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. Methods This paper sought to analyze aggravating risk factors for various TBIs in the New York City borough of Staten Island. Data on eight predictive risk variables were collected at a level 1 trauma center from January 1, 2022, to December 31, 2022: MOI, seizure history, anticoagulant/antiplatelet therapy, alcoholism, age, biological sex, tested alcohol level, and body mass index (BMI). A multinomial logistic regression was estimated to generate risk ratios (RRs), and chi-squared tests were carried out to determine univariate associations. Results It was found that blood thinner use and sex were both significant predictors of various types of TBIs. Additionally, those not tested for alcohol, including pediatric patients, were less likely to suffer most forms of TBI, while BMI had a negligible relationship with any TBI class. The use of blood-thinning agents put patients at an increased risk of concussions (relative risk ratio [RRR]: 1.82; 95% confidence interval [CI]: 1.10-3.02) and undiagnosed intracranial injuries (RRR: 1.90; 95% CI: 1.08-3.34). Men were at higher risk of multiple cranial injuries than women (RRR: 3.62; 95% CI: 1.38-9.48), as well as physical traumas such as brain lacerations and hemorrhages (RRR: 2.81, 95% CI: 1.28-6.18). BMI was weakly correlated with undiagnosed cranial injuries (RRR: 1.04; 95% CI: 1.00-1.08) and slightly uncorrelated with physical traumas (RRR: 0.94; 95% CI: 0.88-1.00). Those not tested for alcohol were at far less risk of multiple TBIs (RRR: 0.08; 95% CI: 0.01-0.66), concussions (RRR: 0.27; 95% CI: 0.11-0.71), and physical brain traumas (RRR: 0.33; 95% CI: 0.13-0.84). No parameter exhibited any statistical significance with skull fractures. Conclusion Particular risk factors for TBIs include biological sex and blood thinner use. Injury prevention efforts should be based on the category of TBI, with a particular focus on blood thinner users becoming concussive post-trauma. Attention should also be paid to men who engage in risky behavior such as binge drinking and crime sustaining more than one brain trauma or isolated brain bleeds. Therefore, improved hospital outreach for fall precautions in nursing homes and targeted interventions for at-risk men are vital for future projects.

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. Then we proceeded to contact these patient's parents via telephone. We asked regarding residual symptoms and signs of concussive injury. Duration out from initial concussive injury ranged from 4 to 68 months. The parents of 66 boys and 34 girls were surveyed. The age of the patients at the time of mild TBI ranged from 1 to 14 years. The injury severity score ranged from 1 to 21. One being the most common Injury severity score. Thirty-three percent of patients had residual effects of concussion at the time of telephone survey. Fourteen percent had memory loss issues, 21% had anxiety/depression issues, 20% had learning disability issues, and 15% had sleep disturbance issues. Duration of time post concussive injury, mechanism, and age did not influence incidence of sequelae. Mild traumatic brain injury has significant long term sequelae. Better identifying characteristics are needed to characterize patients susceptible to long term residual effects of concussion.

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. Data was divided into 2 groups of patients with CSW and those without. The primary endpoint was incidence of adverse effects of CSW in regard to injury severity score (ISS), hospital length of stay (HLOS), ventilator days, ICU length of stay (ICU LOS) and survival to discharge. Data was analyzed using a one-way analysis of variance (ANOVA). RESULTS: A total of 310 consecutive patients with severe head injury (anatomic injury score 3 or greater) were evaluated over a 3-year period. A total of 125 of the 310 patients (40%) were diagnosed with cerebral salt wasting as defined by hyponatremia with appropriate urinary output and salt replacement. Patients with CSW had poorer outcomes in regard to ISS (21.8 vs 14.2, p<0.0001), HLOS (14.1 vs 3.5, p<0.0001), ventilator days (5.0 vs 0.45, p<0.0001), ICU LOS (8.5 vs 1.6, p<0.0001), and survival to discharge (88% vs 99%, p<0.0001). DISCUSSION: Common adverse effects of CSW were noted in this study. Patients with TBI have a predilection towards development of CSW and consequently have poorer outcomes including increased morbidity and mortality. Data is sparse on the duration of CSW and degree of hyponatremia over time. Larger, comparative studies need to be performed to investigate the hyponatremic patient population and the clinical outcomes of those who present with CSW.

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 C16 -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. The coupling of an aryl iodide and an amine is familiar from organometallic chemistry, but has little or no precedent in natural product biosynthesis. These metabolites suggest further that enediyne formation occurs early in the overall biosynthesis, and that even earlier events might convert the C16 -hexaene to a common C15 intermediate that partitions to enediyne and anthraquinone building blocks for the heterodimerization.

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. The existence of threshold differences between vertebral levels was also assessed. All patients underwent postoperative computed tomography (CT) to determine the accuracy of pedicle screw placement. A total of 172 percutaneous pedicle screws were placed in 52 patients. 94.1% of screws were placed at L4, L5 and S1 vertebral levels. No statistically significant differences existed in thresholds of the pedicle access needles, tapscrews and pedicle screws between vertebral levels. In four instances, the pedicle access needle stimulation had a threshold of 5 mA (no breaches were associated). In the rest of occasions, the pedicle access needles had stimulation thresholds above 5 mA. In all instances, tapscrew and pedicle screw thresholds were above 7 mA; the tapscrews and pedicle screws had significantly greater thresholds than the pedicle access needles. No statistically significant differences existed in thresholds between tapscrews and pedicle screws. Postoperative CT imaging revealed one lateral pedicle violation. Both breach rate and false negative rate were 0.5%. No false positive cases were observed. No patients experienced postoperative pedicle screw-related neurologic deficits. A threshold of 5 mA for the pedicle access needle stimulation seems to be safe. Greater than 7 mA should be used for the tapscrew and pedicle screw stimulation.

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. We sought to minimize the potentially deleterious effects of such lobar collapse by using a standardized pulmonary hygiene protocol. Methods We performed a retrospective comparison of lobar collapse incidence among three groups over 21 months: patients without severe TBI who were intubated and mechanically ventilated for greater than 24 hours (i.e. "NO TBI"); patients with severe TBI who were intubated and mechanically ventilated for greater than 24 hours who were not treated with a standardized pulmonary hygiene protocol (i.e. historical "CONTROL"); and patients with severe TBI who were intubated and mechanically ventilated for greater than 24 hours and who were treated with a standardized pulmonary hygiene protocol (i.e. "HYGIENE"). Our analysis excluded patients who had any significant neck injury as we had previously found that pulmonary complications are increased in this subpopulation. Results We reviewed the charts of 310 trauma patients (NO TBI = 104, CONTROL = 101, HYGIENE = 105) and analyzed demographics, injury severity and outcomes, including the incidence of pulmonary lobar collapse. Pulmonary hygiene protocol demonstrated a significant reduction in the incidence of lobar collapse among the HYGIENE group compared to CONTROL, approximating the incidence among patients with no TBI (11% vs 27% vs 10%, respectively, p = 0.0009). No significant difference was noted in ventilator days, intensive care unit length of stay, hospital length of stay, mortality, nor incidence of pneumonia.  Conclusion High-risk TBI patients have a predilection towards the development of pulmonary lobar collapse, which can be significantly reduced by the use of a standardized pulmonary hygiene protocol.

Characterization of an Anthracene Intermediate in Dynemicin Biosynthesis.

Despite the identification of a ß-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. We now present the first evidence for a mid-pathway intermediate in dynemicin A biosynthesis, an iodoanthracene bearing a fused thiolactone, which was shown to be incorporated selectively into the final product. This unusual precursor reflects just how little is understood about these biosynthetic pathways, yet constrains the mechanisms that can act to achieve the key heterodimerization to the anthraquinone-containing subclass of enediynes.

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. chersina. Sequencing produced a short list of putative PKS candidates, yet CRISPR-Cas9 mutants of each locus retained dynemicin production. Subsequently, deletion of two cytochromes P450 in the dynemicin cluster suggested that the dynemicin enediyne PKS, DynE8, may biosynthesize the anthraquinone. Together with 18O-labelling studies, we now present evidence that DynE8 produces the core scaffolds of both the enediyne and anthraquinone, and provide a working model to account for their formation from the programmed octaketide of the enediyne PKS.

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. Uncultured bacteria make up approximately 99% of all species in external environments, and are an untapped source of new antibiotics. We developed several methods to grow uncultured organisms by cultivation in situ or by using specific growth factors. Here we report a new antibiotic that we term teixobactin, discovered in a screen of uncultured bacteria. Teixobactin inhibits cell wall synthesis by binding to a highly conserved motif of lipid II (precursor of peptidoglycan) and lipid III (precursor of cell wall teichoic acid). We did not obtain any mutants of Staphylococcus aureus or Mycobacterium tuberculosis resistant to teixobactin. The properties of this compound suggest a path towards developing antibiotics that are likely to avoid development of resistance.

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. The modified formula for the sampling-noise NEdN works well when applied to the double-sided interferograms of both types of radiance spectra.