Human brains preserve in diverse environments for at least 12 000 years.

The brain is thought to be among the first human organs to decompose after death. The discovery of brains preserved in the archaeological record is therefore regarded as unusual. Although mechanisms such as dehydration, freezing, saponification, and tanning are known to allow for the preservation of the brain on short time scales in association with other soft tissues (≲4000 years), discoveries of older brains, especially in the absence of other soft tissues, are rare. Here, we collated an archive of more than 4400 human brains preserved in the archaeological record across approximately 12 000 years, more than 1300 of which constitute the only soft tissue preserved amongst otherwise skeletonized remains. We found that brains of this type persist on time scales exceeding those preserved by other means, which suggests an unknown mechanism may be responsible for preservation particular to the central nervous system. The untapped archive of preserved ancient brains represents an opportunity for bioarchaeological studies of human evolution, health and disease.

Impact of an Antibiotic Side-Chain-Based Cross-reactivity Chart Combined With Enhanced Allergy Assessment Processes for Surgical Prophylaxis Antimicrobials in Patients With ß-Lactam Allergies.

BACKGROUND: ß-Lactam antibiotics are first-line therapy for perioperative prophylaxis; however, patient-reported allergies often lead to increased prescribing of alternative antibiotics that may increase the incidence of surgical site infections. The R-group side chain of the ß-lactam ring is responsible for allergic cross-reactivity and experts recommend the use of ß-lactams that are structurally dissimilar. METHODS: An internally developed, antibiotic side-chain-based cross-reactivity chart was developed and implemented alongside enhanced allergy assessment processes. This single-center, quasi-experimental study analyzed antibiotic prescribing in all adult patients with a documented ß-lactam allergy undergoing an inpatient surgical procedure between quartile (Q) 1 (2012)-Q3 (2014) (historical group) and Q3 (2016)-Q3 (2018) (intervention group). Propensity-weighted scoring analyses compared categorical and continuous outcomes. Interrupted time-series analysis further analyzed key outcomes. RESULTS: A total of 1119 and 1089 patients were included in the historical and intervention cohorts, respectively. There was a significant difference in patients receiving a ß-lactam alternative antibiotic between cohorts (84.9% vs 15.1%; P < .001). There was a decrease in 30-day readmissions in the intervention cohort (7.9% vs 6.3%; P = .035); however, there was no difference in the incidence of SSIs in patients readmitted (14.8% vs 13%; P = .765). No significant differences were observed in allergic reactions (0.5% vs 0.3%; P = .323), surgical site infections, in-hospital and 30-day mortality, healthcare facility-onset Clostridiodes difficile infection, acute kidney injury, or hospital costs. CONCLUSIONS: Implementation of an antibiotic cross-reactivity chart combined with enhanced allergy assessment processes significantly improved the prescribing of ß-lactam antibiotics for surgical prophylaxis.

Through Their Eyes: Health Care Worker Compliance With Personal Protective Equipment During the COVID-19 Pandemic.

BACKGROUND: Personal protective equipment (PPE) plays a critical role in protecting health care workers (HCWs). During the coronavirus disease-2019 (COVID-19) pandemic, shortages of PPE supplies drastically changed the way PPE was obtained and used by HCWs. PURPOSE: The objective was to investigate the impact of the COVID-19 pandemic and patient isolation type on PPE compliance. METHODS: This investigation was a survey of HCWs at a level 1 trauma teaching hospital regarding PPE compliance patterns prior to and during the COVID-19 pandemic. RESULTS: HCWs reported an increase in PPE compliance during the COVID-19 pandemic. Nearly half (48.6%) of respondents reported that isolation type impacted the decision to wear PPE, of which most were likely to forgo PPE with contact precautions. CONCLUSIONS: HCWs identified multiple barriers to compliance. The underutilization of PPE with contact precautions suggests that the risk of exposure is interpreted as low, and this could be a future target of education.

Health Disparities in Autosomal Dominant Polycystic Kidney Disease (ADPKD) in the United States.

BACKGROUND AND OBJECTIVES: Autosomal dominant polycystic kidney disease (ADPKD) occurs at conception and is often diagnosed decades prior to kidney failure. Nephrology care and transplantation access should be independent of race and ethnicity. However, institutional racism and barriers to health care may affect patient outcomes in ADPKD. We sought to ascertain the effect of health disparities on outcomes in ADPKD by examining age at onset of kidney failure and access to preemptive transplantation and transplantation after dialysis initiation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Retrospective cohort analyses of adults with ADPKD in the United States Renal Data System from January 2000 to June 2018 were merged to US Census income data and evaluated by self-reported race and ethnicity. Age at kidney failure was analyzed in a linear model, and transplant rates before and after dialysis initiation were analyzed in logistic and proportional hazards models in Black and Hispanic patients with ADPKD compared with White patients with ADPKD. RESULTS: A total of 41,485 patients with ADPKD were followed for a median of 25 (interquartile range, 5-54) months. Mean age was 56±12 years; 46% were women, 13% were Black, and 10% were Hispanic. Mean ages at kidney failure were 55±13, 53±12, and 57±12 years for Black patients, Hispanic patients, and White patients, respectively. Odds ratios for preemptive transplant were 0.33 (95% confidence interval, 0.29 to 0.38) for Black patients and 0.50 (95% confidence interval, 0.44 to 0.56) for Hispanic patients compared with White patients. Transplant after dialysis initiation was 0.61 (95% confidence interval, 0.58 to 0.64) for Black patients and 0.78 (95% confidence interval, 0.74 to 0.83) for Hispanic patients. CONCLUSIONS: Black and Hispanic patients with ADPKD reach kidney failure earlier and are less likely to receive a kidney transplant preemptively and after initiating dialysis compared with White patients with ADPKD.

ADAM15 Is Functionally Associated with the Metastatic Progression of Human Bladder Cancer.

ADAM15 is a member of a family of catalytically active disintegrin membrane metalloproteinases that function as molecular signaling switches, shed membrane bound growth factors and/or cleave and inactivate cell adhesion molecules. Aberrant metalloproteinase function of ADAM15 may contribute to tumor progression through the release of growth factors or disruption of cell adhesion. In this study, we utilized human bladder cancer tissues and cell lines to evaluate the expression and function of ADAM15 in the progression of human bladder cancer. Examination of genome and transcriptome databases revealed that ADAM15 ranked in the top 5% of amplified genes and its mRNA was significantly overexpressed in invasive and metastatic bladder cancer compared to noninvasive disease. Immunostaining of a bladder tumor tissue array designed to evaluate disease progression revealed increased ADAM15 immunoreactivity associated with increasing cancer stage and exhibited significantly stronger staining in metastatic samples. About half of the invasive tumors and the majority of the metastatic cases exhibited high ADAM15 staining index, while all low grade and noninvasive cases exhibited negative or low staining. The knockdown of ADAM15 mRNA expression significantly inhibited bladder tumor cell migration and reduced the invasive capacity of bladder tumor cells through MatrigelTM and monolayers of vascular endothelium. The knockdown of ADAM15 in a human xenograft model of bladder cancer inhibited tumor growth by 45% compared to controls. Structural modeling of the catalytic domain led to the design of a novel ADAM15-specific sulfonamide inhibitor that demonstrated bioactivity and significantly reduced the viability of bladder cancer cells in vitro and in human bladder cancer xenografts. Taken together, the results revealed an undescribed role of ADAM15 in the invasion of human bladder cancer and suggested that the ADAM15 catalytic domain may represent a viable therapeutic target in patients with advanced disease.