Medicine and Health Sciences Commons^™

Alcohol Use And Alcohol Use Disorder Differ In Their Genetic Relationships With Ptsd: A Genomic Structural Equation Modelling Approach, Tulsi Patel

VCU's Medical Journal Club: The Work of Future Health Professionals

Posttraumatic stress disorder (PTSD) is associated with an increased alcohol use and increased risk of developing alcohol use disorder (AUD). Previous literature suggests that the genetic association between PTSD and alcohol use differs from that between PTSD and AUD. Researchers in this study used a genomic Structural Equation Modeling, genomicSEM, to analyze data from a larger genome-wide association studies (GWAS). Participants in the study were of European descent.

Researchers investigated the genetic association between PTSD, alcohol use, and AUD through these large scale statistical analyses. Researchers observed a significant improvement in model fit (p < .001). Genetic correlations (rG) between PTSD and AUD were positive (rG: .36, p < .001), while those between PTSD and alcohol use were negative (rG: -0.17, p < .001). Researchers observed that when specific variables for alcohol use and AUD were isolated, key differences resulted in genetic association with PTSD, which indicated that the genetic makeup of alcohol-related behaviors is different in individuals with PTSD.

Effects Of Dextromethorphan On Mdma-Induced Serotonergic Aberration In The Brains Of Non-Human Primates Using [123i]-Adam/Spect, Sky Evans

VCU's Medical Journal Club: The Work of Future Health Professionals

MDMA, a widely used recreational drug belonging to the entactogen class, acts strongly on serotonin and dopamine receptors, potentially inducing neurotoxicity. In a study on primates, MDMA treatment resulted in reduced serotonin transporter levels, persisting for years. However, co-administration with dextromethorphan (DXM), an antitussive with anti-inflammatory properties, appeared to prevent this decrease, suggesting a protective effect against MDMA-induced serotonergic toxicity. The study employed SPECT scans with [123I]-ADAM radioligand to assess serotonin transporter levels in various brain regions, revealing significant differences between treatment groups.

Effect Of Psilocybin On Empathy And Moral Decision-Making, Sky Evans

VCU's Medical Journal Club: The Work of Future Health Professionals

Empathy is the ability for human beings, as well as all other mammals, to understand the mental state of another person on an emotional level. It allows us to feel compassion and promote the well-being of those around us. Impaired empathic abilities lead to severe negative social consequences and influence the development and treatment of several psychiatric disorders, specifically in disorders such as antisocial personality disorder. Furthermore, empathy has been shown to play a crucial role in moral and prosocial behavior. In neuroscience and psychiatry research, the serotonin system has been shown to be involved in modulating empathy and moral …

Infiltrating Cd8+ T Cells Exacerbate Alzheimer’S Disease Pathology In A 3d Human Neuroimmune Axis Model, Jefin Jose, Devam Purohit

VCU's Medical Journal Club: The Work of Future Health Professionals

In this study, Jorfi et al. employed a neuroimmune axis model containing neurons, astrocytes, and microglia to examine the role of immune cells in Alzheimer's disease. Jorfi et al. found that T cells selectively infiltrated the BRAIN compartment of the neuroimmune axis model as compared to B cells and monocytes. Jorfi et al. further found that CD8+ T cells demonstrated heightened cytotoxicity in the Alzheimer's disease brain, illuminating the role of immune cells in neurodegeneration. Upon further examination, the CXCR3-CXCL10 signaling pathway was found to have an important role in inflammation.

A Genome-Wide In Vivo Crispr Screen Identifies Essential Regulators Of T Cell Migration To The Cns In A Multiple Sclerosis Model, Jefin Jose

VCU's Medical Journal Club: The Work of Future Health Professionals

Kendirli et al. (2023) used a CRISPR screen to determine the proteins involved in T cell migration into the CNS in multiple sclerosis. Overall, eighteen facilitators and five brakes to T cell infiltration into the CNS were identified. Kendirli et al. specifically identified ITGA4, FERMT3, and HSP90B1 to make up the adhesion module, CXCR3, GNAI2, and TBX21 to make up the chemotaxis module, and GRK2 and S1PR2 to make up the egress module. This study demonstrated the ability of a CRISPR screen to identify elements in a disease process and thus identify targets for future multiple sclerosis therapies.

The Effect Of Periodic Ketogenic Diet On Newly Diagnosed Overweight And Obese Patients With Type 2 Diabetes, Tryphena Pilli

VCU's Medical Journal Club: The Work of Future Health Professionals

Ketogenic diet can help lower blood glucose levels in newly diagnosed overweight and obese patients with T2DM.

Cd4+ T Helper 2 Cells Suppress Breast Cancer By Inducing Terminal Differentiation, Arjun Jagdeesh

VCU's Medical Journal Club: The Work of Future Health Professionals

In this 2022 publication, Boieri et al. investigated how thymic stromal lymphopoietin (TSLP) can activate CD4+ and CD8+ T cell helper 2 (Th2) for breast cancer suppression. T cell helper 1 (Th1) cells are involved in the targeted immune response by attracting cytotoxic T lymphocytes and natural killer cells. However, Th2 cells are known to inhibit the T cell helper 1 immune response by causing allergic inflammation. Th2 activation in patients with allergic diseases conferred decreased risk of breast cancer. PyMt-tg mice were retroorbitally injected with TSLP and tumor growth and survival rate were compared between wild type mice and …

Inhibition Of Type 1 Immunity With Tofacitinib Is Associated With Marked Improvement In Longstanding Sarcoidosis, Devam Purohit

VCU's Medical Journal Club: The Work of Future Health Professionals

This presentation focused on the inhibition of type 1 immunity with tofacitinib and its effect on patients with sarcoidosis. The drug tofacitinib is mainly a rheumatoid arthritis drug, and the main objective of the study was to see if the drug could be used for sarcoidosis. After the completion of the experiment, it was found that the drug dramatically reduced the CSAMI activity score (a score used to indicate the activity of sarcoidosis) by 82.7% on average after six months of use.

Neural Coding Of Vibration Intensity, Brendon Murphy

VCU's Medical Journal Club: The Work of Future Health Professionals

The article I presented on details effects of the vibrations all of us are surrounded by every day, whether it be cars driving outside, the multitudes of machines running around us, or those we succumb ourselves with the music we listen to and electronics we carry with us everyday may have on our brain. They used EEG to examine correlation of the brain with different intensities of vibration (no vibration, low vibration, and high vibration) applied to the phalanx of the left index finger using a vibrotactile actuator. Their results primarily consisted of analyzing the location of the brain in …

Foxos Modulate Proteasome Activity In Human-Induced Pluripotent Stem Cells Of Huntington’S Disease And Their Derived Neural Cells, Jefin Jose

VCU's Medical Journal Club: The Work of Future Health Professionals

FOXO transcription factors have been implicated in modulating proteasome activity. Liu et al. found that Huntington's disease-induced pluripotent stem cells (HD iPSCs) exhibited greater proteasome activity as well as greater FOXO1 and FOXO4 expression. To determine a possible causal relationship, Liu et al. performed shRNA knockout of these two transcription factors and found that only FOXO4 mediated proteasome activity in pluripotent stem cells. Overexpression of FOXO4 rescued proteasomal defect in HD iPSCs-derived neural progenitor cells (NPCs). Overall, Liu et al. found that FOXO4 specifically modulated proteasome activity in HD iPSCs and their derived NPCs.

Slow-Stroke Back Massage Compared With Music Therapy For Leukemia-Related Pain And Fatigue: A Randomized Controlled Trial, Rhea Tammireddi

VCU's Medical Journal Club: The Work of Future Health Professionals

This presentation focused on the effects of nonpharmacological treatments for leukemia-related pain and fatigue. These types of treatments are becoming more prevalent in today's times due to the risk of opioid addictions with increased pain medications. The study looked at two treatments: slow-back massage therapy and music therapy. Both treatments offer various advantages physically and emotionally. The study separated 114 adults with acute myeloid leukemia into the two treatments group and a control group of standard treatment. The results showed back massage therapy had a stronger and longer effect on the reduction of pain and fatigue.

End Stage Recurrent Glioblastoma Treated With A New Noninvasive Non-Contact Oncomagnetic Device, Devam Purohit

VCU's Medical Journal Club: The Work of Future Health Professionals

This presentation focused on the use of a noninvasive oncomagnetic device for glioblastoma. This treatment is special because it is noninvasive and doesn't pose the side effects of chemotherapy or surgery. The study looked at how the oncomagnetic device affected the size of the tumor after it reappeared in the patient's brain after being surgically removed initially. The device was tested on one patient and it was able to reduce his tumor by 31%.

Anti-Gd2 Antibody Dinutuximab Inhibits Triple-Negative Breast Tumor Growth By Targeting Gd2+ Breast Cancer Stem-Like Cells, Nasser Al-Abdulaly

VCU's Medical Journal Club: The Work of Future Health Professionals

Triple negative breast cancer is an aggressive subtype of breast cancer characterized by its lack of estrogen and progesterone receptors, as well as no or low levels of human epidermal growth factor 2. Ly et al. found that the ganglioside GD2 is highly expressed in a stem cell-like population of triple negative breast cancer tumor and helps with cell adhesion and migration. Using a xenograft model, the researchers determined that targeting this cell population with dinutuximab (anti-GD2 antibody) could prevent tumor growth and metastasis.

Association Of Cag Repeats With Long-Term Progression In Huntington Disease, Jefin Jose

VCU's Medical Journal Club: The Work of Future Health Professionals

The relationship between CAG repeat length and clinical/morphometric decline in Huntington's disease patients beyond the age of onset has not been well characterized. Some studies argue that CAG repeat length does influence clinical decline after the age of onset, while others do not. Langbehn et al. found that clinical condition correlated quadratically with age for every subject with a pathogenic number of CAG repeats in the TRACK-HD and TRACK-ON datasets. Interestingly, those with a higher CAG repeat length experienced a greater rate of clinical decline at each timepoint. Performing a similar analysis using morphometric data, Langbehn et al. found a …

Maternal-Fetal Immune Responses In Pregnant Women Infected With Sars-Cov-2, Arya Hanjagi, Arya Revankar, Meghana Sunkara, Tvisha Vanteru

VCU's Medical Journal Club: The Work of Future Health Professionals

This study aimed to provide more insight into how much of an effect these unique maternal-fetal immune responses have during pregnancy and examine the likelihood of placental infections. Pregnant women with positive RT-PCR results for SARS-CoV-2 and healthy gestational age-matched controls made up the study's two primary groups. The study comprised a total of 23 women, 12 women (8 asymptomatic; 1 with mild symptoms; 3 had severe COVID-19 (requiring oxygen supplementation). Sections from the center of the placenta and placental disk were taken and histologically examined. Researchers obtained and analyzed differences in SARS-CoV-2 human maternal peripheral blood, umbilical cord blood, …

Neurod1 Aav-Based Gene Therapy For Functional Brain Repair After Ischemic Injury Through In Vivo Astrocyte-To-Neuron Conversion, Marlena Ramlatchan

VCU's Medical Journal Club: The Work of Future Health Professionals

This study uses AAV based gene therapy to create an astrocyte- neuron conversion to regain functional abilities damaged by ischemic injuries. NeuroD1 treatment has shown promising results in the treatment of ischemic injuries in rodents and is heading towards clinical trials. Cognitive and motor improvements were shown. The basis of this therapy is to use functional glial cells to promote neurocellular growth, which would restore some function lost as a result of injury.

Disentangling Social-Genetic From Rearing-Environment Effects For Alcohol Use Disorder Using Swedish National Data, Aiman Hanif, Han Tran

VCU's Medical Journal Club: The Work of Future Health Professionals

The presentation introduces Dr. Jessica Salvatore and colleagues’ work, Disentangling Social-Genetic From Rearing-Environment Effects for Alcohol Use Disorder Using Swedish National Data, on the social-genetic effects of having a spouse whose parent(s) is/are affected by alcohol use disorder (AUD). After collecting personal data of over 300,000 Swedish opposite-sex couples, the study used actor-partner interdependence model and logistic regression model to examine the association between a spouse’s AUD predisposition and the proband’s risk of developing AUD. The results showed that the proband is at a high risk of developing AUD upon marrying an AUD-predisposed spouse. The authors concluded that this relationship …

Mesenchymal Stem Cell Therapy For Knee Osteoarthritis: 5 Years Follow- Up Of Three Patients, Shahad Musa

VCU's Medical Journal Club: The Work of Future Health Professionals

This presentation is on the effects of mesenchymal stem cells on osteoarthritis in the knees. Osteoarthritis is the degeneration of cartilage and has very little long-term treatments. Most treatments are geared towards pain management and surgery is an option, but no cure exists to reverse or stop degeneration. Embryonic stem cell research is severely limited, meaning mesenchymal stem cells (adult-derived stem cells) are more accessible to research. In this study, stem cells from the patient’s bone marrow were derived and then injected into the severely damaged knees. Results were conducted six months and five years after. Six months after the …

Β-Amyloid Accumulation In The Human Brain After One Night Of Sleep Deprivation, Shahad Musa

VCU's Medical Journal Club: The Work of Future Health Professionals

This presentation is on the effects of sleep deprivation on β-amyloid accumulation in the brain. During sleep, the glymphatic system is involved in the clearance of metabolic including metabolic wastes. β-amyloid accumulation is directly correlated to impairment of brain function and Alzheimer's disease. Increased sleep or ways to decrease β-amyloid accumulation could be beneficial in the prevention of Alzheimer's. Data collected in the article published by Shokri-Kojori, E. et al. suggests that sleep deprivation negatively affected mood and was correlated with increases in amyloid- β burden in the right hippocampal cluster. Further research on how sleep impacts β-amyloid accumulation should …

Diacylglycerol Lipase-Β Knockout Mice Display A Sex-Dependent Attenuation Of Traumatic Brain Injury-Induced Mortality With No Impact On Memory Or Other Functional Consequences, Jefin Jose

VCU's Medical Journal Club: The Work of Future Health Professionals

Traumatic brain injury has been a concern in recent years with a greater understanding of its effects on the brain. The endocannabinoid system leads to inflammation when activated, leading to a poorer prognosis in vivo for traumatic brain injury patients. In the present study, the researchers wanted to identify the potentially neuroprotective effects of DAGL-β knockout when mice were exposed to traumatic brain injury. Using a variety of different techniques, the researchers were able to conclude that DAGL-β knockout did not lead to neuroprotective benefits but was associated with lower levels of mortality immediately following the injury. In addition, the …

Nsynergistic Antiviral Effect Of Hydroxychloroquine And Azithromycin In Combination Against Sars-Cov-2, Samiya Majid

VCU's Medical Journal Club: The Work of Future Health Professionals

This presentation gives a brief overview of the study conducted by Fantini, J., Chahinian, H., & Yahi, N. on nSynergistic antiviral effect of hydroxychloroquine and azithromycin in combination against SARS-CoV-2: what molecular dynamics studies of virus-host interactions reveal. The study considered two drugs, hydroxychloroquine (CLQ) and azithromyocin (ATM), as potential treatments for curing COVID. Hydroxychloriquine is a drug commonly used in the treatment of malaria but has been shown by recent studies to not be an effective cure against COVID on its own. Azithromyocin is a commonly used antiobiotic that was also considered in this study. Hydroxychloriquine interacts with the …

Outcomes Of Catheter Ablation Of Ventricular Tachycardia Based On Etiology In Nonischemic Heart Disease: An International Ventricular Tachycardia Ablation Center Collaborative Study, Akhila R. Kunuthuru

VCU's Medical Journal Club: The Work of Future Health Professionals

This presentation explores the study conducted by Marmar Vaseghi, Tiffany Y. Hu, Roderick Tung, et al.:

Outcomes of Catheter Ablation of Ventricular Tachycardia Based on Etiology in Nonischemic Heart Disease: An International Ventricular Tachycardia Ablation Center Collaborative Study

Researchers determined the effects of ventricular tachycardia ablation in nonischemic cardiomyopathy (NICM) patients. By studying the six most common etiologies of NICM, researchers came to the conclusion that the etiology of NICM is an important factor when predicting ventricular tachycardia recurrence, death, or cardiac transplantation. The paper also indicated that adjustments were performed to the data to account for confounding factors such …

The Covid-19 Vaccine Development Landscape, Areebah Ahmed

VCU's Medical Journal Club: The Work of Future Health Professionals

This presentation focused on the current ongoing developments for the COVID-19 vaccine as described in The Covid-19 Vaccine Development Landscape by Tung Thanh Le et. al. An overview of the competing companies and the specifics of their vaccine development is presented, along with the current phases. Moderna and Inovio Pharmaceuticals are just a few of the companies working towards the common goal of a proven effective vaccine. Additionally, the presentation contains visuals of the biological components of the virus, as well as discussions of how organizations such as the CEPI (Coalition for Epidemic Preparedness Innovations) have assisted the progress of …

Characterization And Discovery Of A Selective Small Molecule Modulator Of Mitochondrial Complex I Targeting A Unique Binding Site, Jefin Jose

VCU's Medical Journal Club: The Work of Future Health Professionals

Zhang et al. developed a potential therapeutic drug that selectively binds to the IF site of Complex I, revealing the role of ZCM-I-1 as a potential regulator of ROS species within the mitochondria at moderate concentrations. More importantly, the development of this drug has been used to justify the mitochondria dysfunction hypothesis of Alzheimer's Disease. However, the key mechanism for Alzheimers remains unclear.

The Promises Of Neurodegenerative Disease Modeling, Jefin Jose

VCU's Medical Journal Club: The Work of Future Health Professionals

In Jean-Antoine Lepesant's review of The promises of neurodegenerative disease modeling, the author evaluates the present and past roles of molecular genetics in biomedical research and assesses the use of animal models in neurodegenerative disease modeling. Despite posing various ethical issues, particularly surrounding the clinical implications of CRISPR/Cas9, molecular genetics has allowed researchers to determine the pathogenic origin of various diseases as well as mimic the conditions of genetically altered patients. Molecular genetics has also facilitated a transgenic approach to create animal models for mammalian disorders. In particular, D. melanogaster serves as a preliminary research tool in the investigation of …

Impacts Of A National Lockdown On Smallholder Farmers’ Income And Food Security: Empirical Evidence From Two States In India, Samiya Majid

VCU's Medical Journal Club: The Work of Future Health Professionals

This presentation gives a brief overview of the study conducted by Francisco Ceballos, Samyuktha Kannan, & Berber Kramer on the Impacts of a national lockdown on smallholder farmers’ income and food security: Empirical evidence from two states in India. The study considered the disproportionate effect of COVID on economies worldwide, specifically the two states, Haryana and Odisha, in India. The COVID-19 pandemic posed many challenges for small farmers in these two states. National and local policies posed varying challenges for farmers. They were interviewed about these challenges by phone, right after the announcement of the lockdown and harvest season in …

Phase I Trial And Pharmacokinetics Of Fenretinide In Children With Neuroblastoma, Shahad Musa

VCU's Medical Journal Club: The Work of Future Health Professionals

This presentation is on the effect of different dosages of fenretinide on children with neuroblastoma. Neuroblastomas are the second most common malignant tumor growth in children with a high fatal relapse rate. Children diagnosed with this disease have less than a 50% chance of survival within five years of diagnosis. Fenretinid and other retinoids have been extensively studied in vitro, but this article highlights phase I where the safest and most effective dosages lie. Patients' eligibility was based on a list of guidelines, and patients were given the drug for 28 days followed by a seven-day interruption in a cycle. …

Local Administration Of Reveromycina Ointment Suppressed Alveolar Bone Loss In Mice, Samiya Majid

VCU's Medical Journal Club: The Work of Future Health Professionals

This presentation gives an overview of the study conducted by Ken Miyazawa, Yuichiro Asano, Masako Tabuchi, Shunsuke Kako, Makoto Kawatani, Hiroyuki Osada, Hatsuhiko Maeda, and Shigemi Goto on the local administration of ReveromycinA ointment. In the study, ReveromycinA (RMA) ointment was administered non-invasively in the oral cavity of mice. The effectiveness of this ointment was tested by observing whether it was able to inhibit alveolar bone resorption in a mouse with experimentally-induced periodontal disease. The alveolar bone loss in the wild type versus osteoprotegerin-knockout mice showed that localized administration of the RMA ointment resulted in suppressed alveolar bone resorption, reduced …

Glia-Neuron Interactions In The Mammalian Retina, Jefin Jose

VCU's Medical Journal Club: The Work of Future Health Professionals

The investigators reviewed the origin, morphology, and function of the three main classes of glia within the retina. Muller cells ensheath neurons and blood vessels within its functional unit. Astrocytes mediate the blood-retina barrier as well form a network of glial cells called the pangial syncytium, which diffuses excess potassium ions to potassium-deficient areas. Microglia play the role of immunosurveillance through long-fine processes which turn into short, thick processes upon activation. Although these glial cells play roles ancillary to light processing, these glial cells can also play more direct roles in processing. For example, Muller cells are believed to direct …

Immune Checkpoint Molecules In Natural Killer Cells As Potential Targets For Cancer Immunotherapy, Jefin Jose

VCU's Medical Journal Club: The Work of Future Health Professionals

Xu et al summarizes some of the different functions of NK cells, focusing on their ability to secrete cytokines and trigger cancer cell cytotoxicity. NK cells have activating and inhibiting receptors on its cell surface, contributing to the balance of stimulating and suppressing signals for NK cells. In the tumor microenvironment, the receptors on the NK cell surface are altered, contributing to NK dysfunction. Immunotherapies have been developed to target increased NK surface inhibitory receptors and have shown promise. However, there is also evidence that regulatory T cell targeting and ADO mediation may also contribute to NK cell cytotoxicity. Further …