SOARinG to New Heights Through a Structured Medical Student Research Program.

Introduction: Since the US Medical Licensing Examination (USMLE) Step 1 became Pass/Fall in 2022, medical students competing for residency spots must distinguish themselves with alternative criteria. Research experiences and output offer valuable skill development and objective metrics to support competitive residency applications. Objective: We describe the methodological development of a structured program to support, enhance, and track medical student research efforts at the University of South Carolina School of Medicine Greenville, explain the implementation of the program, and summarize initial program outcomes. Methods: The Student Opportunities for Academic Achievement Through Research in Greenville (SOARinG) Program was established to serve as a centralized hub for rising second year medical student research. The program matched medical students with mentored research projects scheduled during the summer following first-year coursework. The program included a required weekly seminar series on research basics and current biomedical literature. SOARinG culminated with a student research symposium for which students submitted abstracts and presented a poster or a talk. Quantitative and qualitative program outcomes of student and mentor satisfaction with the program were measured through surveys. Results and Discussion: The program was successfully implemented in summers 2021 and 2022. Most students (80-95%) in each class engaged in mentored summer research projects. Students reported overall satisfaction with research projects and mentor support. Overall, 69% of students rated their overall research experience in the program as extremely good or very good. Each student submitted an abstract and presented at the program's symposium or alternate research venue. Overall, 97% of research mentors reported that students were adequately prepared for summer research and suggested that students would benefit from additional skills-specific research training. Conclusion: The SOARinG Program provided a formalized process for tracking and showcasing medical student research and allowed for increased student participation in research. Additionally, each participating student produced objective research output, thus enhancing future residency applications.

Urinary Exosomal MicroRNAs as Biomarkers for Obesity-Associated Chronic Kidney Disease.

The early detection of chronic kidney disease (CKD) is key to reducing the burden of disease and rising costs of care. This need has spurred interest in finding new biomarkers for CKD. Ideal bi-omarkers for CKD should be: easy to measure; stable; reliably detected, even when interfering substances are present; site-specific based on the type of injury (tubules vs. glomeruli); and its changes in concentration should correlate with disease risk or outcome. Currently, no single can-didate biomarker fulfills these criteria effectively, and the mechanisms underlying kidney fibrosis are not fully understood; however, there is growing evidence in support of microRNA-mediated pro-cesses. Specifically, urinary exosomal microRNAs may serve as biomarkers for kidney fibrosis. In-creasing incidences of obesity and the recognition of obesity-associated CKD have increased interest in the interplay of obesity and CKD. In this review, we provide: (1) an overview of the current scope of CKD biomarkers within obese individuals to elucidate the genetic pathways unique to obesi-ty-related CKD; (2) a review of microRNA expression in obese individuals with kidney fibrosis in the presence of comorbidities, such as diabetes mellitus and hypertension; (3) a review of thera-peutic processes, such as diet and exercise, that may influence miR-expression in obesity-associated CKD; (4) a review of the technical aspects of urinary exosome isolation; and (5) future areas of research.

Comparison of Human Urinary Exosomes Isolated via Ultracentrifugation Alone versus Ultracentrifugation Followed by SEC Column-Purification.

Chronic kidney disease is a progressive, incurable condition that involves a gradual loss of kidney function. While there are no non-invasive biomarkers available to determine whether individuals are susceptible to developing chronic kidney disease, small RNAs within urinary exosomes have recently emerged as a potential candidate to use for assessing renal function. Ultracentrifugation is the gold standard for urinary exosome isolation. However, extravesicular small RNA contamination can occur when isolating exosomes from biological fluids using ultracentrifugation, which may lead to misidentifying the presence of certain small RNA species in human urinary exosomes. Therefore, we characterized human urinary exosomal preparations isolated by ultracentrifugation alone, or via ultracentrifugation followed by size exclusion chromatography (SEC) column-purification. Using nanoparticle tracking analysis, we identified SEC fractions containing robust amounts of exosome-sized particles, that we further characterized using immunoblotting. When compared to exosomal preparations isolated by ultracentrifugation only, SEC fractionated exosomal preparations showed higher levels of the exosome-positive marker CD81. Moreover, while the exosome-negative marker calnexin was undetectable in SEC fractionated exosomal preparations, we did observe calnexin detection in the exosomal preparations isolated by ultracentrifugation alone, which implies contamination in these preparations. Lastly, we imaged SEC fractionated exosomal preparations using transmission electron microscopy to confirm these preparations contained human urinary exosomes. Our results indicate that combining ultracentrifugation and SEC column-purification exosome isolation strategies is a powerful approach for collecting contaminant-free human urinary exosomes and should be considered when exosomes devoid of contamination are needed for downstream applications.

Utility of Doppler sonography for renal artery stenosis screening in obese children with hypertension.

Pediatric hypertension guidelines recommend Doppler renal ultrasonography as a screening study for the evaluation of possible renal artery stenosis (RAS) in normal-weight children ≥ 8 years of age who are suspected of having RAS and who will cooperate with the procedure. Obese children are excluded because of technical and vascular concerns. There are no data on RI in obese children. This is a retrospective review of children aged 1.5-18 who received Doppler imaging studies over a 10-year period. A total of 174 patients were studied. There was no significant difference between the RI values based on BMI. Of the 174 individuals in the study 22 obtained follow-up CT/MRA after abnormal Doppler ultrasounds. On advanced imaging 3 were confirmed to have RAS. Obesity does not seem to influence RI.RI alone should not be used as a screening tool for RAS. An approach toward diagnosis is suggested based on BMI, renin levels, and ultrasound.

Pseudohyperkalemia in a Patient with T-Cell Acute Lymphoblastic Leukemia and Hyperleukocytosis.

A 7-year-old girl presented with lymphadenopathy and bruising suggestive of leukemia. Complete blood count was significant for white blood cell count of 479,000/mm 3 . Basic metabolic panel sent via pneumatic tube system was significant for potassium > 10 mEq/L. The stat venous blood gas potassium level was 4.6 mEq/L. A 12-lead-ECG showed sinus tachycardia without peaked T-waves. It was determined that this was pseudohyperkalemia associated with significant hyperleukocytosis. This brief report discusses rare causes of pseudohyperkalemia that can be overlooked, and details the postulated mechanisms for pseudohyperkalemia in the setting of hyperleukocytosis.

The Current State of the Diagnosis and Management of Acute Kidney Injury by Pediatric Critical Care Physicians.

OBJECTIVES: Increasingly prevalent in pediatric intensive care, acute kidney injury imparts significant short- and long-term consequences. Despite advances in acute kidney injury research, clinical outcomes are worsening. We surveyed pediatric critical care physicians to describe the current state of acute kidney injury diagnosis and management in critically ill children. DESIGN: Anonymous electronic questionnaire. PARTICIPANTS: Pediatric critical care physicians from academic centers, the Pediatric Acute Lung Injury and Sepsis Investigators network, and/or the pediatric branch of Society of Critical Care Medicine. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 201 surveys initiated, 170 surveys were more than 50% completed and included in our results. The majority of physicians (74%) diagnosed acute kidney injury using serum creatinine and urine output. Acute kidney injury guidelines or criteria were used routinely by 54% of physicians; Risk, Injury, Failure, Loss, and End stage criteria were the most commonly used. Awareness of any acute kidney injury guideline or definition was associated with five-fold higher odds of using any guideline (odds ratio, 5.22; 95% CI, 1.84-14.83) and four-fold higher odds of being dissatisfied with available acute kidney injury biomarkers (odds ratio, 4.88; 95% CI, 1.58-15.05). Less than half of respondents recognized the limitations of serum creatinine. Physicians unaware of the limitations of serum creatinine had two-fold higher odds of being unaware of newer biomarker availability (odds ratio, 2.34; 95% CI, 1.14-4.79). Novel biomarkers were available to 37.6% of physicians for routine use. Physicians with access to novel biomarkers more often practiced in larger (odds ratio, 3.09; 95% CI, 1.18-8.12) and Midwestern (odds ratio, 3.38; 95% CI, 1.47-7.78) institutions. More physicians with access to a novel biomarker reported satisfaction with current acute kidney injury diagnostics (66%) than physicians without access (48%); this finding approached significance (p = 0.07). CONCLUSIONS: Half of PICU attending physicians surveyed are not using recent acute kidney injury guidelines or diagnostic criteria in their practice. There is a positive association between awareness and clinical use of acute kidney injury guidelines. Serum creatinine and urine output are still the primary diagnostics; novel biomarkers are frequently unavailable.

Renal proximal tubule Na,K-ATPase is controlled by CREB-regulated transcriptional coactivators as well as salt-inducible kinase 1.

Sodium reabsorption by the kidney is regulated by locally produced natriuretic and anti-natriuretic factors, including dopamine and norepinephrine, respectively. Previous studies indicated that signaling events initiated by these natriuretic and anti-natriuretic factors achieve their effects by altering the phosphorylation of Na,K-ATPase in the renal proximal tubule, and that protein kinase A (PKA) and calcium-mediated signaling pathways are involved. The same signaling pathways also control the transcription of the Na,K-ATPase ß subunit gene atp1b1 in renal proximal tubule cells. In this report, evidence is presented that (1) both the recently discovered cAMP-regulated transcriptional coactivators (CRTCs) and salt-inducible kinase 1 (SIK1) contribute to the transcriptional regulation of atp1b1 in renal proximal tubule (RPT) cells and (2) renal effectors, including norepinephrine, dopamine, prostaglandins, and sodium, play a role. Exogenously expressed CRTCs stimulate atp1b1 transcription. Evidence for a role of endogenous CRTCs includes the loss of transcriptional regulation of atp1b1 by a dominant-negative CRTC, as well as by a CREB mutant, with an altered CRTC binding site. In a number of experimental systems, SIK phosphorylates CRTCs, which are then sequestered in the cytoplasm, preventing their nuclear effects. Consistent with such a role of SIK in primary RPT cells, atp1b1 transcription increased in the presence of a dominant-negative SIK1, and in addition, regulation by dopamine, norepinephrine, and monensin was disrupted by a dominant-negative SIK1. These latter observations can be explained if SIK1 is phosphorylated and inactivated in the presence of these renal effectors. Our results support the hypothesis that Na,K-ATPase in the renal proximal tubule is regulated at the transcriptional level via SIK1 and CRTCs by renal effectors, in addition to the previously reported control of the phosphorylation of Na,K-ATPase.

Refractory hypotension after bilateral nephrectomies in a Denys-Drash patient with phenylketonuria.

BACKGROUND: Denys-Drash (DDS) syndrome is a rare genetic syndrome resulting from a mutation in the Wilms' tumor suppressor gene 1 (WT1), which presents with early onset nephrotic syndrome progressing rapidly to end-stage kidney disease (ESKD), pseudohermaphroditism, and high rates of Wilms' tumor. CASE-DIAGNOSIS/TREATMENT: We present the case of an infant born with DDS and phenylketonuria with neonatal ESKD and dependence on peritoneal dialysis (PD). This patient developed refractory hypotension after elective bilateral nephrectomies at 10 months of age. Despite outpatient management with sodium supplements and changes in PD fluid removal, the patient was hospitalized for refractory post-prandial hypotension with concurrent lactic acidosis. Blood pressure control and feeding tolerance was achieved using intermittent doses of midodrine, an oral alpha-adrenergic agonist. CONCLUSIONS: We discuss this case to offer a therapeutic option for the rare occurrence of persistent post-nephrectomy hypotension.

Evaluation of robotic minimally invasive surgical skills using motion studies.

Robotic Minimally Invasive Surgery, and the engendered computer-integration, offers unique opportunities for quantitative computer-based surgical-performance evaluation. In this work, we examine extension of traditional manipulative skill assessment, having deep roots in performance evaluation in manufacturing industries, for applicability to robotic surgical skill evaluation. This method relies on: defining task-level segmentation of modular sub-tasks/micro-motions called 'Therbligs' that can be combined to perform a given task; and analyzing intra- and inter-user performance variance by studying surgeons' performance over each 'Therbligs'. Any of the performance metrics of macro-motions-from motion-economy, tool motion measurements to handed-symmetry-can now be extended over the micro-motion temporal segments. Evaluation studies were based on video recordings of surgical tasks in two settings: first, we examined performance of two representative manipulation exercises (peg board and pick-and-place) on a da Vinci surgical SKILLS simulator. This affords a relatively-controlled and standardized test-scenarios for surgeons with varied experience-levels. Second, task-sequences from real surgical videos were analyzed with a list of predefined 'Therbligs' in order to investigate its overall usefulness.