Assessment of Perivascular Space Morphometry Across the White Matter in Huntington's Disease Using MRI.

Background: Perivascular spaces (PVS) are fluid-filled cavities surrounding small cerebral blood vessels. There are limited reports of enlarged PVS across the grey matter in manifest Huntington's disease (HD). Little is known about how PVS morphometry in the white matter may contribute to HD. Enlarged PVS have the potential to both contribute to HD pathology and affect the distribution and success of intraparenchymal and intrathecally administered huntingtin-lowering therapies. Objective: To investigate PVS morphometry in the global white matter across the spectrum of HD. Relationships between PVS morphometry and disease burden and severity measures were examined. Methods: White matter PVS were segmented on 3T T2 W MRI brain scans of 33 healthy controls, 30 premanifest HD (pre-HD), and 32 early manifest HD (early-HD) participants from the Vancouver site of the TRACK-HD study. PVS count and total PVS volume were measured. Results: PVS total count slightly increased in pre-HD (p = 0.004), and early-HD groups (p = 0.005), compared to healthy controls. PVS volume, as a percentage of white matter volume, increased subtly in pre-HD compared to healthy controls (p = 0.044), but not in early-HD. No associations between PVS measures and HD disease burden or severity were found. Conclusions: This study reveals relatively preserved PVS morphometry across the global white matter of pre-HD and early-HD. Subtle morphometric abnormalities are implied but require confirmation in a larger cohort. However, in conjunction with previous publications, further investigation of PVS in HD and its potential impact on future treatments, with a focus on subcortical grey matter, is warranted.

Asymmetric oligomerization state and sequence patterning can tune multiphase condensate miscibility.

Endogenous biomolecular condensates, composed of a multitude of proteins and RNAs, can organize into multiphasic structures with compositionally distinct phases. This multiphasic organization is generally understood to be critical for facilitating their proper biological function. However, the biophysical principles driving multiphase formation are not completely understood. Here we use in vivo condensate reconstitution experiments and coarse-grained molecular simulations to investigate how oligomerization and sequence interactions modulate multiphase organization in biomolecular condensates. We demonstrate that increasing the oligomerization state of an intrinsically disordered protein results in enhanced immiscibility and multiphase formation. Interestingly, we find that oligomerization tunes the miscibility of intrinsically disordered proteins in an asymmetric manner, with the effect being more pronounced when the intrinsically disordered protein, exhibiting stronger homotypic interactions, is oligomerized. Our findings suggest that oligomerization is a flexible biophysical mechanism that cells can exploit to tune the internal organization of biomolecular condensates and their associated biological functions.

Disrupted executive cerebro-cerebellar functional connectivity in alcohol use disorder.

BACKGROUND: Alcohol use disorder (AUD) affects 283 million people worldwide and its prevalence is increasing. Despite the role of the cerebellum in executive control and its sensitivity to alcohol, few studies have assessed its involvement in AUD-relevant functional networks. The goal of this study is to compare resting-state functional connectivity (FC) patterns in abstinent adults with a history of AUD and controls (CTL). We hypothesized that group differences in cerebro-cerebellar FC would be present, particularly within the frontoparietal/executive control network (FPN). METHODS: Twenty-eight participants completed a resting-state functional magnetic resonance imaging (rsfMRI) study. CTL participants had no history of AUD, comorbid psychological conditions, or recent heavy drinking and/or drug use. AUD participants had a history of AUD, with sobriety for at least 30 days prior to data collection. Multivariate pattern analysis, an agnostic, whole-brain approach, was used to identify regions with significant differences in FC between groups. Seed-based analyses were then conducted to determine the directionality and extent of these FC differences. Associations between FC strength and executive function were assessed using correlations with Wisconsin Card Sorting Test (WCST) performance. RESULTS: There were significant group differences in FC in nodes of the FPN, ventral attention network, and default mode network. Post hoc analyses predominantly identified FC differences within the cerebro-cerebellar FPN, with AUD showing significantly less FC within the FPN. In AUD, FC strength between FPN clusters identified in the multivariate pattern analysis (MVPA) analysis (Left Crus II, Right Frontal Cortex) was positively associated with performance on the WCST. CONCLUSIONS: Our results show less engagement of the FPN in individuals with AUD than in CTL. FC strength within this network was positively associated with performance on the WCST. These findings suggest that long-term heavy drinking alters cerebro-cerebellar FC, particularly within networks that are involved in executive function.

Long-Term Outcomes of a Comprehensive Mobile Smoking Cessation Program With Nicotine Replacement Therapy in Adult Smokers: Pilot Randomized Controlled Trial.

BACKGROUND: Increased smartphone ownership has led to the development of mobile smoking cessation programs. Although the related body of evidence, gathered through the conduct of randomized controlled trials (RCTs), has grown in quality and rigor, there is a need for longer-term data to assess associated smoking cessation durability. OBJECTIVE: The primary aim was to compare smoking cessation outcomes at 52 weeks in adult smokers randomized to a mobile smoking cessation program, Pivot (intervention), versus QuitGuide (control). The secondary aims included comparison of other smoking-related behaviors, outcomes and participant feedback, and exploratory analyses of baseline factors associated with smoking cessation. METHODS: In this remote pilot RCT, cigarette smokers in the United States were recruited on the web. Participants were offered 12 weeks of free nicotine replacement therapy (NRT). Data were self-reported via a web-based questionnaire with videoconference biovalidation in participants who reported 7-day point-prevalence abstinence (PPA). Outcomes focused on cessation rates with additional assessment of quit attempts, cigarettes per day (CPD), self-efficacy via the Smoking Abstinence Self-Efficacy Questionnaire, NRT use, and participant feedback. Cessation outcomes included self-reported 7- and 30-day PPA, abstinence from all tobacco products, and continuous abstinence. PPA and continuous abstinence were biovalidated using witnessed breath carbon monoxide samples. Exploratory post hoc regression analyses were performed to identify baseline variables associated with smoking cessation. RESULTS: Participants comprised 188 smokers (n=94, 50% in the Pivot group and n=94, 50% in the QuitGuide group; mean age 46.4, SD 9.2 years; n=104, 55.3% women; n=128, 68.1% White individuals; mean CPD 17.6, SD 9.0). Several cessation rates were higher in the Pivot group (intention to treat): self-reported continuous abstinence was 20% (19/94) versus 9% (8/94; P=.03) for QuitGuide, biochemically confirmed abstinence was 31% (29/94) versus 18% (17/94; P=.04) for QuitGuide, and biochemically confirmed continuous abstinence was 19% (18/94) versus 9% (8/94; P=.046) for QuitGuide. More Pivot participants (93/94, 99% vs 80/94, 85% in the QuitGuide group; P<.001) placed NRT orders (mean 3.3, SD 2.0 vs 1.8, SD 1.6 for QuitGuide; P<.001). Pivot participants had increased self-efficacy via the Smoking Abstinence Self-Efficacy Questionnaire (mean point increase 3.2, SD 7.8, P<.001 vs 1.0, SD 8.5, P=.26 for QuitGuide). QuitGuide participants made more mean quit attempts (7.0, SD 6.3 for Pivot vs 9.5, SD 7.5 for QuitGuide; P=.01). Among those who did not achieve abstinence, QuitGuide participants reported greater CPD reduction (mean -34.6%, SD 35.5% for Pivot vs -46.1%, SD 32.3% for QuitGuide; P=.04). Among those who reported abstinence, 90% (35/39) of Pivot participants and 90% (26/29) of QuitGuide participants indicated that their cessation program helped them quit. CONCLUSIONS: This pilot RCT supports the long-term effectiveness of the Pivot mobile smoking cessation program, with abstinence rates durable to 52 weeks. TRIAL REGISTRATION: ClinicalTrials.gov NCT04955639; https://clinicaltrials.gov/ct2/show/NCT04955639.

An open-source platform for head-fixed operant and consummatory behavior.

Head-fixed behavioral experiments in rodents permit unparalleled experimental control, precise measurement of behavior, and concurrent modulation and measurement of neural activity. Here, we present OHRBETS (Open-Source Head-fixed Rodent Behavioral Experimental Training System; pronounced 'Orbitz'), a low-cost, open-source platform of hardware and software to flexibly pursue the neural basis of a variety of motivated behaviors. Head-fixed mice tested with OHRBETS displayed operant conditioning for caloric reward that replicates core behavioral phenotypes observed during freely moving conditions. OHRBETS also permits optogenetic intracranial self-stimulation under positive or negative operant conditioning procedures and real-time place preference behavior, like that observed in freely moving assays. In a multi-spout brief-access consumption task, mice displayed licking as a function of concentration of sucrose, quinine, and sodium chloride, with licking modulated by homeostatic or circadian influences. Finally, to highlight the functionality of OHRBETS, we measured mesolimbic dopamine signals during the multi-spout brief-access task that display strong correlations with relative solution value and magnitude of consumption. All designs, programs, and instructions are provided freely online. This customizable platform enables replicable operant and consummatory behaviors and can be incorporated with methods to perturb and record neural dynamics in vivo.

Republication of "The Utilization of Internet Resources by Foot and Ankle Patients".

Background: It is critical for patients seeking foot and ankle care to have access to quality online resources, as the treatment of their conditions may involve the use of a variety of diagnostic and therapeutic modalities with which they are unfamiliar. This study was performed to enhance our understanding of if and why patients use Internet-based educational materials, to identify trends in utilization, and to delineate the patient-perceived attributes of quality resources. Methods: Questionnaires were distributed to 150 adult foot and ankle patients. The questionnaire consisted of demographic and Internet utilization questions. Statistical analysis was performed to determine the frequency of responses for each question and the relationship between demographics and Internet usage. Results: Younger patients were more likely to use the Internet (P= .006). However, there were no other significant differences in demographic attributes between patients who did (76%) and did not (24%) utilize the Internet (P <.05). Of the participants who didn't search the Internet about their condition, the most commonly cited reason was they preferred to receive information directly from their physician (47%). Among Internet users, most found the quality of resources to be good or very good (75%). However, many patients were unsure of the specific websites they accessed (66%) and if materials were AOFAS sponsored (18%). When asked about the attributes of a reliable website, patients felt that physician and/or medical society endorsement were most important (52% and 46%, respectively). Conclusion: Although physician and medical society endorsement positively shape patients' opinions of online education materials, patients often struggle in remembering the site they visited and if it was sponsored by a certain society. Despite this, patients are generally satisfied with online foot and ankle education resources. Future works must assess whether patient and physician perceptions of quality Internet resources are correlated. Level of Evidence: Level IV, case series.

Zebrafish Erc1b mediates motor innervation and organization of craniofacial muscles in control of jaw movement.

BACKGROUND: Movement of the lower jaw, a common behavior observed among vertebrates, is required for eating and processing food. This movement is controlled by signals sent from the trigeminal motor nerve through neuromuscular junctions (NMJs) to the masticatory muscles. Dysfunctional jaw movements contribute to craniomandibular disorders, yet the pathophysiology of these disorders is not well understood, as limited studies have been conducted on the molecular mechanisms of jaw movement. RESULTS: Using erc1b/kimm533 genetic loss of function mutant, we evaluated lower jaw muscle organization and innervation by the cranial motor nerves in developing zebrafish. Using time-lapse confocal imaging of the erc1b mutant in a transgenic fluorescent reporter line, we found delayed trigeminal nerve growth and disrupted nerve branching architecture during muscle innervation. By automated 3D image analysis of NMJ distribution, we identified an increased number of small, disorganized NMJ clusters in erc1b mutant larvae compared to WT siblings. Using genetic replacement experiments, we determined the Rab GTPase binding domain of Erc1b is required for cranial motor nerve branching, but not NMJ organization or muscle attachment. CONCLUSIONS: We identified Erc1b/ERC1 as a novel component of a genetic pathway contributing to muscle organization, trigeminal nerve outgrowth, and NMJ spatial distribution during development that is required for jaw movement.

The impact of primary care access on autism spectrum disorder awareness in an underserved population.

American Academy of Pediatrics (AAP) recommendations for Autism Spectrum Disorder (ASD) screening do not specifically address safety-net clinics, which provide multidisciplinary healthcare services to underserved patients. This project explored the potential for ASD screening in safety-net clinics by assessing parental perceived knowledge of ASD at JayDoc Free Clinic, a student-run safety-net clinic in Wyandotte County, Kansas. May through December 2022, patients who reported to be the parent of a minor received a demographic survey and a Likert-style questionnaire assessing perceived knowledge of ASD, including understanding the importance of ASD screening and ASD signs and symptoms. Responses were categorized into positive, negative, and unsure. Demographic variables included the minor's primary care provider (PCP) status. Results were analyzed using bivariate analysis, with chi-square tests for significance (p-value ≤ 0.05). Of the 52 participants who completed at least one Likert response, 55.8% reported their child had a PCP. Responses were somewhat balanced with 44.2% positive for understanding the importance of ASD screening and 53.8% positive for understanding ASD signs and symptoms. For understanding the signs and symptoms of ASD, an unsure response (32.7% of responses) was statistically associated with a lack of PCP (p = 0.017). The balance of positive with negative and unsure responses could reflect lack of ASD knowledge and may relate to healthcare inaccessibility. This is consistent with the significant association between lack of PCP and unsure responses for understanding ASD signs and symptoms. ASD screening and education in safety-net clinics like JayDoc could be valuable, particularly for children without a PCP.

Outcomes of a Comprehensive Mobile Smoking Cessation Program With Nicotine Replacement Therapy in Adult Smokers: Pilot Randomized Controlled Trial.

BACKGROUND: Cigarette smoking remains the leading cause of preventable illness and death, underscoring ongoing need for evidence-based solutions. Pivot, a US Clinical Practice Guideline-based mobile smoking cessation program, comprises a personal carbon monoxide breath sensor; a smartphone app; in-app, text-based human-provided coaching; nicotine replacement therapy; and a moderated web-based community. Promising Pivot cohort studies have established the foundation for comparative assessment. OBJECTIVE: This study aimed to compare engagement, retention, attitudes toward quitting smoking, smoking behavior, and participant feedback between Pivot and QuitGuide, a US Clinical Practice Guideline-based smoking cessation smartphone app from the National Cancer Institute. METHODS: In this remote pilot randomized controlled trial, cigarette smokers in the United States were recruited on the web and randomized to Pivot or QuitGuide. Participants were offered 12 weeks of free nicotine replacement therapy. Data were self-reported via weekly web-based questionnaires for 12 weeks and at 26 weeks. Outcomes included engagement and retention, attitudes toward quitting smoking, smoking behavior, and participant feedback. The primary outcome was self-reported app openings at 12 weeks. Cessation outcomes included self-reported 7- and 30-day point prevalence abstinence (PPA), abstinence from all tobacco products, and continuous abstinence at 12 and 26 weeks. PPA and continuous abstinence were biovalidated via breath carbon monoxide samples. RESULTS: Participants comprised 188 smokers (94 Pivot and 94 QuitGuide): mean age 46.4 (SD 9.2) years, 104 (55.3%) women, 128 (68.1%) White individuals, and mean cigarettes per day 17.6 (SD 9.0). Engagement via mean "total app openings through 12 weeks" (primary outcome) was Pivot, 157.9 (SD 210.6) versus QuitGuide, 86.5 (SD 66.3; P<.001). Self-reported 7-day PPA at 12 and 26 weeks was Pivot, 35% (33/94) versus QuitGuide, 28% (26/94; intention to treat [ITT]: P=.28) and Pivot, 36% (34/94) versus QuitGuide, 27% (25/94; ITT: P=.12), respectively. Self-reported 30-day PPA at 12 and 26 weeks was Pivot, 29% (27/94) versus QuitGuide, 22% (21/94; ITT: P=.32) and Pivot, 32% (30/94) versus QuitGuide, 22% (21/94; ITT: P=.12), respectively. The biovalidated abstinence rate at 12 weeks was Pivot, 29% (27/94) versus QuitGuide, 13% (12/94; ITT: P=.008). Biovalidated continuous abstinence at 26 weeks was Pivot, 21% (20/94) versus QuitGuide, 10% (9/94; ITT: P=.03). Participant feedback, including ease of setup, impact on smoking, and likelihood of program recommendation were favorable for Pivot. CONCLUSIONS: In this randomized controlled trial comparing the app-based smoking cessation programs Pivot and QuitGuide, Pivot participants had higher engagement and biovalidated cessation rates and more favorable user feedback at 12 and 26 weeks. These findings support Pivot as an effective, durable mobile smoking cessation program. TRIAL REGISTRATION: ClinicalTrials.gov NCT04955639; https://clinicaltrials.gov/ct2/show/NCT04955639.

Low glutamate diet improves working memory and contributes to altering BOLD response and functional connectivity within working memory networks in Gulf War Illness.

Gulf War Illness is a chronic multi-symptom disorder with severe cognitive impairments which may be related to glutamate excitotoxicity and central nervous system dysfunction. The low glutamate diet has been proposed as a comprehensive intervention for Gulf War Illness. We examined the effects of the low glutamate diet on verbal working memory using a fMRI N-back task. Accuracy, whole-brain blood oxygen level dependency (BOLD) response, and task-based functional connectivity were assessed at baseline and after 1 month on the diet (N = 24). Multi-voxel pattern analysis identified regions of whole-brain BOLD pattern differences after the diet to be used as seeds for subsequent seed-to-voxel functional connectivity analyses. Verbal working memory accuracy improved after the diet (+ 13%; p = 0.006). Whole-brain BOLD signal changes were observed, revealing lower activation within regions of the frontoparietal network and default mode network after the low glutamate diet. Multi-voxel pattern analysis resulted in 3 clusters comprising parts of the frontoparietal network (clusters 1 and 2) and ventral attention network (cluster 3). The seed-to-voxel analyses identified significant functional connectivity changes post-diet for clusters 1 and 2 (peak p < 0.001, cluster FDR p < 0.05). Relative to baseline, clusters 1 and 2 had decreased functional connectivity with regions in the ventral attention and somatomotor networks. Cluster 2 also had increased functional connectivity with regions of the default mode and frontoparietal networks. These findings suggest that among veterans with Gulf War Illness, the low glutamate diet improves verbal working memory accuracy, alters BOLD response, and alters functional connectivity within two networks central to working memory.

Seahorse brood pouch morphology and control of male parturition in Hippocampus abdominalis.

INTRODUCTION: Syngnathids (seahorses, pipefishes and seadragons) are among the few vertebrates that display male pregnancy. During seahorse pregnancy, males incubate developing embryos embedded in a placenta within a fleshy brood pouch, before expelling fully developed neonates at parturition. The mechanisms underpinning seahorse parturition are poorly understood. METHODS: We examined the morphology of the brood pouch using microcomputed tomography and histological techniques, in combination with physiological assays, to examine how male pot-bellied seahorses (Hippocampus abdominalis) control labour. In female-pregnant vertebrates, nonapeptide hormones (such as vasopressin- and oxytocin-like hormones) produce contractions of gestational smooth muscle to produce labour. RESULTS: Histological analysis of the seahorse brood pouch reveals only scattered small smooth muscle bundles in the brood pouch, and in-vitro application of isotocin (a teleost nonapeptide hormone) to the brood pouch do not produce measurable muscle contractions. Micro-computed tomography shows differences in size and orientation of the anal fin assembly between male and female pot-bellied seahorses, and histological analysis reveals large skeletal muscle bundles attached to the anal fin bones at the male brood pouch opening. DISCUSSION: We conclude that seahorse parturition may be facilitated by contraction of these muscles, which, in combination with body movements, serves to gape open the pouch and expel the neonates. Future biomechanical studies are needed to test this hypothesis.

Staphylococcus aureus adhesion to the host.

Staphylococcus aureus is a pathobiont capable of colonizing and infecting most tissues within the human body, resulting in a multitude of different clinical outcomes. Adhesion of S. aureus to the host is crucial for both host colonization and the establishment of infections. Underlying the pathogen's success is a complex and diverse arsenal of adhesins. In this review, we discuss the different classes of adhesins, including a consideration of the various adhesion sites throughout the body and the clinical outcomes of each infection type. The development of therapeutics targeting the S. aureus host-pathogen interaction is a relatively understudied area. Due to the increasing global threat of antimicrobial resistance, it is crucial that innovative and alternative approaches are considered. Neutralizing virulence factors, through the development of antivirulence agents, could reduce bacterial pathogenicity and the ever-increasing burden of S. aureus infections. This review provides insight into potentially efficacious adhesion-associated targets for the development of novel decolonizing and antivirulence strategies.

Semi-automated Segmentation and Quantification of Perivascular Spaces at 7 Tesla in COVID-19.

While COVID-19 is primarily considered a respiratory disease, it has been shown to affect the central nervous system. Mounting evidence shows that COVID-19 is associated with neurological complications as well as effects thought to be related to neuroinflammatory processes. Due to the novelty of COVID-19, there is a need to better understand the possible long-term effects it may have on patients, particularly linkage to neuroinflammatory processes. Perivascular spaces (PVS) are small fluid-filled spaces in the brain that appear on MRI scans near blood vessels and are believed to play a role in modulation of the immune response, leukocyte trafficking, and glymphatic drainage. Some studies have suggested that increased number or presence of PVS could be considered a marker of increased blood-brain barrier permeability or dysfunction and may be involved in or precede cascades leading to neuroinflammatory processes. Due to their size, PVS are better detected on MRI at ultrahigh magnetic field strengths such as 7 Tesla, with improved sensitivity and resolution to quantify both concentration and size. As such, the objective of this prospective study was to leverage a semi-automated detection tool to identify and quantify differences in perivascular spaces between a group of 10 COVID-19 patients and a similar subset of controls to determine whether PVS might be biomarkers of COVID-19-mediated neuroinflammation. Results demonstrate a detectable difference in neuroinflammatory measures in the patient group compared to controls. PVS count and white matter volume were significantly different in the patient group compared to controls, yet there was no significant association between PVS count and symptom measures. Our findings suggest that the PVS count may be a viable marker for neuroinflammation in COVID-19, and other diseases which may be linked to neuroinflammatory processes.

Artificial food coloring affects EEG power and ADHD symptoms in college students with ADHD: a pilot study.

Objectives: Removing artificial food coloring (AFC) is a common dietary intervention for children with Attention-Deficit/Hyperactivity Disorder (ADHD), but has not been tested in young adults. This pilot study examined the effects of AFC on ADHD symptoms and electroencephalography (EEG) in college students with and without ADHD.Methods: At baseline, control and ADHD participants completed the Adult ADHD Self-Report Scale (ASRS), simple and complex attention measures, and resting-state EEG recordings. ADHD participants (n = 18) and a subset of controls (extended control group or EC, n = 11) avoided AFC in their diet for 2 weeks and then were randomized to a double-blind, placebo-controlled crossover challenge. Subjects received either 225 mg AFC disguised in chocolate cookies or placebo chocolate cookies for 3 days each week, with testing on the third day each week. Baseline comparisons were made using Student's t-test or Wilcoxon rank sum tests and challenge period analyses were run using General Linear Modeling.Results: The ADHD group had significantly greater scores on the ASRS (p < 0.001), confirming a symptom differential between groups; however, there were no differences in attentional measures or EEG at baseline. The AFC challenge resulted in an increase in posterior mean gamma power (p = 0.05), a decrease in posterior relative alpha power (p = 0.04), and a marginal increase in inattentive symptoms (p = 0.08) in the ADHD group. There were no effects of AFC in the EC group.Discussion: This study indicates that AFC exposure may affect brainwave activity and ADHD symptoms in college students with ADHD. Larger studies are needed to confirm these findings.

The relationship between substance use, prior trauma history, and risk of developing post-traumatic stress disorder in the immediate aftermath of civilian trauma.

Many reports have documented the relationship between post-traumatic stress disorder (PTSD) and substance use. Substance use is commonly comorbid with PTSD and is a risk factor for trauma exposure. The aim of this study was to prospectively examine how recent substance use, abuse, or dependence influenced the development of PTSD in the context of a prior trauma history, including child abuse, and the severity of initial trauma reactions. Participants (N = 81) were recruited and assessed at the emergency department of a large urban hospital in Miami and serum levels of common drugs of abuse were measured. Although substance use appeared to be a risk factor for trauma exposure, neither self-reported nor blood toxicology influenced the development of PTSD. Positive toxicology screens were more likely to be associated with a diagnosis of substance abuse or dependence, χ2 (1) = 4.11, p = .04. Participants with a history of physical abuse were more likely to have a positive toxicology screen, χ2 (1) = 4.03, p = .05. The majority of our trauma-exposed subjects (66%) were found to be positive for one or more illicit substances at presentation at the ED. The current findings provide support for the "high risk" hypothesis in which substance use is associated with increased trauma exposure.

Genetic mapping and phenotypic analysis of shotH.3.2 in Drosophila melanogaster.

Genetic screens are used to identify genes involved in specific biological processes. An EMS mutagenesis screen in Drosophila melanogaster identified growth control phenotypes in the developing eye. One mutant line from this screen, H.3.2, was phenotypically characterized using the FLP/FRT system and genetically mapped by complementation analysis and genomic sequencing by undergraduate students participating in the multi-institution Fly-CURE consortium. H.3.2 was found to have a nonsense mutation in short stop (shot), anortholog of the mammalian spectraplakin dystonin (DST). shot and DST are involved in cytoskeletal organization and play roles during cell growth and proliferation.

A missed opportunity: underutilization of inpatient behavioral health services to reduce injection drug use sequelae in Florida.

BACKGROUND: People who inject drugs (PWID) suffer high morbidity and mortality from injection related infections (IRI). The inpatient setting is an ideal opportunity to treat underlying substance use disorder (SUD), but it is unclear how often this occurs. OBJECTIVES: To quantify the utilization of behavioral health services for PWID during inpatient admissions for IRI. METHODS: Data for all hospital admissions in Florida in FY2017 were obtained from the Agency for Healthcare Administration. Hospitalization for IRI were obtained using a validated ICD-10 algorithm and treatment for substance use disorder was quantified using ICD-10-Procedure Coding System (ICD-10-PCS) codes. RESULT: Among the 20,001 IRI admissions, there were 230 patients who received behavioral health services as defined by ICD-10-PCS SAT codes for treatment for SUD. CONCLUSIONS: In a state with a large number of IRI, only a very small portion of admissions received behavioral health services. Increased efforts should be directed to studying referral patterns among physicians and other providers caring for this population and increasing utilization of behavioral health services.

Periaxonal and nodal plasticities modulate action potential conduction in the adult mouse brain.

Central nervous system myelination increases action potential conduction velocity. However, it is unclear how myelination is coordinated to ensure the temporally precise arrival of action potentials and facilitate information processing within cortical and associative circuits. Here, we show that myelin sheaths, supported by mature oligodendrocytes, remain plastic in the adult mouse brain and undergo subtle structural modifications to influence action potential conduction velocity. Repetitive transcranial magnetic stimulation and spatial learning, two stimuli that modify neuronal activity, alter the length of the nodes of Ranvier and the size of the periaxonal space within active brain regions. This change in the axon-glial configuration is independent of oligodendrogenesis and robustly alters action potential conduction velocity. Because aptitude in the spatial learning task was found to correlate with action potential conduction velocity in the fimbria-fornix pathway, modifying the axon-glial configuration may be a mechanism that facilitates learning in the adult mouse brain.

Prior trauma-related experiences predict the development of posttraumatic stress disorder after a new traumatic event.

BACKGROUND: Many reports have documented the relationship between previous traumatic experiences, including childhood trauma, and the development of later life psychopathology, including posttraumatic stress disorder (PTSD). Identification of individuals at greatest risk for the development of PTSD could lead to preventative interventions. The present study examined the developmental course of PTSD after trauma exposure, using histories of previous traumatic experiences and the severity of the reaction to the trauma as predictors. METHODS: Participants (N = 713) were recruited from Emergency Departments in Miami and Atlanta immediately following a traumatic experience. Histories of previous traumatic experiences and the immediate reaction to the new trauma were examined at baseline. Follow-up assessments of PTSD severity were conducted at 1, 3, and 6 months. RESULTS: Histories of child abuse and pre-existing trauma symptoms predicted the immediate response to stress (R2 = .21, p < .001) and the initial trauma reaction (p < .005).) A mixed-model repeated-measures analysis of variance found that immediate stress response and a history of prior trauma (p < .001) significantly predicted the course of PTSD symptoms. Area under the curve (AUC) analyses suggested that the presence of PTSD at each successive assessment was predicted most substantially by the severity of PTSD at the immediately prior follow-up assessment (AUC > 0.86). CONCLUSIONS: The current findings suggest that previous traumatic experiences lead to a greater immediate reaction to trauma and combine to predict the development of PTSD, the maintenance of which is not moderated by these earlier experiences. The identification of people likely to develop PTSD may be aided by the assessment of prior experiences and immediate reactions.