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Abnormalities in brain oscillatory patterns have long been observed in schizophrenia and psychotic disorders more broadly. However, far less is known about aperiodic neural activity in these disorders, which has been linked to excitation/inhibition balance and neuronal population spiking within the brain. Here, we analysed resting-state electroencephalographic (EEG) recordings from 43 first episode schizophrenia spectrum psychosis (FESSP) patients and 28 healthy controls to examine whether aperiodic activity is disrupted in FESSP. We further assessed potential associations between aperiodic activity in FESSP and clinical symptom severity using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), and the Scale for the Assessment of Positive Symptoms (SAPS). We found no significant differences in either the 1/f-like aperiodic exponent or the broadband aperiodic offset between the FESSP and healthy control groups when analysing the global neural signal averaged across all EEG electrodes. Bayesian analyses further supported these non-significant findings. However, additional non-parametric cluster-based permutation analyses did identify reduced aperiodic offset in the FESSP group, relative to controls across broad central, temporal, parietal and select frontal regions. No associations were found between either exponent or offset and clinical symptom severity when examining all FESSP participants, irrespective of antipsychotic medication status. However, offset was shown to predict BPRS and SANS scores in medication naive patients. In sum, this research presents an initial analysis of aperiodic neural activity in FESSP, offering preliminary evidence of altered aperiodic offset in this disorder. This contributes to a broader understanding of disrupted neural dynamics in early psychosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Altered brain connectivity and atypical neural oscillations have been observed in autism, yet their relationship with autistic traits in non-clinical populations remains underexplored. Here, we employ electroencephalography (EEG) to examine functional connectivity, oscillatory power, and broadband aperiodic activity during a dynamic facial emotion processing (FEP) task in 101 typically developing children aged 4-12 years. We investigate associations between these electrophysiological measures of brain dynamics and autistic traits as assessed by the Social Responsiveness Scale, 2nd Edition (SRS-2). Our results revealed that increased FEP-related connectivity across theta (4-7 Hz) and beta (13-30 Hz) frequencies correlated positively with higher SRS-2 scores, predominantly in right-lateralized (theta) and bilateral (beta) cortical networks. Additionally, a steeper 1/ f -like aperiodic slope (spectral exponent) across fronto-central electrodes was associated with higher SRS-2 scores. Greater aperiodic-adjusted theta and alpha oscillatory power further correlated with both higher SRS-2 scores and steeper aperiodic slopes. These findings underscore important links between FEP-related brain dynamics and autistic traits in typically developing children. Future work could extend these findings to assess these EEG-derived markers as potential mechanisms underlying behavioural difficulties in autism., Competing Interests: Conflict of Interest Disclosure: The authors have no conflicts of interest to declare. This research was supported by an Australian Research Council Future Fellowship (PGE; FT160100077). LMO is supported by the NIMH Intramural Research Program (ZIAMH002955). The opinions expressed in this article are the authors’ own and do not reflect the views of the National Institutes of Health, the Department of Health and Human Services, or the United States government.

Several studies have suggested that atypical social processing in neurodevelopmental conditions (e.g. autism) is associated with differences in excitation and inhibition, through changes in the levels of glutamate and gamma-aminobutyric acid (GABA). While associations between baseline metabolite levels and behaviours can be insightful, assessing the neurometabolic response of GABA and glutamate during social processing may explain altered neurochemical function in more depth. Thus far, there have been no attempts to determine whether changes in metabolite levels are detectable using functional MRS (fMRS) during social processing in a control population. We performed Mescher-Garwood point resolved spectroscopy edited fMRS to measure the dynamic response of GABA and glutamate in the superior temporal sulcus (STS) and visual cortex (V1) while viewing social stimuli, using a design that allows for analysis in both block and event-related approaches. Sliding window analyses were used to investigate GABA and glutamate dynamics at higher temporal resolution. The changes of GABA and glutamate levels with social stimulus were largely non-significant. A small decrease in GABA levels was observed during social stimulus presentation in V1, but no change was observed in STS. Conversely, non-social stimulus elicited changes in both GABA and glutamate levels in both regions. Our findings suggest that the current experimental design primarily captures effects of visual stimulation, not social processing. Here, we discuss the feasibility of using fMRS analysis approaches to assess changes in metabolite response., (© 2023 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

The primary inhibitory neurotransmitter γ-aminobutyric acid (GABA) has a prominent role in regulating neural development and function, with disruption to GABAergic signalling linked to behavioural phenotypes associated with neurodevelopmental disorders, particularly autism. Such neurochemical disruption, likely resulting from diverse genetic and molecular mechanisms, particularly during early development, can subsequently affect the cellular balance of excitation and inhibition in neuronal circuits, which may account for the social processing difficulties observed in autism and related conditions. This comprehensive narrative review integrates diverse streams of research from several disciplines, including molecular neurobiology, genetics, epigenetics, and systems neuroscience. In so doing it aims to elucidate the relevance of inhibitory dysfunction to autism, with specific focus on social processing difficulties that represent a core feature of this disorder. Many of the social processing difficulties experienced in autism have been linked to higher levels of the excitatory neurotransmitter glutamate and/or lower levels of inhibitory GABA. While current therapeutic options for social difficulties in autism are largely limited to behavioural interventions, this review highlights the psychopharmacological studies that explore the utility of GABA modulation in alleviating such difficulties., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article to disclose. No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Recreational co-consumption of benzodiazepines and alcohol is a common practise; yet, the cognitive effects of this combination remain poorly understood. This study aimed to investigate the acute cognitive effects of combining a 1 mg dose of alprazolam with a moderate dose of alcohol (target 0.04% blood alcohol concentration (BAC)) in a non-clinical population., Methods: In this randomised, double-blind, placebo-controlled, crossover trial, participants completed computerised cognitive assessments and the brief biphasic alcohol effects scale (B-BAES) after consuming 1 mg of alprazolam, both with and without a moderate dose of alcohol (target 0.04% BAC)., Results: Among 20 healthy participants (mean age = 28.6, SD ± 4.0 years, 60% female), we found that a peak BAC of 0.03% had no significant impact on cognitive performance. Both the individual use of alprazolam and its combination with alcohol resulted in impaired reaction time, digit vigilance, and verbal, spatial and numeric working memory tasks, although an additive effect when alcohol and alprazolam were consumed together was not evident. The most pronounced cognitive effects occurred at 100 min after dosing, coinciding with increased alprazolam concentrations. Sedative effects were heightened with alcohol, alprazolam and their combination while no stimulative effects were reported., Conclusions: Our findings highlight the significant implications of a therapeutic dose of alprazolam on impairing cognitive performance. This is particularly relevant considering the frequency of non-medical alprazolam use. Future studies should explore different dosages, administration timings and long-term effects to inform the development of public health policies and guidelines regarding the combined use of alcohol and benzodiazepines., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Amie C Hayley is currently supported by a Rebecca L Cooper Al and Val Rosenstrauss Fellowship (GNT: F2021894) and was previously supported by an NHMRC Early Career Fellowship (GNT: 1119960) during the conduct of this study. Luke A Downey was supported by a R.D. Wright Biomedical Career Development Fellowship (GNT: 1122577) during the conduct of this study. Blair Aitken, Talitha Ford, Lauren Geier, and Brook A Shiferaw have no conflicts of interests to declare.

Background: Alprazolam, also known by trade-name Xanax, is regularly detected along with alcohol in blood samples of drivers injured or killed in traffic collisions. While their co-consumption is principally legal, policy guidelines concerning fitness-to-drive are lacking and methods to index impairment are underdeveloped., Methods: In this randomized, double-blind, placebo-controlled, crossover trial, we examined whether legally permissible levels of alcohol [target 0.04% blood alcohol concentration (BAC)], alprazolam (1mg), and their combination impacts driving performance, and whether driving impairment can be indexed by ocular activity. Participants completed a test battery consisting of a 40-minute simulated highway drive with ocular parameters assessed simultaneously, the Karolinska Sleepiness Scale, and a confidence to drive assessment following four separate treatment combinations. The predictive efficacy of ocular parameters to identify alcohol and alprazolam-related driving impairment was also examined., Results: Among 21 healthy, fully licensed drivers (37% female, mean age 28.43, SD ± 3.96), driving performance was significantly impacted by alprazolam, alcohol, and their combination. Linear regression models revealed that the odds of an out-of-lane event occurring increased five-fold under the influence alprazolam alone and when combined with alcohol. An increase in gaze transition entropy (GTE) demonstrated the strongest association with the odds of an out-of-lane event occurring in the same minute, with both microsleeps and fixation rate achieving moderate accuracy across treatments., Conclusions: Alprazolam and alcohol, alone and in combination, impaired select aspects of vehicle control over time. GTE, microsleeps, and fixation rate show potential as real-time indicators of driving impairment and crash risk associated with alcohol and alprazolam consumption., Competing Interests: Declaration of Competing Interest AH is currently supported by a Rebecca L Cooper Al and Val Rosenstrauss Fellowship (GNT: F2021894) and was previously supported by an NHMRC Early Career Fellowship (GNT: 1119960) during the conduct of this study. LD was supported by a R.D. Wright Biomedical Career Development Fellowship (GNT: 1122577) during the conduct of this study. BA, TCF and LG have no conflicts of interests to declare. BS is employed by Seeing Machines; however, we confirm that there are no known conflicts of interest associated with this publication and there has been no financial support provided for this work that could have influenced its outcome., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Community-based participatory research (CBPR) partnerships strive to promote community capacity building and sustainability, yet initiatives often suffer when grants or relationships with academic partners end. To address these concerns, researchers hoping to develop truly sustainable CBPR partnerships should consider factors that promote the development of community capacity and, ultimately, independence. In this first-person account, using perspectives gathered from FAVOR, a Connecticut-based family-led advocacy organization and an academic researcher, we examine the practices and experiences of the members of a CBPR partnership focused on using community voice to inform changes in the state's children's behavioral health system of care. These practices ultimately led to FAVOR developing the necessary skills to assume full ownership of the community data-gathering initiative, ensuring that the initiative would be sustained. Through the perspectives of five FAVOR staff and an academic researcher, we describe the factors that contributed to the organization being able to develop the capacity to independently continue their community data-gathering initiative, including description of the training process and staff members' perspectives on training, autonomy, community value, and lessons learned. We use these stories and experiences to provide recommendations for other partnerships striving to promote capacity building and sustainability through community ownership of the research process., (© 2023 Society for Community Research and Action.)

Cannabis-derived compounds, such as cannabidiol (CBD) and delta-9-trans-tetrahydrocannabinol (THC), are increasingly prescribed for a range of clinical indications. These phyto-cannabinoids have multiple biological targets, including the body's endocannabinoid system. There is growing scientific interest in the use of CBD, a non-intoxicating compound, to ameliorate symptoms associated with neurodevelopmental disorders. However, its suitability as a pharmaceutical intervention has not been reliably established in these clinical populations. This systematic review examines the nine published randomised controlled trials (RCTs) that have probed the safety and efficacy of CBD in individuals diagnosed with attention deficit hyperactivity disorder, autism spectrum disorder, intellectual disability, Tourette Syndrome, and complex motor disorders. Studies were identified systematically through searching four databases: Medline, CINAHL complete, PsycINFO, and EMBASE. Inclusion criteria were randomised controlled trials involving CBD and participants with neurodevelopmental disorders. No publication year or language restrictions were applied. Relevant data were extracted from the identified list of eligible articles. After extraction, data were cross-checked between the authors to ensure consistency. Several trials indicate potential efficacy, although this possibility is currently too inconsistent across RCTs to confidently guide clinical usage. Study characteristics, treatment properties, and outcomes varied greatly across the included trials. The material lack of comparable RCTs leaves CBD's suitability as a pharmacological treatment for neurodevelopmental disorders largely undetermined. A stronger evidence base is urgently required to establish safety and efficacy profiles and guide the ever-expanding clinical uptake of cannabis-derived compounds in neurodevelopmental disorders. Prospero registration number: CRD42021267839., Competing Interests: Declaration of competing interest No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The first metatarsophalangeal joint is the most common location for arthritis in the foot. Pain and limited mobility associated with arthritis of the first metatarsophalangeal joint are the hallmarks of this disease. Treatments include shoe modification, orthotic devices, nonsteroidal anti-inflammatory drugs, injections, physical therapy, and surgery. Surgery has been the most perplexing, with surgical treatments ranging from simple ostectomies to fusion of the first metatarsophalangeal joint. Implant arthroplasty, with its various designs and techniques, has yet to be proven as the definitive solution for first metatarsophalangeal joint arthritis or hallux limitus (unlike the knee and hip). Interpositional arthroplasty and tissue-engineered cartilage grafts also have limitations when dealing with osteoarthritis and hallux limitus of the first metatarsophalangeal joint. In this case report, we present a 45-year-old woman with arthritis of the left first metatarsophalangeal joint who underwent surgical intervention by means of a frozen osteochondral allograft transplant to the first metatarsal head.

Sensory deficits are a feature of autism and schizophrenia, as well as the upper end of their non-clinical spectra. The mismatch negativity (MMN), an index of pre-attentive auditory processing, is particularly sensitive in detecting such deficits; however, little is known about the relationship between the visual MMN (vMMN) to facial emotions and autism and schizophrenia spectrum symptom domains. We probed the vMMN to happy, sad, and neutral faces in 61 healthy adults (18-40 years, 32 female), and evaluated their degree of autism and schizophrenia spectrum traits using the Autism Spectrum Quotient (AQ) and Schizotypal Personality Questionnaire (SPQ). The vMMN to happy faces was significantly larger than the vMMNs to sad and neutral faces. The vMMN to happy faces was associated with interpersonal difficulties as indexed by AQ Communication and Attention to Detail subscales, and SPQ associated with more interpersonal difficulties. These data suggest that pre-attentive processing of positive affect might be more specific to the interpersonal features associated with autism and schizophrenia. These findings add valuable insights into the growing body of literature investigating symptom-specific neurobiological markers of autism and schizophrenia spectrum conditions., Competing Interests: The 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., (Copyright © 2022 Ford, Hugrass and Jack.)

Introduction: There are no well-established biomedical treatments for the core symptoms of autism spectrum disorder (ASD). A small number of studies suggest that repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, may improve clinical and cognitive outcomes in ASD. We describe here the protocol for a funded multicentre randomised controlled clinical trial to investigate whether a course of rTMS to the right temporoparietal junction (rTPJ), which has demonstrated abnormal brain activation in ASD, can improve social communication in adolescents and young adults with ASD., Methods and Analysis: This study will evaluate the safety and efficacy of a 4-week course of intermittent theta burst stimulation (iTBS, a variant of rTMS) in ASD. Participants meeting criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ASD (n=150, aged 14-40 years) will receive 20 sessions of either active iTBS (600 pulses) or sham iTBS (in which a sham coil mimics the sensation of iTBS, but no active stimulation is delivered) to the rTPJ. Participants will undergo a range of clinical, cognitive, epi/genetic, and neurophysiological assessments before and at multiple time points up to 6 months after iTBS. Safety will be assessed via a structured questionnaire and adverse event reporting. The study will be conducted from November 2020 to October 2024., Ethics and Dissemination: The study was approved by the Human Research Ethics Committee of Monash Health (Melbourne, Australia) under Australia's National Mutual Acceptance scheme. The trial will be conducted according to Good Clinical Practice, and findings will be written up for scholarly publication., Trial Registration Number: Australian New Zealand Clinical Trials Registry (ACTRN12620000890932)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Atypical white matter (WM) microstructure is commonly implicated in the neuropathophysiology of autism spectrum disorder (ASD). Fixel based analysis (FBA), at the cutting-edge of diffusion-weighted imaging, can account for crossing WM fibers and can provide indices of both WM micro- and macrostructure. We applied FBA to investigate WM structure between 25 (12 males, 13 females) adults with ASD and 24 (12 males, 12 females) matched controls. As the role of biological sex on the neuropathophysiology of ASD is of increasing interest, this was also explored. There were no significant differences in WM micro- or macrostructure between adults with ASD and matched healthy controls. When data were stratified by sex, females with ASD had reduced fiber density and cross-section (FDC), a combined metric comprised of micro- and macrostructural measures, in the corpus callosum, a finding not detected between the male sub-groups. We conclude that micro- and macrostructural WM aberrations are present in ASD, and may be influenced by biological sex., (Copyright © 2020 Kirkovski, Fuelscher, Hyde, Donaldson, Ford, Rossell, Fitzgerald and Enticott.)

Several lines of evidence identify aberrant excitatory-inhibitory neural processes across autism and schizophrenia spectrum disorders, particularly within the psychosocial domain. Such neural processes include increased excitatory glutamate and reduced inhibitory GABA concentrations, which may affect auditory pre-attentive processing as indexed by the mismatch negativity (MMN); thus, an excitation-inhibition imbalance might lead to aberrant MMN, which might in turn drive the relationship between the MMN and psychosocial difficulties. This research has the potential to enhance the neurochemical understanding of the relationship between electrophysiology (MMN) and behavioural/clinical measures (psychosocial difficulties). Thirty-eight adults (18 male, 18-40 years) completed the Schizotypal Personality Questionnaire (SPQ) and Autism-Spectrum Quotient (AQ). Glutamate and GABA concentrations in bilateral superior temporal cortex (STC) were quantified using proton magnetic resonance spectroscopy (1H-MRS) while auditory MMN to a duration deviant was measured with magnetoencephalography. Spearman correlations probed the relationships between STC glutamate/GABA ratios, MMN amplitude and latency, and AQ and SPQ dimensions. Mediation effects of glutamate/GABA ratios on the relationship between MMN and AQ-SPQ dimensions were probed using causal mediation analysis. Only SPQ-interpersonal and AQ-communication were significantly correlated with right hemisphere glutamate/GABA ratios and MMN latency (ps < 0.05), which were themselves correlated (p = .035). Two mediation models were investigated, with right MMN latency as predictor and SPQ-interpersonal and AQ-communication as outcome variables. Right STC glutamate/GABA ratios significantly mediated the relationship between MMN latency and SPQ-interpersonal scores, but only partially mediated the relationship between MMN latency and AQ-communication scores. These findings support the growing body of literature pointing toward an excitation-inhibition imbalance that is central to psychosocial functioning across multi-dimensional spectrum disorders, such as autism and schizophrenia, and provides neurochemical indicators of the processes that underlie psychosocial dysfunction., (Copyright © 2019 Elsevier Inc. All rights reserved.)

This clinical consensus statement of the American College of Foot and Ankle Surgeons focuses on the highly debated subject of the management of adult flatfoot (AAFD). In developing this statement, the AAFD consensus statement panel attempted to address the most relevant issues facing the foot and ankle surgeon today, using the best evidence-based literature available. The panel created and researched 16 statements and generated opinions on the appropriateness of the statements. The results of the research on this topic and the opinions of the panel are presented here., (Copyright © 2019 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Continued human and animal research has strengthened evidence for aberrant excitatory-inhibitory neural processes underlying autism and schizophrenia spectrum disorder psychopathology, particularly psychosocial functioning, in clinical and nonclinical populations. We investigated the extent to which autistic traits and schizotypal dimensions were modulated by the interactive relationship between excitatory glutamate and inhibitory GABA neurotransmitter concentrations in the social processing area of the superior temporal cortex using proton magnetic resonance spectroscopy. In total, 38 non-clinical participants (20 females; age range = 18-35 years, mean (standard deviation) = 23.22 (5.52)) completed the autism spectrum quotient and schizotypal personality questionnaire, and underwent proton magnetic resonance spectroscopy to quantify glutamate and GABA concentrations in the right and left superior temporal cortex. Regression analyses revealed that glutamate and GABA interactively modulated autistic social skills and schizotypal interpersonal features ( p corr < 0.05), such that those with high right superior temporal cortex glutamate but low GABA concentrations exhibited poorer social and interpersonal skills. These findings evidence an excitation-inhibition imbalance that is specific to psychosocial features across the autism and schizophrenia spectra.

B vitamins are essential for optimal brain and body function, and are particularly important for cortical metabolic processes that have downstream effects on mitigating oxidative stress. Oxidative stress has been linked to poor psychological outcomes including psychological distress, which has wide-reaching implications for the community and the workplace. Given work-related stress has been associated with poor mental health outcomes, high-dose B vitamin supplementation may be effective in improving brain function and psychological outcomes via attenuation of oxidative stress. This randomized, double-blind, placebo-controlled study investigated psychological outcomes following 6-month supplementation of a high-B-vitamin multivitamin in a large sample of healthy adults ( n = 108, aged 30-70 years), as well as changes in default mode network functional connectivity in a subset of the original sample ( n = 28). Improvements in occupational stress, general health, perceived stress, depressive symptoms, and mood profiles were identified for both active and placebo groups over time ( p < 0.05 corrected ). Seed-based functional connectivity analysis centered on the posterior cingulate cortex (PCC) showed that connectivity between the PCC and the caudate increased for the active treatment group, but decreased for the placebo group ( p < 0.05 corrected ). These findings reveal a substantial intervention effect for both active and placebo treatments, which could in part be associated with a placebo effect in subjective measures. There was, however, a significant treatment effect in the objective measure of functional connectivity, suggesting that reduced psychological stress and high-B-vitamin multivitamin supplementation may lead to an increase in DMN and caudate functional connectivity, which might reflect a strengthening of neurocircuitry within areas associated with reward and emotion at rest. Future studies should consider a placebo run-in methodology to reduce the placebo effect on the subjective measures of stress., (Copyright © 2019 Downey, Simpson, Ford, McPhee, Suo, Myers, Oliver and Stough.)

The underlying mechanisms of autism and schizophrenia are poorly understood, partly due to a lack of dimension-specific research. Aberrant excitatory and inhibitory neurotransmission are implicated in both conditions, particularly in social dysfunction. This study investigates the extent to which the degree of autistic tendency and psychosis-proneness exclusively and interactively predict excitatory and inhibitory neurotransmitter concentrations in the superior temporal cortex (STC). In 38 adults (18 male, 18-40 years), we obtained autistic tendencies (Autism-Spectrum Quotient [AQ]) and psychosis-proneness scores (Schizotypal Personality Questionnaire [PP]); magnetic resonance spectroscopy (MRS) quantified glutamate and GABA+ concentrations from the STC. Results demonstrated a negative AQ/PP interaction with glutamate concentration for the left STC voxel, where PP increased with glutamate for average AQ, while AQ decreased with glutamate for average-high PP. There was a negative AQ/PP interaction with glutamate/GABA+ ratio for the right STC, AQ increasing with glutamate/GABA+ for low-average PP, while PP decreased with glutamate/GABA+ for high AQ. Consistent with animal studies, we also reveal that overall reduced glutamate/GABA+ ratio might be precipitated by increased right hemisphere GABA+ concentrations. These findings illustrate the importance of considering the concurrent effects of autism and psychosis dimensions on understanding the pathophysiological mechanisms implicated in either condition, and can advance psychopharmacological research into better treatment options for patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

A diet rich in B-group vitamins is essential for optimal body and brain function, and insufficient amounts of such vitamins have been associated with higher levels of neural inflammation and oxidative stress, as marked by increased blood plasma homocysteine. Neural biomarkers of oxidative stress quantified through proton magnetic spectroscopy (1H-MRS) are not well understood, and the relationship between such neural and blood biomarkers is seldom studied. The current study addresses this gap by investigating the direct effect of 6-month high-dose B-group vitamin supplementation on neural and blood biomarkers of metabolism. Using a randomized, double-blind, placebo-controlled design, 32 healthy adults (20 female, 12 male) aged 30⁻65 years underwent blood tests (vitamin B6, vitamin B12, folate, and homocysteine levels) and 1H-MRS of the posterior cingulate cortex (PCC) and dorsolateral prefrontal cortex (DLPFC) before and after supplementation. Results confirmed the supplement was effective in increasing vitamin B6 and vitamin B12 levels and reducing homocysteine, whereas there was no change in folate levels. There were significant relationships between vitamin B6 and N -acetylaspartate (NAA), choline, and creatine, as well as between vitamin B12 and creatine ( p s < 0.05), whereas NAA in the PCC increased, albeit not significantly ( p > 0.05). Together these data provide preliminary evidence for the efficacy of high-dose B-group supplementation in reducing oxidative stress and inflammation through increasing oxidative metabolism. It may also promote myelination, cellular metabolism, and energy storage.

Anxiety is associated with compromised cognitive control functions, such as working memory. State and trait anxiety within the non-clinical population can be utilised to investigate potential neural markers for anxiety, which may help to elucidate potential prevention and intervention methods. Thirty-two healthy adults (20 female, 12 male), aged between 30 and 65 years, performed a 2-back task whilst fMRI BOLD signal was acquired using a 3T scanner. Mean BOLD signal was obtained in cognitive control network regions of interest of: left and right dorsolateral prefrontal cortex (DLPFC) and posterior parietal lobe (PPL), and medial prefrontal cortex (MPFC). State and trait anxiety levels were recorded. Higher overall anxiety was moderately associated with more left and right PPL BOLD signal; there was a weak relationship between anxiety and left DLPFC BOLD signal. MPFC BOLD signal and trait anxiety were moderately associated with overall 2-back task performance. These findings suggest that non-clinical anxiety affects the recruitment of cortical resources during working memory, but that anxiety does not impair performance during a 2-back task., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Autism and schizophrenia spectrum research is typically based on coarse diagnostic classification, which overlooks individual variation within clinical groups. This method limits the identification of underlying cognitive, genetic and neural correlates of specific symptom dimensions. This study, therefore, aimed to identify homogenous subclinical subgroups of specific autistic and schizotypal traits dimensions, that may be utilised to establish more effective diagnostic and treatment practices. Latent profile analysis of subscale scores derived from an autism-schizotypy questionnaire, completed by 1678 subclinical adults aged 18-40 years (1250 females), identified a local optimum of eight population clusters: High, Moderate and Low Psychosocial Difficulties; High, Moderate and Low Autism-Schizotypy; High Psychosis-Proneness; and Moderate Schizotypy. These subgroups represent the convergent and discriminant dimensions of autism and schizotypy in the subclinical population, and highlight the importance of examining subgroups of specific symptom characteristics across these spectra in order to identify the underlying genetic and neural correlates that can be utilised to advance diagnostic and treatment practices., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Auditory processing deficits are frequently identified in autism and schizophrenia, and the two disorders have been shown to share psychosocial difficulties. This study used magnetoencephalography to investigate auditory processing differences for those with a high degree of a non-clinical autistic and schizotypal trait phenotype, Social Disorganisation (SD). Participants were 18 low (9 female) and 19 high (9 female) SD scorers (18-40 years) who completed a three-stimulus auditory oddball paradigm of speech sounds (standard: 100ms 'o', deviant: 150ms 'o', novel: 150ms 'e'). Spatio-temporal cluster analysis revealed increased amplitude for the high SD group in a left (p = 0.006) and a right (p = 0.020) hemisphere cluster in response to the novel non-target. No cluster differences were found in response to the target deviant. These findings suggest that those with a high degree of the SD phenotype recruit more cortical resources when processing unattended, novel speech stimuli, which may lead to psychosocial deficits., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The recreational use of various stimulant drugs has been implicated in the development of movement disorders through dysregulation of the dopaminergic and serotoninergic neurotransmitter systems. The present study investigated psychomotor differences in current and former recreational stimulant drug users compared with nonusing controls. Sixty participants comprised 3 groups: 20 current stimulant drug users (CSUs; 11 men, aged 31.4 ± 9.1 years), 20 former stimulant drug users (FSUs; 5 men, aged 39.1 ± 8.5 years), and 20 nonuser controls (NUCs; 5 men, aged 35.7 ± 6.4 years). Psychomotor arm steadiness for each participant was assessed with a wrist-attached accelerometer during 5 arm positions with eyes open and then eyes closed. Arm-drop of arm position was indicated by the arm longitudinal rotation axis (ALoRA), and tremor was indicated by the overall vector of dynamic body acceleration (VeDBA). Overall, CSUs performed the most poorly on ALoRA (P < .05) and VeDBA indices (P < .05), and FSUs perform almost as poorly on VeDBA indices (P < .05) compared with NUCs. It was concluded that stimulant drug use, primarily MDMA and amphetamines, may result in acute stimulant-induced tremor as well as long-term proprioceptive deficits in terms of arm-droop., (© 2017, The American College of Clinical Pharmacology.)

Background: The autism and schizophrenia spectra overlap to a large degree in the social and interpersonal domains. Similarly, abnormal excitatory glutamate and inhibitory γ-aminobutyric acid (GABA) neurotransmitter concentrations have been reported for both spectra, with the interplay of these neurotransmitters important for cortical excitation to inhibition regulation. This study investigates whether these neurotransmitter abnormalities are specific to the shared symptomatology, and whether the degree of abnormality increases with increasing symptom severity. Hence, the relationship between the glutamate/GABA ratio and autism and schizophrenia spectrum traits in an unmedicated, subclinical population was investigated., Methods: A total of 37 adults (19 female, 18 male) aged 18-38 years completed the Autism Spectrum Quotient (AQ) and Schizotypal Personality Questionnaire (SPQ), and participated in the resting state proton magnetic resonance spectroscopy study in which sequences specific for quantification of glutamate and GABA+ concentration were applied to a right and left superior temporal voxel., Results: There were significant, moderate, positive relationships between right superior temporal glutamate/GABA+ ratio and AQ, SPQ and AQ+SPQ total scores (p<0.05), SPQ subscales Social Anxiety, No Close Friend, Constricted Affect, Odd Behaviour, Odd Speech, Ideas of Reference and Suspiciousness, and AQ subscales Social Skills, Communication and Attention Switching (p<0.05); increased glutamate/GABA+ coinciding with higher scores on these subscales. Only the relationships between glutamate/GABA+ ratio and Social Anxiety, Constricted Affect, Social Skills and Communication survived multiple comparison correction (p< 0.004). Left superior temporal glutamate/GABA+ ratio reduced with increasing restricted imagination (p<0.05)., Conclusion: These findings demonstrate evidence for an association between excitatory/inhibitory neurotransmitter concentrations and symptoms that are shared between the autism and schizophrenia spectra.

Autism and schizophrenia are multi-dimensional spectrum disorders that have substantial phenotypic overlap. This overlap is readily identified in the non-clinical population, and has been conceptualised as Social Disorganisation (SD). This study investigates the balance of excitatory glutamate and inhibitory γ -aminobutyric acid (GABA) concentrations in a non-clinical sample with high and low trait SD, as glutamate and GABA abnormalities are reported across the autism and schizophrenia spectrum disorders. Participants were 18 low (10 females) and 19 high (9 females) SD scorers aged 18 to 40 years who underwent 1 H-MRS for glutamate and GABA+macromolecule (GABA+) concentrations in right and left hemisphere superior temporal (ST) voxels. Reduced GABA+ concentration ( p  = 0.03) and increased glutamate/GABA+ ratio ( p  = 0.003) in the right ST voxel for the high SD group was found, and there was increased GABA+ concentration in the left compared to right ST voxel ( p  = 0.047). Bilateral glutamate concentration was increased for the high SD group ( p  = 0.006); there was no hemisphere by group interaction ( p  = 0.772). Results suggest that a higher expression of the SD phenotype may be associated with increased glutamate/GABA+ ratio in the right ST region, which may affect speech prosody processing, and lead behavioural characteristics that are shared within the autistic and schizotypal spectra.

The auditory mismatch negativity (MMN), a preattentive processing potential, and its magnetic counterpart (MMF) are consistently reported as reduced in schizophrenia and autism spectrum disorders. This study investigates whether MMF characteristics differ between subclinically high and low scorers on the recently discovered shared autism and schizophrenia phenotype, Social Disorganisation. A total of 18 low (10 females) and 19 high (9 females) Social Disorganisation scorers underwent magnetoencephalography (MEG) during a MMF paradigm of 50ms standard (1000Hz, 85%) and 100ms duration deviant tones. MMF was measured from the strongest active magnetometer over the right and left hemispheres (consistent across groups) after 100ms. No differences in MMF power were found, however there was a significant delay in the MMF peak (p=0.007). The P3am (following the MMF) was significantly reduced across both hemispheres for the high Social Disorganisation group (p=0.025), there were no specific hemispheric differences in P3am power or latency. Right MMF peak latency increased with higher scores on the schizotypal subscales Odd Speech, Odd Behaviour and Constricted Affect. Findings suggest that MMF peak latency delay marks a convergence of the autism and schizophrenia spectra at a subclinical. These findings have significant implications for future research methodology, as well as clinical practice., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Social Disorganisation (SD) is a shared autistic and schizotypal phenotype that is present in the subclinical population. Auditory processing deficits, particularly in mismatch negativity/field (MMN/F) have been reported across both spectrum disorders. This study investigates differences in MMN/F cortical spatio-temporal source activity between higher and lower quintiles of the SD spectrum. Sixteen low (9 female) and 19 high (9 female) SD subclinical adults (18-40years) underwent magnetoencephalography (MEG) during an MMF paradigm where standard tones (50ms) were interrupted by infrequent duration deviants (100ms). Spatio-temporal source cluster analysis with permutation testing revealed no difference between the groups in source activation to the standard tone. To the deviant tone however, there was significantly reduced right hemisphere fronto-temporal and insular cortex activation for the high SD group ( p = 0.038). The MMF, as a product of the cortical response to the deviant minus that to the standard, did not differ significantly between the high and low Social Disorganisation groups. These data demonstrate a deficit in right fronto-temporal processing of an auditory change for those with more of the shared SD phenotype, indicating that right fronto-temporal auditory processing may be associated with psychosocial functioning.

In many communities, cannabis is perceived as a low-risk drug, leading to political lobbying to decriminalise its use. Acute and chronic cannabis use has been shown to be harmful to several aspects of psychological and physical health, such as mood states, psychiatric outcomes, neurocognition, driving and general health. Furthermore, cannabis is highly addictive, and the adverse effects of withdrawal can lead to regular use. These in turn have adverse implications for public safety and health expenditure. Although the cannabinoid cannabidiol (CBD) has been shown to have positive health outcomes with its antioxidant, anticonvulsant, anti-inflammatory and neuroprotective properties, high-potency cannabis is particularly damaging due to its high tetrahydrocannabinol (THC), low CDB concentration. It is this high-potency substance that is readily available recreationally. While pharmaceutical initiatives continue to investigate the medical benefits of CDB, "medicinal cannabis" still contains damaging levels of THC. Altogether, we argue there is insufficient evidence to support the safety of cannabis and its subsequent legalisation for recreational use. Furthermore, its use for medicinal purposes should be done with care. We argue that the public conversation for the legalisation of cannabis must include scientific evidence for its adverse effects., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Neuroimaging studies of neuropsychiatric behavior biomarkers across spectrum disorders are typically based on diagnosis, thus failing to account for the heterogeneity of multi-dimensional spectrum disorders such as autism (ASD). Control group trait phenotypes are also seldom reported. Proton magnetic resonance spectroscopy ((1)H-MRS) measures the abundance of neurochemicals such as neurotransmitters and metabolites and hence can probe disorder phenotypes at clinical and sub-clinical levels. This detailed review summarizes and critiques the current (1)H-MRS research in ASD. The literature reports reduced N-acetylaspartate (NAA), glutamate and glutamine (Glx), γ-aminobutyric acid (GABA), creatine and choline, and increased glutamate for children with ASD. Adult studies are few and results are inconclusive. Overall, the literature has several limitations arising from differences in (1)H-MRS methodology and sample demographics. We argue that more consistent methods and greater emphasis on phenotype studies will advance understanding of underlying cortical metabolite disturbance in ASD, and the detection, diagnosis, and treatment of ASD and other multi-dimensional psychiatric disorders.

Behavioral and cognitive dysfunction, particularly social and communication impairments, are shared between autism and schizophrenia spectrum disorders, while evidence for a diametric autism-positive schizophrenia symptom profile is inconsistent. We investigated the shared phenotype at a personality trait level, particularly its resemblance to schizoid personality disorder, as well as differential aspects of the autism-schizophrenia model. Items of the autism spectrum quotient (AQ) and schizotypal personality questionnaire (SPQ) were pseudo-randomly combined, and were completed by 449 (162 male, 287 female) non-clinical participants aged 18-40. A factor analysis revealed three factors; the first represented a shared social disorganization phenotype, the second reflected perceptual oddities specific to schizotypy while the third reflected social rigidity specific to autism. The AQ and SPQ were strongly correlated with Factor 1 (AQ: r = 0.75, p < 0.001; SPQ: r = 0.96, p < 0.001), SPQ score was correlated with Factor 2 (r = 0.51, p < 0.001), particularly in cognitive-perceptual features (r = 0.66, p < 0.001), and AQ score was strongly correlated with Factor 3 (r = 0.76, p < 0.001). Furthermore, there was no relationship between Factor 1 and Factor 2. Thus, there is robust evidence for a shared social disorganization phenotype in autistic and schizotypal tendency, which reflects the schizoid phenotype. Discriminating and independent dimensions of schizotypal and autistic tendency exist in Factors 2 and 3, respectively. Current diagnostic protocols could result in different diagnoses depending on the instrument used, suggesting the need for neuromarkers that objectively differentiate autistic and schizotypal traits and resolve the question of commonality versus co-morbidity.

Metastasis to the foot is rarely presented in the literature. We describe a 56-year-old woman with nonspecific pain in the left foot, ankle, and knee for 3 months. The patient was diagnosed as having urothelial carcinoma with metastasis to the left lower extremity, including the foot. This diagnosis was reached through the combined efforts of radiologic techniques and biopsies. This case discusses the importance of paying close attention to the details of the history and physical examination, performing appropriate tests, and obtaining suitable referrals.

We reviewed the use of compression staples made of the memory metal alloy nitinol for fixation in foot surgery. A retrospective study was performed of 31 feet in 27 patients who underwent arthrodesis or an osteotomy fixated using compression staples. OSStaples (BME, San Antonio, Texas) were used in 18 feet, and Memodyn staples (Telos Medical, Fallston, Maryland) were used in 13 feet. A total of 48 compression staples were implanted. The following procedures were performed and fixated using compression staples: 15 Akin osteotomies, 2 first metatarsal base epiphysiodeses, 3 first metatarsal-cuneiform fusions, 2 naviculocuneiform fusions, 3 calcaneocuboid fusions, 4 talonavicular fusions, 3 subtalar joint fusions, and 2 Evans osteotomies. In our clinical experience, compression staples provide an adequate source of internal fixation in foot surgery. Good bone apposition and stabilization and compression of the bone surfaces before staple fixation are important when using staple fixation to promote an optimal environment for bone healing.

A single prospective group study in adults was performed using a new bioabsorbable screw, the NuGen Fx screw (Linvatec Biomaterials Ltd, Tampere, Finland). This multisite study included five sites and 50 patients (10 patients per site). The goal of this study was to evaluate the efficiency and safety of the NuGen Fx screw system in the fixation of osteotomies, arthrodeses, and fractures in the foot and ankle. We discuss our own results from 12 patients treated at the Kentucky Podiatric Residency Program at Norton Audubon Hospital, Louisville. The number of patients in the study, screw sizes, instrumentation, radiologic evaluation findings, and our overview of this implant are presented.

The quantification of abdominal fat is a marker of health risk. While dual-energy x-ray absorptiometry (DEXA) is easily applied, it measures overall fat, although abdominal fat may be a better indicator of health risk from obesity. We have evaluated whether a subcomponent of DEXA measurements correlates better with computed tomography (CT) for body fat than those traditionally used. Forty-seven healthy adults (22 M/25 F), aged 54.5+/-15.8 yr (mean+/-SD), with BMI of 27.1+/-4.6 kg/m2 participated in a cross-sectional study. Body fat was measured using abdominal CT and DEXA for total fat, trunk fat, and a modified trunk measurement that excludes the chest, termed "lower trunk," and compared. The coefficient of variation for DEXA measurements for trunk, lower trunk, and total body were 1.98, 3.12, and 0.85%, respectively. Mean DEXA for percentage fat ranged from 31.7% to 34.1% for trunk, lower trunk, and total body, compared to 54.2% for abdominal CT (p<0.003 for each pairwise comparison). Lower trunk, whole trunk, and total body DEXA measurements were not different. Measurement of subcomponents of fat content by DEXA is not superior to whole body measurements and remains consistently lower than measurements by CT.

Objective: The purpose of this study was to investigate the effect of exercise occurrence and intensity on albumin excretion in normotensive, normoalbuminuric patients with type 1 diabetes., Research Design and Methods: Eighteen patients (aged 29 +/- 2 years, duration of diabetes 14 +/- 2 years, blood pressure 120 +/- 2/74 +/- 1 mmHg, HbA(1c) 7.0 +/- 0.2% [mean +/- SE]) without microalbuminuria, hypertension, or anti-angiotensin II therapy participated in two exercise studies in a clinical research center. Exercise intensities were defined as moderate (50% heart rate reserve [HRR]) and intense (75% HRR) and were performed in random order. Subjects collected urine for albumin determination on the days before and after exercise. On the day of exercise, subjects exercised for 30 min on a treadmill at the assigned intensity. Timed urine collections were obtained over the day. Blood pressures were measured using an ambulatory blood pressure monitor., Results: Moderate exercise demonstrated no changes in albumin excretion. Intense exercise demonstrated a significant increase in albumin excretion during the first 4 h compared with the rest of the day (P = 0.03) but returned to normal thereafter. Albumin excretion did not exceed normal levels throughout the study. There was no difference in albumin excretion surrounding days of intense exercise. Ambulatory blood pressures demonstrated nocturnal dipping after moderate and intense exercise (P < 0.001)., Conclusions: We have demonstrated that normotensive, normoalbuminuric patients without anti-angiotensin II therapy do not have elevated albumin excretion following exercise intensities experienced by most patients with type 1 diabetes.

From 1998 to 1999, the senior author utilized Allofix cortical bone pins for primary fixation of 40 first metatarsal distal chevron osteotomies and 30 digital arthrodeses in 42 patients. Radiographs of each patient were evaluated for the presence of graft incorporation, union of the osteotomy or fusion site, and postoperative migration of the osseous segments. In 70 procedures, the average time for graft incorporation as evaluated by the absence of graft visualization on radiographs was 4 months. Complications included one case of graft displacement. The results indicate that Allofix cortical bone pins are a reliable, safe, and effective method for the fixation of first metatarsal distal chevron osteotomies and phalangeal arthrodeses of the foot.

Carotenoids and vitamin E are transported in human plasma complexed with lipoproteins. The bulk of them are associated with low-density lipoprotein (LDL), in which form they may act as antioxidants and thus delay the onset of atherosclerosis. We used a simple, rapid, ultracentrifugation technique to fractionate plasma lipoproteins in self-generating gradients of iodixanol (Optiprep), a non-ionic iodinated density gradient medium. The carotenoid content and composition of a number of LDL subfractions was determined by reversed-phase high-performance liquid chromatography. Lycopene, beta-carotene and beta-cryptoxanthin were mainly located in the larger, less-dense LDL particles whereas lutein and zeaxanthin were found preferentially in the smaller, more dense LDL particles. When the antioxidant content of these fractions was expressed per milligram of LDL protein, significantly lower concentrations of carotenoid and vitamin E were found to be associated with the smaller, protein-rich fractions of LDL. Strong positive correlations were found between total carotenoid and vitamin E plasma concentrations and the lag-time of Cu(2+)-mediated oxidation of LDL subfractions. The more dense LDL subfractions, which had lower levels of these antioxidants, were more readily oxidized, highlighting their possible role in atherosclerotic events.

The author presents multiple indications of the Herbert bone screw in foot surgery. Both cannulated and noncannulated systems are discussed along with operative steps for several of the more common procedures performed by the author with this type screw. The Herbert bone screw systems provide another alternative for internal fixation to the surgeon.