Global 3D rocket launch and re-entry air pollutant and CO2 emissions at the onset of the megaconstellation era.

Satellite megaconstellation (SMC) missions are spurring rapid growth in rocket launches and anthropogenic re-entries. These events inject pollutants and carbon dioxide (CO2) in all atmospheric layers, affecting climate and stratospheric ozone. Quantification of these and other environmental impacts requires reliable inventories of emissions. We present a global, hourly, 3D, multi-year inventory of air pollutant emissions and CO2 from rocket launches and object re-entries spanning the inception and growth of SMCs (2020-2022). We use multiple reliable sources to compile information needed to build the inventory and conduct rigorous and innovative cross-checks and validations against launch livestreams and past studies. Our inventory accounts for rocket plume afterburning effects, applies object-specific ablation profiles to re-entering objects, and quantifies unablated mass of objects returning to Earth. We also identify all launches and objects associated with SMC missions, accounting for 37-41% of emissions of black carbon particles, carbon monoxide, and CO2 by 2022. The data are provided in formats for ease-of-use in atmospheric chemistry and climate models to inform regulation and space sustainability policies.

Effect of automated identification of antimicrobial stewardship opportunities for suspected urinary tract infections.

Objective: We aimed to determine whether automated identification of antibiotic targeting suspected urinary tract infection (UTI) shortened the time to antimicrobial stewardship (AS) intervention. Design: Retrospective before-and-after study. Setting: Tertiary and quaternary care academic medical center. Patients: Emergency department (ED) or admitted adult patients meeting best practice alert (BPA) criteria during pre- and post-BPA periods. Methods: We developed a BPA to alert AS pharmacists of potential ASB triggered by the following criteria: ED or admitted status, antibiotic order with genitourinary indication, and a preceding urinalysis with ≤ 10 WBC/hpf. We evaluated the median time from antibiotic order to AS intervention and overall percent of UTI-related interventions among patients in pre-BPA (01/2020-12/2020) and post-BPA (04/15/2021-04/30/2022) periods. Results: 774 antibiotic orders met inclusion criteria: 355 in the pre- and 419 in the post-BPA group. 43 (35 UTI-related) pre-BPA and 117 (94 UTI-related) post-BPA interventions were documented. The median time to intervention was 28 hours (IQR 18-65) in the pre-BPA group compared to 16 hours (IQR 2-34) in the post-BPA group (P < 0.01). Despite absent pyuria, there were six cases with gram-negative bacteremia presumably from a urinary source. Conclusions: Automated identification of antibiotics targeting UTI without pyuria on urinalysis reduced the time to stewardship intervention and increased the rate of UTI-specific interventions. Clinical decision support aided in the efficiency of AS review and syndrome-targeted impact, but cases still required AS clinical review.

Cerebral venous pressures, sinus trans-stenosis gradients, and intracranial pressures are dramatically augmented by head position.

BACKGROUND: Cerebral venous pressures, sinus trans-stenosis gradients, and intracranial pressures are thought to be influenced by head position. OBJECTIVE: To investigate the intracranial manifestations of these changes in patients with cerebral venous outflow disorders (CVD). METHODS: A retrospective chart review was conducted on 22 consecutive adult patients who underwent diagnostic cerebral venography with rotational internal jugular vein (IJV) venography and superior sagittal sinus (SSS) pressure measurements in multiple head positions. Data on venous sinus pressures, IJV pressures, and lumbar puncture (LP) opening pressures (OP) were collected and analyzed. RESULTS: The study found that 21 (96%) patients experienced increases in SSS pressures with head rotation, with a mean increase of 25.4%. Intracranial trans-stenosis gradients showed significant variability with head position. Additionally, LP OP measurements increased by an average of 44.3% with head rotation. Dynamic IJV stenosis was observed in all patients during rotational testing. CONCLUSION: Head position significantly affects cerebral venous pressures, trans-stenosis gradients, and intracranial pressures in patients with CVD or intracranial hypertension. These findings highlight the need for dynamic venography in the diagnostic evaluation of these conditions to better understand their pathophysiology and improve treatment strategies.

Extended shortwave infrared absorbing antiaromatic fluorenium-indolizine chromophores.

Shortwave infrared (SWIR, 1000-1700 nm) and extended SWIR (ESWIR, 1700-2700 nm) absorbing materials are valuable for applications including fluorescence based biological imaging, photodetectors, and light emitting diodes. Currently, ESWIR absorbing materials are largely dominated by inorganic semiconductors which are often costly both in raw materials and manufacturing processes used to produce them. The development of ESWIR absorbing organic molecules is thus of interest due to the tunability, solution processability, and low cost of organic materials compared to their inorganic counterparts. Herein, through the combination of heterocyclic indolizine donors and an antiaromatic fluorene core, a series of organic chromophores with absorption maxima ranging from 1470-2088 nm (0.84-0.59 eV) and absorption onsets ranging from 1693-2596 nm (0.73-0.48 eV) are designed and synthesized. The photophysical and electrochemical properties of these chromophores, referred to as FluIndz herein, are described via absorption spectroscopy in 17 solvents, cyclic voltammetry, solution photostability, and transient absorption spectroscopy. Molecular orbital energies, predicted electronic transitions, and antiaromaticity are compared to higher energy absorbing chromophores using density functional theory. The presence of thermally accessible diradical states is demonstrated using density functional theory and EPR spectroscopy, while XRD crystallography confirms structural connectivity and existence as a single molecule. Overall, the FluIndz chromophore scaffold exhibits a rational means to access organic chromophores with extremely narrow optical gaps.

Salmonella re-engineers the intestinal environment to break colonization resistance in the presence of a compositionally intact microbiota.

The gut microbiota prevents harmful microbes from entering the body, a function known as colonization resistance. The enteric pathogen Salmonella enterica serovar (S.) Typhimurium uses its virulence factors to break colonization resistance through unknown mechanisms. Using metabolite profiling and genetic analysis, we show that the initial rise in luminal pathogen abundance was powered by a combination of aerobic respiration and mixed acid fermentation of simple sugars, such as glucose, which resulted in their depletion from the metabolome. The initial rise in the abundance of the pathogen in the feces coincided with a reduction in the cecal concentrations of acetate and butyrate and an increase in epithelial oxygenation. Notably, these changes in the host environment preceded changes in the microbiota composition. We conclude that changes in the host environment can weaken colonization resistance even in the absence of overt compositional changes in the gut microbiota.

Idiopathic intracranial hypertension pathogenesis: The jugular hypothesis.

In spite of expanding research, idiopathic intracranial hypertension (IIH) and its spectrum conditions remain challenging to treat. The failure to develop effective treatment strategies is largely due to poor agreement on a coherent disease pathogenesis model. Herein we provide a hypothesis of a unifying model centered around the internal jugular veins (IJV) to explain the development of IIH, which contends the following: (1) the IJV are prone to both physiological and pathological compression throughout their course, including compression near C1 and the styloid process, dynamic muscular/carotid compression from C3 to C6, and lymphatic compression; (2) severe dynamic IJV stenosis with developments of large cervical gradients is common in IIH-spectrum patients and significantly impacts intracranial venous and cerebrospinal fluid (CSF) pressures; (3) pre-existing IJV stenosis may be exacerbated by infectious/inflammatory etiologies that induce retromandibular cervical lymphatic hypertrophy; (4) extra-jugular venous collaterals dilate with chronic use but are insufficient resulting in impaired aggregate cerebral venous outflow; (5) poor IJV outflow initiates, or in conjunction with other factors, contributes to intracranial venous hypertension and congestion leading to higher CSF pressures and intracranial pressure (ICP); (6) glymphatic congestion occurs but is insufficient to compensate and this pathway becomes overwhelmed; and (7) elevated intracranial CSF pressures triggers extramural venous sinus stenosis in susceptible individuals that amplifies ICP elevation producing severe clinical manifestations. Future studies must focus on establishing norms for dynamic cerebral venous outflow and IJV physiology in the absence of disease so that we may better understand and define the diseased state.

Accuracy of self-reported treated hypertension in the women's health initiative: Comparisons with medication inventories.

Few studies have reported on the accuracy of self-reported hypertension history among older postmenopausal women, which was this study's objective. Participants were postmenopausal women enrolled in the Osteoporosis and Periodontal Disease (OsteoPerio) study, an ancillary investigation of the Women's Health Initiative Observational Study (WHI-OS) at the Buffalo, New York, clinical site. Participants self-reported their history of physician diagnosed hypertension treated with medication at WHI-OS enrollment (1993-1998; n = 1342, mean age 63 years), then 3 years later at OsteoPerio enrollment (1997-2001; n = 1342), and again at OsteoPerio Year 5 follow-up (2002-2005; n = 1020). At each time point, medication inventories were recorded and served as the criterion with which self-report was compared in the present study. Physician diagnosed-treated hypertension was also self-reported annually on mailed health update questionnaires in the WHI-OS and were compared against medication inventory at the subsequent clinic exam. Of those participants who self-reported a history of hypertension at WHI enrollment, OsteoPerio enrollment, and OsteoPerio Year 5 follow-up, 41.2%, 90.3%, and 94.4%, respectively, had anti-hypertensive pills in their medication inventory. Across the three time points, sensitivity and specificity ranged from 0.72 to 0.98 and from 0.85 to 0.95, and kappa coefficients ranged from 0.52 to 0.79 when comparing self-report with medication inventory. For self-reported newly physician-diagnosed and treated hypertension on the annual health update questionnaire, 88.4% and 95.2% of those reporting hypertension had anti-hypertensive pills in the subsequent medication inventory. In general, sensitivity and kappa were lower in women aged ≥70 versus < 70 years and in those with history of cardiovascular disease and diabetes compared to those without these comorbidities. In this cohort of postmenopausal women, self-reported physician diagnosed and treated hypertension demonstrated moderate to high accuracy when compared against anti-hypertensive medication use documented by pill inventory, particularly for those who were younger and managing fewer comorbidities.

BASELINE SUSCEPTABILITY AND FIRST OBSERVATION OF KNOCKDOWN RESISTANCE IN AEDES TAENIORHYNCHUS POPULATION OF ST. JOHNS COUNTY, FLORIDA.

The black saltmarsh mosquito, Aedes taeniorhynchus, is a prominent nuisance mosquito within St. Johns County, Florida. Due to their characteristically large outbreaks, and the elevated amount of insecticide application correlated with the outbreaks, local populations of Ae. taeniorhynchus are at an increased risk of developing insecticide resistance. This study was established to form a baseline susceptibility of Ae. taeniorhynchus against two technical grade materials, permethrin, and chlorpyrifos. Centers for Disease Control and Prevention bottle bioassays were conducted with technical-grade materials during two outbreaks in the fall of 2023. Results indicated a baseline susceptibility against the materials tested, but most notably, the phenotypic expression of knockdown resistance (kdr) was observed. Results highlight the need for continued monitoring and investigation into the resistance status and resistance level of this common Florida species.

Mitoregulin self-associates to form likely homo-oligomeric pore-like structures.

We and others previously found that a misannotated long noncoding RNA encodes for a conserved mitochondrial transmembrane microprotein named Mitoregulin (Mtln). Beyond an established role for Mtln in lipid metabolism, Mtln has also been shown to more broadly influence mitochondria, boosting respiratory efficiency and Ca 2+ retention capacity, while lowering ROS, yet the underlying mechanisms remain unresolved. Prior studies have identified possible Mtln protein interaction partners; however, a lack of consensus persists, and no claims have been made about Mtln's structure. We previously noted two key published observations that seemingly remained overlooked: 1) endogenous Mtln co-immunoprecipitates with epitope-tagged Mtln at high efficiency, and 2) Mtln primarily exists in a ∼66 kDa complex. To investigate if Mtln may self-oligomerize into higher-order complexes, we performed co-immunoprecipitation, protein modeling simulations, and native gel assessments of Mtln-containing complexes in cells and tissues, as well as tested whether synthetic Mtln protein itself forms oligomeric complexes. Our combined results provide strong support that Mtln self-associates and likely forms a hexameric pore-like structure.

Epithelial hypoxia maintains colonization resistance against Candida albicans.

Antibiotic treatment promotes the outgrowth of intestinal Candida albicans, but the mechanisms driving this fungal bloom remain incompletely understood. We identify oxygen as a resource required for post-antibiotic C. albicans expansion. C. albicans depleted simple sugars in the ceca of gnotobiotic mice but required oxygen to grow on these resources in vitro, pointing to anaerobiosis as a potential factor limiting growth in the gut. Clostridia species limit oxygen availability in the large intestine by producing butyrate, which activates peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling to maintain epithelial hypoxia. Streptomycin treatment depleted Clostridia-derived butyrate to increase epithelial oxygenation, but the PPAR-γ agonist 5-aminosalicylic acid (5-ASA) functionally replaced Clostridia species to restore epithelial hypoxia and colonization resistance against C. albicans. Additionally, probiotic Escherichia coli required oxygen respiration to prevent a post-antibiotic bloom of C. albicans, further supporting the role of oxygen in colonization resistance. We conclude that limited access to oxygen maintains colonization resistance against C. albicans.

Separation-dependent near-field effects in Mie scattering spectra of two optically trapped aerosol droplets.

The backscattering of ultraviolet and visible light by a model organic (squalane) aerosol droplet (1.0

Long-term Musculoskeletal Consequences of Chemotherapy in Pediatric Mice.

Thanks to recent progress in cancer research, most children treated for cancer survive into adulthood. Nevertheless, the long-term consequences of anticancer agents are understudied, especially in the pediatric population. We and others have shown that routinely administered chemotherapeutics drive musculoskeletal alterations, which contribute to increased treatment-related toxicity and long-term morbidity. Yet, the nature and scope of these enduring musculoskeletal defects following anticancer treatments and whether they can potentially impact growth and quality of life in young individuals remain to be elucidated. Here, we aimed at investigating the persistent musculoskeletal consequences of chemotherapy in young (pediatric) mice. Four-week-old male mice were administered a combination of 5-FU, leucovorin, irinotecan (a.k.a., Folfiri) or the vehicle for up to 5 wk. At time of sacrifice, skeletal muscle, bones, and other tissues were collected, processed, and stored for further analyses. In another set of experiments, chemotherapy-treated mice were monitored for up to 4 wk after cessation of treatment. Overall, the growth rate was significantly slower in the chemotherapy-treated animals, resulting in diminished lean and fat mass, as well as significantly smaller skeletal muscles. Interestingly, 4 wk after cessation of the treatment, the animals exposed to chemotherapy showed persistent musculoskeletal defects, including muscle innervation deficits and abnormal mitochondrial homeostasis. Altogether, our data support that anticancer treatments may lead to long-lasting musculoskeletal complications in actively growing pediatric mice and support the need for further studies to determine the mechanisms responsible for these complications, so that new therapies to prevent or diminish chemotherapy-related toxicities can be identified.

"I know now that it's something that you can do something about": Deductive thematic analysis of experiences at an arts-based dementia risk reduction exhibit.

Dementia is one of the leading global health crises. Despite the devastating impacts of the illness, general population knowledge pertaining to risk reduction is still limited. Previous research on the impact of dementia risk reduction campaigns has largely focused on awareness rather than behaviour change. Our research introduced an arts-based exhibit to address dementia modifiability, aiming to enhance effectiveness by providing an immersive experience for altering adults' perceptions of risk reduction and lifestyle behaviours. Interviews were conducted with adults (n = 38 [13 male, 25 female]) who attended an interactive dementia awareness and risk reduction exhibit. Data was analysed using deductive thematic analysis within the Health Belief Model framework to determine key mechanisms of behaviour change. Four key themes encompassing exhibit significance and factors underlying behaviour change were identified. Participants recounted positive experiences, particularly being engaged by the artistic aspects of the exhibit, and recorded heightened engagement in behaviours supporting dementia risk reduction post-exhibit. Areas for improvement included the need for a take-home summary and variation in formats. Participants described prior encounters with dementia and their age as factors which influenced their engagement with dementia risk reduction behaviour, with younger participants reporting lesser engagement with risk reduction information. Our research found that arts-based educational initiatives have the potential to advance public understanding and promote behavioural changes for dementia risk reduction. Our study recommends enhancing the impact of future interventions by employing innovative formats and tailoring them to varied audiences, with a specific emphasis on engaging younger individuals.

Teams in Transition: Increasing Role of Advanced Practice Providers in Antimicrobial Use and Infectious Diseases Consultation.

Background: Advanced practice providers (APPs) have taken on increasing responsibilities as primary team members in acute care hospitals, but the impact of this practice shift on antimicrobial prescribing and infectious diseases (ID) consultation requests is unknown. Here we describe longitudinal trends in antimicrobial days of therapy (DOT) and ID consultation by attributed provider type in 3 hospitals. Methods: We performed a retrospective time series analysis of antimicrobial use and ID consultation from July 2015 to June 2022 at a major university hospital and 2 community hospitals. We evaluated antimicrobial DOT and ID consultation over time and assessed attribution to 3 groups of providers: attending physicians, trainees, and APPs. We used multinomial logistic regression to measure changes in percentage of DOT and ID consultation across the clinician groups over time using physicians as the referent. Results: Baseline distribution of antimicrobial DOT and ID consultation varied by practice setting, but all subgroups showed increases in the proportion attributable to APPs. Large increases were seen in the rate of ID consultation, increasing by >30% during the study period. At our university hospital, by study end >40% of new ID consults and restricted antimicrobial days were attributed to APPs. Conclusions: Hospitals had differing baseline patterns of DOT attributed to provider groups, but all experienced increases in DOT attributed to APPs. Similar increases were seen in changes to ID consultation. APPs have increasing involvement in antimicrobial use decisions in the inpatient setting and should be engaged in future antimicrobial stewardship initiatives.

Pioneering Patient-Specific Approaches for Precision Surgery Using Imaging and Virtual Reality.

Endovascular treatment of complex vascular anomalies shifts the risk of open surgical procedures to the benefit of minimally invasive endovascular procedural solutions. Complex open surgical procedures used to be the only option for the treatment of a myriad of conditions like pulmonary and aortic valve replacement as well as cerebral aneurysm repair. However, due to advancements in catheter-delivered devices and operator expertise, these procedures (along with many others) can now be performed through minimally invasive procedures delivered through a central or peripheral vein or artery. The decision to shift from an open procedure to an endovascular approach is based on multi-modal imaging, often including 3D Digital Imaging and Communications in Medicine (DICOM) imaging datasets. Utilizing these 3D images, our lab generates 3D models of the pathologic anatomy, thereby allowing the pre-procedural analysis necessary to pre-plan critical components of the catheterization lab procedure, namely, C-arm positioning, 3D measurement, and idealized road-map generation. This article describes how to take segmented 3D models of patient-specific pathology and predict generalized C-arm positions, how to measure critical two-dimensional (2D) measurements of 3D structures relevant to the 2D fluoroscopy projections, and how to generate 2D fluoroscopy roadmap analogs that can assist in proper C-arm positioning during catheterization lab procedures.

Fndc5 is translated from an upstream ATG start codon and cleaved to produce irisin myokine precursor protein in humans and mice.

Witmer et al. provide genomic and molecular evidence to demonstrate that Fndc5 (irisin myokine precursor protein) is translated in humans from an overlooked upstream ATG codon.

Experimentally manipulated anger activates implicit cognitions about social hierarchy.

A correlational pilot study (N = 143) and an integrative data analysis of two experiments (total N = 377) provide evidence linking anger to the psychology of social hierarchy. The experiments demonstrate that the experience of anger increases the psychological accessibility of implicit cognitions related to social hierarchy: compared to participants in a control condition, participants in an anger-priming condition completed word stems with significantly more hierarchy-related words. We found little support for sex differences in the effect of anger on implicit hierarchy-related cognition; effects were equivalent across male and female participants. Findings fit with functionalist evolutionary views of anger suggesting that anger may motivate the use of dominance to strive for high social rank in group hierarchies. Implications for downstream behaviour, including aggression and negotiation, are discussed.

A Baker's Dozen of Top Antimicrobial Stewardship Intervention Publications in 2022.

Keeping abreast of the antimicrobial stewardship-related articles published each year is challenging. The Southeastern Research Group Endeavor identified antimicrobial stewardship-related, peer-reviewed literature that detailed an actionable intervention during 2022. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight actionable interventions used by antimicrobial stewardship programs to capture potentially effective strategies for local implementation.