Optogenetic deactivation of amygdalo-auditory cortex circuit

Introduction: While the functions of many amygdalar circuits have been widely studied, the role of the direct amygdalo-auditory cortex (AM-AC) circuit is unknown. Objective: Understand the function of the direct projection from the amygdala to the auditory cortex. Methods: Two experiments were performed. In Experiment 1:Electrophysiology was utilized to record single and multi-unit responses from the auditory cortex. Optogenetic activation or deactivation of the amygdalo-auditory cortex circuit was then utilized to examine changes to auditory neuron firing rate during normal and deactivation scenarios. In Experiment 2, the protocols for experiment 1 were tested in animals with a sound-induced tinnitus to determine whether deactivation of the amygdalo-auditory cortex circuit would influence the tinnitus perception. In both experiments, fluorescent labeling from the optogenetic injection was examined in the amygdala and auditory cortex. Results: The optogenetic vector construct provided both anterograde and retrograde labeling. The injection site was isolated to the lateral and basal nuclei of the amygdala. Labeled neurons included pyramidal and multipolar cells. Within the auditory cortex, a few pyramidal neurons were observed bilaterally throughout both primary and secondary areas of the auditory cortex. In addition, a large number of en-passant and terminal boutons were observed throughout layers 1-6 but predominantly in layers 5 and 6. Recording of neurons in the auditory cortex were characterized by best frequency. Deactivation of the amygdala projection to auditory cortex caused a significant inhibition of cortical firing rates in both multiunit and single-unit recordings. This inhibition occurred only during the time of the amygdala projection deactivation. In our tinnitus animals, the tinnitus was eliminated during the amygdala projection deactivation. However, the tinnitus immediately recovered when the pathway was released from deactivation. Conclusion: While most of the amygdalar projection neurons to the auditory cortex are pyramidal (i.e., glutamatergic), the overall influence of the pathway was inhibitory. Therefore, this pathway is likely to contact inhibitory circuits within the cortex. The timing of inhibition and release from inhibition occurred within a manner of milliseconds. No long-term effects were observed. Therefore, we hypothesize that the amygdalo-auditory cortex circuit may provide quick modulatory influences on cortex that may help to prime cortical circuits for subsequent inputs from the nucleus basalis (a projection that has longer-lasting influences on cortical function)

A systemic review of efficacy, ratings and top football gear for concussion prevention in 2024

Introduction: Concussions in football pose significant health risks, requiring the implementation of effective protective gear to reduce the incidence of head injuries. Helmets and mouthguards are standard equipment, but their true effectiveness remains debated. Objective: This study aimed to systematically evaluate the efficacy of modern football protective gear, specifically helmets and mouthguards, in the prevention of concussions. Methods: Following PRISMA guidelines, a comprehensive search was conducted in PubMed, Cochrane Library, Google Scholar, and Embase. A total of 3,894 studies were reviewed, and 35 studies met the inclusion criteria. Independent reviewers analyzed the studies to determine the impact of helmets and mouthguards on concussion rates, reconciling discrepancies through a third-party decision. No funding or third-party data collection was required. Results: The analysis revealed that helmets incorporating MIPS and TPU cushioning were effective in reducing concussion rates by 40%. However, the efficacy of headgear and mouthguards was inconsistent across studies. Headgear was found to slightly increase the risk of concussion, while mouthguards provided minimal protection, reducing concussion incidence by 19% in some studies but lacking statistical significance in others. Conclusion: Helmets are the most effective piece of protective gear in reducing the risk of concussions in football. While mouthguards may offer some protective benefit, their impact on concussion prevention remains limited. Further research is necessary to explore alternative measures, such as policy changes, to improve concussion prevention strategies in football

Use of Simulation for Teaching Biomedical Sciences to Undergraduate Medical Students- A Scoping Review

Objective: The objective of this scoping review is to understand the extent and type of evidence in relation to the use of simulation or SIM-based medical education pedagogies to teach biomedical sciences to undergraduate medical students in accredited medical schools, globally. The review considers literature published between 2014-2024. Introduction: Simulation, which could be generally described as a computer-based or structured model and practice that replicates the processes, behavior, or characteristics of a real-world system or phenomenon, especially for the purpose of education or training, is increasingly becoming popular and relevant in medical education. However, discrete publications with relatively diverse experiences and outcomes require a critical appraisal and synthesis of evidence towards informing best practices and policies. Inclusion criteria: The review only considered reports about populations of students enrolled in accredited undergraduate medical education programs that train medical doctors including DO/MD/MBBS/MBChB or equivalents in any country. Simulation, as a concept is considered as reportedly used in the context of teaching knowledge, skills or practice-related attitudes in biomedical science disciplines. Articles published in English Language were considered. Methods: An initial search of the Cochrane and JBI’s Evidence-based Practice databases in October 2023 found no similar review. For this review, the primary databases searched included PubMed, ERIC, and Google Scholar. Only articles published in English between 2014-2024 were considered. The JBI SUMARI was the platform for screening, approval, extraction, synthesis and review. For screening and appraisal, two or more members of the review team were required to approve an article. Results: A total of 20 articles were considered for this review out of the initial yield of 2,671. These included: 4 Analytical Cross-Sectional Studies- 2 from Australia, 1 from the USA and 1 from China; 3 Systematic Review and Research Syntheses; 3 Randomized Controlled Trials- 1 from China and 2 from Italy; 6 Quasi-Experimental Studies- 1 from Taiwan, 1 from the Netherlands, 1 from the both China and United Kingdom, 1 from Sweden, 1 from Indonesia and 1 from the United States; and 4 Text and Opinion Studies. Findings highlight the growing use of simulation and technology-enhanced learning in medical education, improving competency, retention, and engagement. Simulation, in its various fidelities and modalities including those aided by VR, AR, and PBL enhance motivation and skills but cannot fully replace hands-on training. Limitations include inconsistent assessment impacts, cost challenges, and accessibility concerns. Conclusion: Simulation and technology-enhanced learning improve engagement, skills, and retention in medical education. Integration with traditional pedagogies or methods maximizes effectiveness. Virtual simulations aided by technologies, VR or AR offer immersive experiences but require careful implementation. Further research is needed to optimize training, address costs, and enhance curriculum integration

Arachnidism leading to a complicated infection in a middle aged female

Arachnids are known to seek out dark, undisturbed areas, where they can be secluded. Although generally not known for their aggression towards humans, they are known to bite when prompted. Most bites occur unknowingly while cleaning a storage area, putting on clothing/shoes, doing yard-work, or even rolling over in bed. Often, the bite is painless. The severity of a patient’s reaction to the bite originates from the genus of arachnida, the amount of venom injected, and the individual’s sensitivity to it. Several types of arachnid venoms are known to be cytotoxic and hemolytic. While many initial bites are commonly painless, they can become increasingly painful over time. In rare circumstances, their venom is known to cause additional symptoms such as joint pain, seizures, organ failure, myalgias, death, disseminated intravascular coagulation (DIC), fever, weakness, malaise, hemolytic anemia, nausea, and headache. We present the case of a 41 y/o female who presented with chest pain, generalized body aches, nausea, fatigue, and left lower limb pain. The patient initially noticed a lesion on her left lower extremity while shaving on the day of presentation and reported that it was rapidly spreading upwards alongside a sudden onset of fatigue and pain. Patient met sepsis criteria upon admission with leukocytosis, tachycardia, tachypnea, fever, and source of infection of possible cellulitis of the lower extremity. Computed tomography angiography (CTA) was negative for pulmonary embolism, chest X-ray showed no acute findings, venous doppler revealed no deep vein thrombosis, and computed tomography (CT) of lower left extremity showed soft tissue edema throughout the calf consistent with cellulitis, no abscess, skin thickening, or osseous involvement. Patient was started on IV Vancomycin and Zosyn with no initial improvement and worsening symptoms over the course of several days. Antibiotics were then changed to meropenem with no improvement. Initial blood culture, wound culture, and MRSA tests cultures were negative. A five millimeter punch biopsy was then performed that showed benign skin with nonspecific hemorrhagic changes. The patient then underwent several months of wound care initially starting inpatient and continuing in the outpatient setting. This report presents a case about the unusual etiology of the patient’s condition of venomous arachnidism with discussion of the variety of the differential diagnosis that were considered while patient was actively managed

The role of the PTHrP/Ihh feedback loop in the unusual growth plate location in mammalian metatarsals and pisiforms.

BACKGROUND: Longitudinal skeletal growth takes place in the cartilaginous growth plates. While growth plates are found at either end of conventional long bones, they occur at a variety of locations in the mammalian skeleton. For example, the metacarpals and metatarsals (MT) in the hands and feet form only a single growth plate at one end, and the pisiform in the wrist is the only carpal bone to contain a growth plate. We take advantage of this natural anatomical variation to test which components of the PTHrP/Ihh feedback loop, a fundamental regulator of chondrocyte differentiation, are specific to growth plate function. RESULTS: Parathyroid hormone-like hormone (Pthlh), the gene that transcribes parathyroid hormone-related peptide (PTHrP), is expressed in the reserve zone of the growth plate-forming end of the MT. At the opposite end, the absence of a PTHrP+ reserve zone results in premature chondrocyte differentiation and Indian hedgehog (Ihh) expression. Pthlh is expressed in the reserve zone of the developing pisiform, confirming the existence of a true growth plate. CONCLUSION: A pool of PTHrP+ reserve zone chondrocytes is a defining characteristic of growth plates, and its patterning may be key to evolved differences in growth plate location in the mammalian skeleton

Bladder Neoplasia in the Setting of Polycystic Kidney Disease: Observations from a Post-Mortem Case Study

Introduction Polycystic kidney disease (PKD) is a serious genetic condition where many fluid-filled sacs, called cysts, grow in the kidneys, often leading to long-term kidney problems and kidney failure. It mainly shows up as autosomal dominant polycystic kidney disease (ADPKD), affecting about 1 in 400 to 1,000 people. Beyond affecting the kidneys, PKD is now understood to be a condition that can involve other parts of the body, including the liver, pancreas, and, rarely, the bladder. While the kidney-related issues of PKD, like cyst growth and its risks, have been well researched, the possibility of cancer developing in other organs, especially the bladder, is still a largely unexplored area in medical studies. This lack of knowledge is important because recent findings suggest that the environment inside these cysts might share features with solid tumors, such as uncontrolled cell growth, difficulty in cell death, and increased blood vessel formation, prompting questions about whether PKD patients might be more prone to cancer overall. Objectives The main goal of this study is to examine the details of bladder cancer found during a post-mortem examination of a patient with polycystic kidney disease, focusing on what the cancer looks like under a microscope and how it might be connected to the cysts already present. These objectives aim to deepen our understanding of bladder cancer in PKD for future studies and better care based on what we learn from this post-mortem case and the latest research. Methods This study was conducted in a cadaver laboratory, examining a preserved specimen diagnosed with polycystic kidney disease (PKD) and coexisting bladder neoplasia. A detailed gross anatomical dissection was performed to assess the extent of cystic involvement in the kidneys and any pathological changes associated with the bladder tumor. The kidneys were systematically dissected to evaluate cyst distribution, size, and impact on surrounding structures, while the bladder was examined for tumor location, size, invasion into adjacent tissues, and any signs of metastasis. Histological samples from the kidneys and bladder were obtained and processed for microscopic examination. Findings were compared to known clinical presentations of PKD and bladder neoplasia to determine potential anatomical and pathological correlations. Results Will be further evaluated with the return of histological specimens. Conclusion The cadaveric dissection revealed extensive cystic involvement of the kidneys consistent with polycystic kidney disease (PKD), alongside a bladder neoplasm demonstrating localized invasion. Gross and histological analysis highlighted structural alterations in renal architecture due to cyst expansion, potentially influencing urinary tract dynamics and neoplastic progression. The coexistence of these conditions suggests a possible interplay between chronic renal pathology and bladder tumor development, warranting further investigation into shared pathophysiological mechanisms. These findings contribute to the anatomical and pathological understanding of PKD and bladder neoplasia, emphasizing the value of cadaveric studies in correlating disease processes with clinical implications

The Underdiagnosis: Addressing the Underdiagnosis of the Female Athlete Triad and Relative Energy Deficiency in Sport

Introduction: Many elite athletes train their whole lives to reach elite status. For another set of athletes, their sports careers were cut short for one reason or another. The underdiagnosing of the Female Athlete Triad (Triad) or Relative Energy Deficiency in Sport (RED-S) might be the reason for some athletes. A few main barriers have prevented the medical community from accurately diagnosing athletes suffering from the Triad and RED-S. Objective: This study investigates the critical barriers to early and accurate detection of the Triad and RED-S. Key obstacles include insufficient research, limited physician education, and inadequate awareness among athletes and their support networks. This research identifies these gaps and proposes targeted solutions to mitigate underdiagnosis, enhance clinical recognition, and safeguard athletic health and performance. Methods: A thorough literature review was conducted to study the importance of education and awareness in effectively identifying the Triad and RED-S among athletes. To be selected, studies had to be published after 2010 and be included in a peer-reviewed journal. The only databases used were Google Scholar and the Philadelphia College of Osteopathic Medicine Library. Results: One of the first barriers is that the prevalence of RED-S and the Triad is unknown to the medical community. Current research estimates that the prevalence of RED-S is between 22- 58%. One estimate claims that among endurance sports athletes, the prevalence of RED-S can be as high as 23-80% in females and 15-70% in males. Another major challenge to adequately diagnosing the Triad and RED-S is the physicians’ awareness of the condition. Awareness of RED-S and the Triad varies vastly among medical specialties. Awareness was highest among orthopedic surgery, obstetrics and gynecology, and physical medicine and rehabilitation/rheumatology. Awareness was lowest in psychiatry, radiology, and anesthesia. The last barrier to effectively identifying RED-S and the Triad is that athletes and their entourage ( coaches, parents, sports medicine staff) lack knowledge. One study showed that 78% of collegiate female track and field athletes and 70% of collegiate coaches did not receive education on RED-S. Discussion: These highlighted barriers have prevented the medical and athletic community from adequately diagnosing athletes suffering from the Triad and RED-S. Physicians, athletes, parents, and supporting sports staff must be educated on proper nutrition and the signs and symptoms of the Triad and RED-S. More research is also needed to help the medical community understand the prevalence of RED-S and the Triad and develop effective ways to diagnose patients. There needs to be an awareness campaign to educate healthcare professionals about RED-S and how to screen patients. Medical schools should educate students on using current screening tools like the Low EA in Females Questionnaire (LEAF-Q) and RED-S clinical assessment tool (RED-S CAT). Lastly, the medical community must take an interdisciplinary approach to diagnose and treat Triad and RED-S. This might include working with nutritionists, athletic trainers, team staff, and psychologists

Crystals and biomarker analysis via synovial fluid sampling in patients with knee effusion with radiographic correlation

Purpose: Synovial fluid biomarker analysis is a developing modality for subcategorizing arthritis type. We examined radiographic evidence of chondrocalcinosis and osteoarthritis severity in relation to their respective biomarker levels or detection on the Synovasure® RISC panel. Methods and Study Design: This is a monocentric, cross-sectional, non-controlled, and non-randomized, case series study. Patients with a knee effusion and planned arthrocentesis were included. 800 synovial fluid samples were obtained from consenting eligible patients as part of standard of care and sent via Synovasure specimen kits for analysis. Samples were further categorized based on biomarker results. Results: A total of 800 synovial fluid samples were analyzed. Crystals were found to be present in 166 (N= 20.8%) of samples. Isolated crystals included calcium pyrophosphate (N=148; 18.5%) and monosodium urate (N= 17; 2.13%), with one sample screening positive for both (N=1; 0.13%). The mean Cartilage Oligomeric Matrix Protein (COMP)/Interleukin-8 (IL-8) ratio was 30.6 (SD = 26). 305 subjects (38.3%) had a Kellgren-Lawrence (KL) grade of 4 representing a plurality for the total cohort. The COMP/IL-8 ratio was found to increase with ascending KL-grade (p-value \u3c 0.001). Chondrocalcinosis was found on radiographic review in 144 subjects (18.1%), 100 samples (60.2%) of which were noted also to be positive for intracellular and/or extracellular crystals (p-value \u3c 0.001). A subset of the cohort (N=210) was analyzed for comorbid history of gout, with 29 (13.8%) being identified via retrospective chart review. Among the subjects with crystal positivity, 24 (14.5%) also had comorbid gout (p=0.766). Conclusions: This study demonstrates statistically significant findings with respect to the presence of radiographic chondrocalcinosis and crystal detection positivity rates via synovial fluid analysis. It also demonstrates a significant correlation between arthritis severity, as qualified by radiographic KL grade, and the ratio of COMP to IL-8. Calcium pyrophosphate crystals were predominant in subjects with radiographic chondrocalcinosis. Significance: This study highlights the relationship between crystals, biomarkers, and their associated conditions, emphasizing the crucial role of synovial fluid analysis in diagnosing and treating arthritis. Acknowledgements: The study group would like to acknowledge Zimmer Biomet for its role in sample processing and data collation

Comparative Functional Outcomes for Ischemic Stroke Patients with and without COVID-19

Background: COVID-19, primarily a respiratory illness caused by SARS-CoV-2, is associated with vascular complications like ischemia due to endothelial injury, hypercoagulability, and inflammation. This study examines how COVID-19 affects functional outcomes of ischemic stroke patients. Methods: Ischemic stroke patients admitted to our Joint Commission-certified primary stroke center were retrospectively analyzed from March 1, 2020, to March 1, 2022. A subgroup analysis was conducted for patients during the vaccination period (April 14, 2021, to March 1, 2022). Patients were included if they were ≥18 years old and had a stroke on admission or during hospitalization. Univariate and multivariable analyses were used, with a significance threshold of p\u3c 0.05. Results: Out of 1,171 patients, those who tested positive for COVID-19 had significantly worse outcomes. Demographics, clinical data, and outcomes are found in Table 1. COVID-19 Positive patients experienced fewer days between stroke and death (4 days vs. 25 days, p=0.047), higher modified Rankin Scale (mRS) scores at discharge (3 vs. 1, p=0.001), and increased rates of altered consciousness (41.46% vs. 21.86%, p=0.03). In the vaccination period subgroup, COVID-positive patients had fewer days from stroke to death (4 days vs. 42 days, p=0.047), worse mRS scores (3 vs. 1, p=0.009), longer delays in discharge placement (0 vs. 1 day, p=0.020), and higher rates of altered consciousness (57.89% vs. 23.71%, p=0.001). Additionally, COVID-negative patients were more likely to be discharged home (49.52% vs. 36.84%, p=0.021). Multivariable analysis identified higher NIHSS at admission (OR: 1.028 [1.003–1.053], p=0.027), older age (OR: 1.027 [1.011–1.045], p=0.001), and a history of diabetes (OR: 1.596 [1.056–2.413], p=0.027) as increased mortality risks. Discussion & Conclusion: COVID-19 is associated with worse recovery outcomes and discharge delays for ischemic stroke patients compared to those without COVID-19. Further research is needed to explore these differences and their implications for stroke management amid the ongoing global health crisis

Acculturation, Self-Esteem, Family Norms, and Disordered Eating Behaviors in South Asian Women

This study investigated the relationships among acculturation, self-esteem, family norms, and disordered eating behaviors among South Asian women living in the United States. Although research suggests culture plays a role in the etiology of eating disorders, little information on the experiences of South Asian women exists. This study sought to fill this gap in the literature. Using a cross-sectional, quantitative survey-based design, 151 South Asian women provided insight into their experiences with family norms, acculturation, self-esteem, and eating behaviors. Results indicated that acculturation was not significantly associated with disordered eating. However, self-esteem was found to be negatively associated with disordered eating behaviors. Likewise, traditional family norms and expectations were found to be significantly associated with healthier eating habits. This study highlights the need for further exploration of the role of cultural factors, self-esteem, and family systems in terms of the development and maintenance of eating disorders