Citations

Abstract There are limited resources for guidance on the transition from fellowship into a new faculty role in pediatric infectious diseases. This review aims to address this gap and provides a framework for a successful transition that is composed of four essential pillars—(1) stepping into your role, (2) finding your niche, (3) building your network, and (4) self-care—all of which are supported by strong mentorship/sponsorship and continual realignment with one’s personal mission statement. In addition to providing general principles and guidance, this review also outlines specific steps that a junior faculty member can take to expand their influence and build a successful, fulfilling career in pediatric infectious diseases.

Aging and many illnesses and injuries impair skeletal muscle mass and function, but the molecular mechanisms are not well understood. To better understand the mechanisms, we generated and studied transgenic mice with skeletal muscle–specific expression of growth arrest and DNA damage inducible α (GADD45A), a signaling protein whose expression in skeletal muscle rises during aging and a wide range of illnesses and injuries. We found that GADD45A induced several cellular changes that are characteristic of skeletal muscle atrophy, including a reduction in skeletal muscle mitochondria and oxidative capacity, selective atrophy of glycolytic muscle fibers, and paradoxical expression of oxidative myosin heavy chains despite mitochondrial loss. These cellular changes were at least partly mediated by MAP kinase kinase kinase 4, a protein kinase that is directly activated by GADD45A. By inducing these changes, GADD45A decreased the mass of muscles that are enriched in glycolytic fibers, and it impaired strength, specific force, and endurance exercise capacity. Furthermore, as predicted by data from mouse models, we found that GADD45A expression in skeletal muscle was associated with muscle weakness in humans. Collectively, these findings identify GADD45A as a mediator of mitochondrial loss, atrophy, and weakness in mouse skeletal muscle and a potential target for muscle weakness in humans.

Background Acute pericarditis (AP) is considered a cardiovascular complication in patients with COVID‐19. We aimed to ass‐ess the incidence, associated complications, and clinical impact of AP on hospitalized patients with COVID‐19. Methods and Results In this retrospective cohort study, International Classification of Diseases, Tenthth Revision, Clinical Modification ( ICD‐10 ) codes were used to identify patients with COVID‐19 with or without AP in the National Inpatient Sample 2020 database. We compared outcomes between AP and non‐AP groups before and after propensity‐score matching for patient and hospital demographics and relevant comorbidities. A total of 211 619 patients with a primary diagnosis of COVID‐19 were identified, including 983 (0.46%) patients who had a secondary diagnosis of AP. Before matching, patients with COVID‐19 with AP were younger (59.93±19.24 years old versus 64.29±16.82 years old) and more likely to have anemia (40.5% versus 19.9%), cancer (6.7% versus 3.6%), and chronic kidney disease (29.3% versus 19.6%) (all P <0.05). After matching, patients with COVID‐19 with AP (n=980), when compared with the matched non‐AP group (n=2936), had higher rates of mortality (21.3% versus 11.1%, P <0.001), cardiac arrest (5.0% versus 2.6%, P <0.001), cardiogenic shock (4.2% versus 0.5%, P <0.001), ventricular arrhythmia (4.7% versus 1.9%, P <0.001), acute kidney injury (38.3% versus 28.9%, P <0.001), acute congestive heart failure (14.3% versus 4.8%, P <0.001), and longer length of stay (7.00±10.00 days versus 5.00±7.00 days, P <0.001) and higher total charges ($75066.5±$130831.3 versus $44824.0±$63660.5, P <0.001). Conclusions In hospitalized patients with COVID‐19, AP is a rare but severe in‐hospital complication and is associated with worse in‐hospital outcomes.

Germline pathogenic variants in the DNA mismatch repair (MMR) genes (Lynch syndrome) predispose to colorectal (CRC) and endometrial (EC) cancer. Lynch syndrome specific tumor features were evaluated for their ability to support the ACMG/InSiGHT framework in classifying variants of uncertain clinical significance (VUS) in the MMR genes. Twenty-eight CRC or EC tumors from 25 VUS carriers (6xMLH1, 9xMSH2, 6xMSH6, 4xPMS2), underwent targeted tumor sequencing for the presence of microsatellite instability/MMR-deficiency (MSI-H/dMMR) status and identification of a somatic MMR mutation (second hit). Immunohistochemical testing for the presence of dMMR crypts/glands in normal tissue was also performed. The ACMG/InSiGHT framework reclassified 7/25 (28%) VUS to likely pathogenic (LP), three (12%) to benign/likely benign, and 15 (60%) VUS remained unchanged. For the seven re-classified LP variants comprising nine tumors, tumor sequencing confirmed MSI-H/dMMR (8/9, 88.9%) and a second hit (7/9, 77.8%). Of these LP reclassified variants where normal tissue was available, the presence of a dMMR crypt/gland was found in 2/4 (50%). Furthermore, a dMMR endometrial gland in a carrier of an MSH2 exon 1-6 duplication provides further support for an upgrade of this VUS to LP. Our study confirmed that identifying these Lynch syndrome features can improve MMR variant classification, enabling optimal clinical care.

Abstract Magee, MK, Fields, JB, Jagim, AR, and Jones, MT. Fat-free mass index in a large sample of National Collegiate Athletic Association men and women athletes from a variety of sports. J Strength Cond Res 38(2): 311–317, 2024—Fat-free mass index (FFMI) can be used to categorize fat-free mass (FFM) relative to height. Normative values have been established in a variety of sports, as has suggested lower and upper thresholds of FFMI. However, FFMI has not been reported in a large sample of athletes, representing both sexes and multiple sport types. The purpose of this study was to evaluate differences in FFMI and establish normative values across a large sample of collegiate sports. A total of 1,961 athletes (men: n = 596, 10 sports; women: n = 1,365, 8 sports) participated. Height and mass were measured using a stadiometer and calibrated digital scale, respectively. Fat-free mass was assessed with air displacement plethysmography and used to calculate FFMI. Kruskal-Wallis test and one-way analysis of variance evaluated differences in FFMI in women's and men's sports, respectively. When collapsed across sport type and stratified by sex, men had a higher FFMI (21.5 ± 1.9 kg·m −2 vs. 17.9 ± 1.8 kg·m −2 ; p < 0.001). Differences occurred in FFMI across sport. In women, basketball athletes had the highest FFMI (18.9 kg·m −2 ) and highest 99th percentile for FFMI, whereas rowers had the lowest (16.9 kg·m −2 ). In men, throwers had the highest FFMI (25.7 kg·m −2 ) and highest 99th percentile, whereas volleyball athletes had the lowest (19.9 kg·m −2 ). Differences in FFMI may be attributable to dietary habits and physiological demands of respective sports. These results can provide information relative to differences in FFMI values across sports. In addition, sport-specific normative values can be used as benchmarks and targets for training, nutrition, and goal setting.

BACKGROUND AND OBJECTIVES: The transorbital approach varies by the extent of bony removal and the target. Orbital rim-sparing transorbital approach with removal of only the orbit's posterior wall provides optimal cosmetic results, without the need for reconstruction. The size of this corridor, limited by the medial globe retraction, has not yet been defined and is difficult to determine in cadavers because of postmortem tissue desiccation. By using patient-specific models in virtual reality, precise areas and degrees of surgical freedom (AOF and DOF, respectively) provided by globe retraction were calculated. These measurements define a potential maximum safe AOF and DOF, as well as the globe retraction, needed to achieve a sufficient surgical corridor. METHODS: Using a virtual reality system, transorbital rim-preserving craniectomies were performed. The axial and sagittal DOF as well as AOF were calculated lateral to the globe, limited by the orbital rim and globe, with an anterior clinoid target. The DOFs and AOFs were calculated for each degree of medial globe retraction and analyzed using paired t tests. RESULTS: With only 5 mm of retraction, the AOF was 886 mm 2 , while at 10 mm, the AOF was 1546 mm 2 . This increase between 5 and 10 mm allowed for the largest increase in surgical working corridor ( P = .02). At 15 mm of retraction (previously studied point at which intraocular pressure raises), the AOF averaged 2189 mm 2 and axial DOF averaged 23.1°. Eighteen DOF (a previously studied point needed to achieve sufficient working space for 2 instruments) was achieved at 11 mm on average, generating 1675 mm 2 AOF. CONCLUSION: Globe retraction of 11 mm is needed to achieve sufficient DOF for 2 surgical instruments, and 15 mm of retraction is a conservative limit that provides comparable AOFs with similar cranial approaches.

Cardiovascular disease is often a disease of aging. Considerable advances in our understanding of the biological mechanisms of aging have been made; yet, cardiovascular disease remains the leading cause of death in the United States urging a continued search for novel risk factors to target for preventing and treating disease. Mental stress (MS) is emerging as an important risk factor, and while progress has been made in understanding the link between MS and cardiovascular disease, the precise mechanisms of a putative causal relationship require greater clarification. In the current review, we (1) summarize our current understanding of the pathological effects of MS on vascular health; (2) describe important aspects of the pathobiology of vascular aging including inflammation, oxidative stress, mitochondrial dysfunction as well as novel processes such as genomic instability, epigenetic alterations, and nutrient signal pathways; (3) highlight similarities in the downstream biologic effects of aging and MS on vascular health with an emphasis on cellular and molecular processes that could be used to develop novel prognostic markers and treatment strategies for cardiovascular disease; (4) discuss lifestyle and pharmacological methods that target indicators of aging whose role could be translated into approaches managing the effects of MS; and (5) outline important future steps that should be considered in this area of research including the need for prospective clinical trials and for creating greater collaboration between preclinical aging researchers and clinical investigators managing MS.