 h (IQR 1-2). More than half of cases (53%) were transferred due to hospital policy regarding surgical treatment of minors, and 25% due to lack of urology coverage. Time from initial ED site to OR was nearly doubled for the transfer group (median 4.5 vs 2.5 h, p = 0.02). Despite a higher rate of orchiectomy in the primary group (43 vs 22%, p = 0.01), this difference was not significant after stratification by symptom duration. The estimated average cost of care for patients transferred was twice that of primary patients ($15,082 vs $6898). DISCUSSION: Transfer of pediatric patients in our state for testicular torsion has increased in recent years. Hospital policies and local urology coverage are primary drivers of patient transfer which nearly doubled time to surgical intervention and more than doubled cost of care. Clinical outcomes were driven by delayed presentation. CONCLUSION: Transfer of pediatric patients for testicular torsion nearly doubles time to surgical intervention and more than doubles cost of care. Restrictive hospital policies and gaps in rural hospital urology coverage present opportunities to improve the quality and efficiency of care for these children.

Sequence reliance of the Drosophila context-dependent transcription factor CLAMP.

Despite binding similar cis elements in multiple locations, a single transcription factor (TF) often performs context-dependent functions at different loci. How factors integrate cis sequence and genomic context is still poorly understood and has implications for off-target effects in genetic engineering. The Drosophila context-dependent TF chromatin-linked adaptor for male-specific lethal proteins (CLAMP) targets similar GA-rich cis elements on the X-chromosome and at the histone gene locus but recruits very different, locus-specific factors. We discover that CLAMP leverages information from both cis element and local sequence to perform context-specific functions. Our observations imply the importance of other cues, including protein-protein interactions and the presence of additional cofactors.

Erratum: Gene replacement therapy in a schwannoma mouse model of neurofibromatosis type 2.

[This corrects the article DOI: 10.1016/j.omtm.2022.06.012.].

Reproductive output and other adult life-history traits of black soldier flies grown on different organic waste and by-products.

The interest in mass-rearing black soldier fly (Hermetia illucens) larvae for food and feed is rapidly increasing. This is partly sparked by the ability of the larvae to efficiently valorise a wide range of organic waste and by-products. Primarily, research has focused on the larval stage, hence underprioritizing aspects of the adult biology, and knowledge on reproduction-related traits such as egg production is needed. We investigated the impact of different organic waste and by-products as larval diets on various life-history traits of adult black soldier flies in a large-scale experimental setup. We reared larvae on four different diets: spent Brewer's grain, ground carrots, Gainesville diet, and ground oranges. Traits assessed were development time to pupa and adult life-stages, adult body mass, female lifespan, egg production, and egg hatch. Larval diet significantly impacted development time to pupa and adult, lifespan, body size, and egg production. In general, flies reared on Brewer's grain developed up to 4.7 d faster, lived up to 2.3 d longer, and produced up to 57% more eggs compared to flies reared on oranges on which they performed worst for these traits. There was no effect of diet type on egg hatch, suggesting that low-nutritious diets, i.e. carrots and oranges, do not reduce the quality but merely the quantity of eggs. Our results demonstrate the importance of larval diet on reproductive output and other adult traits, all important for an efficient valorisation of organic waste and by-products, which is important for a sustainable insect-based food and feed production.

Occupational Radiation Exposure During Pregnancy: A Survey of Urologists on Perception, Experience, and Practice Patterns.

Introduction: The field of urology is predominantly male; however, there has been an increasing number of women in the workforce. Peak reproductive years frequently overlap with residency training and early attending career timelines. Exposure to ionizing radiation is a common occupational hazard in many procedural specialties. The use of radiation, for example, in interventional cardiology and interventional radiology, has shown little adjustments in practice patterns, with no adverse outcomes reported among pregnant physicians in their fields in the setting of appropriate radiation safety measures. The impact of radiation exposure during pregnancy for urologists is largely unknown. Our objective was to determine attitudes and practices of urologists related to radiation exposure and to characterize the experience of urologists who have previously been pregnant. Methods: An anonymous online survey was distributed through relevant society membership bases, which included the Endourological Society and the Society for Women in Urology, and social media. Demographics, practice patterns, and changes to practice patterns were recorded for respondents. Statistical analysis was performed in R studio. Results: There were 384 respondents, 255 of whom identified as women. Of these, 164 had been previously pregnant. Female respondents were younger, completed training more recently, and were more likely to have adjusted their caseload due to radiation concerns compared with their male counterparts. Of women who had been pregnant, few had access to policies for who to notify (19%), policies for safety precautions (22%), custom-fitted lead (35%), and maternity lead (20%). Most women (66%) relied on their own research for guidance on radiation safety during pregnancy, while some (41%) also used information from colleagues or mentors. Forty-six percent of women would have taken greater precautions during pregnancy than they did. Conclusions: Access to the appropriate tools to safely navigate pregnancy is inconsistent among practicing urologists. Evidence-based guidelines are needed to better empower pregnant urologists.

Impact of Dobbs v. Jackson Women's Health Organization on Professional Decision-Making Among Urology Applicants.

MATERIALS AND METHODS: An Institutional Review Board-exempt REDCap survey was distributed through the Society of Academic Urologists to all 508 applicants registered for the 2023 Urology Match following the rank list submission deadline on January 10, 2023. The survey closed on February 1, 2023. Responses were anonymized, aggregated, and characterized using descriptive statistics. Thematic mapping of open text comments was performed by 2 reviewers. RESULTS: The response rate was 42% (215/508). Eighty-eight percent of respondents disapproved of the Dobbs ruling. Twenty percent of respondents (15% male/24% female) eliminated programs in states where abortion is illegal. Fifty-nine percent (51% male/70% female) would be concerned for their or their partner's health if they matched in a state where abortion was illegal, and 66% (55% male/82% female) would want their program to assist them or their partner if they required abortion care during residency. Due to the competitive nature of Urology, 68% of applicants reported feeling at least somewhat obligated to apply in states where abortion legislation conflicts with their beliefs. Of the 65 comments provided by respondents, 4 common themes emerged: (1) avoidance of states with restrictive abortion laws; (2) inability to limit applications because of the competitiveness of urology; (3) impacts on personal health care; and (4) desire for advocacy from professional urology organizations. CONCLUSION: The Dobbs ruling will impact the urology workforce by affecting urology applicants' decision-making regarding residency selection and ranking. Although the competitiveness of the Urology Match pressures applicants to apply broadly, many are taking reproductive health care access into consideration.

Daily Ecological Momentary Assessments of Pain and Ability to Work After Ureteroscopy and Stenting.

Introduction: Ureteral stents can cause significant patient discomfort, yet the temporal dynamics and impact on activities remain poorly characterized. We employed an automated tool to collect daily ecological momentary assessments (EMAs) regarding pain and the ability to work following ureteroscopy with stenting. Our aims were to assess feasibility and better characterize the postoperative patient experience. Materials and Methods: As an exploratory endpoint within an ongoing clinical trial, patients undergoing ureteroscopy with stenting were asked to complete daily EMAs for 10 days postoperatively or until the stent was removed. Questionnaires were distributed through text messages and included a pain scale (0-10) and a single item from the validated Patient-Reported Outcomes Measurement Information System Ability to Participate in Social Roles and Activities instrument, as well as days missed from work or school. Results: Among the first 65 trial participants, 59 completed at least 1 EMA (overall response rate 91%). Response rates were >85% for each time point through postoperative day (POD)10. Median respondent age was 58 years (interquartile range [IQR] 50-67), and 56% were female. Stones were 54% renal and 46% ureteral, with a median diameter of 9 mm (IQR 7-10). Median stent dwell time was 7 days (IQR 6-8). Pain scores were highest on POD1 (median score 4) and declined on each subsequent day, reaching a median score of 2 on POD5. Sixty-three percent of patients on POD1 reported that they had trouble performing their usual work at least sometimes, but by POD5, this was <50% of patients. Patients who work or attend school reported a median of 1 day missed (IQR 0-2). Conclusions: An automated daily EMA system for capturing patient-reported outcomes was demonstrated to be feasible with sustained excellent engagement. Patients with stents reported the worst pain and interference with work on POD1, with steady improvements thereafter, and by POD5, the majority of patients had minimal pain or trouble performing their usual work. This work is associated with a registered clinical trial [NCT05026710].

The current state of training in pain medicine fellowships: An Association of Pain Program Directors (APPD) survey of program directors.

INTRODUCTION: The Accreditation Council for Graduate Medical Education (ACGME) approved the first pain medicine fellowship programs over three decades ago, designed around a pharmacological philosophy. Following that, there has been a rise in the transition of pain medicine education toward a multidisciplinary interventional model based on a tremendous surge of contemporaneous literature in these areas. This trend has created variability in clinical experience and education amongst accredited pain medicine programs with minimal literature evaluating the differences and commonalities in education and experience of different pain medicine fellowships through Program Director (PD) experiences. This study aims to gather insight from pain medicine fellowship program directors across the country to assess clinical and interventional training, providing valuable perspectives on the future of pain medicine education. METHODS: This study involved 56 PDs of ACGME-accredited pain fellowship programs in the United States. The recruitment process included three phases: advanced notification, invitation, and follow-up to maximize response rate. Participants completed a standard online questionnaire, covering various topics such as subcategory fields, online platforms for supplemental education, clinical experience, postgraduate practice success, and training adequacy. RESULTS: Surveys were completed by 39/56 (69%) standing members of the Association of Pain Program Directors (APPD). All PDs allowed fellows to participate in industry-related and professional society-related procedural workshops, with 59% encouraging these workshops. PDs emphasized the importance of integrity, professionalism, and diligence for long-term success. Fifty-four percent of PDs expressed the need for extension of fellowship training to avoid supplemental education by industry or pain/spine societies. CONCLUSION: This study highlights the challenge of providing adequate training in all Pain Medicine subtopics within a 12-month pain medicine fellowship. PDs suggest the need for additional training for fellows and discuss the importance of curriculum standardization.

Perceived autonomy during childbirth predicts mothers' parental self-efficacy: A prospective cohort study.

Experience during childbirth is an important predictor of mothers' later well-being. Using the framework of Self-Determination Theory and, we hypothesized that the degree to which women felt autonomy over their choices during childbirth would be reflected in their later confidence as parents, termed Parental Self-Efficacy (PSE). We assessed PSE as well as depressive symptoms before birth (T1, approximately 36 weeks pregnant) and after birth (T2, approximately 5 weeks postpartum). Perceptions of autonomy during childbirth were measured at T2 using the Perceived Control in Childbirth scale. Using hierarchical linear regression, we found that mothers' perceived autonomy during childbirth predicted their postpartum PSE, controlling for prenatal PSE, pre- and postnatal depression, number of childbirth interventions, and overall birth satisfaction. These data suggest that care providers' support for women's autonomy in childbirth impacts how women feel about themselves as mothers in the postpartum months.

Mitochondrial complex I activity in microglia sustains neuroinflammation.

Sustained smouldering, or low-grade activation, of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis1. Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells2. However, how these metabolic features act to perpetuate inflammation of the central nervous system is unclear. Here, using a multiomics approach, we identify a molecular signature that sustains the activation of microglia through mitochondrial complex I activity driving reverse electron transport and the production of reactive oxygen species. Mechanistically, blocking complex I in pro-inflammatory microglia protects the central nervous system against neurotoxic damage and improves functional outcomes in an animal disease model in vivo. Complex I activity in microglia is a potential therapeutic target to foster neuroprotection in chronic inflammatory disorders of the central nervous system3.

Entanglement and ingestion of microfibers by the oyster pea crab Zaops ostreum, an endosymbiont of the eastern oyster Crassostrea virginica.

The kleptoparasitic pea crab Zaops ostreum lives within the gills of bivalves, including the economically important eastern oyster Crassostrea virginica. Previous research along the east coast of central Florida has found an average of 2.3 pieces of plastic per oyster. The goals of our research were to determine if filter-feeding oysters transfer microfibers to Z. ostreum via the crab: 1) actively consuming plastic particles, or 2) passively becoming entangled in microfibers. Our results show that both occur. While only 11.6 % of Z. ostreum (total n = 122) consumed microfibers, those that did had up to 14 pieces in their soft tissues. Similarly, only 7.4 % of Z. ostreum had microfibers entangled around their appendages. Mean lengths of consumed and entangled fibers were similar, 1.9 and 2.7 mm, respectively. Additional research is needed to understand the positive and negative impacts of microfibers associated with pea crabs on both species.

Switchable Coacervate Formation via Amino Acid Functionalization of Poly(dehydroalanine).

Our group recently developed a family of side-chain amino acid-functionalized poly(S-alkyl-l-homocysteines), Xaa-CH (Xaa = generic amino acid), which possess the ability to form environmentally responsive coacervates in water. In an effort to further study how the molecular structure affects polypeptide coacervate formation, we prepared side-chain amino acid-functionalized poly(S-alkyl-rac-cysteines), Xaa-rac-C, via post-polymerization modification of poly(dehydroalanine), ADH. The use of the ADH platform allowed straightforward synthesis of a diverse range of side-chain amino acid-functionalized polypeptides via direct reaction of unprotected l-amino acid 2-mercaptoethylamides with ADH. Despite their differences in the main-chain structure, we found that Xaa-rac-C can form coacervates with properties similar to those seen with Xaa-CH. These results suggest that the incorporation of side-chain amino acids onto polypeptides may be a way to generally favor coacervation. The incorporation of l-methionine in Met-rac-C allowed the preparation of coacervates with improved stability against high ionic strength media. Further, the presence of additional thioether groups in Met-rac-C resulted in an increased solubility change upon oxidation allowing facile reversible redox switching of coacervate formation in aqueous media.

A classification system for youth outpatient behavioral health services billed to medicaid.

Rates of youth behavioral health concerns have been steadily rising. Administrative data can be used to study behavioral health service utilization among youth, but current methods that rely on identifying an associated behavioral health diagnosis or provider specialty are limited. We reviewed all procedure codes billed to Medicaid for youth in one U.S. county over a 10-year period. We identified 158 outpatient behavioral health procedure codes and classified them according to service type. This classification system can be used by health services researchers to better characterize youth behavioral health service utilization.

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.

"Living with Loss": A qualitative exploration of existential fears among people with advanced lung cancer in online lung cancer support groups.

OBJECTIVES: With targeted therapies, people are surviving longer with advanced lung cancer and engaging in online lung cancer support communities. While these groups provide a sense of community, witnessing the death of peers can lead to emotional distress. This qualitative study aims to (1) explore the experience of witnessing death in online cancer support groups; (2) identify factors that contribute to the emotional struggles of witnessing the death of peers; and (3) identify strategies/options for dealing with losses in the cancer community. METHODS: We conducted a cross-sectional analysis of qualitative interviews exploring existential concerns with participants (n = 25) from oncogene-specific online lung cancer support groups. The principal investigator conducted study interviews between August 2018 and March 2019 where participants were asked about their cancer experiences and existential concerns. We used thematic analysis and NVIVO 11 software to examine and store the de-identified interview data. RESULTS: Participants indicated that they had often witnessed their peers die and felt the pain of the loss. Factors that played a part in their struggle with witnessing others' death included the closeness of the relationship with the person, the age of the person who died, seeing oneself in the experience of the other dying, disparities in care, and losing touch in the final stages. Participants used varied coping strategies such as celebrating the life of the individual who died, engaging in advocacy efforts, not focusing on the loss, participating in therapy, and bringing self-preserving thoughts. SIGNIFICANCE OF RESULTS: Our study highlights the importance of addressing existential fears in online lung cancer support groups and incorporating conversations about death in spaces that deal with cancer.