Neurocognitive Considerations and Impacts in Chronic Migraines

Migraine, characterized by moderate-to-severe headache, may arise from neurological, psychological, orthopedic, metabolic, or endocrine origins. Pain associated with migraine, while commonly cited as the primary patient concern, only represents a small portion of short- and long-term effects caused by the condition. Many presenting cases include neuromuscular dysfunction, increased neuronal firing, inflammation, and cortical spreading depression. These effects can induce multiple symptoms such as pain, aura, brain fog, confusion, hangover, multiple hypersensitivities, and decreased memory capacity. These effects and symptoms can lead to neurocognitive and neuropsychological deficiencies in many patients. This study aims to investigate the relationship between migraines and neurocognitive function

Exercise Blocks Ethanol-Induced Kappa Opioid Receptor Sensitization in Nucleus Accumbens and Ventral Tegmental Area

Exercise has been increasingly used as an adjunctive therapy in the treatment of alcohol use disorder (AUD). Despite this, the mechanism by which it influences the mesolimbic circuitry changes underlying alcohol addiction is not well understood. Previous studies have shown alcohol dependence to lead to upregulation of the Dynorphin-Kappa Opioid Receptor (KOR) system, making it a potential target for therapeutics. Thus, gaining a better understanding of these pathways will help develop evidence-based guidelines for integrating exercise into therapies for the treatment of AUD

Whole-Body Vibration Alleviates Symptoms of Morphine Withdrawal

Whole-body vibration at 80 Hz has previously been shown to blunt neuropathological markers and behavioral symptoms of alcohol dependence. Here, we evaluate its ability to ameliorate symptoms of morphine use and withdrawal. Behavioral and neurophysiological symptoms of withdrawal were reduced significantly by whole-body vibration treatment

DNA Extraction Method Development for Ocular Tissues

Purpose: DNA extraction kits are traditionally developed to work with liquid tissues such as blood, saliva, and swabs, but some have been proposed to work with solid tissues. Somatic variation in cancers can be important for tumor subtyping and treatment guidance, including ocular tumors. Additionally, epigenetic marks such as 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are tissue-specific and change in disease states, particularly evident in diabetic retinopathy and age-related macular degeneration. Commercial DNA extraction kits are available from several vendors, but the various kits have different strengths and weaknesses, and the removal of PCR inhibitors will vary with each kit. This project investigates the yield and purity of DNA from ocular tissues using commercial DNA extraction kits. Methods: Cornea, neural retina, RPE/choroid layer, optic nerve, and capsular bag were collected and aliquoted into 15 mg aliquots. Extractions were performed using the following kits: DNEasy Blood and Tissue Kit (Qiagen;), GeneJET Genomic DNA Purification Kit (ThermoFisher Scientific), Monarch HMW DNA Extraction Kit for Tissue (New England Biosciences), and genomicPrep Mini Spin Kit (Cytiva). DNA was quantified using the Qubit Fluorometer and molecular weight was checked by agarose gel. Several more kits are currently being tested. Results: All four kits yielded high molecular weight DNA (above 20 kbp). The Monarch HMW kit yielded DNA with significantly higher molecular weights. The DNA yields per milligram of tissue were highest using the DNEasy Blood and Tissue Kit for optic nerve, neural retina, and RPE/choroid. The yield was highest for the cornea using the genomicPrep Mini Spin Kit. Only the genomicPrep Mini Spin Kit yielded sufficient DNA for quantification from the capsular bag, and total yields were minimal (600 ng or less). Additional kits are currently being tested, but initial results indicate that several commercial kits will be sufficient for DNA extraction of ocular tissues. Further work is needed to purify epithelial cells and stem cells from the intraocular lens. Conclusions: Of the kits tested, all are sufficient to obtain significant amounts of DNA from all ocular tissues aside from the capsular bag. The Monarch HMW yielded the highest molecular weight, but significantly lower quantities of DNA than the other kits, indicating that it may not be ideal for most purposes. Protocol development for the capsular bag is still underway

Exploring Glucose Dysregulation in Migraine: Insights from Continuous Glucose Monitoring

Despite being associated with hypoglycemia for nearly a century, a definitive relationship between migraines and glucose dysregulation remains elusive. Accumulating evidence suggests that migraines are in part due to a metabolic mismatch between cerebral demand and available energy. Research analyzing plasma glucose levels and migraine activity may further elucidate this interface between metabolic dysregulation and migraine pathophysiology and may potentially open avenues for therapeutic interventions targeting holistic metabolism for migraine management

Investigating the Interplay between Glucose Regulation, Neural Activity, and Motivation: A Novel Approach Utilizing Vibration Stimulation

This research explores the intricate relationship between glucose regulation, neural activity, and motivation in key brain regions, including the hypothalamus, basal ganglia, ventral tegmental area (VTA), and nucleus accumbens (NA). We aim to unravel the potential relationship of these factors on dopamine (DA) release and the broader implications for mental health, glucose regulation, well-being, and overall health. Our innovative approach involves using a chair that causes heterodyned whole-body vibration designed to stimulate DA release from the VTA and NA, areas associated with motivation and rewards

Magnetic Resonance Guided Radiation Therapy for Pancreatic Adenocarcinoma, Advantages, Challenges, Current Approaches, and Future Directions

Introduction: Pancreatic adenocarcinoma (PAC) has some of the worst treatment outcomes for any solid tumor. PAC creates substantial difficulty for effective treatment with traditional RT delivery strategies primarily secondary to its location and limited visualization using CT. Several of these challenges are uniquely addressed with MR-guided RT. We sought to summarize and place into context the currently available literature on MR-guided RT specifically for PAC. Methods: A literature search was conducted to identify manuscript publications since September 2014 that specifically used MR-guided RT for the treatment of PAC. Clinical outcomes of these series are summarized, discussed, and placed into the context of the existing pancreatic literature. Multiple international experts were involved to optimally contextualize these publications. Results: Over 300 manuscripts were reviewed. A total of 6 clinical outcomes publications were identified that have treated patients with PAC using MR guidance. Successes, challenges, and future directions for this technology are evident in these publications. MR-guided RT holds theoretical promise for the treatment of patients with PAC. As with any new technology, immediate or dramatic clinical improvements associated with its use will take time and experience. There remain no prospective trials, currently publications are limited to small retrospective experiences. The current level of evidence for MR guidance in PAC is low and requires significant expansion. Future directions and ongoing studies that are currently open and accruing are identified and reviewed. Conclusions: The potential promise of MR-guided RT for PAC is highlighted, the challenges associated with this novel therapeutic intervention are also reviewed. Outcomes are very early, and will require continued and long term follow up. MR-guided RT should not be viewed in the same fashion as a novel chemotherapeutic agent for which dosing, administration, and toxicity has been established in earlier phase studies. Instead, it should be viewed as a novel procedural intervention which must be robustly tested, refined and practiced before definitive conclusions on the potential benefits or detriments can be determined. The future of MR-guided RT for PAC is highly promising and the potential implications on PAC are substantial

Coronaridine congeners attenuate fentanyl seeking during prolonged abstinence

Background: The prevalence of opioid use disorder (OUD) has reached epidemic proportions with a record-breaking number of overdose deaths. Over 70% of the record-breaking number of overdose deaths are caused by synthetic opioids, including fentanyl. Fentanyl is commonly administered intravenously or by inhalation (smoking/vaping), which results in rapid drug bioavailability in the brain. There is a current need to identify a novel pharmacologic therapy to treat OUD, and there is increasing evidence to support the use of novel compounds referred to as coronaridine congeners to treat OUD and other psychiatric illnesses. In preclinical models, coronaridine congeners have been shown to decrease self-administration of drugs of abuse and induce antidepressant and anxiolytic effects. Here we used a preclinical fentanyl vapor self-administration model and fast-scan cyclic voltammetry (FSCV) to study the anti-addictive effects of two coronaridine congeners, 18-methoxycoronaridine (18-MC) and catharanthine (Cath).Methods: C57BL/6J mice were trained to self-administer vaporized fentanyl (5 mg/mL) or vehicle in airtight operant chambers. Mice self-administered vapor for 1 hour per day for 10 days (sessions were conducted for 5 consecutive days, followed by 2 days off). Chambers were equipped with two nosepokes, one active and one inactive. A successful response in the active nosepoke resulted in a vapor delivery that coincided with the presentation of a cue light, followed by a 1-minute timeout period. Mice learned to self-administer vapor with 3-second vapor deliveries for the first 3 days of training, which was then reduced to 1.5-second vapor deliveries the remaining 7 days. After training, mice were returned to their home cages for a forced abstinence period. Cue-induced drug seeking tests were conducted on abstinence days (AD) 20 and 25. During cue-induced seeking tests, successful responses in the active nosepoke resulted in presentation of the drug-associated cue, but no vapor was delivered (i.e. extinction conditions). Cue-induced drug seeking tests were conducted using a crossover design where half of subjects received coronaridine treatment (18-MC or Cath), while the other half received vehicle (ddH2O), on AD20. On AD25, subjects received the opposite treatment compared to AD20. Mice were injected (i.p.) with either vehicle or coronaridine treatment 1 hour before seeking tests. To examine the molecular mechanism of coronaridine congeners, FSCV was conducted on dopaminergic pre-synaptic terminals in the nucleus accumbens (NAc) neurons to measure dopamine (DA) release in the presence of 18-MC and Cath with or without nicotinic acetylcholine receptor antagonists.Results: We found that both 18-MC and Cath significantly reduced fentanylseeking during prolonged abstinence with no effect on mice that had previously self-administered vehicle. Furthermore, FSCV revealed that 18-MC and Cath significantly reduced DA release onto NAc neurons.Conclusion: In this study, we report that both 18-MC and Cath decrease fentanyl seeking during prolonged abstinence. DA release is important for opioid-related behaviors, and we found that 18-MC and Cath reduce DA release in the NAc, a mechanism that may underlie the effect of coronaridine congeners on fentanyl seeking. Together, these results provide evidence that coronaridine congeners may be promising novel compounds for the pharmacotherapeutic treatment of OUD

To observe or not to observe peers when learning physical examination skills; That is the question

Background: Learning physical examination skills is an essential element of medical education. Teaching strategies include practicing the skills either alone or in-group. It is unclear whether students benefit more from training these skills individually or in a group, as the latter allows them to observing their peers. The present study, conducted in a naturalistic setting, investigated the effects of peer observation on mastering psychomotor skills necessary for physical examination. Methods. The study included 185 2§ssup§nd§esup§-year medical students, participating in a regular head-to-toe physical examination learning activity. Students were assigned either to a single-student condition (n = 65), in which participants practiced alone with a patient instructor, or to a multiple-student condition (n = 120), in which participants practiced in triads under patient instructor supervision. The students subsequently carried out a complete examination that was videotaped and subsequently evaluated. Student's performance was used as a measure of learning. Results: Students in the multiple-student condition learned more than those who practiced alone (8