A Critical Examination of the Clinical Diagnosis of Functional Tic-like Behaviors.

BACKGROUND: Since the COVID-19 pandemic, movement disorder clinics have seen an increase in patients with an unusual type of tic-like symptoms: young adults with abrupt onset complex behaviors. It was quickly suspected that these patients suffered from functional neurological symptoms, later named Functional Tic-Like Behaviors (FTLB). Subsequent research on the differential diagnosis between FTLB and tics has been substantial and led to the development of diagnostic checklists. OBJECTIVES: We conducted a theoretical reappraisal of the FTLB literature to clarify the validity of the concept and its diagnostic implications. METHODS: This paper addresses several key aspects of the current FTLB literature: circular reasoning, the complications of the FTLB phenomenology and demographics, the impact of FTLB on tic literature at large, and issues with alignment of the FTLB concept with the diagnostic criteria for functional disorders. RESULTS: The clinical approach to FTLB might involve circular reasoning due to a lack of clinical benchmarks. The FTLB phenomenology and demographics may need more work to ensure a lack of bias and a proper description of this patient group including a clear distinction from tics. The impact of the FTLB discussion on the wider literature needs consideration. The validation of positive signs may help with both these endeavors and pave way to the inclusion of FTLB within psychiatric classification systems. Furthermore, the coexistence of FTLB and tics within the same patient needs to be addressed. CONCLUSION: More research may be needed to fully establish the diagnosis of FTLB and differentiate it from tics.

Characteristics of preterm births during COVID-19 mitigation measures.

BACKGROUND: During the COVID-19 pandemic, mitigation measures were associated with a reduction in preterm birth rates; while not clearly proven, this observation has sparked significant interest. AIM: To understand the cause of this reduction by exploring the characteristics of preterm birth cohorts. MATERIAL AND METHODS: We performed a retrospective cohort study where we compared women who delivered preterm in three Melbourne maternity hospitals and conceived between November 2019 and February 2020 (mitigation measures-exposed cohort) to women who delivered preterm and conceived between November 2018 and February 2019 (non-exposed cohort). We compared maternal characteristics, pregnancy complications, antenatal interventions, intrapartum care, and indications for delivery. RESULTS: In the exposed cohort, 252/3129 women delivered preterm (8.1%), vs 298/3154 (9.4%) in the non-exposed cohort (odds ratio (OR) 0.84, 95% CI 0.70-1.00, P = 0.051). The baseline characteristic of two cohorts were comparable. Rates of spontaneous preterm labour (sPTL) without preterm pre-labour rupture of membranes (PPROM) were lower in the exposed cohort (13.1% vs 24.2%, OR 0.47, P = 0.001) while PPROM occurred more often (48.0% vs 35.6%, OR 1.67, P = 0.003). With a non-statistically significant prolongation of pregnancy in the cohort exposed to mitigation measures for both sPTL without PPROM (35.4 vs 34.9 weeks, P = 0.703) and PPROM (35.6 vs 34.9 weeks, P = 0.184). The rate of spontaneous labour after PPROM was higher in the exposed cohort compared to the non-exposed cohort (40.1% vs 24.1%, OR 2.09, P < 0.001). CONCLUSION: The reduction in preterm delivery during mitigation measures may have been driven by a reduction in spontaneous labour without PPROM, which seemed to result in more PPROM later in pregnancy.

Optimizing GABAA receptor antagonism for the induction of long-term potentiation in the mouse and rat dentate gyrus in vitro.

The reliable induction of long-term potentiation (LTP) in the dentate gyrus (DG) in vitro requires the blockade of the γ-aminobutyric acid A (GABAA) receptor. In these studies we examined the effectiveness of the specific GABAA receptor antagonist bicuculline methiodide (BMI) in facilitating LTP in the DG from hippocampal slices obtained from either C57Bl/6 mice or Sprague-Dawley rats, two commonly used species for electrophysiology. In the C57Bl/6 mice, maximal short-term potentiation and LTP in the DG were produced with a concentration of 5 mM BMI. In contrast, a concentration of 10 µM BMI was required to produce maximal short-term potentiation and LTP in the DG of Sprague-Dawley rats. These results reveal that there are species differences in the optimal amount of BMI required to produce robust and reliable long-term potentiation in the rodent DG in vitro and highlight the need to take consideration of the species being sued when choosing concentrations of pharmacological agents to employ for electrophysiological use.

A rare case of perforated Meckle's diverticulitis: a case report.

Meckle's diverticulum is the most common embryological anomaly of the small bowel that is rarely seen in adults. It is caused by the incomplete closure of the vitelline or omphalomesenteric duct. Those who are symptomatic from Meckle's diverticulum have varied clinical presentations, which raise significant challenges with diagnostic and management options. We report a case of a 47-year-old male who presented to the hospital with clinical signs of appendicitis but was found to have perforated Meckle's diverticulitis with faecoliths on computed tomography imaging and laparoscopy. Furthermore, histopathology revealed an ectopic gastric tissue cell type, which is a rare finding. This was definitively managed surgically with laparoscopic resection of Meckle's diverticulum and appendicectomy.

Anesthetic challenges in patients with multicompartmental lymphatic failure after Fontan palliation undergoing transcatheter thoracic duct decompression.

Lymphatic flow abnormalities are central to the development of protein losing enteropathy, plastic bronchitis, ascites and pleural effusions in patients palliated to the Fontan circulation. These complications can occur in isolation or multicompartmental (two or more). The treatment of multicompartmental lymphatic failure aims at improving thoracic duct drainage. Re-routing the innominate vein to the pulmonary venous atrium decompresses the thoracic duct, as atrial pressure is lower than systemic venous pressure in Fontan circulation. Transcatheter thoracic duct decompression is a new minimally invasive procedure that involves placing covered stents from the innominate vein to the atrium. Patients undergoing this procedure require multiple general anesthetics, presenting challenges in managing the sequelae of disordered lymphatic flow superimposed on Fontan physiology. We reviewed the first 20 patients at the Center for Lymphatic Imaging and Intervention at a tertiary care children's hospital presenting for transcatheter thoracic duct decompression between March 2018 and February 2023. The patients ranged in age from 3 to 26 years. The majority had failed prior catheter-based lymphatic intervention, including selective embolization of abnormal lympho-intestinal and lympho-bronchial connections to treat lymphatic failure in a single compartment. Fourteen had failure in three lymphatic compartments. Patients were functionally impaired (ASA 3-5) with significant comorbidities. Concurrent with thoracic duct decompression, three patients required fenestration closure for the resultant decrease in oxygen saturation. Ten patients had improvement in symptoms, seven had no changes and three have limited follow up. Five (25%) of these patients were deceased as of January 2024 due to non-lymphatic complications from Fontan failure.

Predictors of Impairment and Self-Concept in Children and Adolescents with Persistent Tic Disorder.

This study examined predictors of, and associations between, self-concept, demographic variables, and clinical measures in fifty-eight children and adolescents with Persistent Tic Disorder (PTD; 44 males, Mage = 11.9 years, SD = 2.74). Participants completed measures that assessed self-concept, tic severity, tic-related impairment, and comorbid psychological symptoms. Results showed that generalized anxiety disorder, major depressive disorder, persistent depressive disorder, total tic severity, number and complexity of tics, and total and social tic-related impairment were associated with self-concept. Tic-related social impairment mediated the relationship between tic severity and self-concept. Exploratory analyses found that total tic severity, motor tic severity, and vocal tic severity, as well as the number, intensity, and interference of tics predicted social tic-related impairment. Results suggest that treatments to reduce the number and complexity of tics, with additional focus on navigating social interactions, may serve to decrease tic severity and impairment, and in turn, improve self-concept.

Creatine and pregnancy outcomes: a prospective cohort study of creatine metabolism in low-risk pregnant females.

BACKGROUND: Physiological adaptations during pregnancy alter nutrient and energy metabolism. Creatine may be important for maintaining cellular energy homeostasis throughout pregnancy. However, the impact of pregnancy on endogenous and exogenous creatine availability has never been comprehensively explored. OBJECTIVES: To undertake a prospective cohort study and determine the physiological ranges of creatine and associated metabolites throughout human pregnancy. METHODS: Females with a singleton low-risk pregnancy were recruited at an Australian health service. Maternal blood and urine were collected at 5-time points from 10-36 weeks of gestation, and cord blood and placental samples were collected at birth. Creatine and associated amino acids and metabolites of creatine synthesis were analyzed. Dietary data were captured to determine effects of exogenous creatine intake. Associations between creatine metabolism and neonatal growth parameters were examined. RESULTS: Two hundred and eighty-two females were included. Maternal plasma creatine remained stable throughout pregnancy [ß: -0.003 µM; 95% confidence interval (CI): -0.07, 0.07; P = 0.94], though urinary creatine declined in late gestation (ß: 0.38 µM/mmol/L creatinine (CRN); 95% CI: -0.47, -0.29; P < 0.0001). Plasma guanidinoacetate (GAA; the precursor to creatine during endogenous synthesis) fell from 10-29 weeks of gestation before rising until birth (ß: -0.38 µM/mmol/L CRN; 95% CI: -0.47, -0.29; P < 0.0001). Urinary GAA followed an opposing pattern (ß: 2.52 µM/mmol/L CRN; 95% CI: 1.47, 3.58, P < 0.001). Animal protein intake was positively correlated with maternal plasma creatine until ∼32 weeks of gestation (ß: 0.07-0.18 µM; 95% CI: 0.006, 0.25; P ≤ 0.001). There were no links between creatine and neonatal growth, but increased urinary GAA in early pregnancy was associated with a slight reduction in head circumference at birth (ß: -0.01 cm; 95% CI: -0.02, -0.004; P = 0.003). CONCLUSIONS: Although maternal plasma creatine concentrations were highly conserved, creatine metabolism appears to adjust throughout pregnancy. An ability to maintain creatine concentrations through diet and shifts in endogenous synthesis may impact fetal growth. This trial was registered at [registry name] as ACTRN12618001558213.

Functional Tic-Like Behaviors: A Common Comorbidity in Patients with Tourette Syndrome.

BACKGROUND: Comorbid functional tic-like behaviors (FTB) have been described only rarely in patients with Tourette syndrome (TS). OBJECTIVES: We present the first large sample of patients suffering from TS and FTB to raise awareness of this clinical presentation and to guide how to differentiate one from the other. METHODS: We analyzed clinical data of 71 patients (n = 27 [38.0%] female, mean age: 21.5, range: 11-55) with TS + FTB. RESULTS: In the majority of patients, FTB started abruptly on average 15 years after tic onset with "treatment-resistant" complex movements and ("coprophenomena-like") vocalizations preceded by timely related psychological stressors. Psychological evaluation revealed evidence for internal conflicts (79%), emotional dysregulation (56%), and maintaining factors (70%). About one third of patients had a positive history for further medically unexplained symptoms. Compared to a large TS sample (n = 1032), patients with TS + FTB were more likely to be female, and presented significantly more common with "coprophenomena-like" symptoms, atypical influential factors, atypical descriptions of premonitory sensations, and higher rates of comorbid obsessive-compulsive disorder and "self-injurious" behavior. CONCLUSIONS: Based on our data it can be assumed that FTB is a common comorbidity in TS, similar to functional overlay in other movement disorders and epilepsy. Before classifying a patient as suffering from treatment-resistant TS, FTB should be ruled out.

Cannabinoids in the Treatment of Selected Mental Illnesses: Practical Approach and Overview of the Literature.

Although an increasing number of patients suffering from mental illnesses self-medicate with cannabis, current knowledge about the efficacy and safety of cannabis-based medicine in psychiatry is still extremely limited. So far, no cannabis-based finished product has been approved for the treatment of a mental illness. There is increasing evidence that cannabinoids may improve symptoms in autism spectrum disorder (ASD), Tourette syndrome (TS), anxiety disorders, and post-traumatic stress disorder (PTSD). According to surveys, patients often use cannabinoids to improve mood, sleep, and symptoms of attention deficit/hyperactivity disorder (ADHD). There is evidence suggesting that tetrahydrocannabinol (THC) and THC-containing cannabis extracts, such as nabiximols, can be used as substitutes in patients with cannabis use disorder.Preliminary evidence also suggests an involvement of the endocannabinoid system (ECS) in the pathophysiology of TS, ADHD, and PTSD. Since the ECS is the most important neuromodulatory system in the brain, it possibly induces beneficial effects of cannabinoids by alterations in other neurotransmitter systems. Finally, the ECS is an important stress management system. Thus, cannabinoids may improve symptoms in patients with mental illnesses by reducing stress.Practically, cannabis-based treatment in patients with psychiatric disorders does not differ from other indications. The starting dose of THC-containing products should be low (1-2.5 mg THC/day), and the dose should be up-titrated slowly (by 1-2.5 mg every 3-5 days). The average daily dose is 10-20 mg THC. In contrast, cannabidiol (CBD) is mainly used in high doses>400 mg/day.

Overview and Clinical Applications of Artificial Intelligence and Machine Learning in Cardiac Anesthesiology.

Artificial intelligence- (AI) and machine learning (ML)-based applications are becoming increasingly pervasive in the healthcare setting. This has in turn challenged clinicians, hospital administrators, and health policymakers to understand such technologies and develop frameworks for safe and sustained clinical implementation. Within cardiac anesthesiology, challenges and opportunities for AI/ML to support patient care are presented by the vast amounts of electronic health data, which are collected rapidly, interpreted, and acted upon within the periprocedural area. To address such challenges and opportunities, in this article, the authors review 3 recent applications relevant to cardiac anesthesiology, including depth of anesthesia monitoring, operating room resource optimization, and transthoracic/transesophageal echocardiography, as conceptual examples to explore strengths and limitations of AI/ML within healthcare, and characterize this evolving landscape. Through reviewing such applications, the authors introduce basic AI/ML concepts and methodologies, as well as practical considerations and ethical concerns for initiating and maintaining safe clinical implementation of AI/ML-based algorithms for cardiac anesthesia patient care.

Characterization of a Structurally Distinct ATP-Dependent Reactivating Factor of Adenosylcobalamin-Dependent Lysine 5,6-Aminomutase.

Several anaerobic bacterial species, including the Gram-negative oral bacterium Fusobacterium nucleatum, ferment lysine to produce butyrate, acetate, and ammonia. The second step of the metabolic pathway─isomerization of ß-l-lysine to erythro-3,5-diaminohexanoate─is catalyzed by the adenosylcobalamin (AdoCbl) and pyridoxal 5'-phosphate (PLP)-dependent enzyme, lysine 5,6-aminomutase (5,6-LAM). Similar to other AdoCbl-dependent enzymes, 5,6-LAM undergoes mechanism-based inactivation due to loss of the AdoCbl 5'-deoxyadenosyl moiety and oxidation of the cob(II)alamin intermediate to hydroxocob(III)alamin. Herein, we identified kamB and kamC, two genes responsible for ATP-dependent reactivation of 5,6-LAM. KamB and KamC, which are encoded upstream of the genes corresponding to α and ß subunits of 5,6-LAM (kamD and kamE), co-purified following coexpression of the genes in Escherichia coli. KamBC exhibited a basal level of ATP-hydrolyzing activity that was increased 35% in a reaction mixture that facilitated 5,6-LAM turnover with ß-l-lysine or d,l-lysine. Ultraviolet-visible (UV-vis) spectroscopic studies performed under anaerobic conditions revealed that KamBC in the presence of ATP/Mg2+ increased the steady-state concentration of the cob(II)alamin intermediate in the presence of excess ß-l-lysine. Using a coupled UV-visible spectroscopic assay, we show that KamBC is able to reactivate 5,6-LAM through exchange of the damaged hydroxocob(III)alamin for AdoCbl. KamBC is also specific for 5,6-LAM as it had no effect on the rate of substrate-induced inactivation of the homologue, ornithine 4,5-aminomutase. Based on sequence homology, KamBC is structurally distinct from previously characterized B12 chaperones and reactivases, and correspondingly adds to the list of proteins that have evolved to maintain the cellular activity of B12 enzymes.

Medicinal Use of Different Cannabis Strains: Results from a Large Prospective Survey in Germany.

BACKGROUND: Up to now, it is unclear whether different medicinal cannabis (MC) strains are differently efficacious across different medical conditions. In this study, the effectiveness of different MC strains was compared depending on the disease to be treated. METHODS: This was an online survey conducted in Germany between June 2020 and August 2020. Patients were allowed to participate only if they received a cannabis-based treatment from pharmacies in the form of cannabis flowers prescribed by a physician. RESULTS: The survey was completed by n=1,028 participants. Most participants (58%) have used MC for more than 1 year, on average, 5.9 different strains. Bedrocan (pure tetrahydrocannabinol to pure cannabidiol [THC:CBD]=22:<1) was the most frequently prescribed strain, followed by Bakerstreet (THC:CBD=19:<1) and Pedanios 22/1 (THC:CBD=22:1). The most frequent conditions MC was prescribed for were different pain disorders, psychiatric and neurological diseases, and gastrointestinal symptoms. Overall, the mean patient-reported effectiveness was 80.1% (range, 0-100%). A regression model revealed no association between the patient-reported effectiveness and the variety. Furthermore, no influence of the disease on the choice of the MC strain was detected. On average, 2.1 side effects were reported (most commonly dry mouth (19.5%), increased appetite (17.1%), and tiredness (13.0%)). However, 29% of participants did not report any side effects. Only 398 participants (38.7%) indicated that costs for MC were covered by their health insurance. CONCLUSIONS: Patients self-reported very good efficacy and tolerability of MC. There was no evidence suggesting that specific MC strains are superior depending on the disease to be treated.

Genomic evidence for the suitability of Göttingen Minipigs with a rare seizure phenotype as a model for human epilepsy.

Epilepsy is a complex genetic disorder that affects about 2% of the global population. Although the frequency and severity of epileptic seizures can be reduced by a range of pharmacological interventions, there are no disease-modifying treatments for epilepsy. The development of new and more effective drugs is hindered by a lack of suitable animal models. Available rodent models may not recapitulate all key aspects of the disease. Spontaneous epileptic convulsions were observed in few Göttingen Minipigs (GMPs), which may provide a valuable alternative animal model for the characterisation of epilepsy-type diseases and for testing new treatments. We have characterised affected GMPs at the genome level and have taken advantage of primary fibroblast cultures to validate the functional impact of fixed genetic variants on the transcriptome level. We found numerous genes connected to calcium metabolism that have not been associated with epilepsy before, such as ADORA2B, CAMK1D, ITPKB, MCOLN2, MYLK, NFATC3, PDGFD, and PHKB. Our results have identified two transcription factor genes, EGR3 and HOXB6, as potential key regulators of CACNA1H, which was previously linked to epilepsy-type disorders in humans. Our findings provide the first set of conclusive results to support the use of affected subsets of GMPs as an alternative and more reliable model system to study human epilepsy. Further neurological and pharmacological validation of the suitability of GMPs as an epilepsy model is therefore warranted.

Australian psychologists' knowledge, confidence, and practices in fetal alcohol spectrum disorder diagnostic assessment.

BACKGROUND: Fetal alcohol spectrum disorder (FASD) is a neurodevelopmental disorder caused by prenatal alcohol exposure (PAE). There are many documented barriers to FASD diagnostic assessment, including a limited number of trained clinicians. This study aimed to establish baseline levels of Australian psychologists' knowledge and practices in FASD assessment to develop training and improve future diagnostic capacity. METHODS: An online survey was completed by 106 Australian psychologists. The survey elicited respondents' demographics, knowledge about FASD, confidence in various aspects of assessment and perceived future training needs. RESULTS: Respondents reported a broad understanding of the FASD diagnostic term and potential harm of prenatal alcohol exposure (PAE). However, most respondents were not confident in their ability to conduct the psychometric assessments that provide a diagnostic assessment of FASD or ask about PAE. There was a significant positive correlation between the number of correct knowledge items and the psychologists' confidence in conducting FASD assessments. The clinical neuropsychologists demonstrated significantly greater knowledge and confidence in applying FASD diagnostic criteria and assessing PAE than school, clinical, and other psychologists. Most psychologists were more confident in their ability to apply the diagnostic criteria for other neurodevelopmental disorders. CONCLUSIONS: Recognition of FASD is growing in Australia, however, further work is required to improve clinicians' understanding of and confidence in completing FASD assessments. Most participants indicated a preference for online training to learn more about FASD assessment.

The Effect of Nabiximols on Driving Ability in Adults with Chronic Tic Disorders: Results of a Substudy Analysis of the Double-Blind, Randomized, Placebo-Controlled CANNA-TICS Trial.

Background: The multicenter, randomized, double-blind, parallel-group, phase IIIb CANNA-TICS (CANNAbinoids in the treatment of TICS) trial showed clear trends for improvement of tics, depression, and quality of life with nabiximols versus placebo in adult patients with Gilles de la Tourette syndrome and other chronic tic disorders. Although in general nabiximols was well tolerated, it is unclear whether treatment using this cannabis extract influences driving skills in patients with chronic tic disorders. Methods: Here we report results of the "Fitness to Drive" substudy of the CANNA-TICS trial. The key endpoint was fitness to drive as a binary criterion with a computerized assessment at baseline and after 9 weeks of stable treatment (week 13) with nabiximols or placebo. A patient was considered unfit to drive according to the German Federal Highway Research Institute guidelines. Results: In the substudy, a total of 64 patients (76.6% men, mean±standard deviation of age: 36.8±13.9) were recruited at two study sites. The number of patients who were fit to drive increased from 24 (55.8%) at baseline to 28 (71.8%) at week 13 among 43 patients treated with nabiximols, and decreased from 14 (66.7%) to 10 (52.6%) among 21 patients who received placebo. The risk difference (nabiximols - placebo) was 0.17 (95% confidence interval=-0.08 to 0.43) in favor of nabiximols. Specifically, only 2 of 24 (8.3%) patients in the nabiximols, but 4 of 14 (28.6%) patients in the placebo group changed for the worse from fit (at baseline) to unfit (at week 13) to drive, whereas 8 of 19 (42.1%) patients in the nabiximols, and only 2 of 7 (28.6%) patients in the placebo group improved from unfit to fit. Conclusion: Treatment with nabiximols does not impair skills relevant to driving in those patients with tic disorders who were fit to drive at baseline and even improved fitness to drive in a subset of patients who were unfit to drive before start of treatment. EudraCT number: 2016-000564-42.

Deep learning for transesophageal echocardiography view classification.

Transesophageal echocardiography (TEE) imaging is a vital tool used in the evaluation of complex cardiac pathology and the management of cardiac surgery patients. A key limitation to the application of deep learning strategies to intraoperative and intraprocedural TEE data is the complexity and unstructured nature of these images. In the present study, we developed a deep learning-based, multi-category TEE view classification model that can be used to add structure to intraoperative and intraprocedural TEE imaging data. More specifically, we trained a convolutional neural network (CNN) to predict standardized TEE views using labeled intraoperative and intraprocedural TEE videos from Cedars-Sinai Medical Center (CSMC). We externally validated our model on intraoperative TEE videos from Stanford University Medical Center (SUMC). Accuracy of our model was high across all labeled views. The highest performance was achieved for the Trans-Gastric Left Ventricular Short Axis View (area under the receiver operating curve [AUC] = 0.971 at CSMC, 0.957 at SUMC), the Mid-Esophageal Long Axis View (AUC = 0.954 at CSMC, 0.905 at SUMC), the Mid-Esophageal Aortic Valve Short Axis View (AUC = 0.946 at CSMC, 0.898 at SUMC), and the Mid-Esophageal 4-Chamber View (AUC = 0.939 at CSMC, 0.902 at SUMC). Ultimately, we demonstrate that our deep learning model can accurately classify standardized TEE views, which will facilitate further downstream deep learning analyses for intraoperative and intraprocedural TEE imaging.

Neuropsychological profiles of adolescents sentenced to detention in Western Australia with and without prenatal alcohol exposure.

BACKGROUND/AIMS: Youth with prenatal alcohol exposure (PAE) are under-recognised in the justice system, warranting improved identification. This study aimed to compare neuropsychological profiles of adolescents, with and without PAE and identify neuropsychological tasks predictive of PAE-group membership. It was hypothesised that participants with PAE would score significantly lower on neuropsychological tests. METHODS: Participants included 85 young people sentenced to detention (mean 15.7 years, 78 males), 46 with PAE. A one-way-multivariate analysis of variance tested differences in neuropsychological functioning between PAE/No-PAE groups, while logistic regression determined tests predictive of PAE. RESULTS: No statistically significant difference in test scores emerged between groups, and regression was not indicative of any models predictive of PAE-group membership. Neuropsychological profiles were characterised by both strengths and weaknesses, with lower verbal and mathematical skills. CONCLUSION(S): While no statistically significant differences were found between the groups, the results provided a unique insight into the neurocognitive profile of Australian youth in detention. Routine screening assessments were recommended for young people sentenced to detention.