Effect of a physiotherapy-directed rehabilitation programme on patients with multidirectional instability of the glenohumeral joint: a multimodal interventional MRI study protocol.

INTRODUCTION: Altered neuromuscular control of the scapula and humeral head is a typical feature of multidirectional instability (MDI) of the glenohumeral joint, suggesting a central component to this condition. A previous randomised controlled trial showed MDI patients participating in the Watson Instability Program 1 (WIP1) had significantly improved clinical outcomes compared with a general shoulder strength programme. The aim of this paper is to outline a multimodal MRI protocol to identify potential ameliorative effects of the WIP1 on the brain. METHODS AND ANALYSIS: Thirty female participants aged 18-35 years with right-sided atraumatic MDI and 30 matched controls will be recruited. MDI patients will participate in 24 weeks of the WIP1, involving prescription and progression of a home exercise programme. Multimodal MRI scans will be collected from both groups at baseline and in MDI patients at follow-up. Potential brain changes (primary outcome 1) in MDI patients will be probed using region-of-interest (ROI) and whole-brain approaches. ROIs will depict areas of functional alteration in MDI patients during executed and imagined shoulder movements (MDI vs controls at baseline), then examining the effects of the 24-week WIP1 intervention (baseline vs follow-up in MDI patients only). Whole-brain analyses will examine baseline versus follow-up voxel-wise measures in MDI patients only. Outcome measures used to assess WIP1 efficacy will include the Western Ontario Shoulder Index and the Melbourne Instability Shoulder Score (primary outcomes 2 and 3). Secondary outcomes will include the Tampa Scale for Kinesiophobia, Short Form Orebro, Global Rating of Change Score, muscle strength, scapular upward rotation, programme compliance and adverse events. DISCUSSION: This trial will establish if the WIP1 is associated with brain changes in MDI. ETHICS AND DISSEMINATION: Participant confidentiality will be maintained with publication of results. Swinburne Human Research Ethics Committee (Ref: 20202806-5692). TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trial Registry (ACTRN12621001207808).

Neurodesk: an accessible, flexible and portable data analysis environment for reproducible neuroimaging.

Neuroimaging research requires purpose-built analysis software, which is challenging to install and may produce different results across computing environments. The community-oriented, open-source Neurodesk platform ( https://www.neurodesk.org/ ) harnesses a comprehensive and growing suite of neuroimaging software containers. Neurodesk includes a browser-accessible virtual desktop, command-line interface and computational notebook compatibility, allowing for accessible, flexible, portable and fully reproducible neuroimaging analysis on personal workstations, high-performance computers and the cloud.

Total intravenous anaesthesia with propofol and remifentanil is associated with reduction in operative time in surgery for glioblastoma when compared with inhalational anaesthesia with sevoflurane.

BACKGROUND: Total intravenous anaesthesia (TIVA) is emerging as a preferred neuroanaesthetic agent compared with inhalational anaesthetic (IA) agents. We asked if TIVA with propofol and remifentanil was associated with shorter operative times compared to IA using sevoflurane in brain tumour surgery under GA. METHODS: We performed a retrospective analysis of all patients undergoing surgery for glioblastoma (GBM). We assessed choice of GA agent (TIVA or IA) with total time patient was under GA (anaesthetic time), operative time and time taken to recover fully from GA (recovery time). RESULTS: Over a two year period 263 patients underwent surgery under GA for their GBM including 188 craniotomy operations, 63 burr hole biopsy procedures and 12 open biopsy procedures. Of these, 79 operations took place under TIVA and 184 operations under IA. TIVA was associated with significantly reduced mean operative time including time taken to wake up in theatre (104 min with TIVA, 129 min with IA; p = 0.02). TIVA was also associated with trends toward shorter mean recovery time (118 min, versus 135 min with IA; p = 0.08) and shorter mean anaesthetic time (163 min, versus 181 min with IA; p = 0.07). There was no difference between TIVA and IA groups as regards duration of inpatient stay, readmission rates, complications or survival. CONCLUSIONS: TIVA with propofol and remifentanil may reduce anaesthetic, operative and recovery times in patients undergoing surgery for their GBM. These findings may be attributable to favourable effects on intracranial pressure and cerebral perfusion, as well as rapid recovery from GA. In addition to clinical advantages, there may be financial and logistical benefits.

nBu4N+[AgI(CF3)2]-: Trifluoromethylated Argentate Derived from Fluoroform and Its Reaction with (Hetero)Aryl Diazonium Salts.

The preparation of a well-defined trifluoromethylated argentate nBu4N+[Ag(CF3)2]- 1 from fluoroform was described. The complex was stable in the solid state and in solution under an inert atmosphere. Treatment of a variety of (hetero)aryl diazonium tetrafluoroborates with nBu4N+[Ag(CF3)2]- 1 generated trifluoromethylated (hetero)arenes in good to excellent yields. Preliminary experiments were conducted, and a reasonable mechanism of the reaction was proposed.

Neuroimaging Insights: Kava's (Piper methysticum) Effect on Dorsal Anterior Cingulate Cortex GABA in Generalized Anxiety Disorder.

Generalised Anxiety Disorder (GAD) is a prevalent, chronic mental health disorder. The measurement of regional brain gamma-aminobutyric acid (GABA) offers insight into its role in anxiety and is a potential biomarker for treatment response. Research literature suggests Piper methysticum (Kava) is efficacious as an anxiety treatment, but no study has assessed its effects on central GABA levels. This study investigated dorsal anterior cingulate (dACC) GABA levels in 37 adult participants with GAD. GABA was measured using proton magnetic resonance spectroscopy (1H-MRS) at baseline and following an eight-week administration of Kava (standardised to 120 mg kavalactones twice daily) (n = 20) or placebo (n = 17). This study was part of the Kava for the Treatment of GAD (KGAD; ClinicalTrials.gov: NCT02219880), a 16-week intervention study. Compared with the placebo group, the Kava group had a significant reduction in dACC GABA (p = 0.049) at eight weeks. Baseline anxiety scores on the HAM-A were positively correlated with GABA levels but were not significantly related to treatment. Central GABA reductions following Kava treatment may signal an inhibitory effect, which, if considered efficacious, suggests that GABA levels are modulated by Kava, independent of reported anxiety symptoms. dACC GABA patterns suggest a functional role of higher levels in clinical anxiety but warrants further research for symptom benefit. Findings suggest that dACC GABA levels previously un-examined in GAD could serve as a biomarker for diagnosis and treatment response.

Neurodesk: An accessible, flexible, and portable data analysis environment for reproducible neuroimaging.

Neuroimaging data analysis often requires purpose-built software, which can be challenging to install and may produce different results across computing environments. Beyond being a roadblock to neuroscientists, these issues of accessibility and portability can hamper the reproducibility of neuroimaging data analysis pipelines. Here, we introduce the Neurodesk platform, which harnesses software containers to support a comprehensive and growing suite of neuroimaging software (https://www.neurodesk.org/). Neurodesk includes a browser-accessible virtual desktop environment and a command line interface, mediating access to containerized neuroimaging software libraries on various computing platforms, including personal and high-performance computers, cloud computing and Jupyter Notebooks. This community-oriented, open-source platform enables a paradigm shift for neuroimaging data analysis, allowing for accessible, flexible, fully reproducible, and portable data analysis pipelines.

Brain Morphological Characteristics of Cognitive Subgroups of Schizophrenia-Spectrum Disorders and Bipolar Disorder: A Systematic Review with Narrative Synthesis.

Despite a growing body of research, there is yet to be a cohesive synthesis of studies examining differences in brain morphology according to patterns of cognitive function among both schizophrenia-spectrum disorder (SSD) and bipolar disorder (BD) individuals. We aimed to provide a systematic overview of the morphological differences-inclusive of grey and white matter volume, cortical thickness, and cortical surface area-between cognitive subgroups of these disorders and healthy controls, and between cognitive subgroups themselves. An initial search of PubMed and Scopus databases resulted in 1486 articles of which 20 met inclusion criteria and were reviewed in detail. The findings of this review do not provide strong evidence that cognitive subgroups of SSD or BD map to unique patterns of brain morphology. There is preliminary evidence to suggest that reductions in cortical thickness may be more strongly associated with cognitive impairment, whilst volumetric deficits may be largely tied to the presence of disease.

Emergency Services Capacity of a Rural Community in Guatemala.

INTRODUCTION: Access to emergency care is an essential part of the health system. Improving access to emergency services in low- and middle-income countries (LMIC) decreases mortality and reduces global disparities; however, few studies have assessed emergency services resources in LMICs. To guide future improvements in care, we performed a comprehensive assessment of the emergency services capacity of a rural community in Guatemala serving a mostly indigenous population. METHODS: We performed an exhaustively sampled cross-sectional survey of all healthcare facilities providing urgent and emergent care in the four largest cities surrounding Lake Atitlán using the Emergency Services Resource Assessment Tool (ESRAT). RESULTS: Of 17 identified facilities, 16 agreed to participate and were surveyed: nine private hospitals; four public clinics; and three public hospitals, including the region's public departmental hospital. All facilities provided emergency services 24/7, and a dedicated emergency unit was available at 67% of hospitals and 75% of clinics. A dedicated physician was present in the emergency unit during the day at 67% of hospitals and 75% of clinics. Hospitals had a significantly higher percentage of available equipment compared to clinics (85% vs 54%, mean difference 31%; 95% confidence interval (CI) 23-37%; P = 0.004). There was no difference in availability of laboratory tests between public and private hospitals or between cities. Private hospitals had access to a significantly higher percentage of medications compared to clinics (56% vs 27%, mean difference 29%; 95% CI 9-49%; P = 0.024). CONCLUSION: We found a high availability of emergency services and universal availability of personal protective equipment but a severe shortage of critical medications in clinics, and widespread shortage of pediatric equipment.

West Nile Virus and Other Domestic Nationally Notifiable Arboviral Diseases - United States, 2020.

Arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bite of infected mosquitoes and ticks. West Nile virus (WNV), mainly transmitted by Culex species mosquitos, is the leading cause of domestically acquired arboviral disease in the United States (1). Other arboviruses cause sporadic cases of disease and occasional outbreaks. This report summarizes passive data for nationally notifiable domestic arboviruses in the United States reported to CDC for 2020. Forty-four states reported 884 cases of domestic arboviral disease, including those caused by West Nile (731), La Crosse (88), Powassan (21), St. Louis encephalitis (16), eastern equine encephalitis (13), Jamestown Canyon (13), and unspecified California serogroup (2) viruses. A total of 559 cases of neuroinvasive WNV disease were reported, for a national incidence of 0.17 cases per 100,000 population. Because arboviral diseases continue to cause serious illness and the locations of outbreaks vary annually, health care providers should consider arboviral infections in patients with aseptic meningitis or encephalitis that occur during periods when ticks and mosquitoes are active, perform recommended diagnostic testing, and promptly report cases to public health authorities to guide prevention strategies and messaging.

Modeling the mechanical stiffness of pancreatic ductal adenocarcinoma.

Despite improvements in the understanding of disease biology, pancreatic ductal adenocarcinoma (PDAC) remains the most malignant cancer of the pancreas. PDAC constitutes ∼95% of all pancreatic cancers, and it is highly resistant to therapeutics. The increased tissue rigidity, which stems from the rich fibrotic stroma in the tumor microenvironment, is central to disease development, physiology, and resistance to drug perfusion. Pancreatic stellate cells (PSCs) are responsible for overproduction of extracellular matrix in the fibrotic stroma, and this is exacerbated by the overexpression of transforming growth factor-ß (TGF-ß). However, there are few in vitro PDAC models, which include both PSCs and TGF-ß or mimic in vivo-like tumor stiffness. In this study, we present a three-dimensional in vitro PDAC model, which includes PSCs and TGF-ß, and recapitulates PDAC tissue mechanical stiffness. Using oscillatory shear rheology, we show the mechanical stiffness of the model is within range of the PDAC tissue stiffness by day 21 of culture and highlight that the matrix environment is essential to adequately capture PDAC disease. PDAC is a complex, aggressive disease with poor prognosis, and biophysically relevant in vitro PDAC models, which take into account tissue mechanics, will provide improved tumor models for effective therapeutic assessment.

No influence of sex on the relationship between schizotypy factors and executive control across the schizophrenia spectrum.

Sex differences in symptoms and executive control across schizophrenia spectrum disorders (SSD) are consistently reported. Similarly, these findings of sex differences are also observed in schizotypy, that is, schizophrenia-like features occurring in healthy individuals in the absence of a clinical diagnosis. This study aimed to examine the relationships between performance on three major domains of executive control: performance monitoring, response inhibition, and cognitive set-shifting, and schizotypy factor scores in both SSD patients and healthy controls (HCs), and whether sex moderated any relationships observed. A total of 111 (67 males and 44 females) patients with SSD and 258 (129 males and 129 females) HCs were included in this study. Schizotypal personality traits (in both SSD and HC) was assessed using the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE). Executive control performance was assessed using seven tasks. Stepwise linear regressions revealed that performance on cognitive set-shifting tasks was significantly associated with the introvertive anhedonia, cognitive disorganisation, and unusual experiences subscales of the O-LIFE. When sex was examined as a moderator, it was not a significant moderator of any of the relationships between cognitive set-shifting tasks and schizotypy factors. The results suggest that independent of sex, cognitive set-shifting ability is associated to an increased vulnerability to schizotypal personality traits, although performance monitoring and response inhibition did not.

Characterization of facial emotion recognition in bipolar disorder: Focus on emotion mislabelling and neutral expressions.

Increasing evidence suggests that facial emotion recognition is impaired in bipolar disorder (BD). However, patient-control differences are small owing to ceiling effects on the tasks used to assess them. The extant literature is also limited by a relative absence of attention towards identifying patterns of emotion misattribution or understanding whether neutral faces are mislabelled in the same way as ones displaying emotion. We addressed these limitations by comparing facial emotion recognition performance in BD patients and healthy controls on a novel and challenging task. Thirty-four outpatients with BD I and 32 demographically matched healthy controls completed a facial emotion recognition task requiring the labelling of neutral and emotive faces displayed at low emotional intensities. Results indicated that BD patients were significantly less accurate at labelling faces than healthy controls, particularly if they displayed fear or neutral expressions. There were no between-group differences in response times or patterns of emotion mislabelling, with both groups confusing sad and neutral faces, although BD patients also mislabelled sad faces as angry. Task performance did not significantly correlate with mood symptom severity in the BD group. These findings suggest that facial emotion recognition impairments in BD extend to neutral face recognition. Emotion misattribution occurs in a similar, albeit exaggerated manner in patients with BD compared to healthy controls. Future behavioural and neuroimaging research should reconsider the use of neutral faces as baseline stimuli in their task designs.

External speech processing and auditory verbal hallucinations: A systematic review of functional neuroimaging studies.

It has been documented that individuals who hear auditory verbal hallucinations (AVH) exhibit diminished capabilities in processing external speech. While functional neuroimaging studies have attempted to characterise the cortical regions and networks facilitating these deficits in a bid to understand AVH, considerable methodological heterogeneity has prevented a consensus being reached. The current systematic review investigated the neurobiological underpinnings of external speech processing deficits in voice-hearers in 38 studies published between January 1990 to June 2020. AVH-specific deviations in the activity and lateralisation of the temporal auditory regions were apparent when processing speech sounds, words and sentences. During active or affective listening tasks, functional connectivity changes arose within the language, limbic and default mode networks. However, poor study quality and lack of replicable results plague the field. A detailed list of recommendations has been provided to improve the quality of future research on this topic.

Carbon Monoxide Releasing Molecule A1 Reduces Myocardial Damage After Acute Myocardial Infarction in a Porcine Model.

ABSTRACT: Infarct size is a major determinant of outcomes after acute myocardial infarction (AMI). Carbon monoxide-releasing molecules (CORMs), which deliver nanomolar concentrations of carbon monoxide to tissues, have been shown to reduce infarct size in rodents. We evaluated efficacy and safety of CORM-A1 to reduce infarct size in a clinically relevant porcine model of AMI. We induced AMI in Yorkshire White pigs by inflating a coronary angioplasty balloon to completely occlude the left anterior descending artery for 60 minutes, followed by deflation of the balloon to mimic reperfusion. Fifteen minutes after balloon occlusion, animals were given an infusion of 4.27 mM CORM-A1 (n = 7) or sodium borate control (n = 6) over 60 minutes. Infarct size, cardiac biomarkers, ejection fraction, and hepatic and renal function were compared amongst the groups. Immunohistochemical analyses were performed to compare inflammation, cell proliferation, and apoptosis between the groups. CORM-A1-treated animals had significant reduction in absolute infarct area (158 ± 16 vs. 510 ± 91 mm2, P < 0.001) and infarct area corrected for area at risk (24.8% ± 2.6% vs. 45.2% ± 4.0%, P < 0.0001). Biochemical markers of myocardial injury also tended to be lower and left ventricular function tended to recover better in the CORM-A1 treated group. There was no evidence of hepatic or renal toxicity with the doses used. The cardioprotective effects of CORM-A1 were associated with a significant reduction in cell proliferation and inflammation. CORM-A1 reduces infarct size and improves left ventricular remodeling and function in a porcine model of reperfused MI by a reduction in inflammation. These potential cardioprotective effects of CORMs warrant further translational investigations.

A Systematic Review of Cognition-Brain Morphology Relationships on the Schizophrenia-Bipolar Disorder Spectrum.

The nature of the relationship between cognition and brain morphology in schizophrenia-spectrum disorders (SSD) and bipolar disorder (BD) is uncertain. This review aimed to address this, by providing a comprehensive systematic investigation of links between several cognitive domains and brain volume, cortical thickness, and cortical surface area in SSD and BD patients across early and established illness stages. An initial search of PubMed and Scopus databases resulted in 1486 articles, of which 124 met inclusion criteria and were reviewed in detail. The majority of studies focused on SSD, while those of BD were scarce. Replicated evidence for specific regions associated with indices of cognition was minimal, however for several cognitive domains, the frontal and temporal regions were broadly implicated across both recent-onset and established SSD, and to a lesser extent BD. Collectively, the findings of this review emphasize the significance of both frontal and temporal regions for some domains of cognition in SSD, while highlighting the need for future BD-related studies on this topic.

Aging in Context: Incorporating Everyday Experiences Into the Study of Subjective Age.

The age that a person feels is a strong predictor of their well-being and long-term health, beyond chronological age, showing that people have a self-awareness that provides insight into their aging process. It appears this insight has broad implications for a person's everyday life and functioning. One's subjective age is shaped by metacognitive beliefs about aging, including both expectations about typical changes but most notably the awareness and interpretation of personal experiences. Subjective age has been described as multidimensional, aligning with life domains such as cognitive, social, and physical functioning. This perspective, coupled with laboratory studies that manipulate subjective age, suggests that situational context has an important role in determining the age a person feels. Here we review literature on subjective age with a focus on how research and theoretical perspectives should be adapted to integrate momentary experiences. We propose a contextual model that will help discriminate the links between situational influences and subjective age, as well as resulting behaviors that impact health and well-being. While most research has considered subjective age to be a relatively stable variable, we provide a novel account of how daily life offers a variety of situational contexts and experiences that directly impact the age a person feels at a given moment. We propose that studying moment-to-moment context is a critical next step in understanding the associations between subjective age, lifestyle choices, and health outcomes.

Brain morphology does not clearly map to cognition in individuals on the bipolar-schizophrenia-spectrum: a cross-diagnostic study of cognitive subgroups.

BACKGROUND: Characterisation of brain morphological features common to cognitively similar individuals with bipolar disorder (BD) and schizophrenia spectrum disorders (SSD) may be key to understanding their shared neurobiological deficits. In the current study we examined whether three previously characterised cross-diagnostic cognitive subgroups differed among themselves and in comparison to healthy controls across measures of brain morphology. METHOD: T1-weighted structural magnetic resonance imaging scans were obtained for 143 individuals; 65 healthy controls and 78 patients (SSD, n = 40; BD I, n = 38) classified into three cross-diagnostic cognitive subgroups: Globally Impaired (n = 24), Selectively Impaired (n = 32), and Superior/Near-Normal (n = 22). Cognitive subgroups were compared to each other and healthy controls on three separate analyses investigating (1) global, (2) regional, and (3) vertex-wise comparisons of brain volume, thickness, and surface area. RESULTS: No significant subgroup differences were evident in global measures of brain morphology. In region of interest analyses, the Selectively Impaired subgroup had greater right accumbens volume than those Superior/Near-Normal subgroup and healthy controls, and the Superior/Near-Normal subgroup had reduced volume of the left entorhinal region compared to all other groups. In vertex-wise comparisons, the Globally Impaired subgroup had greater right precentral volume than the Selectively Impaired subgroup, and thicker cortex in the postcentral region relative to the Superior/Near-Normal subgroup. LIMITATIONS: Exploration of medication effects was limited in our data. CONCLUSIONS: Although some differences were evident in this sample, generally cross-diagnostic cognitive subgroups of individuals with SSD and BD did not appear to be clearly distinguished by patterns in brain morphology.

The activity and connectivity of the facial emotion processing neural circuitry in bipolar disorder: a systematic review.

BACKGROUND: Facial emotion processing abnormalities may be a trait feature of bipolar disorder (BD). These social cognitive impairments may be due to alterations in the neural processing of facial affective information in visual ("core"), and limbic and prefrontal ("extended") networks, however, the precise neurobiological mechanism(s) underlying these symptoms are unclear. METHODS: We conducted a systematic review to appraise the literature on the activity and connectivity of the facial emotion processing neural circuitry in BD. Two reviewers undertook a search of the electronic databases PubMed, Scopus and PsycINFO, to identify relevant literature published since inception up until September 2019. Study eligibility criteria included; BD participants, neuroimaging, and facial emotion processing tasks. RESULTS: Out of an initial yield of 6121 articles, 66 were eligible for inclusion in this review. We identified differences in neural activity and connectivity within and between occipitotemporal, limbic, and prefrontal regions, in response to facial affective stimuli, in BD compared to healthy controls. LIMITATIONS: The methodologies used across studies varied considerably. CONCLUSIONS: The findings from this review suggest abnormalities in both the activity and connectivity of facial emotion processing neural circuitry in BD. It is recommended that future research aims to further define the connectivity and spatiotemporal course of neural events within and between occipitotemporal, limbic, and prefrontal regions.

Greater activation of the response inhibition network in females compared to males during stop signal task performance.

Previous neuroimaging studies have reported differences in regional brain activation between males and females during stop signal task performance, suggesting the presence of sex-linked differences in brain network organization of inhibitory ability. Despite a growing literature on sex differences during stop signal task performance, a consensus still has not been reached due to variations in task design and analysis methods. Due to these disparate findings we used up to date stop signal task methods to compare behavioral performance and associated brain activation between males and females using an event-related functional magnetic resonance imaging design. We observed that males were faster in inhibiting their responses, but females exhibited marked increased in stopping network activation, in addition to increased activation of the anterior insula and left amygdala. These findings suggest that males and females process stop signals differently.