Reinforcement of Core Foundational Science Concepts during Clinical Rotations: A Strategy to Enhance Medical Student Learning and Diagnostic Reasoning.

Cognitive science principles can facilitate integrating and retaining basic science concepts during the clinical years of undergraduate medical education. We hypothesized that reinforcing foundational science concepts during the core clerkship experiences fosters the development of clinical reasoning in medical students. A patient simulation session on diabetic ketoacidosis (DKA) in the pediatric clerkship was chosen to pilot the program. We introduced an intervention in which a team of clinical and foundational science faculty facilitates student discussions, helping them connect important physiological and pathophysiological concepts to the disorder's clinical presentation, diagnosis, and management. The student survey reported that 87% strongly agreed that it helped them reinforce their understanding of foundational science concepts related to clinical cases. The NBME subject exam results of the pediatric clerkships from the corresponding years were subjected to a cognitive diagnostic assessment called the DINA model analysis. The student content mastery in acid-base disorders was improved following the intervention (student mastery of skills, 0.73 vs 0.80, P=0.035). Similarly, analysis of the Step 2 Clinical Knowledge (CK) skills from the NBME subject exam item analysis reports showed improvement in the skill "diagnosis" on the topic of diabetes (probability value- before and after the intervention, respectively, 0.73 and 0.85, p=0.04) following implementation. Our study shows the impact of foundational science reinforcement during clinical clerkships in developing undergraduate medical students' clinical reasoning and diagnostic skills.

Paraoxonases at the Heart of Neurological Disorders.

Paraoxonase enzymes serve as an important physiological redox system that participates in the protection against cellular injury caused by oxidative stress. The PON enzymes family consists of three members (PON-1, PON-2, and PON-3) that share a similar structure and location as a cluster on human chromosome 7. These enzymes exhibit anti-inflammatory and antioxidant properties with well-described roles in preventing cardiovascular disease. Perturbations in PON enzyme levels and their activity have also been linked with the development and progression of many neurological disorders and neurodegenerative diseases. The current review summarizes the available evidence on the role of PONs in these diseases and their ability to modify risk factors for neurological disorders. We present the current findings on the role of PONs in Alzheimer's disease, Parkinson's disease, and other neurodegenerative and neurological diseases.

Novel Model of Oxalate Diet-Induced Chronic Kidney Disease in Dahl-Salt-Sensitive Rats.

Diet-induced models of chronic kidney disease (CKD) offer several advantages, including clinical relevance and animal welfare, compared with surgical models. Oxalate is a plant-based, terminal toxic metabolite that is eliminated by the kidneys through glomerular filtration and tubular secretion. An increased load of dietary oxalate leads to supersaturation, calcium oxalate crystal formation, renal tubular obstruction, and eventually CKD. Dahl-Salt-Sensitive (SS) rats are a common strain used to study hypertensive renal disease; however, the characterization of other diet-induced models on this background would allow for comparative studies of CKD within the same strain. In the present study, we hypothesized that SS rats on a low-salt, oxalate rich diet would have increased renal injury and serve as novel, clinically relevant and reproducible CKD rat models. Ten-week-old male SS rats were fed either 0.2% salt normal chow (SS-NC) or a 0.2% salt diet containing 0.67% sodium oxalate (SS-OX) for five weeks.Real-time PCR demonstrated an increased expression of inflammatory marker interleukin-6 (IL-6) (p < 0.0001) and fibrotic marker Timp-1 metalloproteinase (p < 0.0001) in the renal cortex of SS-OX rat kidneys compared with SS-NC. The immunohistochemistry of kidney tissue demonstrated an increase in CD-68 levels, a marker of macrophage infiltration in SS-OX rats (p < 0.001). In addition, SS-OX rats displayed increased 24 h urinary protein excretion (UPE) (p < 0.01) as well as significant elevations in plasma Cystatin C (p < 0.01). Furthermore, the oxalate diet induced hypertension (p < 0.05). A renin-angiotensin-aldosterone system (RAAS) profiling (via liquid chromatography-mass spectrometry; LC-MS) in the SS-OX plasma showed significant (p < 0.05) increases in multiple RAAS metabolites including angiotensin (1-5), angiotensin (1-7), and aldosterone. The oxalate diet induces significant renal inflammation, fibrosis, and renal dysfunction as well as RAAS activation and hypertension in SS rats compared with a normal chow diet. This study introduces a novel diet-induced model to study hypertension and CKD that is more clinically translatable and reproducible than the currently available models.

Impact of COVID-19 infection on baseline autonomic symptoms in patients with preexisting postural tachycardia syndrome and orthostatic intolerance: A retrospective study.

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) and dysautonomia following a SARS-CoV-2 infection have been recently reported. The underlying mechanism of dysautonomia is not well understood. The impact of this viral illness on the underlying autonomic symptoms has not been studied in patients with a pre-existing POTS diagnosis. Our study aims to report the impact of a COVID-19 infection on patients with preexisting POTS, both during the acute phase of the disease and post-recovery. METHODS: Institutional Review Board (IRB) approval was obtained to access charts of the study subjects. All patients with known POTS disease who acquired COVID-19 infection between April 2020 and May 2021 were included. The end point of the study was worsening POTS related symptoms including orthostatic dizziness, palpitation, fatigue and syncope/ presyncope post COVID-19 infection that required escalation of therapy. Basic demographics, details of POTS diagnosis, medications, Additional information regarding COVID 19 infection, duration of illness, need for hospitalization, worsening of POTS symptoms, need for ED visits, the type of persisting symptoms and vaccination status were obtained from the retrospective chart review. RESULTS: A total of 41 patients were studied. The alpha-variant was the most common causing SARS-CoV-2 infection. 27% (11 patients) of them had tested positive for COVID- 19 infection more than once. About 38 (92.7%) of them reported having worsening of their baseline POTS symptoms during the active infection phase. About 28 patients (68%) experienced worsening of their dysautonomia symptoms for at least 1-6 months post infection. Nearly 30 patients (73.2%) required additional therapy for their symptom control and improvement. CONCLUSIONS: Patients with pre-existing POTS, most experienced a worsening of their baseline autonomic symptoms after suffering the COVID-19 infection which required additional pharmacotherapy for their symptom improvement.

Sex differences in myocarditis hospitalizations: Rates, outcomes, and hospital characteristics in the National Readmission Database.

Inflammation of the myocardium, or myocarditis, presents with varied severity, from mild to life-threatening such as cardiogenic shock or ventricular tachycardia storm. Existing data on sex-related differences in its presentation and outcomes are scarce. Using the Nationwide Readmission Database (2016-2019), we identified myocarditis hospitalizations and stratified them according to sex to either males or females. Multivariable regression analyses were used to determine the association between sex and myocarditis outcomes. The primary outcome was in-hospital mortality, and the secondary outcomes included sudden cardiac death (SCD), cardiogenic shock (CS), use of mechanical circulatory support (MCS), and 90-day readmissions. We found a total of 12,997 myocarditis hospitalizations, among which 4,884 (37.6 %) were females. Compared to males, females were older (51 ± 15.6 years vs. 41.9 ± 14.8 in males) and more likely to have connective tissue disease, obesity, and a history of coronary artery disease. No differences were noted between the two groups with regards to in-hospital mortality (adjusted odds ratio [aOR] 1.20; confidence interval [CI] 0.93-1.53; P = 0.16), SCD (aOR:1.18; CI 0.84-1.64; P = 0.34), CS (aOR: 1.01; CI 0.85-1.20;P = 0.87), or use of MCS (aOR: 1.07; CI:0.86-1.34; P = 0.56). In terms of interventional procedures, females had lower rates of coronary angiography (aOR: 0.78; CI 0.70-0.88; P < 0.01), however, similar rates of right heart catheterization (aOR 0.93; CI:0.79-1.09; P = 0.36) and myocardial biopsy (aOR: 1.16; CI:0.83-1.62; P = 0.38) compared to males. Additionally, females had a higher risk of 90-day all-cause readmission (aOR: 1.25; CI: 1.16-1.56; P < 0.01) and myocarditis readmission (aOR:1.58; CI 1.02-2.44; P = 0.04). Specific predictors of readmission included essential hypertension, congestive heart failure, malignancy, and peripheral vascular disease. In conclusion, females admitted with myocarditis tend to have similar in-hospital outcomes with males; however, they are at higher risk of readmission within 90 days from hospitalization. Further studies are needed to identify those at higher risk of readmission.

Mercury poisoning from artisanal gold mining equipment.

Artisanal and small-scale gold mining uses mercury to isolate gold from ore. Although uncommon in the United States, it is more common in poor and undeveloped countries. This practice requires heating mercury, which vaporizes into an odorless gas that can be inspired and absorbed into the blood. Inspired mercury vapors place individuals at risk of acute mercury toxicity and its subsequent chronic sequelae. We report a case of incidentally detected mercury foreign bodies in a 56-year-old male with a prior history of accidental mercury poisoning due to prior contact with artisanal gold mining equipment.

Clinical and Radiological Features of Menetrier's Disease: A Case Report and Review of the Literature.

We present a case report describing the diagnosis and management of a patient who presents with a rare diagnosis of Menetrier's disease. This condition poses a diagnostic challenge to clinicians due to its nonspecific clinical presentation and is oftentimes misdiagnosed for more common gastric disorders. Menetrier's disease is characterized by gastric mucosal hypertrophy and subsequent protein loss, resulting in gastric symptoms and widespread edema. While the etiology remains unclear, notable associations have been observed with Helicobacter pylori (H. pylori) infection and overexpression of transforming growth factor-alpha (TGF-a). The management often involves supportive measures with medical and surgical interventions for refractory cases and when necessary. This report includes a comprehensive review of the literature on the clinical presentation, diagnostic approach, and management of this rare disease. By documenting such cases in the medical literature, we aim to enhance the clinician's ability to recognize and manage this disorder, thereby preventing the development of more severe manifestations such as gastric carcinoma.

Inferior mesenteric vein thrombophlebitis secondary to acute diverticulitis.

Inferior mesenteric vein thrombophlebitis is an uncommon condition. Most cases of portal-mesenteric thrombophlebitis affect either the portal vein or superior mesenteric vein; it is not known why the inferior mesenteric vein is less affected. Thrombophlebitis typically occurs following inflammatory intra-abdominal processes, such as diverticulitis. Diverticulitis is a common condition in the Western world, with several common complications, such as fistula formation and bowel wall perforation. However, although diverticulitis is a common cause of portal-mesenteric thrombophlebitis, thrombophlebitis is still a rare complication of diverticulitis. We present a case of diverticulitis complicated with interior mesenteric vein thrombophlebitis with gas extension into the portal vein.

Marchiafava-Bignami disease: Case presentation and radiological imaging.

Marchiafava-Bignami disease (MBD) is a rare vitamin B deficiency classically associated with alcoholism. MBD damages the corpus callosum and presents with nonspecific neurological symptoms. Radiological imaging is critical for diagnosing MBD and commencing subsequent treatment, which often consists of vitamin B supplementation. We present a case of MBD in a 56-year-old male with alcohol use disorder, epilepsy, schizophrenia, post-traumatic stress disorder, and cardiovascular risk factors. The patient presented with general neurological symptoms, and there were several potential diagnoses to consider based on the patient's history. Radiological imaging was necessary for diagnosis. This case demonstrates the role radiological imaging plays in the workup of MBD.

Hypothermia as an Adjunctive Therapy to Percutaneous Intervention in ST-Elevation Myocardial Infarction: A Systematic Review and Meta-Analysis of Randomized Control Trials.

INTRODUCTION: In the setting of acute ST-elevation myocardial infarction (STEMI), several randomized control trials (RCTs) suggested a potential benefit with the use of therapeutic hypothermia (TH). However, results from previous studies are contradictory. METHOD: We performed a comprehensive literature search for studies that evaluated the efficacy and safety of adjunctive TH compared to the standard percutaneous coronary intervention (PCI) in awake patients with STEMI. The primary outcomes were the infarct size (IS) and microvascular obstruction (MVO) assessed by cardiac imaging at the end of follow-up. The secondary outcomes were major adverse cardiovascular events (MACE), procedure-related complications, and door-to-balloon time. Relative risk (RR) or the mean difference (MD) and corresponding 95 % confidence intervals (CIs) were calculated using the random-effects model. RESULTS: A total of 10 RCTs, including 706 patients were included. As compared to standard PCI, TH was not associated with a statistically significant improvement in the IS (MD: -0.87 %, 95%CI: -2.97, 1.23; P = 0.42) or in the MVO (MD: 0.11 %, 95%CI: -0.06, 0.27; P = 0.21). MACE and its components were comparable between the two groups. However, the TH approach was associated with an increased risk of infection and prolonged door-to-balloon time. Furthermore, there was a trend in the TH group toward an increased incidence of stent thrombosis and paroxysmal atrial fibrillation. CONCLUSIONS: According to our meta-analysis of published RCTs, TH is not beneficial in awake patients with STEMI and has a marginal safety profile with potential for care delays. Larger-scale RCTs are needed to further clarify our results.

Comparing the Efficacy and Safety of Adalimumab and Vedolizumab in Treating Moderate to Severe Crohn's Disease and Ulcerative Colitis.

Background: Numerous patients with inflammatory bowel disease (IBD) do not respond to conventional or biological therapy. Adalimumab (ADA) and vedolizumab (VDZ), according to certain research, may be a useful alternative treatment for these people. The purpose of this study was to assess the effectiveness and safety of using ADA and VDZ to treat moderate to severe IBD: Crohn's disease (CD) and ulcerative colitis (UC). Methods: We searched PubMed, Medline, Web of Science, Scopus, the Cochrane Library, Embase, Google Scholar, CINAHL, Clinicaltrials.gov, and WHO trials registry (ICTRP). Randomized controlled trials (RCTs) comparing ADA or VDZ with placebo in participants with active CD or UC were included. The primary outcomes were the clinical response and remission at induction and maintenance phases and mucosal healing. The secondary outcome was the incidence of profound negative events. The research used Comprehensive Meta-Analysis version 3 (Biostat Inc., USA). Results: Eighteen RCTs were incorporated, in which 11 studies described the usefulness and safeness of ADA or VDZ in CD patients, and seven studies investigated the efficacy and safety of ADA or VDZ in UC patients. The meta-analysis revealed that both ADA and VDZ treatments were superior to placebo for producing clinical remission and eliciting clinical response at induction and maintenance phases in individuals with moderately to severely active CD or UC. Interestingly, we found that ADA was superior to VDZ as first-line treatment for patients with CD, but not UC. Conclusion: ADA and VDZ are effective and safe in CD and UC patients. However, RCTs of a larger number of patients are still required for better assessing the safety profile of ADA and VDZ.

Epididymo-orchitis secondary to colovesical fistula.

Epididymo-orchitis is a common urological condition that can be caused by a variety of etiologies, including retrograde extension of a urinary tract infection. Colovesical fistulas are frequent sequelae of diverticulitis that allow for communication between the colon and urinary bladder. Such fistulas facilitate the spread of enteric bacteria into the urinary bladder, with possible subsequent spread throughout the rest of the genitourinary system. Retrograde extension into the epididymis and testis is very rare, however. We present the case of a 38 year old man with epididymo-orchitis secondary to a colovesical fistula.

Toward Development of Neuron Specific Transduction After Systemic Delivery of Viral Vectors.

Widespread transduction of the CNS with a single, non-invasive systemic injection of adeno-associated virus is now possible due to the creation of blood-brain barrier-permeable capsids. However, as these capsids are mutants of AAV9, they do not have specific neuronal tropism. Therefore, it is necessary to use genetic tools to restrict expression of the transgene to neuronal tissues. Here we compare the strength and specificity of two neuron-specific promoters, human synapsin 1 and mouse calmodulin/calcium dependent kinase II, to the ubiquitous CAG promoter. Administration of a high titer of virus is necessary for widespread CNS transduction. We observed the neuron-specific promoters drive comparable overall expression in the brain to the CAG promoter. Furthermore, the neuron-specific promoters confer significantly less transgene expression in peripheral tissues compared with the CAG promoter. Future experiments will utilize these delivery platforms to over-express the Alzheimer-associated pathological proteins amyloid-beta and tau to create mouse models without transgenesis.