Teleassault: A Case of Patient Violence During a Telepsychiatry Encounter.

Background: Telemedicine in psychiatry (telepsychiatry) is an emerging and rapidly developing tool which is used in many areas of psychiatry. While telepsychiatry has been shown to be efficacious and improves access to psychiatric care, it can also help to mitigate the risk of bodily injury caused by patient assault. The telepsychiatry equipment, however, may be vulnerable to damage from patient assault. Patient Case: We present the case of a 24 year old man being treated for disorganized behaviors and delusional thoughts at a regional hospital. As the regional hospital did not have access to psychiatry, telepsychiatry consultation was used. This patient behaved with violence towards the telepsychiatry equipment. Discussion: There currently is no literature establishing best practices to minimize the risk of violence towards equipment during telepsychiatry encounters. Using this case report, we aim to illustrate the risk of violence in telepsychiatry encounters and to discuss best practices to minimize this risk.

Using Academic Consultation-Liaison Telepsychiatry to Meet the Mental Health Needs of Complex, Medically Ill Patients in Underserved Areas: A Case Report.

Background: The nationwide shortage of mental health resources often disproportionately affects rural areas. As innovative strategies are required to address mental health resource shortages in rural areas, telepsychiatry consultation (TPC) may represent a population health-oriented approach to bridge this gap. In this case report, we examine the use of TPC from an academic consultation-liaison psychiatry service to a rural community hospital. Case Report: We describe the case of a woman with Wernicke encephalopathy seeking to leave the hospital against medical advice and the role that the TPC service played in the patient's evaluation and management, including assessing decision-making capacity. Discussion: We then examine benefits and limitations of the service, including a narrative review of the relevant, but limited, available literature as well as suggestions for how the service may be improved and incorporated into psychiatry residency and fellowship training in the future.

The role of tyrosine hydroxylase-dopamine pathway in Parkinson's disease pathogenesis.

BACKGROUND: Parkinson's disease (PD) is characterized by selective and progressive dopamine (DA) neuron loss in the substantia nigra and other brain regions, with the presence of Lewy body formation. Most PD cases are sporadic, whereas monogenic forms of PD have been linked to multiple genes, including Leucine kinase repeat 2 (LRRK2) and PTEN-induced kinase 1 (PINK1), two protein kinase genes involved in multiple signaling pathways. There is increasing evidence to suggest that endogenous DA and DA-dependent neurodegeneration have a pathophysiologic role in sporadic and familial PD. METHODS: We generated patient-derived dopaminergic neurons and human midbrain-like organoids (hMLOs), transgenic (TG) mouse and Drosophila models, expressing both mutant and wild-type (WT) LRRK2 and PINK1. Using these models, we examined the effect of LRRK2 and PINK1 on tyrosine hydroxylase (TH)-DA pathway. RESULTS: We demonstrated that PD-linked LRRK2 mutations were able to modulate TH-DA pathway, resulting in up-regulation of DA early in the disease which subsequently led to neurodegeneration. The LRRK2-induced DA toxicity and degeneration were abrogated by wild-type (WT) PINK1 (but not PINK1 mutations), and early treatment with a clinical-grade drug, α-methyl-L-tyrosine (α-MT), a TH inhibitor, was able to reverse the pathologies in human neurons and TG Drosophila models. We also identified opposing effects between LRRK2 and PINK1 on TH expression, suggesting that functional balance between these two genes may regulate the TH-DA pathway. CONCLUSIONS: Our findings highlight the vital role of the TH-DA pathway in PD pathogenesis. LRRK2 and PINK1 have opposing effects on the TH-DA pathway, and its balance affects DA neuron survival. LRRK2 or PINK1 mutations can disrupt this balance, promoting DA neuron demise. Our findings provide support for potential clinical trials using TH-DA pathway inhibitors in early or prodromic PD.

The MMAAS Project: An Observational Human Study Investigating the Effect of Anabolic Androgenic Steroid Use on Gene Expression and the Molecular Mechanism of Muscle Memory.

OBJECTIVE: It remains unknown whether myonuclei remain elevated post anabolic-androgenic steroid (AAS) usage in humans. Limited data exist on AAS-induced changes in gene expression. DESIGN: Cross-sectional/longitudinal. SETTING: University. PARTICIPANTS: Fifty-six men aged 20 to 42 years. INDEPENDENT VARIABLES: Non-resistance-trained (C) or resistance-trained (RT), RT currently using AAS (RT-AS), of which if AAS usage ceased for ≥18 weeks resampled as Returning Participants (RP) or RT previously using AAS (PREV). MAIN OUTCOME MEASURES: Myonuclei per fiber and cross-sectional area (CSA) of trapezius muscle fibers. RESULTS: There were no significant differences between C (n = 5), RT (n = 15), RT-AS (n = 17), and PREV (n = 6) for myonuclei per fiber. Three of 5 returning participants (RP1-3) were biopsied twice. Before visit 1, RP1 ceased AAS usage 34 weeks before, RP2 and RP3 ceased AAS usage ≤2 weeks before, and all had 28 weeks between visits. Fiber CSA decreased for RP1 and RP2 between visits (7566 vs 6629 µm 2 ; 7854 vs 5677 µm 2 ) while myonuclei per fiber remained similar (3.5 vs 3.4; 2.5 vs 2.6). Respectively, these values increased for RP3 between visits (7167 vs 7889 µm 2 ; 2.6 vs 3.3). CONCLUSIONS: This cohort of past AAS users did not have elevated myonuclei per fiber values, unlike previous research, but reported AAS usage was much lower. Training and AAS usage history also varied widely among participants. Comparable myonuclei per fiber numbers despite decrements in fiber CSA postexposure adheres with the muscle memory mechanism, but there is variation in usage relative to sampling date and low numbers of returning participants.

Anti-HLA-A2-CAR Tregs prolong vascularized mouse heterotopic heart allograft survival.

Alloantigen-specific regulatory T cell (Treg) therapy is a promising approach for suppressing alloimmune responses and minimizing immunosuppression after solid organ transplantation. Chimeric antigen receptor (CAR) targeting donor alloantigens can confer donor reactivity to Tregs. However, CAR Treg therapy has not been evaluated in vascularized transplant or multi-MHC mismatched models. Here, we evaluated the ability of CAR Tregs targeting HLA-A2 (A2-CAR) to prolong the survival of heterotopic heart transplants in mice. After verifying the in vitro activation, proliferation, and enhanced suppressive function of A2-CAR Tregs in the presence of A2-antigen, we analyzed the in vivo function of Tregs in C57BL/6 (B6) mice receiving A2-expressing heart allografts. A2-CAR Treg infusion increased the median survival of grafts from B6.HLA-A2 transgenic donors from 23 to 99 days, whereas median survival with polyclonal Treg infusion was 35 days. In a more stringent model of haplo-mismatched hearts from BALB/cxB6.HLA-A2 F1 donors, A2-CAR Tregs slightly increased median graft survival from 11 to 14 days, which was further extended to >100 days when combined with a 9-day course of rapamycin treatment. These findings demonstrate the efficacy of CAR Tregs, alone or in combination with immunosuppressive agents, toward protecting vascularized grafts in fully immunocompetent recipients.

Independent predictors of mortality for patients with traumatic renal injury.

PURPOSE: To investigate the parameters of renal trauma, including emergent intervention type, that predict the mortality of patients with traumatic renal injury. METHODS: A retrospective database analysis was performed on patients who sustained a traumatic renal parenchymal injury identified by the 2017 National Trauma Data Bank. Data were analyzed to identify differences in hospital length of stay, ER and hospital disposition, and mortality based on patient age, gender, race, Injury Severity Score, renal injury grade, and need for emergent intervention (angioembolization versus open surgery). Logistic regression was used to correlate intervention type and trauma parameters to mortality. RESULTS: A total of 4,876 of 1,004,440 trauma patients (0.49%) had a traumatic renal injury. Of those, 220 (4.5%) underwent an emergent intervention-29 (0.59%) angioembolization and 191 (3.9%) open renal surgery. 83 patients with a blunt renal trauma (2.0%) underwent renal intervention, whereas 136 (21.0%) with a penetrating injury required a procedure. Forty-five of the 220 patients (20.5%) who had a renal intervention died, while 377 of 4,656 (8.1%) who did not have an intervention died. Multiple logistic regression identified black race, age > 45 years, penetrating trauma, and ISS > 15 to be independent predictors of mortality. Neither angioembolization nor open renal surgery was associated with a significantly higher likelihood of mortality in the multivariable model. CONCLUSION: While procedural interventions are associated with higher mortality for patients with traumatic renal injury, other factors, such as race, age, trauma type, and injury severity may be more predictive of death under care.

Advancing the Mission of Consultation-Liaison Psychiatry Through Innovation in Teaching.

BACKGROUND: Consultation-liaison (C-L) psychiatry, similar to other medical specialties, relies on the education of students, residents, fellows, and life-long learners for growth of the field. C-L psychiatry is unique as it exists at the intersection of psychiatry with other medical subspecialties. Traditional teaching methods have been used in C-L psychiatry programs for more than 50 years, while technology has recently advanced as available resources and the learning styles of today's learners have evolved. A growing number of younger trainees are taking advantage of new ways to learn. OBJECTIVES: We sought to examine both traditional and novel teaching methodologies and how each of these educational methodologies fits within adult learning theory and in the context of how digital natives learn about C-L psychiatry. METHODS: In this narrative review, we drew upon the experiences of the authors as both life-long learners and educators. We then reviewed the literature pertaining to teaching methods that have been used in C-L psychiatry as well as emerging methods that could potentially be used in C-L psychiatry. RESULTS: C-L psychiatry has used traditional teaching methods such as readings, didactic lectures, case-based rounds, and problem-based learning. Novel teaching methodologies such as teaching rotations, simulations, social media, podcasts, movie clubs, and the use of mobile tablet computers have been used in general psychiatry and other medical specialties, while literature specific to C-L psychiatry was sparse. CONCLUSIONS: Opportunities abound to make use of new teaching methodologies and technologies to appeal to future generations of C-L psychiatrists.

Interacting With Providers: An Intersectional Exploration of the Experiences of Carers of Aboriginal Children With a Disability.

Intersectionality has potential to create new ways to describe disparities and craft meaningful solutions. This study aimed to explore Aboriginal carers' experiences of interactions with health, social, and education providers in accessing services and support for their child. Carers of Aboriginal children with a disability were recruited from an Australian metropolitan Aboriginal community-controlled health service. In-depth, semistructured interviews were conducted with 19 female carers. Intersectionality was applied as an analytical framework due to the inherent power differentials for Aboriginal Australians and carers for people with a disability. Marginalization and a lack of empowerment were evident in the experiences of interactions with providers due to cultural stereotypes and racism, lack of cultural awareness and sensitivity, and poverty and homelessness. Community-led models of care can help overcome the intersectional effects of these identities and forms of oppression in carers' interactions with providers and enhance access to care.

Varied pathological and therapeutic response effects associated with CHCHD2 mutant and risk variants.

Mutations and polymorphic risk variant of coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) have been associated with late-onset Parkinson disease. In vivo pathological evidence of CHCHD2 mutations is currently lacking. Utilizing transgenic Drosophila model, we examined the relative pathophysiologic effect of the pathogenic (c.182C>T, p.Thr61Ile and c.434G>A, p.Arg145Gln) and the risk (c.5C>T, p.Pro2Leu) CHCHD2 variants. All the transgenic models exhibited locomotor dysfunction that could be exacerbated by rotenone exposure, dopaminergic neuron degeneration, reduction in lifespan, mitochondrial dysfunction, oxidative stress, and impairment in synaptic transmission. However, both mutants showed more severe early motor dysfunction, dopaminergic neuronal loss, and higher hydrogen peroxide production compared with the risk variant. p.Thr61Ile (co-segregated in three independent PD families) displayed the most severe phenotype followed by p.Arg145Gln (present only in index patient). We treated the transgenic flies with Ebselen, a mitochondrial hydrogen peroxide scavenger compound; Ebselen appears to be more effective in ameliorating motor function in the mutant than the risk variant models. We provide the first in vivo evidence of the pathological effects associated with CHCHD2 mutations. There was a difference in the pathological and drug response effects between the pathogenic and the risk variants. Ebselen may be a useful neuroprotective drug for carriers of CHCHD2 mutations.

F-box protein 7 mutations promote protein aggregation in mitochondria and inhibit mitophagy.

The mutations of F-box protein 7 (FBXO7) gene (T22M, R378G and R498X) are associated with a severe form of autosomal recessive juvenile-onset Parkinson's disease (PD) (PARK 15). Here we demonstrated that wild-type (WT) FBXO7 is a stress response protein and it can play both cytoprotective and neurotoxic roles. The WT FBXO7 protein is vital to cell mitophagy and can facilitate mitophagy to protect cells, whereas mutant FBXO7 inhibits mitophagy. Upon stress, the endogenous WT FBXO7 gets up-regulated, concentrates into mitochondria and forms FBXO7 aggregates in mitochondria. However, FBXO7 mutations aggravate deleterious FBXO7 aggregation in mitochondria. The FBXO7 aggregation and toxicity can be alleviated by Proline, glutathione (GSH) and coenzyme Q10, whereas deleterious FBXO7 aggregation in mitochondria can be aggravated by prohibitin 1 (PHB1), a mitochondrial protease inhibitor. The overexpression of WT FBXO7 could lead to FBXO7 protein aggregation and dopamine neuron degeneration in transgenic Drosophila heads. The elevated FBXO7 expression and aggregation were identified in human fibroblast cells from PD patients. FBXO7 can also form aggregates in brains of PD and Alzheimer's disease. Our study provides novel pathophysiologic insights and suggests that FBXO7 may be a potential therapeutic target in FBXO7-linked neuron degeneration in PD.

Experiences and needs of carers of Aboriginal children with a disability: a qualitative study.

BACKGROUND: Australian parents/carers of a person with a disability experience higher rates of depression, more financial stress, and are twice as likely to be in poor physical health than the general population. Aboriginal and Torres Strait Islander peoples experience worse health, social and economic outcomes than other Australians, and those with a disability face 'double disadvantage'. This study aimed to better understand the experiences and needs of parents/carers/families of Aboriginal children with a disability. METHODS: Semi-structured in-depth interviews were conducted with parents or primary carers of Aboriginal children aged zero-eight with disability. Interviews were analysed using thematic analysis. RESULTS: Nineteen women (sixteen mothers and three grandmothers) were interviewed. More than half were lone carers (without a partner or spouse). Participants described their experiences, including challenges and facilitators, to providing and accessing care, impacts on their health and wellbeing, and associated economic and non-economic costs of caregiving. Financial strain and social isolation was particularly prominent for lone carers. CONCLUSIONS: Tailoring services to the needs of carers of Aboriginal children with a disability means supporting kinship caregiving, facilitating engagement with other Aboriginal families, and streamlining services and systems to mitigate costs. The experiences described by our participants depict an intersection of race, socio-economic status, gender, disability, and caregiving. Services and funding initiatives should incorporate such intersecting determinants in planning and delivery of holistic care.

Thiol peroxidases ameliorate LRRK2 mutant-induced mitochondrial and dopaminergic neuronal degeneration in Drosophila.

Mutations in leucine-rich repeat kinase 2 (LRRK2) are common causes of familial Parkinson's disease (PD). LRRK2 has been shown to bind peroxiredoxin-3 (PRDX3), the most important scavenger of hydrogen peroxide in the mitochondria, in vitro. Here, we examined the interactions of LRRK2 and PRDX3 in Drosophila models by crossing transgenic LRRK2 and PRDX3 flies. As proof of principle experiments, we subsequently challenged LRRK2 and LRRK2/PRDX3 flies with a peroxidase mimic, Ebselen. We demonstrated that co-expression of PRDX3 with the LRRK2 kinase mutant G2019S in bigenic Drosophila ameliorated the G2019S mutant-induced reduction in peroxidase capacity, loss of dopaminergic neurons, shortened lifespan and mitochondrial defects of flight muscles in monogenic flies expressing the G2019S alone. Challenges with Ebselen recapitulated similar rescue of these phenotypic features in mutant-expressing Drosophila. The peroxidase mimic preserved neuronal and mitochondrial and neuronal integrity and improved mobility and survival in mutant-expressing Drosophila. Taken together, our study provides the first in vivo evidence to suggest that phosphoinhibition of endogenous peroxidases could be a mechanism in LRRK2-induced oxidant-mediated neurotoxicity. Our therapeutic experiments also highlight the potential of thiol peroxidases as neuroprotective agents in PD patients carrying LRRK2 mutations.

Navigating the journey of Aboriginal childhood disability: a qualitative study of carers' interface with services.

BACKGROUND: The disadvantage experienced by Aboriginal and Torres Strait Islander children with a disability is well recognized. The long term consequences of failing to address disability on health, education and employment underlies the importance of early intervention. Caregivers experience a disproportionate burden and have challenges accessing services. The aim of this study was to describe the carer journey of accessing support and services. METHODS: We conducted in-depth semi-structured interviews with nineteen parents and carers of Aboriginal children aged 0-8 years. The children were patients at a child developmental clinic at a metropolitan area Aboriginal health service in Eastern Australia. Interpretive phenomenological analysis was applied to transcribed verbatim accounts. RESULTS: Four themes were developed using the 'journey' metaphor to describe the carer pathway of accessing support and services at the community, service and policy levels. Themes included 1) the need for increased signage within communities via community education, information and awareness, 2) wrong way signs, roundabouts and roadblocks encountered when accessing services, 3) alternate routes can facilitate the journey, and 4) incompatibility of inflexible bureaucratic road rules and lived realities. CONCLUSIONS: The challenges of caring for a child with a disability are indisputable and these can be compounded for people experiencing socio-economic disadvantage and marginalisation. Overcoming challenges to service access faced by carers of Aboriginal children with a disability will require investment in community, services and policy to tailor culturally appropriate models of care.

Rebalancing the Immune System to Treat Type 1 Diabetes.

In type 1 diabetes (T1D), the immune system mistakenly attacks the pancreatic islet ß cells resulting in the loss of insulin secretion. Insulin-replacement therapy developed more than a century ago provided means to manage the symptoms of diabetes without addressing the root cause of the disease-the faulty immune system. A healthy immune system has built-in mechanisms to limit unwanted, excessive immune activation and prevents damages to self-tissues. These immune self-tolerance mechanisms are often impaired in autoimmune patients including those with T1Ds. Understanding how immune self-tolerance is broken in patients with T1D can inform the design of new curative therapies that correct the immune defects. In this paper, we will summarize the mechanisms of immune tolerance, review their relevance to T1Ds, and discuss novel therapeutic approaches to rebalance the immune system for the treatment of T1Ds.

Does KUB play a role in the diagnosis of bladder bowel dysfunction?

INTRODUCTION: Kidney ureter bladder radiography (KUB) is widely used for the evaluation of constipation in children with bladder and bowel dysfunction (BBD); however, there is varying evidence to support its routine diagnostic use. One drawback to KUB is radiation exposure. The dangers of radiation in children are well-documented, and per As Low As Reasonably Achievable, non-beneficial radiation should be avoided. This risk is especially high in children who undergo repeated imaging in the follow up of constipation treatment. OBJECTIVE: We sought to assess the utility of KUB in diagnosing children with BBD by comparing it to four diagnostic tests and/or validated instruments: the Dysfunctional Voiding Symptom Score (DVSS), Rome IV criteria, rectal diameter on ultrasound (RD), and the Bristol Stool Form Score (BSFS). STUDY DESIGN: We prospectively enrolled a cohort of patients presenting to an academic pediatric urology practice with symptoms of BBD. Severity of stool burden on KUB (mild, moderate, or severe), RD on ultrasound (≥3.4 cm), DVSS, Rome IV, and BSFS were obtained for each patient. All imaging was interpreted by a pediatric radiologist and pediatric urologist. Primary outcomes were the association between the four diagnostic tests and KUB stool burden. Bivariate analysis of all individual variables versus KUB was performed, as well as multivariate regressions to determine if multiple measures were predictive of KUB stool burden when combined. RESULTS: Between October 2020 and May 2022, 50 patients were enrolled. All children were under the age of 18, with a median age of 8 years (IQR 3-13). 38 % were male. Median BMI-for-age-percentile was 80.8 (IQR 50.3-98.3). When comparing individual variables to KUB in bivariate analyses, it was found that RD on ultrasound is predictive of significant stool burden on KUB (p = 0.03). No other individual variables were predictive. In the multivariate analyses, no combination of tests was found to be predictive of KUB. DISCUSSION: We compared the effectiveness of four commonly used diagnostic tests in children with BBD to validate the use of KUB. In conclusion, our results support the use of RD on ultrasound as a non-radiating alternative to KUB to assess stool burden. Data also suggest that KUB for fecal load does not correlate with urinary (DVSS) or bowel (Rome IV, BSFS) symptoms in BBD, and that symptoms scores should still be used independently for diagnosis and monitoring of treatment response. CONCLUSION: In conclusion, KUB has a limited role in the diagnosis of BBD.

Harnessing regulatory T cells to establish immune tolerance.

Engineered regulatory T (Treg) cells have emerged as precision therapeutics aimed at inducing immune tolerance while reducing the risks associated with generalized immunosuppression. This Viewpoint highlights the opportunities and challenges for engineered Treg cell therapies in treating autoimmune and other inflammatory diseases.

The Evaluation of Gastric Emptying Using Nuclear Scintigraphy Compared to Three-Dimensional Multi-detector Computed Tomography (3D-MDCT) Gastric Volumetry in the Assessment of Poor Weight Loss Following Sleeve Gastrectomy.

BACKGROUND: Poor weight loss and weight regain are principal challenges following laparoscopic sleeve gastrectomy (LSG). There is a lack of standardised assessments and diagnostic tests to stratify the status post-LSG and determine whether anatomical or physiological problem exists. We aimed to compare nuclear scintigraphy gastric emptying with CT volumetric analysis of sleeve anatomy and determine the impact of anatomy on physiological function and its correlation with weight loss. MATERIALS AND METHODS: Patients greater than 12 months post-LSG were categorised into optimal weight loss (OWL) (n = 29) and poor weight loss groups (PWL) (n = 50). All patients underwent a protocolised nuclear scintigraphy and three-dimensional multi-detector computed tomography (3D-MDCT) gastric volumetry imaging. RESULTS: Post-operative % total weight loss in OWL was 26.2 ± 10.5% vs. 14.2 ± 10.7% in the PWL group (p value < 0.0001). The PWL group had significantly more delayed gastric emptying half-time than OWL (34.1 ± 18.8 vs. 19.5 ± 4.7, p value < 0.0001). Gastric emptying half-time showed statistically significant correlations with weight loss parameters (BMI; r = 0.215, p value 0.048, %EWL; r = - 0.336, p value 0.002 and %TWL; r = - 0.379, p value < 0.001). The median gastric volume on 3D-MDCT did not differ between the OWL (246 (IQR 50) ml) and PWL group (262 (IQR 129.5) ml), p value 0.515. Nuclear scintigraphy gastric emptying half-time was the most highly discriminant measure. A threshold of 21.2 min distinguished OWL from PWL patients with 86.4% sensitivity and 68.4% specificity. CONCLUSION: Nuclear scintigraphy is a potentially highly accurate tool in the functional assessment of sleeve gastrectomy physiology. It appears to perform better as a diagnostic test than volumetric assessment. Gastric volume did not correlate with weight loss outcomes. We have established diagnostic criteria of greater than 21 min to assess sleeve failure, which is linked to suboptimal weight loss outcomes.