The occurrence of hematuria during a right heart catheterization can be a sign of renal perforation, a rare but life-threatening complication that could be developed due to the misdirection of wire into the abdominopelvic venous plexus. We showed this complication could be managed with venoplasty of the common iliac vein.

A 53-year-old woman with a history of acute myeloid leukemia received a second allogenic hematopoietic stem cell transplant (HSCT) and was prescribed, among other medications, acyclovir and letermovir (480 mg daily oral dose) for prophylaxis of respectively herpes simplex and cytomegalovirus infection. The patient was admitted in the intensive care unit (ICU) for dyspnea and oliguria. Laboratory investigations revealed acute kidney injury, but also a severe and progressive lactic acidosis. Liver function tests were within normal range. The combination of lactic acidosis, hypoglycaemia and acylcarnitine profile in plasma suspected a mitochondrial toxicity. Letermovir therapy was interrupted and determination of plasma letermovir pharmacokinetics revealed a prolonged terminal half-life (40.7 h) that was not significantly influenced by continuous venovenous hemofiltration. Exploration for genetic polymorphisms revealed that the patient was SLCO1B1*5/*15 (c.521T>C homozygous carrier and c.388A>G heterozygous carrier) with a predicted non-functional OATP1B1 protein. The relationship between letermovir accumulation and development of lactic acidosis requires further observations.

Introduction Very preterm birth is associated with lung function impairment later in life, but several aspects have not been studied. We aimed to comprehensively assess lung function at school age in very preterm infants and term controls, with special emphasis on bronchopulmonary dysplasia (BPD), sex and bronchodilator response. Methods At 12 years of age, 136 children born very preterm (85 with and 51 without BPD), and 56 children born at term performed spirometry, body plethysmography, impulse oscillometry, measurement of diffusion capacity and multiple breath washout, before and after bronchodilator inhalation. Results Airway symptoms and a diagnosis of asthma were more common in children born very preterm. These children had more airflow limitation, seen as lower FEV 1 (p<0.001), FEV 1/FVC (p=0.011) and FEF 25-75 (p<0.001), and a higher total and peripheral airway resistance compared to term born controls. There was no difference in total lung capacity, but air trapping and lung clearance index were higher in children born very preterm. Diffusion capacity was lower in children born very preterm, especially in those with a diagnosis of BPD. In most other tests, the differences between preterm-born children with or without BPD were smaller than between children born preterm versus at term. Boys born preterm had more lung function deficits than preterm born girls. In children born very preterm, airway obstruction was to a large extent reversible. Conclusion At 12 years of age, children born very preterm had lower lung function than children born at term in most aspects. Airway obstruction improved markedly after bronchodilator inhalation, and there was only little difference between children with or without BPD.

Title: Symptomatic Hyperammonemia Secondary to Recombinant Erwinia AsparaginaseCatherine E. Martin, Pharm.D., Department of Pharmacy – Ambulatory Service, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USAMira A. Kohorst, M.D., Department of Pediatric and Adolescent Medicine, Division of Pediatric Hematology/Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USAAsmaa Ferdjallah, M.D., M.P.H, Department of Pediatric and Adolescent Medicine, Division of Pediatric Hematology/Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USAJessica L. Kalmes, APRN, C.N.P., M.S.N, Department of Pediatric and Adolescent Medicine, Division of Pediatric Hematology/Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USAHeather M. Johnson, APRN, C.N.P., M.S.N, Department of Pediatric and Adolescent Medicine, Division of Pediatric Hematology/Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USAPaul J. Galardy, M.D., Department of Pediatric and Adolescent Medicine, Division of Pediatric Hematology/Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USAShakila P. Khan, M.D., Department of Pediatric and Adolescent Medicine, Division of Pediatric Hematology/Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USAAlexis K. Kuhn, Pharm.D., Department of Pharmacy – Ambulatory Service, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USACorresponding author: Catherine E. Martin; address: 200 First Street SW, Rochester, MN 55905; phone: 507-284-2695; fax: 507-266-4912; email: [email protected] text word count: 967Number of tables, figures, and supporting information: NoneShort running title: Hyperammonemia after recombinant Erwinia asparaginaseKeywords: Asparaginase, hyperammonemia, pediatrics, Erwinia, leukemiaAbbreviations

Probing the structures of amyloid-beta (Aβ) peptides in the early steps of aggregation is extremely difficult experimentally and computationally. Yet, this knowledge is extremely important as small oligomers are the most toxic species. Experiments and simulations on Aβ42 monomer point to random coil conformations with either transient helical or β-strand content. Our current conformational description of small Aβ42 oligomers is funneled toward amorphous aggregates with some β-sheet content and rare excited states with well-ordered assemblies of β-sheets. In this study, we emphasize another view based on metastable α-helix bundle oligomers spanning the C-terminus residues which are predicted by the machine-learning AlphaFold2 method and supported indirectly by low-resolution experimental data on many amyloid polypeptides. This finding has consequences in designing drugs to reduce aggregation and toxicity.

Classical molecular dynamics simulations were used to study the separation of carbon dioxide from methane by three formulations of the deep eutectic solvent (DES) ethaline (choline chloride: ethylene glycol at 1:2, 1:4 and 1:8 molar ratios), in the bulk and confined inside carbon and titania slit pores of two different pore widths, 2 nm and 5 nm. The highest permselectivities (~20) are observed for 1:2 ethaline in a 5 nm carbon pore, followed by the 1:4 DES in a 5 nm graphite pore, 1:2 ethaline in a 2 nm carbon pore and the 1:8 bulk DES. Our results indicate that variations in the ratio of ethylene glycol, which in turn affect the interactions of all DES species with the gas molecules and the different pore walls, plus confinement effects resulting from varying the pore sizes, can affect the gas separation performance of these systems in complex ways.

Bird song is crucial for attracting mates and defending territories, but different types of song or different singing behaviours may be involved in acquiring or maintaining each resource. Furthermore, male songbirds may adjust when and where they sing throughout the breeding season, depending on their breeding stage. However, such relationships remain untested in several avian taxa. Here, we studied male Bermuda White-eyed Vireos (Vireo griseus bermudianus), a passerine with two distinct song types (discrete and rambling), to test the mate attraction, territory defence, and nesting stage hypotheses. We compare song rate and song perch height among different stages of the breeding season and during the non-breeding season. We show that male vireos produce both song types during the breeding and non-breeding seasons, suggesting dual roles in mate choice and territorial defence. Singing rate did not differ between the two seasons, but, within the breeding season, males without nesting duties had significantly higher song rates than males with nesting duties. Song rate was lowest during the nestling stage, which coincided with the highest rate of nest predation. Song perch height was higher during the breeding season versus non-breeding season, among males without nesting duties compared to males with nesting duties, and when males produced discrete versus rambling songs. Our findings suggest that male vireos increase their conspicuousness to prospecting females by increasing singing rate and song perch height, and that they sing during the breeding and non-breeding seasons to defend year-round territories. Collectively, our study supports the mate attraction and territory defence hypotheses of bird song and suggests that Bermuda White-eyed Vireos adjust their singing rate in response to nest predation risk.

Background and Purpose: Cardiovascular disease (CVD) affects up to half of the patients with chronic obstructive pulmonary disease (COPD), which exerts deleterious impact on health outcomes and survivability. Vascular endothelial dysfunction marks the onset of cardiovascular disease. The present study examined the effect of a potent NADPH Oxidase (NOX) inhibitor and free-radical scavenger, apocynin, on COPD-related CVD. Experimental Approach: Male BALB/c mice were exposed to either room air (Sham) or cigarette smoke (CS) generated from 9 cigarettes per day, 5 days a week for up to 24 weeks with or without apocynin treatment (5 mg·kg-1·day-1, intraperitoneal injection). Key Results: Eight-weeks of apocynin treatment reduced airway neutrophil infiltration (by 42%) and completely preserved endothelial function and endothelial nitric oxide synthase (eNOS) activity against the oxidative insults of CS exposure. These preservative effects were maintained up until the 24-week time point. 24-week of apocynin treatment exhibited marked benefits on airway inflammation (reduced infiltration of macrophage, neutrophil and lymphocyte) and lung function decline (hyperinflation), and prevented airway collagen deposition by CS exposure. Conclusion and Implications: Limiting NOX activity may slow COPD progression and lower CVD risk, particularly when signs of oxidative stress become evident.

Primary intramedullary spinal cord lymphoma (PISCL) is a rare cause of myelopathies. As PISCL is often underrecognized, delaying appropriate treatment, we sought to describe its presentation. We report two clinical cases of pediatric patients. The diagnosis of PISCL must be considered in a patient with symptoms of acute myelopathies.

Understanding the evolutionary consequences of anthropogenic change is imperative for estimating long-term species resilience. While contemporary genomic data can provide us with important insights into recent demographic histories, investigating past change using present genomic data alone has limitations. In comparison, temporal genomics studies, defined herein as those that incorporate time series genomic data, leverage museum collections and repeated field sampling to directly examine evolutionary change. As temporal genomics is applied to more systems, species, and questions, best practices can be helpful guides to make the most efficient use of limited resources. Here, we conduct a systematic literature review to synthesize the effects of temporal genomics methodology on our ability to detect evolutionary changes. We focus on studies investigating recent change within the past 200 years, highlighting evolutionary processes that have occurred during the past two centuries of accelerated anthropogenic pressure. We first identify the most frequently studied taxa, systems, questions, and drivers, before highlighting overlooked areas where further temporal genomic studies may be particularly enlightening. Then, we provide guidelines for future study and sample designs while identifying key considerations that may influence statistical and analytical power. Our aim is to provide recommendations to a broad array of researchers interested in using temporal genomics in their work.

Self-sufficient cytochromes P450 of the sub-family CYP116B have gained great attention in biotechnology due to their ability to catalyze challenging reactions towards a wide range of organic compounds without the need of a separate reductase partner. However, these P450s are often unstable in solution and their activity is limited to short reaction time. As the isolated heme domain of CYP116B5 has been shown to work as a peroxygenase with H2O2 without the need for expensive NAD(P)H, in this work protein engineering was used to generate a chimeric enzyme (CYP116B5-SOX), in which the native reductase domain is replaced by a monomeric sarcosine oxidase (MSOX) that is able to produce H2O2 with a controlled and continuous release in time. The full-length form enzyme (CYP116B5-fl) is expressed and characterized for the first time, allowing a detailed comparison to both the isolated heme domain (CYP116B5-hd) and CYP116B5-SOX. The catalytic activity of the three forms of the enzyme was studied using p-nitrophenol as substrate, and adding NADPH (CYP116B5-fl), H2O2 (CYP116B5-hd) and sarcosine (CYP116B5-SOX) as direct or indirect source of electrons. CYP116B5-SOX outperforms CYP116B5-fl by 10 folds and CYP116B5-hd by 3 folds, in terms of p-nitrocatechol produced per mg of enzyme per minute. CYP116B5-SOX represents an optimal model to exploit CYP116B5 and the same protein engineering approach could be used for P450s of the same class.

Formulas to calculate multivector exponentials in a basis-free representation and orthonormal basis are presented for an arbitrary Clifford geometric algebra , . The formulas are based on the analysis of roots of characteristic polynomial of a multivector. Elaborate examples how to use the formulas in practice are presented. The results are generalised to arbitrary functions of multivector and may be useful in the quantum circuits or in the problems of analysis of evolution of the entangled quantum states.

We present a rare case of anagrelide-induced pericardial effusion that is presented with tamponade physiology in a patient with essential thrombocythemia. After cautiously weighing the risks and benefits of further invasive interventions following an unsuccessful pericardiocentesis, the decision was to stop anagrelide while managing the pericardial effusion medically.

Miliary tuberculosis (MTB) is a rare, disseminated, and active form of tuberculosis caused by Mycobacterium tuberculosis bacilli. It is mostly seen in immune-compromised patients but is sometimes reported in immune-competent hosts. We reported a 40-year-old immune-competent patient who presented with pyrexia of unknown origin.

We are hopeful that CTFR modulation does have a positive impact of bone health, but we have concerns about this study design being used to support the hypothesis.

December 12, 2022To the Editors of the Journal of Cardiovascular Electrophysiology:Please find the editorial for manuscript ID JCE-22-0730.R2 attached.Thank you,Steven Zweibel MDTitle: What We Don’t Know Might Harm Our Patients: AF Detection Utilizing a Single Chamber ICDShort Title: Atrial Arrhythmia Detection in Single Chamber ICD PatientsSteven L. Zweibel MD, FACC, FHRS

RATIONALE Boron isotopes are a powerful tool for pH reconstruction in marine carbonates and as tracer for fluid-mineral interaction in geochemistry. Micro-analytical approaches based on laser ablation multi-collector inductively coupled plasma mass spectrometry (LA-MC-ICP-MS) often suffer from effects induced by the sample matrix. In this study, we investigated matrix-independent analyses of B isotopic ratios and applied this technique to cold-water corals. METHODS We employed a customized 193 nm femtosecond laser ablation system (Solstice, Spectra-Physics) coupled to a MC-ICP-MS (Nu Plasma II, Nu Instruments) equipped with electron multipliers for in situ measurements of B isotope ratios (11B/10B) at the micron-scale. We analyzed various reference materials of silicate and carbonate matrices using non-matrix match calibration without employing any correction mode. This approach was then applied to investigates defined increments in coral samples from a Chilean fjord. RESULTS We obtained accurate B isotope ratios with a precision of ± 0.9‰ (2 SD) for various reference materials including silicate glasses (GOR132-G, StHs6/80-G, ATHO-G, and NIST SRM 612), clay (IAEA-B-8) and carbonate (JCp-1) using the silicate glass NIST SRM 610 as calibration standard, which shows that neither laser-induced nor ICP-related matrix effects are detectable. The application to cold-water corals (Desmophyllum dianthus) reveal little intra-skeleton variations in δ11B with average values between 23.27 and 26.09‰. CONCLUSIONS Our instrumental set-up provides accurate and precise B isotopic ratios independently of the sample matrix at the micron-scale. This approach opens a wide field of application in geochemistry, including pH reconstruction in biogenic carbonates and deciphering processes related to fluid-mineral interaction.

Rationale. Femtoamp and picoamp electrospray ionization characteristics of a non-polar solvent were explored. The direct ESI-MS analysis of chloroform extract solution enabled rapid analysis of perfluorinated sulfonic acid (PFS) analytes in drinking water. Methods. Neat chloroform solvent and extracts were directly used in a typical wire-in ESI setup using micrometer emitter tips. Ionization currents were measured with femtoamp sensitivity while ramping the spray voltage from 0 to -5000 V. Methanol was used to illustrate the characteristics of spraying chloroform. The effect of spray voltage and inlet temperature was studied. A liquid-liquid extraction workflow was developed to analyze PFOS in drinking water using an ion trap mass spectrometer. Results. The ionization onset of chloroform solution was 41 ± 17 fA at 300 V. The ionization current gradually increased with voltage while remaining below 100 pA when using voltage up to -5000 V. PFOS ion signal was significantly enhanced to improve the detection limit to 25 ppt in chloroform. Coupled with a liquid-liquid extraction workflow, detection limits of 0.38-5.1 ppt, and a quantitation range of 5-400 ppt were achieved for perfluorinated sulfonic compounds in 1 mL drinking water samples. Conclusions. Femtoamp and picoamp modes expand the solvent compatibility range of electrospray ionization and can enable quantitative analysis in ppt concentrations.