Representation of Older Adults in the ACC/AHA/SCAI Guideline for Coronary Artery Revascularization.

This cross-sectional study assesses the generalizability of the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions (ACC/AHA/SCAI) guideline by examining the representation of older adults in studies cited in the guideline.

Comparative genetic, biochemical, and biophysical analyses of the four E. coli ABCF paralogs support distinct functions related to mRNA translation.

Multiple paralogous ABCF ATPases are encoded in most genomes, but the physiological functions remain unknown for most of them. We herein compare the four Escherichia coli K12 ABCFs - EttA, Uup, YbiT, and YheS - using assays previously employed to demonstrate EttA gates the first step of polypeptide elongation on the ribosome dependent on ATP/ADP ratio. A Δ uup knockout, like Δ ettA , exhibits strongly reduced fitness when growth is restarted from long-term stationary phase, but neither Δ ybiT nor Δ yheS exhibits this phenotype. All four proteins nonetheless functionally interact with ribosomes based on in vitro translation and single-molecule fluorescence resonance energy transfer experiments employing variants harboring glutamate-to-glutamine active-site mutations (EQ 2 ) that trap them in the ATP-bound conformation. These variants all strongly stabilize the same global conformational state of a ribosomal elongation complex harboring deacylated tRNA Val in the P site. However, EQ 2 -Uup uniquely exchanges on/off the ribosome on a second timescale, while EQ 2 -YheS-bound ribosomes uniquely sample alternative global conformations. At sub-micromolar concentrations, EQ 2 -EttA and EQ 2 -YbiT fully inhibit in vitro translation of an mRNA encoding luciferase, while EQ 2 -Uup and EQ 2 -YheS only partially inhibit it at ~10-fold higher concentrations. Moreover, tripeptide synthesis reactions are not inhibited by EQ 2 -Uup or EQ 2 -YheS, while EQ 2 -YbiT inhibits synthesis of both peptide bonds and EQ 2 -EttA specifically traps ribosomes after synthesis of the first peptide bond. These results support the four E. coli ABCF paralogs all having different activities on translating ribosomes, and they suggest that there remains a substantial amount of functionally uncharacterized "dark matter" involved in mRNA translation.

Characteristics, Management, and Outcomes of Patients With Osteosarcoma: An Analysis of Outcomes From the National Cancer Database.

INTRODUCTION: Previous studies about osteosarcoma patient characteristics, management, and outcomes have limited patient numbers, combine varied tumor types, and/or are older studies. METHODS: Patients with osteosarcoma from the 2004 to 2015 National Cancer Database data sets were separated into axial, appendicular, and other. Demographic and treatment data as well as 1-, 5-, and 10-year survival were determined for each group. A multivariate Cox analysis of patient variables with the likelihood of death was performed, and the Kaplan Meier survival curves were generated. RESULTS: Four thousand four hundred thirty patients with osteosarcoma (3,435 appendicular, 810 axial, and 185 other) showed survival at 1-year, 5-year, and 10-year and was highest among the appendicular cohort (91.17%, 64.43%, and 58.58%, respectively). No change in survival was seen over the periods studied. The likelihood of death was greater with increasing age category, distant metastases, and treatment with radiation alone but less with appendicular primary site, treatment with surgery alone, or surgery plus chemotherapy. DISCUSSION: Despite advances in tumor management, surgical excision remains the best predictor of survival for osteosarcomas. No difference was observed in patient survival from 2004 to 2015 and, as would be expected, distant metastases were a poor prognostic sign, as was increasing age, male sex, and axial location.

Population characteristics, outcomes, and centerwide insights of the Zimbabwe national experience with the SIGN intramedullary nail (2013-2020).

PURPOSE: SIGN Fracture international is a non-profit organization that provides intramedullary nails to SIGN centres at no cost for intra-operative fracture fixation in exchange for cases being uploaded to the SIGN Online Surgical Database (SOSD). The SIGN program was introduced in Zimbabwe in 2013 and had expanded to nine hospitals at the end of 2020. This study aimed to evaluate the population characteristics and clinical outcomes of patients who received the SIGN nail in Zimbabwe as well as intranational trends across SIGN centres. METHODS: We conducted a retrospective review of the SOSD for all cases carried out in Zimbabwe between 2013 and 2020. RESULTS: A total of 1764 patients received operative fixation over the period. The majority were young (36.83 ± 15.13) years and male (74%). The average time to surgery was 22 ± 20.5 days with over 69% of patients getting surgery after more than ten days. Femur fracture fixation (72%) was the most common procedure with road traffic accidents (RTAs) being the most common cause of fractures (73%). The majority of patients had no follow-up (61%). Of patients with follow-up, 4% reported infection, 2% deformity, and 78% with healing X-rays. There were large differences in volume of patients at different centres with no significant trends in outcomes. CONCLUSION: The SIGN program allows for safe surgery in Zimbabwe. There are large intranational differences of no particular trend across SIGN centres which may be improved through more intranational knowledge sharing. Improved follow-up would allow for more insights to be gleaned from the database.

A rare case of lupoid leishmaniasis defying diagnosis for a decade.

Cutaneous leishmaniasis (CL) is a common disease affecting millions in endemic areas worldwide. We present a case of lupoid leishmaniasis, a rare variant of CL, which clinically mimicked sarcoidosis and/or granulomatous rosacea for 10 years until ultimate diagnosis. An 82-year-old U.S. citizen with an extensive travel history presented with a 10-year history of facial plaques on the cheeks and was previously diagnosed and treated as sarcoidosis. Multiple biopsies (previously and at presentation) revealed tuberculoid granulomas with negative special stains for microorganisms and negative sterile tissue cultures for acid-fast bacilli, bacteria, and fungal organisms. A diagnosis of granulomatous rosacea was rendered and multiple medical therapies were attempted, none with sustained improvement. Repeat biopsy of a new lesion revealed intracellular organisms consistent with leishmaniasis, which was confirmed by polymerase chain reaction (PCR). Lupoid leishmaniasis is a rare presentation of CL including facial plaques that can mimic granulomatous diseases affecting the face including sarcoidosis and granulomatous rosacea. CL can sometimes be challenging to diagnose through standard histopathologic examination; immunohistochemistry for CD1a can be used to augment tissue-based examination and PCR should be sent early in cases with sufficient concern.

Time Course and Size of Blood-Brain Barrier Opening in a Mouse Model of Blast-Induced Traumatic Brain Injury.

An increasing number of studies have reported blood-brain barrier (BBB) dysfunction after blast-induced traumatic brain injury (bTBI). Despite this evidence, there is limited quantitative understanding of the extent of BBB opening and the time course of damage after blast injury. In addition, many studies do not report kinematic parameters of head motion, making it difficult to separate contributions of primary and tertiary blast-loading. Detailed characterization of blast-induced BBB damage may hold important implications for serum constituents that may potentially cross the compromised barrier and contribute to neurotoxicity, neuroinflammation, and persistent neurologic deficits. Using an in vivo bTBI model, systemic administration of sodium fluorescein (NaFl; 376 Da), Evans blue (EB; 69 kDa when bound to serum albumin), and dextrans (3-500 kDa) was used to estimate the pore size of BBB opening and the time required for recovery. Exposure to blast with 272 ± 6 kPa peak overpressure, 0.69 ± 0.01 ms duration, and 65 ± 1 kPa*ms impulse resulted in significant acute extravasation of NaFl, 3 kDa dextran, and EB. However, there was no significant acute extravasation of 70 kDa or 500 kDa dextrans, and minimal to no extravasation of NaFl, dextrans, or EB 1 day after exposure. This study presents a detailed analysis of the time course and pore size of BBB opening after bTBI, supported by a characterization of kinematic parameters associated with blast-induced head motion.