Dynemicin A Derivatives as Potential Cancer Chemotherapeutics by Mutasynthesis.

The enediyne antitumor antibiotics have remarkable structures and exhibit potent DNA cleavage properties that have inspired continued interest as cancer therapeutics. Their complex structures and high reactivity, however, pose formidable challenges to their production and development in the clinic. We report here proof-of-concept studies using a mutasynthesis strategy to combine chemical synthesis of select modifications to a key iodoanthracene-γ-thiolactone intermediate in the biosynthesis of dynemicin A and all other known anthraquinone-fused enediynes (AFEs).

Multinomial Estimations of Predictive Risk Factors for Traumatic Brain Injuries.

Introduction Traumatic brain injuries (TBIs) affect millions of patients each year, with more than 220,000 hospitalizations in 2019 and 64,000 deaths in 2020 alone. TBIs span a plethora of injuries including cerebral contusions and lacerations, axonal injuries, optic pathway disruptions, and skull fractures. Previous research has established that characteristics such as sex, mechanism of injury (MOI), and blood-thinning agents have some causal connections to a variety of cranial traumas.

Pulmonary Hygiene Protocol Reduces Incidence of Lobar Collapse in Severe Traumatic Brain Injury.

Background Traumatic brain injury (TBI) is a common cause of death among injured patients. In addition to neurologic sequelae which may increase mortality risk, trauma patients suffering severe TBI (Glasgow Coma Score≤8) have a predilection for pulmonary complications. We have previously demonstrated that patients with severe TBI who were intubated and mechanically ventilated are at greater risk of radiographic pulmonary lobar collapse that necessitates advanced directional suctioning and/or bronchoscopy.

Delayed Sequelae Related to Mild Traumatic Brain Injury in Children.

Delayed sequelae from mild traumatic brain injury (Glasgow Coma Score at admission >13, TBI) has been documented in case reports however larger studies of these effects are sparse. We undertook a telephone based survey to assess the long term sequelae of TBI. We tracked 100 pediatric TBI patients via our trauma registry for demographic data including age, injury severity, and mechanism of injury.

Cerebral Salt Wasting in Traumatic Brain Injury Is Associated with Increased Morbidity and Mortality.

Introduction: In the setting of cerebral injury, cerebral salt wasting (CSW) is a potential cause of hyponatremia, which contributes to adverse effects and mortality.

Objective: The primary objective of this study was to evaluate the clinical outcomes of severe traumatic brain injury (TBI) patients complicated by CSW.

Methods: A retrospective data analysis was performed on data collected from patients with TBI with an abbreviated injury scale (AIS) greater than 3.

C-N-Coupled Metabolites Yield Insights into Dynemicin A Biosynthesis.

The biosynthesis of the three structural subclasses of enediyne antitumor antibiotics remains largely unknown beyond a common C -hexaene precursor. For the anthraquinone-fused subtype, however, an unexpected iodoanthracene γ-thiolactone was established to be a mid-pathway intermediate to dynemicin A. Having deleted a putative flavin-dependent oxidoreductase from the dynemicin biosynthetic gene cluster, we can now report four metabolites that incorporate the iodoanthracene and reveal the formation of the C-N bond linking the anthraquinone and enediyne halves emblematic of this structural subclass.

Application of different thresholds for instrumentation device testing in minimally invasive lumbosacral spine fixation.

The main aim of this study was evaluating the reliability of stimulus-evoked electromyography (using different thresholds for stimulation of the instrumentation devices) for minimally invasive pedicle screw placement in the lumbosacral spine. A threshold of 5 mA was applied for the pedicle access needle. 7 mA was applied for the tapscrew and pedicle screw stimulation.

Characterization of an Anthracene Intermediate in Dynemicin Biosynthesis.

Despite the identification of a β-hydroxyhexaene produced by the enediyne polyketide synthases (PKSs), the post-PKS biosynthetic steps to the individual members of this antitumor and antibiotic family remain largely unknown. The massive biosynthetic gene clusters (BGCs) that direct the formation of each product caution that many steps could be required. It was recently demonstrated that the enediyne PKS in the dynemicin A BGC from Micromonospora chersina gives rise to both the anthraquinone and enediyne halves of the molecule.

A dual role for a polyketide synthase in dynemicin enediyne and anthraquinone biosynthesis.

Dynemicin A is a member of a subfamily of enediyne antitumour antibiotics characterized by a 10-membered carbocycle fused to an anthraquinone, both of polyketide origin. Sequencing of the dynemicin biosynthetic gene cluster in Micromonospora chersina previously identified an enediyne polyketide synthase (PKS), but no anthraquinone PKS, suggesting gene(s) for biosynthesis of the latter were distant from the core dynemicin cluster. To identify these gene(s), we sequenced and analysed the genome of M.

A new antibiotic kills pathogens without detectable resistance.

Antibiotic resistance is spreading faster than the introduction of new compounds into clinical practice, causing a public health crisis. Most antibiotics were produced by screening soil microorganisms, but this limited resource of cultivable bacteria was overmined by the 1960s. Synthetic approaches to produce antibiotics have been unable to replace this platform.

Noise-equivalent change in radiance for misalignment noise in a double-sided interferogram.

Engineers designing optical alignment servo systems for Michelson interferometers and Fourier-transform infrared spectrometers need to predict the amount of noise expected from the small and randomly varying amounts of misalignment that occur as the servo attempts to maintain alignment while taking data. A formula is derived for the noise-equivalent change in radiance due to this effect and the formula's accuracy is demonstrated by comparison of its predictions to the errors found in simulated interferometer measurements contaminated by misalignment noise.

Noise-equivalent change in radiance for sampling noise in a double-sided interferogram.

The formula for the noise-equivalent change in radiance (NEdN) for sampling noise [Appl. Opt. 38, 139 (1999)] can work well when applied to the double-sided interferograms of radiance spectra dominated by isolated emission lines, but it does not work well when applied to broad, slowly varying radiance spectra such as a Planck blackbody curve.