Examination of multiple drug arrests reported to the Maine Diversion Alert Program.

PURPOSE: Much of the responsibility for the increasing drug overdoses in the US has been attributed to opioids but most opioid overdoses also involve another drug. The objective of this study was to identify the drugs involved in polysubstance arrests. The substances that were more likely to be found in conjunction with other substances, using the drug arrests reported to Maine's Diversion Alert Program (DAP) were examined. METHODS: Single and multiple drug arrests were quantified (N = 9,216). Multiple drug arrest percentages were compared to single drug arrest percentages to create a Multiple-to-Single Ratio (MSR) specific to each drug family and each drug to identify over (MSR > 1) and under-representation (MSR < 1). RESULTS: Over three-fifths (63.8%) of all arrests involved a single drug. Opioids accounted for over-half (53.5%) of single arrests, followed by stimulants (27.7%) and hallucinogens (7.7%). Similarly, nearly two-fifths (39.6%) of multiple arrests were for opioids, followed by stimulants (30.8%) and miscellaneous (13.0%). Miscellaneous psychoactive prescription substances (e.g. clonidine, gabapentin, cyclobenzaprine, hydroxyzine) had the highest (1.51) MSR of any drug family. Conversely, stimulants (0.63), opioids (0.42), and hallucinogens (0.35) were significantly underrepresented in polysubstance arrests. Carisoprodol (8.80), amitriptyline (6.34), and quetiapine (4.69) had the highest MSR. Bath-salts (0.34), methamphetamine (0.44), and oxycodone (0.54) had the lowest MSR. CONCLUSION: The misuse of opioids, both alone and in conjunction with another drug, deserves continued surveillance. In addition, common prescription drugs with less appreciated misuse potential, especially carisoprodol, amitriptyline, and quetiapine, require greater attention for their ability to enhance the effects of other drugs.

Serial magnetic resonance imaging findings during severe attacks of familial hemiplegic migraine type 2: a case report.

BACKGROUND: Hemiplegic migraines represent a heterogeneous disorder with various presentations. Hemiplegic migraines are classified as sporadic or familial based on the presence of family history, but both subtypes have an underlying genetic etiology. Mutations in the ATP1A2 gene are responsible for Familial Hemiplegic type 2 (FHM2) or the sporadic hemiplegic migraine (SHM) counterpart if there is no family history of the disorder. Manifestations include migraine with aura and hemiparesis along with a variety of other symptoms likely dependent upon the specific mutation(s) present. CASE PRESENTATION: We report the case of an adult man who presented with headache, aphasia, and right-sided weakness. Workup for stroke and various infectious agents was unremarkable during the patient's extended hospital stay. We emphasize the changes in the Magnetic Resonance Imaging (MRI) over time and the delay from onset of symptoms to MRI changes in Isotropic Diffusion Map (commonly referred to as Diffusion Weighted Imaging (DWI)) as well as Apparent Diffusion Coefficient (ADC). CONCLUSIONS: We provide a brief review of imaging findings correlated with signs/symptoms and specific mutations in the ATP1A2 gene reported in the literature. Description of the various mutations and consequential presentations may assist neurologists in identifying cases of Hemiplegic Migraine, which may include transient changes in ADC and DWI imaging throughout the course of an attack.

Redeployment of Dental Core Trainees in the United Kingdom due to Coronavirus Disease 2019.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has affected professionals in all fields; none more so than medical and dental professionals. As dental core trainees (DCT) working in hospitals, we have been at the forefront of the crisis and one of the first in line for redeployment. Therefore, we decided to investigate the impact of COVID-19 on the redeployment of DCTs across the UK. MATERIALS AND METHODS: Data for this study was collected and shared between three project researchers. All researchers were undergoing dental core training in Oral Surgery and Restorative dentistry at Guy's Hospital, London. An online survey was sent out via email and online social media platforms to reach as many DCTs as possible in the United Kingdom. Implied consent was obtained by respondents on submission of the survey.The survey consisted of five sections and was branched, with respondents answering different sections depending on their redeployment status. No qualitative data was collected, as all questions included in the survey were dichotomous or multiple-choice questions. The last two questions were in the form of a 5-point Likert scale, inviting respondents to rate five statements from strongly agree to strongly disagree. RESULTS: A total of 150 participants responded, of which 34% had been redeployed due to the pandemic. The majority of DCTs were redeployed to an intensive care unit or similar setting, and over 75% of those redeployed were working with either COVID-19 positive/suspect patients. Additionally, 23.8% of respondents had stopped patient contact due to their medical status. CONCLUSION: Many DCTs have been deployed to departments outside of their specialty and expressed some anxiety as a result. Inevitably, this has resulted in disruption to their training program and education over the last few months. The response across the United Kingdom has been understandably variable due to the differing demands of the hospital trusts within which the DCTs work.

Retrograde interferon-gamma signaling induces major histocompatibility class I expression in human-induced pluripotent stem cell-derived neurons.

Objective: Injury-associated axon-intrinsic signals are thought to underlie pathogenesis and progression in many neuroinflammatory and neurodegenerative diseases, including multiple sclerosis (MS). Retrograde interferon gamma (IFN γ) signals are known to induce expression of major histocompatibility class I (MHC I) genes in murine axons, thereby increasing the susceptibility of these axons to attack by antigen-specific CD8+ T cells. We sought to determine whether the same is true in human neurons. Methods: A novel microisolation chamber design was used to physically isolate and manipulate axons from human skin fibroblast-derived induced pluripotent stem cell (iPSC)-derived neuron-enriched neural aggregates. Fluorescent retrobeads were used to assess the fraction of neurons with projections to the distal chamber. Axons were treated with IFN γ for 72 h and expression of MHC class I and antigen presentation genes were evaluated by RT-PCR and immunofluorescence. Results: Human iPSC-derived neural stem cells maintained as 3D aggregate cultures in the cell body chamber of polymer microisolation chambers extended dense axonal projections into the fluidically isolated distal chamber. Treatment of these axons with IFN γ resulted in upregulation of MHC class I and antigen processing genes in the neuron cell bodies. IFN γ-induced MHC class I molecules were also anterogradely transported into the distal axon. Interpretation: These results provide conclusive evidence that human axons are competent to express MHC class I molecules, suggesting that inflammatory factors enriched in demyelinated lesions may render axons vulnerable to attack by autoreactive CD8+ T cells in patients with MS. Future work will be aimed at identifying pathogenic anti-axonal T cells in these patients.

HPLC-UV method for measuring nicotinamide N-methyltransferase activity in biological samples: evidence for substrate inhibition kinetics.

Nicotinamide N-methyltransferase (NNMT, E.C. 2.1.1.1) N-methylates nicotinamide to produce 1-methylnicotinamide. Enhanced NNMT activity is a feature of many types of cancer, and has been linked to processes such as tumour metastasis, resistance to radiotherapy and tumour drug resistance. As such, inhibition of NNMT activity is a promising therapeutic target for cancer therapy. To screen for NNMT inhibitors, there is a need for a standardised, rapid and cost-effective NNMT assay. Here, we describe a cell-free assay coupled with ion-pairing reverse-phase HPLC-UV detection of 1-methylnicotinamide which requires minimal sample manipulation, is linear over 2.5 orders of magnitude with limits of detection and quantification of 0.05 and 0.15nmol 1-methylnicotinamide/100µL injection respectively. The assay was sufficiently sensitive to measure basal hepatic 1-methylnicotinamide concentration and NNMT activity in mouse, rabbit and human liver. 1-Methylnicotinamide concentration and the NNMT kinetic parameters specific activity, Vmax and Km all demonstrated species differences. NNMT also demonstrated substrate inhibition kinetics in all three species, which again was species-specific in term of calculated Ki. This assay demonstrates improved sensitivity over other previously published methods whilst lacking many of their drawbacks such as extensive sample preparation, use of non-physiological substrates and radioisotopic labelling.

Assessing the risk of multiple gestation in gonadotropin intrauterine insemination cycles.

OBJECTIVE: The purpose of this study was to analyze factors for their ability to predict multiple gestation in women who undergo controlled ovarian hyperstimulation with gonadotropins (follicle-stimulating hormone/human menopausal gonadotropin) and intrauterine insemination. STUDY DESIGN: This was a retrospective analysis of the clinical and laboratory variables that are associated with multiple gestation. Data for 6 variables in 678 cycles of gonadotropin/intrauterine insemination between 1990 and 1999 were analyzed with survival analysis, Cox regression analysis, and multiple logistic regression. RESULTS: There were 99 clinical pregnancies among 678 cycles (14.6% per cycle) in 306 women. Of the 14 women with multiple gestations (14.1% of pregnancies), 11 women had twins, 2 women had triplets, and 1 woman had quadruplets. Age, days of gonadotropin treatment, total dose of gonadotropin, and number of follicles that were >or=15 mm at the time of human chorionic gonadotropin administration were statistically significant predictors of multiple gestation in >or=1 of the statistical models. CONCLUSION: The risk of multiple gestation with controlled ovarian hyperstimulation/intrauterine insemination in this study was relatively low. In addition to age, several controllable variables that are associated with multiple gestation were identified.