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Previously, tillage has been found to reduce early-season phosphorus(P) uptake from soil in continuous maize cropping systems. This reduced P uptake has often been associated with delayed colonization of roots by arbuscular mycorrhizal (AM) fungi. Our aim was to determine if similar responses occur in maize-soybean rotations, which are more typical of current farming in Ontario, Canada. Similar responses wereexpected because both are AM crops, and the mechanism by which tillage reduces P uptake is thought to be a negative impact on the development of effective mycorrhizae. Simultaneous field experiments with either maize-soybean-maize or soybean-maize-soybean rotations were conducted in 1992-4. Treatments imposed were no-till (NT), ridge-tillage (RT), and conventional tillage using a moldboard plow (MP). In 1993, early-season dry mass of maize was similar among treatments, but colonization of maize roots by AM fungi and P uptake of maize were stimulated by NT and RT, compared with MP. In 1994, early growth was more rapid overall than in 1993, but it was reduced in the NT and RT treatments compared with MP for reasons not related to P. For soybean, AM colonization in NT and RT systems was higher than with MP, but P uptake was unchanged. As was found for maize in 1994, early-season shoot dry mass of soybean was higher in the MP treatment than with NT, but both in 1993 and 1994. We conclude that colonization of both maize andsoybean by AM fungi is susceptible to slower development in tilled systems, and that for maize, stimulation of P uptake under reduced tillage can occur in rotations with soybean just as easily as it does with continuous maize. Taken with other studies, the data here suggest that responses to tillage of colonization of roots by AM fungi and ofP uptake could apply to many cropping systems. The slow early-seasonshoot growth seen in some years in response to reduced tillage is discussed. [ABSTRACT FROM AUTHOR]

Background: The cerebellar vermis is implicated in cognition and emotion, two key components of the psychotic-affective spectrum that includes schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD)., Methods: Volumes [N = 391; 97 SCZ, 78 BD, 103 MDD, and 113 healthy controls (HC)] and seed-to-whole brain functional connectivity (FC) [N = 136; 33 SCZ, 23 BD, 51 MDD, and 29 HC] of total vermis and its subregions, V1 (anterior), V2 (posterior superior), and V3 (posterior inferior), were examined across SCZ, BD, MDD, and HC in samples enriched for first episode individuals. The relationship between vermis volumes and FC and cognitive measures were explored., Results: Significant diagnosis (p = 0.05) and diagnosis by subregion (p = 0.02) effects on vermis volumes were observed across the four groups, particularly in V2 (p = 0.01) with decreased V2 volumes in SCZ compared to BD (p FDR  = 0.01). SCZ, BD, and MDD had significant effects on vermis FC, with SCZ having the greatest effects. SCZ had effects on FC of V1, V2, and V3 with broadly distributed cortical and subcortical regions, while BD and MDD effects were observed in FC of V2 and V3 with frontotemporal regions. Exploratory analyses found significant canonical correlation between V3 FC and WM and visual learning for SCZ and MDD. No significant associations were shown between vermis volumes and cognitive measures., Conclusions: Structural and functional alterations of the vermis appear to vary across the psychotic-affective spectrum of SCZ, BD, and MDD. Posterior vermis may be a key neural intersection between affective and psychotic psychopathology., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Importance: Influenza vaccine effectiveness (VE) is commonly assessed against prevention of illness that requires medical attention. Few studies have evaluated VE against secondary influenza infections., Objective: To determine the estimated effectiveness of influenza vaccines in preventing secondary infections after influenza was introduced into households., Design, Settings, and Participants: During 3 consecutive influenza seasons (2017-2020), primary cases (the first household members with laboratory-confirmed influenza) and their household contacts in Tennessee and Wisconsin were enrolled into a prospective case-ascertained household transmission cohort study. Participants collected daily symptom diaries and nasal swabs for up to 7 days. Data were analyzed from September 2022 to February 2024., Exposures: Vaccination history, self-reported and verified through review of medical and registry records., Main Outcomes and Measures: Specimens were tested using reverse transcription-polymerase chain reaction to determine influenza infection. Longitudinal chain binomial models were used to estimate secondary infection risk and the effectiveness of influenza vaccines in preventing infection among household contacts overall and by virus type and subtype and/or lineage., Results: The analysis included 699 primary cases and 1581 household contacts. The median (IQR) age of the primary cases was 13 (7-38) years, 381 (54.5%) were female, 60 (8.6%) were Hispanic, 46 (6.6%) were non-Hispanic Black, 553 (79.1%) were Non-Hispanic White, and 343 (49.1%) were vaccinated. Among household contacts, the median age was 31 (10-41) years, 833 (52.7%) were female, 116 (7.3%) were Hispanic, 78 (4.9%) were non-Hispanic Black, 1283 (81.2%) were non-Hispanic White, 792 (50.1%) were vaccinated, and 356 (22.5%) had laboratory-confirmed influenza during follow-up. The overall secondary infection risk of influenza among household contacts was 18.8% (95% CI, 15.9% to 22.0%). The risk was highest among children and was 20.3% (95% CI, 16.4% to 24.9%) for influenza A and 15.9% (95% CI, 11.8% to 21.0%) for influenza B. The overall estimated VE for preventing secondary infections among unvaccinated household contacts was 21.0% (95% CI, 1.4% to 36.7%) and varied by type; estimated VE against influenza A was 5.0% (95% CI, -22.3% to 26.3%) and 56.4% (95% CI, 30.1% to 72.8%) against influenza B., Conclusions and Relevance: After influenza was introduced into households, the risk of secondary influenza among unvaccinated household contacts was approximately 15% to 20%, and highest among children. Estimated VE varied by influenza type, with demonstrated protection against influenza B virus infection.

Objectives: The objective study was to investigate the safety and efficacy of electroconvulsive therapy (ECT) in a retrospective cohort of pediatric patients., Methods: A single-site retrospective analysis was conducted of patients aged younger than 18 years who received ECT in a private university hospital from January 28, 2012 to April 8, 2023. Treatment efficacy and adverse events were determined retrospectively through review of the medical record., Results: A total of 36 pediatric patients met the inclusion criteria. Catatonia was the most common presenting indication for ECT, followed by psychosis and suicidal ideation. For all patients, Clinical Global Impressions-Improvement scale scores indicated that it was very likely for a subject to experience at least "much improvement" with the estimated probability of receiving a Clinical Global Impressions-Improvement scale score better than 3 of 0.852 (t.s. = 16.3; P < 0.001; 95% confidence interval, 0.711-0.931). All patients with catatonia demonstrated a positive clinical response and experienced a statistically significant reduction in total Bush-Francis Catatonia Rating Scale scores observed ( t = 11.9; df = 20; SD = 6.3; P < 0.001; 95% confidence interval, 12.6-17.9). No significant adverse events were reported for any patient in the cohort. However, 14 (38.9%) patients experienced prolonged seizures, all of which were terminated with propofol (mean, 49.7 mg)., Conclusions: This study provides further data supporting the safe and effective use of pediatric ECT in the treatment of various psychiatric conditions. However, more research is needed to determine the risk factors associated with prolonged seizures and the optimal seizure parameters in young people., Competing Interests: J.R.S. receives funding from the National Institute of Child and Human Development. J.R.S. also receives support from Axial and Roche. J.L. receives funding from Harvard Medical School Dupont Warren Fellowship and Livingston Awards. He has received equity in Revival Therapeutics, Inc. The other authors have no conflicts of interest or financial disclosures to report., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Catatonia is a neuropsychiatric disorder that occurs in pediatric patients with a range of associated medical, psychiatric, and neurodevelopmental disorders (NDDs). This study describes hospital care of pediatric catatonia patients and compares treatments for neurotypical patients and those with NDDs., Methods: Retrospective cohort study from 1/1/2018 to 6/1/2023 of two academic medical centers of patients aged 18 and younger with catatonia. Patients were retrospectively assessed using the clinical global impressions-improvement (CGI-I) by two independent reviewers., Results: One hundred sixty-five patients were hospitalized for catatonia, of whom 50.3% had an NDD. Median age was 15. One hundred sixty-four patients were treated with a benzodiazepine, with a median maximum 24-hour dose of 6 mg lorazepam-equivalents, which did not differ for patients with and without NDDs. Electroconvulsive therapy (ECT) was utilized in 14.5% of patients. Median length of medical hospitalization was 5 days and hospitalizations were longer in neurotypical patients than in patients with NDDs. In an ordinal regression model, the probability of observing at least "much improvement" (CGI < 3) was 88.3% (95% CI: 82.4% to 92.3%), with NDD diagnosis associated with a lower odds of clinical response., Conclusions: The probability of patients achieving a CGI-I score indicating at least "much improvement" was 88.3%. Administered benzodiazepine dose and ECT treatment were similar for all patients, but neurotypical patients had longer hospitalizations than those with NDDs and had a higher odds of a more favorable clinical response. Research under controlled conditions is needed to optimize and endure equitable catatonia treatment in youth., Competing Interests: JL receives funding from Harvard Medical School Dupont Warren Fellowship and Livingston Awards, the Rappaport Foundation, and the Foundation for Prader-Willi Research. He has received equity and consulting fees from Revival Therapeutics, Inc. JAC receives funding from the Harvard Medical School Dupont-Warren Fellowship, the Chen Institute Mass General Neuroscience Transformative Scholar Award, and the Louis V. Gerstner Award. GF has received equity from Revival Therapeutics, IP royalties from Adya Health and is on the scientific advisory board of Being Health. JRS receives funding from Roche, Axial Therapeutics, and the National Institute of Child and Human Development.All other authors report no disclosures.

Background: Adolescence coincides with a dramatic rise in the onset of psychiatric conditions including depression. Depression symptoms may be particularly prevalent and impairing for youth with autism spectrum disorder (ASD). While prior research suggests adolescence is associated with worsening depression symptoms for typically developing (TD) and autistic youth, it is unclear if they follow a similar course., Method: The study examined the trajectory of depressive symptoms in autistic and neurotypical youth over a 4-year longitudinal study using linear and logistic mixed effects models. In youth with clinically relevant depressive scores (t-score > 65), moderating factors (i.e., diagnosis, age, puberty, sex) were explored. During Year 1, the sample included 244 youth 10-to-13 years: 140 in the ASD group (36 females) and 104 in the TD group (46 females)., Results: Autistic youth had elevated depression scores compared to TD peers (p < 0.001) and females were higher than males in both groups (p = 0.001). There was significant diagnosis by age (p < 0.001) and diagnosis by pubertal stage (p < 0.05) interactions. In the ASD group, elevated depressive scores presented in early adolescence and decreased during middle adolescence and puberty, whereas the TD group showed the opposite trend with an increase in depression symptoms with advancing development., Limitations: Limitations include an unequal sex distribution (fewer females), non-representative autistic sample (e.g., cognition and race/ethnicity), and potential confound of the COVID-19 pandemic., Conclusions: Autistic youth present with higher rates of depressive symptoms early in development; yet, approaching middle adolescence and puberty, the symptom trajectory in the autistic youth declines coinciding with an increase in the TD youth. While group trajectories are divergent, they lead to similar levels of depression in late adolescence with higher symptoms in females. Findings suggest a period of quiescence in depressive symptomology influenced by biopsychosocial factors impacting affective profiles., (© 2024. The Author(s).)

Background: The social world is often stressful for individuals with autism spectrum disorder (ASD). Research shows youth with ASD demonstrate physiological hyperreactivity to some social stressors (e.g., interaction) but not others (e.g., evaluation); therefore, this study examined diagnosis (ASD or typical development (TD)), social context, perceived anxiety, and physiological responsivity across multiple stress systems; namely, the hypothalamic pituitary adrenal (HPA) axis and autonomic nervous system (ANS)., Method: This study examined 244 ten-to-thirteen-year-olds with ASD (N = 140) or TD (N = 104). Physiological responses, measured by salivary cortisol, heart rate (HR), and respiratory sinus arrhythmia (RSA), were assessed before and after a social evaluative threat paradigm (Trier Social Stress Test; TSST) and social interaction (Trier Social Stress Test- Friendly; TSST-F). Mediation models examined the relationships between anxiety, diagnosis, and physiology., Results: Significant three-way interactions were observed for cortisol (p=0.007) and HR (p=0.002), suggesting diagnostic groups respond differently across context and time points. There was no significant interaction for RSA (p=0.149), although ASD youth had significantly lower RSA overall (p=0.038). State and trait anxiety did not mediate the relationship between diagnosis and physiology (all p>0.05)., Conclusions: Findings emphasize the critical role of context and a multisystem approach in examination of physiological social stress in youth with ASD. Results provide a foundation to elucidate unique response patterns across physiological systems to more precisely identify those with heightened physiological arousal across social contexts. It is proposed that future identification of subtypes may ultimately inform approaches for enhancing social engagement., Competing Interests: Conflict of Interest The authors do not have any conflicts of interest to declare.

Background: Catatonia, a form of acute brain dysfunction typically linked with severe affective and psychotic disorders, occurs in critical illness with delirium and coma. Delirium and coma are associated with mortality, though catatonia's relationship with mortality is unclear. We aim to describe whether catatonia, delirium, and coma are associated with mortality., Methods: We enrolled a convenience cohort of critically ill adults (N = 378) at an academic medical center. We assessed catatonia, delirium, and coma using the Bush-Francis Catatonia Rating Scale, the Confusion Assessment Method for the Intensive Care Unit and the Richmond Agitation-Sedation Scale, respectively. We tested the associations between previous day brain dysfunction state occurrence with in-hospital and one-year mortality using multivariable time-dependent risk models. Additionally, we tested the association between brain dysfunction duration and one-year mortality., Results: Catatonia was not associated with death on the day after diagnosis during hospitalization, and neither previous catatonia occurrence nor duration was associated with one-year mortality. Delirium was not associated with death on any day following diagnosis during hospitalization, and neither previous delirium occurrence nor duration was associated with one-year mortality. The occurrence of coma was associated with death on any day after diagnosis during hospitalization (HR 2.30,CI 1.19-4.44,p = 0.014), as well as through one year following hospital discharge (HR 1.68,CI 1.09-2.59,p = 0.02)., Conclusions: Coma, but neither catatonia nor delirium, was associated with future day in-hospital and one-year mortality. More research is needed to understand catatonia's clinical impact. Delirium results differ from existing literature likely due to cohort demographics and size. Coma results highlight the prognostic significance of suppressed arousal while critically ill., Competing Interests: Declaration of competing interest The authors disclose that the research was conducted in the absence of any commercial or financial relationships that could be seen as a potential conflict of interest., (Published by Elsevier B.V.)

Background: The ongoing COVID-19 pandemic has led to hundreds of millions of infections worldwide. Although differences in COVID-19 hospitalization rates between males and females have been described, many infections in the general population have been mild, and the severity of symptoms during the course of COVID-19 in non-hospitalized males and females is not well understood., Methods: We conducted a case-ascertained study to examine household transmission of SARS-CoV-2 infections in Nashville, Tennessee, between April 2020 and April 2021. Among enrolled ambulatory adult participants with laboratory-confirmed SARS-CoV-2 infections, we assessed the presence and severity of symptoms (total, systemic, and respiratory) daily using a symptoms severity questionnaire, from illness onset and throughout the 2-week follow-up period. We compared the mean daily symptom severity scores (0-3: none, mild, moderate, and severe) and change in symptoms between males and females using a multivariable linear mixed effects regression model., Results: The analysis included 223 enrolled adults with SARS-CoV-2 infection (58% females, mostly white, non-Hispanic) from 146 households with 2917 total daily symptom reports. The overall mean severity of total symptoms reported over the illness period was 1.04 and 0.90 for females and males, respectively. Mean systemic and respiratory scores were higher for females than for males ( p  < 0.001). In multivariable analyses, females reported more severe total and systemic symptoms during the illness period compared with males. However, no significant differences in reported respiratory symptoms were observed., Conclusions: Our findings indicate that among ambulatory adults with SARS-CoV-2 infections, females reported slightly higher symptom severity during their illness compared with males., Competing Interests: C.G.G. reports grants from Syneos Health, the National Institutes of Health, the Food and Drug Administration, the Agency for Health Care Research and Quality, and consultation fees from Merck. The other authors have no potential conflicts of interest to report., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: An analysis of practice is conducted by the American Board of Physical Therapy Specialties (ABPTS) every 10 years to revalidate, update, and revise the description of specialty practice (DSP) for each specialty. The Geriatric Specialty Council recently conducted an analysis of practice and revised its content consistent with established procedures by the ABPTS., Purpose: The purpose of this article is threefold: first, to describe the process of the most recent practice analysis; second, to report revisions to the description of specialty practice based on the analysis of practice; and third, to identify elements of practice that define current specialist practice in geriatric physical therapy., Methods: A 10-member committee of subject matter experts (SMEs) and a psychometric consultant developed a survey instrument addressing geriatric physical therapy specialty practice areas. The survey was initially pilot-tested and subsequently administered online to a sample of 801 board-certified geriatric clinical specialists. The consultant facilitated the consensus process to determine decision rules in selecting the final competencies describing current geriatric physical therapy specialty practice., Results: A total of 372 respondents fully or partially completed the survey, resulting in a response rate of 46.4%. Based on a priori decision rules regarding survey data, consensus of the group of SMEs, and input from the ABPTS, the DSP for geriatric physical therapy specialty practice was revised. Revisions (elimination [-] of prior items and addition [+] of new items) were made in Section 1: Knowledge Areas (-8 and +6), in Section 2: Professional Roles, Responsibilities, and Values (-14 and +4), and Section 3: Practice Expectations (-53 and +28)., Conclusion: The revised DSP will be used as the basis for the development of the examination blueprint for the specialist examination in geriatric physical therapy and the curricula for residency programs in geriatric physical therapy., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 APTA Geriatrics, An Academy of the American Physical Therapy Association.)

Increasing age and puberty affect the hypothalamic pituitary adrenal (HPA) axis maturation, which is likely associated with an increase in environmental demands (e.g., social) and vulnerability for the onset of psychiatric conditions (e.g., depression). There is limited research as to whether such patterns are consonant in youth with autism spectrum disorder (ASD), a condition marked by social challenges, dysregulation of the HPA axis, and higher rates of depression setting the stage for enhanced vulnerability during this developmental period.The current study interrogated diurnal cortisol by examining (1) cortisol expression longitudinally over the pubertal transition between autistic and neurotypical youth, (2) the trajectory of diurnal cortisol and the unique contributions of age vs. puberty, and (3) potential sex differences. As hypothesized, results indicate autistic compared to typically developing youth demonstrate a shallower diurnal slope and elevated evening cortisol. These differences were in the context of higher cortisol and flatter rhythms based on age and pubertal development. Also, sex-based differences emerged such that females in both groups had higher cortisol, flatter slopes, and higher evening cortisol than males. The results show that despite the trait-like stability of diurnal cortisol, HPA maturation is impacted by age, puberty, sex, as well as an ASD diagnosis.

Traumatic brain injury is common, and often results in debilitating consequences. Even mild traumatic brain injury leaves approximately 20% of patients with symptoms that persist for months. Despite great clinical need there are currently no approved pharmaceutical interventions that improve outcomes after traumatic brain injury. Increased understanding of the endocannabinoid system in health and disease has accompanied growing evidence for therapeutic benefits of Cannabis sativa. This has driven research of Cannabis' active chemical constituents (phytocannabinoids), alongside endogenous and synthetic counterparts, collectively known as cannabinoids. Also of therapeutic interest are other Cannabis constituents, such as terpenes. Cannabinoids interact with neurons, microglia, and astrocytes, and exert anti-inflammatory and neuroprotective effects which are highly desirable for the management of traumatic brain injury. In this review, we comprehensively appraised the relevant scientific literature, where major and minor phytocannabinoids, terpenes, synthetic cannabinoids, and endogenous cannabinoids were assessed in TBI, or other neurological conditions with pathology and symptomology relevant to TBI, as well as recent studies in preclinical TBI models and clinical TBI populations., (© 2023. The Author(s).)

Optic nerve injury causes secondary degeneration, a sequela that spreads damage from the primary injury to adjacent tissue, through mechanisms such as oxidative stress, apoptosis, and blood-brain barrier (BBB) dysfunction. Oligodendrocyte precursor cells (OPCs), a key component of the BBB and oligodendrogenesis, are vulnerable to oxidative deoxyribonucleic acid (DNA) damage by 3 days post-injury. However, it is unclear whether oxidative damage in OPCs occurs earlier at 1 day post-injury, or whether a critical 'window-of-opportunity' exists for therapeutic intervention. Here, a partial optic nerve transection rat model of secondary degeneration was used with immunohistochemistry to assess BBB dysfunction, oxidative stress, and proliferation in OPCs vulnerable to secondary degeneration. At 1 day post-injury, BBB breach and oxidative DNA damage were observed, alongside increased density of DNA-damaged proliferating cells. DNA-damaged cells underwent apoptosis (cleaved caspase3+), and apoptosis was associated with BBB breach. OPCs experienced DNA damage and apoptosis and were the major proliferating cell type with DNA damage. However, the majority of caspase3+ cells were not OPCs. These results provide novel insights into acute secondary degeneration mechanisms in the optic nerve, highlighting the need to consider early oxidative damage to OPCs in therapeutic efforts to limit degeneration following optic nerve injury.

Adolescence is a critical period of postnatal development characterized by social, emotional, and cognitive changes. These changes are increasingly understood to depend on white matter development. White matter is highly vulnerable to the effects of injury, including secondary degeneration in regions adjacent to the primary injury site which alters the myelin ultrastructure. However, the impact of such alterations on adolescent white matter maturation is yet to be investigated. To address this, female piebald-virol-glaxo rats underwent partial transection of the optic nerve during early adolescence (postnatal day (PND) 56) with tissue collection two weeks (PND 70) or three months later (PND 140). Axons and myelin in the transmission electron micrographs of tissue adjacent to the injury were classified and measured based on the appearance of the myelin laminae. Injury in adolescence impaired the myelin structure in adulthood, resulting in a lower percentage of axons with compact myelin and a higher percentage of axons with severe myelin decompaction. Myelin thickness did not increase as expected into adulthood after injury and the relationship between the axon diameter and myelin thickness in adulthood was altered. Notably, dysmyelination was not observed 2 weeks postinjury. In conclusion, injury in adolescence altered the developmental trajectory, resulting in impaired myelin maturation when assessed at the ultrastructural level in adulthood.

Introduction: Pediatric catatonia is a highly co-morbid condition with treatment options often limited to electroconvulsive therapy (ECT) or lorazepam. However, lorazepam may not be readily available, and access to ECT is limited by restrictive legislation and stigma. This study aims to provide alternative treatment options for pediatric catatonia., Methods: The study involved a single-site retrospective analysis of a private university hospital in the southern United States. The study included patients under eighteen with catatonia who received psychopharmacologic treatment with an agent other than lorazepam. The patients were evaluated with the Bush-Francis Catatonia Rating Scale (BFCRS), Kanner Catatonia Severity Scale (KCS), and Kanner Catatonia Examination (KCE) at the time of initial evaluation and upon stabilization. A retrospective clinical global impressions-improvement (CGI-I) score was assigned by four authors., Results: 102 pediatric patients diagnosed with catatonia were identified, and 31 met criteria for the study. 20 (65%) were white, 6 (19%) were Black, 4 (13%) were Hispanic, and 1 (3%) were Indian. Most patients ( N = 18; 58%) were insured by Medicaid. The mean age at the time of catatonia diagnosis was 13.5 years. All patients were stabilized on either clonazepam or diazepam, with 21 (68%) requiring treatment with an additional medication of either an anti-epileptic, N-methyl-D-aspartate (NMDA) receptor antagonist, and aripiprazole or clozapine. Statistically significant reductions in the BFCRS [ t = 11.2, df = 30, std = 6.3, p < 0.001, 95% CI = (7.8, 15.1)], KCS [ t = 4.6, df = 38, p < 0.001, 95% CI = (12.0, 31.0)], and KCE [ t = 7.8, df = 30, std = 1.8, p < 0.001, 95% CI = (1.9, 3.2)] were observed. For CGI-I the results showed that the estimated probability of observing a score better than no change (>4) is 0.976 [t.s. = 43.2, p < 0.001, 95% CI = (0.931,0.992)], indicating the average subject is expected to experience some improvement., Discussion: In conclusion, all patients responded to these treatments with improvement in their catatonic symptoms. Alternative pharmacologic interventions for catatonia, including benzodiazepines other than lorazepam, valproic acid, NMDA receptor antagonists, and atypical antipsychotics were safe and effective in treating catatonia in this population., Competing Interests: Conflict of interest JL receives equity from Revival Therapeutics. The author LW declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Mild traumatic brain injury (mTBI) causes structural, cellular and biochemical alterations which are difficult to detect in the brain and may persist chronically following single or repeated injury. Lipids are abundant in the brain and readily cross the blood-brain barrier, suggesting that lipidomic analysis of blood samples may provide valuable insight into the neuropathological state. This study used liquid chromatography-mass spectrometry (LC-MS) to examine plasma lipid concentrations at 11 days following sham (no injury), one (1×) or two (2×) mTBI in rats. Eighteen lipid species were identified that distinguished between sham, 1× and 2× mTBI. Three distinct patterns were found: (1) lipids that were altered significantly in concentration after either 1× or 2× F mTBI: cholesterol ester CE (14:0) (increased), phosphoserine PS (14:0/18:2) and hexosylceramide HCER (d18:0/26:0) (decreased), phosphoinositol PI(16:0/18:2) (increased with 1×, decreased with 2× mTBI); (2) lipids that were altered in response to 1× mTBI only: free fatty acid FFA (18:3 and 20:3) (increased); (3) lipids that were altered in response to 2× mTBI only: HCER (22:0), phosphoethanolamine PE (P-18:1/20:4 and P-18:0/20:1) (increased), lysophosphatidylethanolamine LPE (20:1), phosphocholine PC (20:0/22:4), PI (18:1/18:2 and 20:0/18:2) (decreased). These findings suggest that increasing numbers of mTBI induce a range of changes dependent upon the lipid species, which likely reflect a balance of damage and reparative responses.

Cuprizone is a copper-chelating agent that induces pathology similar to that within some multiple sclerosis (MS) lesions. The reliability and reproducibility of cuprizone for inducing demyelinating disease pathology depends on the animals ingesting consistent doses of cuprizone. Cuprizone-containing pelleted feed is a convenient way of delivering cuprizone, but the efficacy of these pellets at inducing demyelination has been questioned. This study compared the degree of demyelinating disease pathology between mice fed cuprizone delivered in pellets to mice fed a powdered cuprizone formulation at an early 3 week demyelinating timepoint. Within rostral corpus callosum, cuprizone pellets were more effective than cuprizone powder at increasing astrogliosis, microglial activation, DNA damage, and decreasing the density of mature oligodendrocytes. However, cuprizone powder demonstrated greater protein nitration relative to controls. Furthermore, mice fed control powder had significantly fewer mature oligodendrocytes than those fed control pellets. In caudal corpus callosum, cuprizone pellets performed better than cuprizone powder relative to controls at increasing astrogliosis, microglial activation, protein nitration, DNA damage, tissue swelling, and reducing the density of mature oligodendrocytes. Importantly, only cuprizone pellets induced detectable demyelination compared to controls. The two feeds had similar effects on oligodendrocyte precursor cell (OPC) dynamics. Taken together, these data suggest that demyelinating disease pathology is modelled more effectively with cuprizone pellets than powder at 3 weeks. Combined with the added convenience, cuprizone pellets are a suitable choice for inducing early demyelinating disease pathology., (© 2021. The Author(s).)