Administration of the American Board of Anesthesiology's virtual APPLIED Examination: successes, challenges, and lessons learned.

In response to the COVID-19 pandemic, the American Board of Anesthesiology transitioned from in-person to virtual administration of its APPLIED Examination, assessing more than 3000 candidates for certification purposes remotely in 2021. Four hundred examiners were involved in delivering and scoring Standardized Oral Examinations (SOEs) and Objective Structured Clinical Examinations (OSCEs). More than 80% of candidates started their exams on time and stayed connected throughout the exam without any problems. Only 74 (2.5%) SOE and 45 (1.5%) OSCE candidates required rescheduling due to technical difficulties. Of those who experienced "significant issues", concerns with OSCE technical stations (interpretation of monitors and interpretation of echocardiograms) were reported most frequently (6% of candidates). In contrast, 23% of examiners "sometimes" lost connectivity during their multiple exam sessions, on a continuum from minor inconvenience to inability to continue. 84% of SOE candidates and 89% of OSCE candidates described "smooth" interactions with examiners and standardized patients/standardized clinicians, respectively. However, only 71% of SOE candidates and 75% of OSCE candidates considered themselves to be able to demonstrate their knowledge and skills without obstacles. When compared with their in-person experiences, approximately 40% of SOE examiners considered virtual evaluation to be more difficult than in-person evaluation and believed the remote format negatively affected their development as an examiner. The virtual format was considered to be less secure by 56% and 40% of SOE and OSCE examiners, respectively. The retirement of exam materials used virtually due to concern for compromise had implications for subsequent exam development. The return to in-person exams in 2022 was prompted by multiple factors, especially concerns regarding standardization and security. The technology is not yet perfect, especially for testing in-person communication skills and displaying dynamic exam materials. Nevertheless, the American Board of Anesthesiology's experience demonstrated the feasibility of conducting large-scale, high-stakes oral and performance exams in a virtual format and highlighted the adaptability and dedication of candidates, examiners, and administering board staff.

Late Ordovician eurypterid preserves oldest euchelicerate musculature in pyrite.

Pyritization of soft tissues of invertebrates is rare in the fossil record. In New York State, it occurs in black shales of the Lorraine Group (Late Ordovician), the best-known example of which is Beecher's Trilobite Bed. Exceptional preservation at the quarry where this bed is exposed allowed detailed examination of trilobite and ostracod soft-tissue anatomy. Here, we present the first example of a eurypterid (sea scorpion) currently ascribed to Carcinosomatidae from this deposit that also preserves the first evidence for mesosomal musculature in eurypterids. This specimen demonstrates that eurypterid musculature can be preserved in pyrite and evidences the oldest example of euchelicerate muscles within the fossil record. Sulfur isotope data illustrate that pyrite rapidly replicated muscle tissue in the early burial environment, prior to the pyritization of biomineralized exoskeleton and cuticular trilobite limbs. This discovery therefore expands the limited fossil record of euchelicerate musculature, while extending the taphonomic scope for preservation of detailed internal structures, more broadly, within arthropods.

Comparative Uptake Patterns of Radioactive Iodine and [18F]-Fluorodeoxyglucose (FDG) in Metastatic Differentiated Thyroid Cancers.

Background: Metastatic differentiated thyroid cancer (DTC) represents a molecularly heterogeneous group of cancers with varying radioactive iodine (RAI) and [18F]-fluorodeoxyglucose (FDG) uptake patterns potentially correlated with the degree of de-differentiation through the so-called "flip-flop" phenomenon. However, it is unknown if RAI and FDG uptake patterns correlate with molecular status or metastatic site. Materials and Methods: A retrospective analysis of metastatic DTC patients (n = 46) with radioactive 131-iodine whole body scan (WBS) and FDG-PET imaging between 2008 and 2022 was performed. The inclusion criteria included accessible FDG-PET and WBS studies within 1 year of each other. Studies were interpreted by two blinded radiologists for iodine or FDG uptake in extrathyroidal sites including lungs, lymph nodes, and bone. Cases were stratified by BRAF V600E mutation status, histology, and a combination of tumor genotype and histology. The data were analyzed by McNemar's Chi-square test. Results: Lung metastasis FDG uptake was significantly more common than iodine uptake (WBS: 52%, FDG: 84%, p = 0.04), but no significant differences were found for lymph or bone metastases. Lung metastasis FDG uptake was significantly more prevalent in the papillary pattern sub-cohort (WBS: 37%, FDG: 89%, p = 0.02) than the follicular pattern sub-cohort (WBS: 75%, FDG: 75%, p = 1.00). Similarly, BRAF V600E+ tumors with lung metastases also demonstrated a preponderance of FDG uptake (WBS: 29%, FDG: 93%, p = 0.02) than BRAF V600E- tumors (WBS: 83%, FDG: 83%, p = 1.00) with lung metastases. Papillary histology featured higher FDG uptake in lung metastasis (WBS: 39%, FDG: 89%, p = 0.03) compared with follicular histology (WBS: 69%, FDG: 77%, p = 1.00). Patients with papillary pattern disease, BRAF V600E+ mutation, or papillary histology had reduced agreement between both modalities in uptake at all metastatic sites compared with those with follicular pattern disease, BRAF V600E- mutation, or follicular histology. Low agreement in lymph node uptake was observed in all patients irrespective of molecular status or histology. Conclusions: The pattern of FDG-PET and radioiodine uptake is dependent on molecular status and metastatic site, with those with papillary histology or BRAF V600E+ mutation featuring increased FDG uptake in distant metastasis. Further study with an expanded cohort may identify which patients may benefit from specific imaging modalities to recognize and surveil metastases.

Fluoroquinolone-resistant Campylobacter in backyard and commercial broiler production systems in the United States.

Objectives: Campylobacter spp. are one of the leading foodborne pathogens in the world, and chickens are a known reservoir. This is significant considering broiler chicken is the top consumed meat worldwide. In the USA, backyard poultry production is increasing, but little research has been done to investigate prevalence and antimicrobial resistance associated with Campylobacter in these environments. Methods: Our study encompasses a farm-to-genome approach to identify Campylobacter and investigate its antimicrobial resistance phenotypically and genotypically. We travelled to 10 backyard and 10 integrated commercial broiler farms to follow a flock throughout production. We sampled at days 10, 31 and 52 for backyard and 10, 24 and 38 for commercial farms. Bird faecal (n = 10) and various environmental samples (soil n = 5, litter/compost n = 5, and feeder and waterer swabs n = 6) were collected at each visit and processed for Campylobacter. Results: Our results show a higher prevalence of Campylobacter in samples from backyard farms (21.9%) compared to commercial (12.2%). Most of our isolates were identified as C. jejuni (70.8%) and the remainder as C. coli (29.2%). Antimicrobial susceptibility testing reveals phenotypic resistance to ciprofloxacin (40.2%), an important treatment drug for Campylobacter infection, and tetracycline (46.6%). A higher proportion of resistance was found in C. jejuni isolates and commercial farms. Whole-genome sequencing revealed resistance genes, such as tet(O) and gyrA_T86I point mutation, that may confer resistance. Conclusion: Overall, our research emphasizes the need for interventions to curb prevalence of resistant Campylobacter spp. on broiler production systems.

The Global Experience of Laryngeal Transplantation: Series of Eleven Patients in Three Continents.

BACKGROUND: The loss of laryngeal function affects breathing, swallowing, and voice, thus severely compromises quality of life. Laryngeal transplantation has long been suggested as a solution for selected highly affected patients with complete laryngeal function loss. OBJECTIVE: To obtain insights regarding the advantages, weaknesses, and limitations of this procedure and facilitate future advances, we collected uniform data from all known laryngeal transplants reported internationally. METHODOLOGY: A case series. Patients were enrolled retrospectively by each institutional hospital or clinic. Eleven patients with complete loss of laryngeal function undergoing total laryngeal transplantation between 1998 and 2018 were recruited. RESULTS: After a minimum of 24 months follow-up, three patients had died (27%), and there were two graft explants in survivors, one total and one partial, due to chronic rejection. In the remaining cases, voice was functional in 62.5% and 50% achieved decannulation. Swallowing was initially restricted, but only one patient was gastrostomy-dependent by 6 months and all had normal or near-normal swallowing by the end of year two after transplantation. Median follow-up was 73 months. Functional (voice, swallowing, airway) recovery peaked between 12 and 24 months. CONCLUSIONS: Laryngeal transplantation is a complex procedure with significant morbidity. Significant improvements in quality of life are possible for highly selected individuals with end-stage laryngeal disorders, including laryngeal neoplasia, but further technical and pharmacological developments are required if the technique is to be more widely applicable. An international registry should be created to provide better quality pooled data for analysis of outcomes of any future laryngeal transplants. LEVEL OF EVIDENCE: IV Laryngoscope, 2024.

Tissue-based T cell activation and viral RNA persist for up to 2 years after SARS-CoV-2 infection.

The mechanisms of postacute medical conditions and unexplained symptoms after SARS-CoV-2 infection [Long Covid (LC)] are incompletely understood. There is growing evidence that viral persistence, immune dysregulation, and T cell dysfunction may play major roles. We performed whole-body positron emission tomography imaging in a well-characterized cohort of 24 participants at time points ranging from 27 to 910 days after acute SARS-CoV-2 infection using the radiopharmaceutical agent [18F]F-AraG, a selective tracer that allows for anatomical quantitation of activated T lymphocytes. Tracer uptake in the postacute COVID-19 group, which included those with and without continuing symptoms, was higher compared with prepandemic controls in many regions, including the brain stem, spinal cord, bone marrow, nasopharyngeal and hilar lymphoid tissue, cardiopulmonary tissues, and gut wall. T cell activation in the spinal cord and gut wall was associated with the presence of LC symptoms. In addition, tracer uptake in lung tissue was higher in those with persistent pulmonary symptoms specifically. Increased T cell activation in these tissues was also observed in many individuals without LC. Given the high [18F]F-AraG uptake detected in the gut, we obtained colorectal tissue for in situ hybridization of SARS-CoV-2 RNA and immunohistochemical studies in a subset of five participants with LC symptoms. We identified intracellular SARS-CoV-2 single-stranded spike protein-encoding RNA in rectosigmoid lamina propria tissue in all five participants and double-stranded spike protein-encoding RNA in three participants up to 676 days after initial COVID-19, suggesting that tissue viral persistence could be associated with long-term immunologic perturbations.

Cooperative Phosphine-Photoredox Catalysis Enables N-H Activation of Azoles for Intermolecular Olefin Hydroamination.

Catalytic intermolecular olefin hydroamination is an enabling synthetic strategy that offers direct and atom-economical access to a variety of nitrogen-containing compounds from abundant feedstocks. However, despite numerous advances in catalyst design and reaction development, hydroamination of N-H azoles with unactivated olefins remains an unsolved problem in synthesis. We report a dual phosphine and photoredox catalytic protocol for the hydroamination of numerous structurally diverse and medicinally relevant N-H azoles with unactivated olefins. Hydroamination proceeds with high anti-Markovnikov regioselectivity and N-site selectivity. The mild conditions and high functional group tolerance of the reaction permit the rapid construction of molecular complexity and late-stage functionalization of bioactive compounds. N-H bond activation is proposed to proceed via polar addition of the N-H azole to a phosphine radical cation, followed by P-N α-scission from a phosphoranyl radical intermediate. Reactivity and N-site selectivity are classified by azole N-H BDFE and nitrogen-centered radical spin density, respectively, which can serve as a useful predictive aid in extending the reaction to unseen azoles.

Simulating realistic patient profiles from pharmacokinetic models by a machine learning postprocessing correction of residual variability.

We address the problem of model misspecification in population pharmacokinetics (PopPK), by modeling residual unexplained variability (RUV) by machine learning (ML) methods in a postprocessing step after conventional model building. The practical purpose of the method is the generation of realistic virtual patient profiles and the quantification of the extent of model misspecification, by introducing an appropriate metric, to be used as an additional diagnostic of model quality. The proposed methodology consists of the following steps: After developing a PopPK model, the individual residual errors IRES = DV-IPRED, are computed, where DV are the observations and IPRED the individual predictions and are modeled by ML to obtain IRESML. Correction of the IPREDs can then be carried out as DVML = IPRED + IRESML. The methodology was tested in a PK study of ropinirole, for which a PopPK model was developed while a second deliberately misspecified model was also considered. Various supervised ML algorithms were tested, among which Random Forest gave the best results. The ML model was able to correct individual predictions as inspected in diagnostic plots and most importantly it simulated realistic profiles that resembled the real data and canceled out the artifacts introduced by the elevated RUV, even in the case of the heavily misspecified model. Furthermore, a metric to quantify the extent of model misspecification was introduced based on the R2 between IRES and IRESML, following the rationale that the greater the extent of variability explained by the ML model, the higher the degree of model misspecification present in the original model.

Enzymatic and Non-enzymatic Collagen Cross-Links and Fracture Occurrence in Type 1 Diabetes Patients.

Increased fracture risk in type 1 diabetes (T1D) patients is not fully captured by bone mineral density (BMD) by DXA. Advanced glycation end-products (AGEs) have been implicated in the increased fracture risk in T1D, yet recent publications question this. To test the hypothesis that enzymatic collagen cross-links rather than AGEs correlate with fracture incidence in T1D, we analyzed iliac crest biopsies from sex-matched, fracturing T1D patients (N = 5; T1DFx), 6 non-fracturing T1D patients (T1DNoFx), and 6 healthy subjects, by Raman microspectroscopy as a function of tissue age (based on double fluorescent labels), in intracortical and trabecular bone, to determine pyridinoline (Pyd), ε-N-Carboxymethyl-L-lysine, and pentosidine (PEN)). There were no differences in the clinical characteristics between the T1DFx and T1DNoFx groups. At trabecular forming surfaces, T1DFx patients had higher PEN and Pyd content compared to T1DNoFx ones. Previous studies have shown that elevated PEN does not necessarily correlate with fracture incidence in postmenopausal, long-term T1D patients. On the other hand, the elevated Pyd content in the T1DFx patients would be consistent with published studies showing a significant correlation between elevated trivalent enzymatic collagen cross-links and fracture occurrence independent of BMD. Collagen fibers with high Pyd content are more brittle. Thus, a plausible suggestion is that it is the enzymatic collagen cross-links that either by themselves or in combination with the adverse effects of increased AGE accumulation that result in fragility fracture in T1D.

The Effect of Shift Timing on Cesarean Delivery Outcomes and Operative Noise Levels.

OBJECTIVE: Intraoperative noise exposure has been associated with an increased risk of complications, communication errors, and stress among surgical team members. This study evaluates intraoperative noise levels in cesarean deliveries during different shift times, for example, night shifts, day shifts, and hand-off times between shifts. STUDY DESIGN: This is a secondary analysis of a prospective observational study which measured volume in decibels, percentage of time above safe levels (>60 dB), startle noise events (events with rapid increase of decibel level above baseline noise), and peak levels (>75 dB) for cesarean deliveries during a 3-month preintervention and postintervention study. This secondary analysis of noise data evaluated whether there were differences in noise for cases occurring during day shifts (6:31 a.m.-4:59 p.m.), night shifts (6:01 p.m.-5:29 a.m.), and hand-off times (5:30 a.m.-6:30 a.m. and 5:00 p.m.-6:00 p.m.). Correlates and postoperative complications during the respective shifts were additionally analyzed. RESULTS: Noise data were collected for a total of 312 cesarean deliveries; 203 occurred during the day shift, 94 during the night shift, and 15 during hand-off times. Median noise in decibels, median noise at various key intraoperative points, number of startle events, percentage of time above 60 dB, and above 75 dB had no significant differences throughout the various shift times. Significantly larger numbers of postpartum hemorrhages, unscheduled, urgent, and STAT cesarean deliveries occurred at hand-off times and on night shifts. CONCLUSION: Noise levels during cesarean deliveries did not significantly vary when comparing night shifts, day shifts, and hand-off times, despite significantly higher numbers of urgent and STAT cases occurring overnight and during hand-off times. However, more than 60% of case time had noise levels exceeding those considered safe. This suggests that ambient background noise may be contributing more to overall noise levels rather than the specific clinical scenario at hand. KEY POINTS: · Noise in cesarean delivery operating rooms frequently exceeded recommended levels.. · Noise in cesarean delivery operating rooms did not vary with shift type.. · Hand-off times had higher rates of urgent and STAT cesareans.. · Night shifts had higher rates of urgent and STAT cesareans..

Immunosuppressive therapy for IgA nephropathy in children.

BACKGROUND: IgA nephropathy (IgAN) is the most common cause of primary glomerulonephritis. It is a heterogeneous disease with different presentations and high morbidity. Thirty per cent of adults and 20% of children (followed into adulthood) will have a 50% decline in kidney function or develop kidney failure after 10 years. OBJECTIVES: To determine the benefits and harms of immunosuppressive therapy for the treatment of IgAN in children. SEARCH METHODS: We contacted the Information Specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 03 October 2023 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) investigating the treatment of IgAN in children with immunosuppressive therapies compared to placebo, no treatment, supportive care, standard therapy (Japanese protocol), other immunosuppressive therapies or non-immunosuppressive therapies. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed the risk of bias. Random effects meta-analyses were used to summarise estimates of treatment effects. Treatment effects were expressed as risk ratios (RR) and 95% confidence intervals (CI) for dichotomous outcomes, and the mean difference (MD) and 95% CI for continuous outcomes. The risk of bias was assessed using the Cochrane risk of bias tool for RCTs and the ROBIN-I tool for NRSIs. The certainty of the evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). MAIN RESULTS: This review included 13 studies with 686 participants. Ten RCTs included 334 children and 191 adults, and three NRSIs included 151 participants, all children. Most participants had mild kidney disease. The risk of bias was unclear for most of the domains relating to allocation concealment, blinding of participants, personnel, and outcome assessment. In children with IgAN, it is uncertain if corticosteroid (steroid) therapy, compared to placebo reduces proteinuria (1 study, 64 children and young adults: RR 0.47, 95% CI 0.13 to 1.72; low certainty evidence) or the decline in estimated glomerular filtration rate (eGFR) (1 study, 64 children and young adults: RR 0.47, 95% CI 0.09 to 2.39; low certainty evidence). It is uncertain if steroids reduce proteinuria compared to supportive care (2 studies, 61 children: RR 0.04, 95% CI -0.83 to 0.72; low certainty evidence). Adverse events associated with steroid therapy were not assessed due to heterogeneity in steroid protocols, including dose and duration, and lack of systematic assessment for adverse events in the included studies. Azathioprine, mycophenolate mofetil, mizoribine, or cyclophosphamide alone or in combination with steroid therapy had uncertain effects on improving proteinuria or preventing eGFR decline in children with IgAN. Fish oil, vitamin E and tonsillectomy had uncertain effects on improving proteinuria or preventing eGFR decline. Effects of other immunosuppressive therapies, secondary outcomes and adverse events were not assessed due to insufficient data. AUTHORS' CONCLUSIONS: There is a lack of high-quality evidence to guide the management of IgAN in children. There is no evidence to indicate that steroids, other immunosuppressive therapies, or tonsillectomy, when added to optimal supportive care, prevent a decline in eGFR or proteinuria in children with IgAN. Available studies were few, with small numbers, low-quality evidence, high or uncertain risk of bias, did not systematically assess harms associated with treatment, or report net benefits or harms. Severe cases and atypical presentations of IgAN were not included in the reviewed studies, and our findings cannot be generalised to these situations.

Chromosome-Scale, De Novo, Phased Genome Assemblies of Three Australian Limes: Citrus australasica, C. inodora, and C. glauca.

Huanglongbing (HLB) is a severe citrus disease worldwide. Wild Australian limes like Citrus australasica, C. inodora, and C. glauca possess beneficial HLB resistance traits. Individual trees of the three taxa were extensively used in a breeding program for over a decade to introgress resistance traits into commercial-quality citrus germplasm. We generated high-quality, phased, de novo genome assemblies of the three Australian limes using PacBio long-read sequencing. The genome assembly sizes of the primary and alternate haplotypes were determined for C. australasica (337 Mb/335 Mb), C. inodora (304 Mb/299 Mb), and C. glauca (376 Mb/379 Mb). The nine chromosome-scale scaffolds included 86-91% of the genome sequences generated. The integrity and completeness of the assembled genomes were estimated to be at 97.2-98.8%. Gene annotation studies identified 25,461 genes in C. australasica, 27,665 in C. inodora, and 30,067 in C. glauca. Genes belonging to 118 orthogroups were specific to Australian lime genomes compared to other citrus genomes analyzed. Significantly fewer canonical resistance (R) genes were found in C. inodora and C. glauca (319 and 449, respectively) compared to C. australasica (576), C. clementina (579), and C. sinensis (651). Similar patterns were observed for other gene families associated with potential HLB resistance, including Phloem protein 2 (PP2) and Callose synthase (CalS) genes predicted in the Australian lime genomes. The genomic information on Australian limes developed in the present study will help understand the genetic basis of HLB resistance.

Organic Synthesis Away from Equilibrium: Contrathermodynamic Transformations Enabled by Excited-State Electron Transfer.

ConspectusChemists have long been inspired by biological photosynthesis, wherein a series of excited-state electron transfer (ET) events facilitate the conversion of low energy starting materials such as H2O and CO2 into higher energy products in the form of carbohydrates and O2. While this model for utilizing light-driven charge transfer to drive catalytic reactions thermodynamically "uphill" has been extensively adapted for small molecule activation, molecular machines, photoswitches, and solar fuel chemistry, its application in organic synthesis has been less systematically developed. However, the potential benefits of these approaches are significant, both in enabling transformations that cannot be readily achieved using conventional thermal chemistry and in accessing distinct selectivity regimes that are uniquely enabled by excited-state mechanisms. In this Account, we present work from our group that highlights the ability of visible light photoredox catalysis to drive useful organic transformations away from their equilibrium positions, addressing a number of long-standing synthetic challenges.We first discuss how excited-state ET enabled the first general methods for the catalytic anti-Markovnikov hydroamination of unactivated alkenes with alkyl amines. In these reactions, an excited-state iridium(III) photocatalyst reversibly oxidizes secondary amine substrates to their corresponding aminium radical cations (ARCs). These electrophilic N-centered radicals can then react with olefins to furnish valuable tertiary amine products with complete anti-Markovnikov regioselectivity. Notably, some of these products are less thermodynamically stable than their corresponding amine and alkene starting materials. We next present a strategy for light-driven C-C bond cleavage within various aliphatic alcohols mediated by homolytic activation of alcohol O-H bonds by excited-state proton-coupled electron transfer (PCET). The resulting alkoxy radical intermediates then undergo C-C ß-scission to ultimately provide isomeric linear carbonyl products that are often higher in energy than their cyclic alcohol precursors. Applications of this chemistry for the light-driven depolymerization of lignin biomass, commercial phenoxy resin, hydroxylated polyolefin derivatives, and thermoset polymers are presented as well. We then describe a method for the contrathermodynamic positional isomerization of highly substituted olefins by means of cooperative photoredox and chromium(II) catalysis. In this work, generation of an allylchromium(III) species that can undergo highly regioselective in situ protodemetalation enables access to a less substituted and thermodynamically less stable positional isomer. Product selectivity in this reaction is determined by the large differential in oxidation potentials between differently substituted olefin isomers. Lastly, we discuss a light-driven deracemization reaction developed in collaboration with the Miller group, wherein a racemic urea substrate undergoes spontaneous optical enrichment upon visible light irradiation in the presence of an iridium(III) chromophore, a chiral Brønsted base, and a chiral peptide thiol. Excellent levels of enantioselectivity are achieved via sequential and synergistic proton transfer (PT) and H atom transfer (HAT) steps. Taken together, these examples highlight the ability of excited-state ET events to enable access to nonequilibrium product distributions across a wide range of catalytic, redox-neutral transformations in which photons are the only stoichiometric reagents.

Rapid volcanic ash entombment reveals the 3D anatomy of Cambrian trilobites.

Knowledge of Cambrian animal anatomy is limited by preservational processes that result in compaction, size bias, and incompleteness. We documented pristine three-dimensional (3D) anatomy of trilobites fossilized through rapid ash burial from a pyroclastic flow entering a shallow marine environment. Cambrian ellipsocephaloid trilobites from Morocco are articulated and undistorted, revealing exquisite details of the appendages and digestive system. Previously unknown anatomy includes a soft-tissue labrum attached to the hypostome, a slit-like mouth, and distinctive cephalic feeding appendages. Our findings resolve controversy over whether the trilobite hypostome is the labrum or incorporates it and establish crown-group euarthropod homologies in trilobites. This occurrence of moldic fossils with 3D soft parts highlights volcanic ash deposits in marine settings as an underexplored source for exceptionally preserved organisms.

Perfusion Techniques in Kidney Allograft Preservation to Reduce Ischemic Reperfusion Injury: A Systematic Review and Meta-Analysis.

The limited supply and rising demand for kidney transplantation has led to the use of allografts more susceptible to ischemic reperfusion injury (IRI) and oxidative stress to expand the donor pool. Organ preservation and procurement techniques, such as machine perfusion (MP) and normothermic regional perfusion (NRP), have been developed to preserve allograft function, though their long-term outcomes have been more challenging to investigate. We performed a systematic review and meta-analysis to examine the benefits of MP and NRP compared to traditional preservation techniques. PubMed (MEDLINE), Embase, Cochrane, and Scopus databases were queried, and of 13,794 articles identified, 54 manuscripts were included (n = 41 MP; n = 13 NRP). MP decreased the rates of 12-month graft failure (OR 0.67; 95%CI 0.55, 0.80) and other perioperative outcomes such as delayed graft function (OR 0.65; 95%CI 0.54, 0.79), primary nonfunction (OR 0.63; 95%CI 0.44, 0.90), and hospital length of stay (15.5 days vs. 18.4 days) compared to static cold storage. NRP reduced the rates of acute rejection (OR 0.48; 95%CI 0.35, 0.67) compared to in situ perfusion. Overall, MP and NRP are effective techniques to mitigate IRI and play an important role in safely expanding the donor pool to satisfy the increasing demands of kidney transplantation.

Protocol for producing hyperpolarized 13C-bicarbonate for clinical MRI of extracellular pH in aggressive tumors.

Tumor acidosis is one of the hallmarks indicating the initiation and progression of various cancers. Here, we present a protocol for preparing a hyperpolarized (HP) 13C-bicarbonate tissue pH MRI imaging contrast agent to detect aggressive tumors. We describe the steps for the formulation and polarization of a precursor molecule 13C-glycerol carbonate (13C-GLC), the post-dissolution reaction, and converting HP 13C-GLC to an injectable HP 13C-bicarbonate solution. We then detail procedures for MRI data acquisition to generate tumor pH maps for assessing tumor aggressiveness. For complete details on the use and execution of this protocol, please refer to Mu et al.1.

Most people's life satisfaction matches their personality traits: True correlations in multitrait, multirater, multisample data.

Despite numerous meta-analyses, the true extent to which life satisfaction reflects personality traits has remained unclear due to overreliance on a single method to assess both and insufficient attention to construct overlaps. Using data from three samples tested in different languages (Estonian, N = 20,886; Russian, N = 768; English, N = 600), we combined self- and informant-reports to estimate personality domains' and nuances' true correlations (rtrue) with general life satisfaction (LS) and satisfactions with eight life domains (DSs), while controlling for single-method and occasion-specific biases and random error, and avoiding direct construct overlaps. The associations replicated well across samples. The Big Five domains and nuances allowed predicting LS with accuracies up to rtrue ≈ .80-.90 in independent (sub)samples. Emotional stability, extraversion, and conscientiousness correlated rtrue ≈ .30-.50 with LS, while its correlations with openness and agreeableness were small. At the nuances level, low LS was most strongly associated with feeling misunderstood, unexcited, indecisive, envious, bored, used, unable, and unrewarded (rtrue ≈ .40-.70). Supporting LS's construct validity, DSs had similar personality correlates among themselves and with LS, and an aggregated DS correlated rtrue ≈ .90 with LS. LS's approximately 10-year stability was rtrue = .70 and its longitudinal associations with personality traits mirrored cross-sectional ones. We conclude that without common measurement limitations, most people's life satisfaction is highly consistent with their personality traits, even across many years. So, satisfaction is usually shaped by these same relatively stable factors that shape personality traits more broadly. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Free essential amino acid feeding improves endurance during resistance training via DRP1-dependent mitochondrial remodelling.

BACKGROUND: Loss of muscle strength and endurance with aging or in various conditions negatively affects quality of life. Resistance exercise training (RET) is the most powerful means to improve muscle mass and strength, but it does not generally lead to improvements in endurance capacity. Free essential amino acids (EAAs) act as precursors and stimuli for synthesis of both mitochondrial and myofibrillar proteins that could potentially confer endurance and strength gains. Thus, we hypothesized that daily consumption of a dietary supplement of nine free EAAs with RET improves endurance in addition to the strength gains by RET. METHODS: Male C57BL6J mice (9 weeks old) were assigned to control (CON), EAA, RET (ladder climbing, 3 times a week), or combined treatment of EAA and RET (EAA + RET) groups. Physical functions focusing on strength or endurance were assessed before and after the interventions. Several analyses were performed to gain better insight into the mechanisms by which muscle function was improved. We determined cumulative rates of myofibrillar and mitochondrial protein synthesis using 2H2O labelling and mass spectrometry; assessed ex vivo contractile properties and in vitro mitochondrial function, evaluated neuromuscular junction (NMJ) stability, and assessed implicated molecular singling pathways. Furthermore, whole-body and muscle insulin sensitivity along with glucose metabolism, were evaluated using a hyperinsulinaemic-euglycaemic clamp. RESULTS: EAA + RET increased muscle mass (10%, P < 0.05) and strength (6%, P < 0.05) more than RET alone, due to an enhanced rate of integrated muscle protein synthesis (19%, P < 0.05) with concomitant activation of Akt1/mTORC1 signalling. Muscle quality (muscle strength normalized to mass) was improved by RET (i.e., RET and EAA + RET) compared with sedentary groups (10%, P < 0.05), which was associated with increased AchR cluster size and MuSK activation (P < 0.05). EAA + RET also increased endurance capacity more than RET alone (26%, P < 0.05) by increasing both mitochondrial protein synthesis (53%, P < 0.05) and DRP1 activation (P < 0.05). Maximal respiratory capacity increased (P < 0.05) through activation of the mTORC1-DRP1 signalling axis. These favourable effects were accompanied by an improvement in basal glucose metabolism (i.e., blood glucose concentrations and endogenous glucose production vs. CON, P < 0.05). CONCLUSIONS: Combined treatment with balanced free EAAs and RET may effectively promote endurance capacity as well as muscle strength through increased muscle protein synthesis, improved NMJ stability, and enhanced mitochondrial dynamics via mTORC1-DRP1 axis activation, ultimately leading to improved basal glucose metabolism.

Endogenous Opioids and Exercise-Related Hypoalgesia: Modern Models, Measurement, and Mechanisms of Action.

This chapter will focus on the role exercise appears to have on activation and modulating factors within the central nervous system related to endogenous like opioids and its possible contribution to exercise-induced hypoalgesia. The implications for the exercise-mediated alterations of CNS activation factors related to opioids, specifically endorphins and enkephalins, will be presented. In this update, we discuss utilization of new technology and methods to monitor mechanisms of opioid involvement to suggest their contribution with exercise mediated hypoalgesia as well as their relationships to alterations of perceptions of pain and mood. Several special populations were included to suggest that not all individuals will respond to the exercise by mediating hypoalgesia. Factors that may confound the current understanding and suggestions from the recent literature will be presented as well as suggestions for future investigations.