Anterior cruciate ligament primary repair revision rates are increased in skeletally mature patients under the age of 21 compared to reconstruction, while adults (>21 years) show no significant difference: A systematic review and meta-analysis.

PURPOSE: To evaluate the impact of age as a risk factor on the revision rates of anterior cruciate ligament (ACL) primary repair (ACLPR), dynamic intraligamentary stabilization (DIS) and bridge-enhanced ACL restoration (BEAR) compared to ACL reconstruction (ACLR). METHODS: A systematic literature search was performed for comparative studies comparing outcomes for ACLPR, DIS or BEAR to ACLR. A random-effects meta-analysis was performed to assess nondifferentiated and age-differentiated (skeletally mature patients ≤21 and >21 years) ACL revision and reoperation risk, as well as results for subjective outcomes. Methodological study quality was assessed using the Risk of Bias Tool 2.0c and Methodological Index for Nonrandomized Studies tools. RESULTS: A total of 12 studies (n = 1277) were included. ACLR demonstrated a lower nonage-stratified revision risk at 2 years versus ACLPR, DIS and BEAR, but a similar revision risk at 5 years when compared to DIS. However, an age-stratified analysis demonstrated a significantly increased ACLPR revision risk as compared to ACLR in skeletally mature patients ≤21 years of age (risk ratios [RR], 6.33; 95% confidence interval [CI], 1.18-33.87, p = 0.03), while adults (>21 years) showed no significant difference between groups (RR, 1.48; 95% CI, 0.25-8.91, n.s.). Furthermore, DIS reoperation rates were significantly higher than respective ACLR rates (RR, 2.22; 95% CI, 1.35-3.65, p = 0.002), whereas BEAR (RR, 1.07; 95% CI, 0.41-2.75, n.s.) and ACLPR (RR, 0.81; 95% CI, 0.21-3.09, n.s.) showed no differences. IKDC scores were equivalent for all techniques. However, ACLPR exhibited significantly better FJS (mean difference, 11.93; 95% CI, 6.36-17.51, p < 0.0001) and Knee injury and Osteoarthritis Outcome Score Symptoms (mean difference, 3.01; 95% CI, 0.42-5.60, p = 0.02), along with a lower Tegner activity reduction. CONCLUSIONS: ACLPR in skeletally mature patients ≤21 years of age is associated with up to a six-fold risk increase for ACL revision surgery compared to ACLR; however, adults (>21 years) present no significant difference. Based on the current data, age emerges as a crucial risk factor and should be considered when deciding on the appropriate treatment option in proximal ACL tears. LEVEL OF EVIDENCE: Level III.

Structural and mechanistic studies on human LONP1 redefine the hand-over-hand translocation mechanism.

AAA+ enzymes use energy from ATP hydrolysis to remodel diverse cellular targets. Structures of substrate-bound AAA+ complexes suggest that these enzymes employ a conserved hand-over-hand mechanism to thread substrates through their central pore. However, the fundamental aspects of the mechanisms governing motor function and substrate processing within specific AAA+ families remain unresolved. We used cryo-electron microscopy to structurally interrogate reaction intermediates from in vitro biochemical assays to inform the underlying regulatory mechanisms of the human mitochondrial AAA+ protease, LONP1. Our results demonstrate that substrate binding allosterically regulates proteolytic activity, and that LONP1 can adopt a configuration conducive to substrate translocation even when the ATPases are bound to ADP. These results challenge the conventional understanding of the hand-over-hand translocation mechanism, giving rise to an alternative model that aligns more closely with biochemical and biophysical data on related enzymes like ClpX, ClpA, the 26S proteasome, and Lon protease.

Meiofauna at a tropical sandy beach in the SW Atlantic: the influence of seasonality on diversity.

Background: Sandy beaches are dynamic environments housing a large diversity of organisms and providing important environmental services. Meiofaunal metazoan are small organisms that play a key role in the sediment. Their diversity, distribution and composition are driven by sedimentary and oceanographic parameters. Understanding the diversity patterns of marine meiofauna is critical in a changing world. Methods: In this study, we investigate if there is seasonal difference in meiofaunal assemblage composition and diversity along 1 year and if the marine seascapes dynamics (water masses with particular biogeochemical features, characterized by temperature, salinity, absolute dynamic topography, chromophoric dissolved organic material, chlorophyll-a, and normalized fluorescent line height), rainfall, and sediment parameters (total organic matter, carbonate, carbohydrate, protein, lipids, protein-to-carbohydrate, carbohydrate-to-lipids, and biopolymeric carbon) affect significatively meiofaunal diversity at a tropical sandy beach. We tested two hypotheses here: (i) meiofaunal diversity is higher during warmer months and its composition changes significatively among seasons along a year at a tropical sandy beach, and (ii) meiofaunal diversity metrics are significantly explained by marine seascapes characteristics and sediment parameters. We used metabarcoding (V9 hypervariable region from 18S gene) from sediment samples to assess the meiofaunal assemblage composition and diversity (phylogenetic diversity and Shannon's diversity) over a period of 1 year. Results: Meiofauna was dominated by Crustacea (46% of sequence reads), Annelida (28% of sequence reads) and Nematoda (12% of sequence reads) in periods of the year with high temperatures (>25 °C), high salinity (>31.5 ppt), and calm waters. Our data support our initial hypotheses revealing a higher meiofaunal diversity (phylogenetic and Shannon's Diversity) and different composition during warmer periods of the year. Meiofaunal diversity was driven by a set of multiple variables, including biological variables (biopolymeric carbon) and organic matter quality (protein content, lipid content, and carbohydrate-to-lipid ratio).

Dysferlin Enables Tubular Membrane Proliferation in Cardiac Hypertrophy.

BACKGROUND: Cardiac hypertrophy compensates for increased biomechanical stress of the heart induced by prevalent cardiovascular pathologies but can result in cardiac failure if left untreated. We hypothesized that the tail-anchored protein dysferlin with multiple Ca2+-binding C2-domains is critical for the integrity of the transverse-axial tubule (TAT) network inside cardiomyocytes and contributes to the proliferation of TAT endomembranes during pressure overload-induced cardiac hypertrophy. OBJECTIVE: To reveal the impact of the membrane fusion and repair protein dysferlin on TAT network stabilization and proliferation necessary for the hypertrophic growth of cardiomyocytes. METHODS AND RESULTS: Super-resolution light and electron microscopy of mouse cardiomyocytes identified a specific localization of dysferlin in a vesicular compartment in nanometric proximity to contact sites of the TAT network with the sarcoplasmic reticulum, a.k.a. junctional complexes for Ca2+-induced Ca2+ release. Mass spectrometry was used to characterize the cardiac dysferlin interactome, thereby identifying a novel protein interaction with the membrane-tethering sarcoplasmic reticulum protein juncophilin-2, a putative interactor of L-type Ca2+ channels and ryanodine receptor Ca2+ release channels in junctional complexes. While the dysferlin knockout caused a mild progressive phenotype of dilated cardiomyopathy in the mouse heart, global proteome analysis revealed changes preceding systolic failure. Following transverse aortic constriction, dysferlin protein expression was significantly increased in hypertrophied wild-type myocardium, while dysferlin knockout animals presented markedly reduced left-ventricular hypertrophy. Live-cell membrane imaging demonstrated a profound reorganization of the TAT network in wild-type left-ventricular myocytes post-transverse aortic constriction with robust proliferation of axial tubules, which critically depended on the increased expression of dysferlin within newly emerging tubule components. CONCLUSIONS: Dysferlin represents a new molecular target in cardiac disease that protects the integrity of tubule-sarcoplasmic reticulum junctional complexes for regulated excitation-contraction coupling and controls TAT network reorganization and tubular membrane proliferation in cardiomyocyte hypertrophy induced by pressure overload.

Normothermic regional perfusion in controlled DCD liver procurement: Outcomes of the Swedish national implementation protocol.

Liver transplantation using donors after controlled circulatory death (cDCD) is associated with poorer graft survival and increased incidence of non-anastomotic biliary strictures (NAS) compared to livers procured from brain dead donors (DBD). The use of Normothermic regional perfusion (NRP) during cDCD procurement may improve post-transplant outcome and reduce the incidence of NAS. In Sweden cDCD liver transplantation was introduced through a national pilot protocol with mandatory NRP. This study aims to evaluate the outcome of cDCD liver transplantation during the pilot period. Donor and recipient data were collected on all cDCD liver transplants during the pilot period between 2020 - December 2022. Outcome on NAS, patient- and graft survival, early allograft dysfunction, acute kidney injury, and comprehensive complication index was compared to a matched cohort of 28 patients transplanted with a DBD liver between 2018-2022. 18 patients were transplanted with a liver from a cDCD donor after using NRP. Mean functional warm ischemia time was 29±6 minutes. Mean lactate reduction during NRP was 8.7±2.4 mmol/L, end NRP perfusate ALT was 1.4±1 µkat/L. When comparing cDCD liver transplant recipients to DBD, no significant differences were observed in the incidence of NAS, patient and graft survival, comprehensive complication index, early allograft dysfunction, nor acute kidney injury. Study protocol MRCP in cDCD patients showed no signs of subclinical biliary strictures. Evaluation of the Swedish national pilot of cDCD liver transplantation with mandatory NRP shows comparable outcomes to a matched DBD cohort with 94.4 one-year patient and graft survival and no incidence of NAS within the first year.

Outcomes and Performance Following Posteromedial Elbow Debridement in Major League Baseball Players.

BACKGROUND: Overhead athletes are particularly susceptible to elbow valgus extension overload syndrome and development of pathologic changes in the posteromedial elbow. Though arthroscopic débridement/osteophyte resection is frequently performed, few studies have analyzed the outcomes of this procedure, and none have specifically addressed professional level athletes. HYPOTHESIS/PURPOSE: We hypothesized that following posteromedial elbow débridement, Major League Baseball (MLB) pitchers would exhibit a higher rate of ulnar collateral ligament (UCL) reconstruction than baseline incidence in the existing literature, along with a decline in pitching performance. METHODS: Using publicly accessible websites, MLB athletes undergoing posteromedial elbow débridement from 2007 to 2022 were identified. Demographic information, procedure details, return to play (RTP) information, return to the disabled/injured list (DL/IL), subsequent UCL reconstruction, and pitching statistics were analyzed. Pitching performance metrics included Earned Runs Average (ERA), Walks Plus Hits Per Innings Pitched (WHIP), innings pitched, and fastball velocity. RESULTS: A total of 39 MLB players, including 26 pitchers, were included. Within the first three seasons after surgery, 82.1% (n=32) of players returned to play at the MLB level at a mean time of 176.1 ± 69 days. Pitchers exhibited a return to play (RTP) rate of 76.9% (n=20) at 175.8 ± 16 days. A total of 38.5% (n=10) of pitchers returned to the DL/IL for elbow-related issues within three seasons. Subsequent UCL reconstruction was seen only in pitchers, with a frequency of 19.2% (n=5). No statistically significant differences between single season pre/postoperative pitching metrics were identified. A small but significant (p<0.05) decrease in fastball velocity (94.4 vs 92.84; p=0.02) was observed over a three-season comparison. CONCLUSION: Contrary to our hypothesis, this study demonstrates that posteromedial elbow débridement is a viable surgery in MLB athletes, with RTP rate of 82.1% and no increase in rate of UCL reconstruction. Furthermore, there was no significant difference in single season pre- and postoperative statistical pitching performance. However, over three years postoperatively, there was a 38.5% rate of return to the DL/IL for ongoing elbow ailment and a significant decrease in pitch velocity, raising some concern over the longevity of postoperative improvements.

Bis-sulfonamido-2-phenylbenzoxazoles Validate the GroES/EL Chaperone System as a Viable Antibiotic Target.

We recently reported on small-molecule inhibitors of the GroES/GroEL chaperone system as potential antibiotics against Escherichia coli and the ESKAPE pathogens but were unable to establish GroES/GroEL as the cellular target, leading to cell death. In this study, using two of our most potent bis-sulfonamido-2-phenylbenzoxazoles (PBZs), we established the binding site of the PBZ molecules using cryo-EM and found that GroEL was the cellular target responsible for the mode of action. Cryo-EM revealed that PBZ1587 binds at the GroEL ring-ring interface (RRI). A cellular reporter assay confirmed that PBZ1587 engaged GroEL in cells, but cellular rescue experiments showed potential off-target effects. This prompted us to explore a closely related analogue, PBZ1038, which is also bound to the RRI. Biochemical characterization showed potent inhibition of Gram-negative chaperonins but much lower potency of chaperonin from a Gram-positive organism, Enterococcus faecium. A cellular reporter assay showed that PBZ1038 also engaged GroEL in cells and that the cytotoxic phenotype could be rescued by a chromosomal copy of E. faecium GroEL/GroES or by expressing a recalcitrant RRI mutant. These data argue that PBZ1038's antimicrobial action is exerted through inhibition of GroES/GroEL, validating this chaperone system as an antibiotic target.

Gut membrane proteins as candidate antigens for immunization of mice against the tick Amblyomma sculptum.

Amblyomma sculptum is widely distributed in Brazil and is the main vector of Rickettsia rickettsii, the causative agent of the Brazilian spotted fever (BSF). Tick gut proteins play an essential role in blood feeding, digestion, and protection of gut epithelium. Therefore, many of these were investigated as potential vaccine targets for tick-control strategies. The present study aimed to select transcripts corresponding to putative immunogenic proteins in the A. sculptum gut epithelial membrane, produce recombinant proteins and evaluate them as antigens against A. sculptum infestations. Three gut proteins - AsMucin, AsAPP, and AsLAMP - and a chimeric protein (rAsChimera) based on 22 peptides containing putative B cell epitopes from seven different gut proteins were evaluated as anti-A. sculptum antigens. Mice immunizations revealed that all recombinant targets elicited humoral response with significantly increased IgG levels compared to controls. For rAsChimera, IgG levels remained significantly higher than controls up to 75 days after the end of the immunization. Challenge trials revealed that vaccination with the chimeric protein was the most effective against A. sculptum, inducing 100 % nymph mortality and reaching 80.8 % efficacy against females. The other three proteins did not induce relevant protection, as AsAPP had only 26.6 % efficacy, whereas AsMucin and AsLAMP induced no protection. These data indicate that targeting gut protein immunogenic regions may be an effective strategy for a vaccine formulation againstA. sculptum.

Type of calcineurin inhibitor and long-term outcomes following liver transplantation in patients with primary biliary cholangitis - an ELTR study.

Background & Aims: Tacrolimus has been associated with recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT), which in turn may reduce survival. This study aimed to assess the association between the type of calcineurin inhibitor used and long-term outcomes following LT in patients with PBC. Methods: Survival analyses were used to assess the association between immunosuppressive drugs and graft or patient survival among adult patients with PBC in the European Liver Transplant Registry. Patients who received a donation after brain death graft between 1990 and 2021 with at least 1 year of event-free follow-up were included. Results: In total, 3,175 patients with PBC were followed for a median duration of 11.4 years (IQR 5.9-17.9) after LT. Tacrolimus (Tac) was registered in 2,056 (64.8%) and cyclosporin in 819 (25.8%) patients. Following adjustment for recipient age, recipient sex, donor age, and year of LT, Tac was not associated with higher risk of graft loss (adjusted hazard ratio [aHR] 1.07, 95% CI 0.92-1.25, p = 0.402) or death (aHR 1.06, 95% CI 0.90-1.24, p = 0.473) over cyclosporin. In this model, maintenance mycophenolate mofetil (MMF) was associated with a lower risk of graft loss (aHR 0.72, 95% CI 0.60-0.87, p <0.001) or death (aHR 0.72, 95% CI 0.59-0.87, p <0.001), while these risks were higher with use of steroids (aHR 1.31, 95% CI 1.13-1.52, p <0.001, and aHR 1.34, 95% CI 1.15-1.56, p <0.001, respectively). Conclusions: In this large LT registry, type of calcineurin inhibitor was not associated with long-term graft or recipient survival, providing reassurance regarding the use of Tac post LT in the population with PBC. Patients using MMF had a lower risk of graft loss and death, indicating that the threshold for combination treatment with Tac and MMF should be low. Impact and implications: This study investigated the association between immunosuppressive drugs and the long-term survival of patients with primary biliary cholangitis (PBC) following donation after brain death liver transplantation. While tacrolimus has previously been related to a higher risk of PBC recurrence, the type of calcineurin inhibitor was not related to graft or patient survival among patients transplanted for PBC in the European Liver Transplant Registry. Additionally, maintenance use of mycophenolate was linked to lower risks of graft loss and death, while these risks were higher with maintenance use of steroids. Our findings should provide reassurance for physicians regarding the continued use of Tac after liver transplantation in the population with PBC, and suggest potential benefit from combination therapy with mycophenolate.

Genomic Consequences of Isolation and Inbreeding in an Island Dingo Population.

Dingoes come from an ancient canid lineage that originated in East Asia around 8,000 to 11,000 years BP. As Australia's largest terrestrial predator, dingoes play an important ecological role. A small, protected population exists on a world heritage listed offshore island, K'gari (formerly Fraser Island). Concern regarding the persistence of dingoes on K'gari has risen due to their low genetic diversity and elevated inbreeding levels. However, whole-genome sequence data is lacking from this population. Here, we include five new whole-genome sequences of K'gari dingoes. We analyze a total of 18 whole-genome sequences of dingoes sampled from mainland Australia and K'gari to assess the genomic consequences of their demographic histories. Long (>1 Mb) runs of homozygosity (ROHs)-indicators of inbreeding-are elevated in all sampled dingoes. However, K'gari dingoes showed significantly higher levels of very long ROH (>5 Mb), providing genomic evidence for small population size, isolation, inbreeding, and a strong founder effect. Our results suggest that, despite current levels of inbreeding, the K'gari population is purging strongly deleterious mutations, which, in the absence of further reductions in population size, may facilitate the persistence of small populations despite low genetic diversity and isolation. However, there may be little to no purging of mildly deleterious alleles, which may have important long-term consequences, and should be considered by conservation and management programs.

High-resolution single-particle imaging at 100-200 keV with the Gatan Alpine direct electron detector.

Developments in direct electron detector technology have played a pivotal role in enabling high-resolution structural studies by cryo-EM at 200 and 300 keV. Yet, theory and recent experiments indicate advantages to imaging at 100 keV, energies for which the current detectors have not been optimized. In this study, we evaluated the Gatan Alpine detector, designed for operation at 100 and 200 keV. Compared to the Gatan K3, Alpine demonstrated a significant DQE improvement at these energies, specifically a âˆ¼ 4-fold improvement at Nyquist at 100 keV. In single-particle cryo-EM experiments, Alpine datasets yielded better than 2 Å resolution reconstructions of apoferritin at 120 and 200 keV on a ThermoFisher Scientific (TFS) Glacios microscope fitted with a non-standard SP-Twin lens. We also achieved a âˆ¼ 3.2 Å resolution reconstruction of a 115 kDa asymmetric protein complex, proving Alpine's effectiveness with complex biological samples. In-depth analysis revealed that Alpine reconstructions are comparable to K3 reconstructions at 200 keV, and remarkably, reconstruction from Alpine at 120 keV on a TFS Glacios surpassed all but the 300 keV data from a TFS Titan Krios with GIF/K3. Additionally, we show Alpine's capability for high-resolution data acquisition and screening on lower-end systems by obtaining âˆ¼ 3 Å resolution reconstructions of apoferritin and aldolase at 100 keV and detailed 2D averages of a 55 kDa sample using a side-entry cryo holder. Overall, we show that Gatan Alpine performs well with the standard 200 keV imaging systems and may potentially capture the benefits of lower accelerating voltages, bringing smaller sized particles within the scope of cryo-EM.

Measurement of the mandibular canal and mandibular incisive canal using cone beam tomography in adults from South Brazil.

PURPOSE: To identify and measure the distance from the dental apices to the mandibular (MC) and mandibular incisive (MIC) canals, the diameter of the MC and the distances of the mental foramen (MF). METHODS: In this retrospective study, cone-beam computed tomography scans of 144 adult patients (males and females) from a dental school in South Brazil were evaluated. Cross-sections were selected on the MC and the MIC paths, perpendicular to the mandibular base, and measurements were taken from the dental apices to the mandibular cortices. The measurement and location of the mandibular and mental foramen on both sides were compared. Paired t-tests compared sides, while Student's t-tests compared sexes (P < 0.05). RESULTS: The distance from the dental apices to the upper wall of the MC was closest in the third molar and farthest in the central incisor region. In both sexes and sides, the path of the MC is in most cases lingually in the molar regions and moves to the buccal region from the second premolar. The MF emerges in the regions between the premolars or near the second premolar. CONCLUSION: The results of this study highlight the importance of evaluating specific individual characteristics of a given population.

Structural insights into the regulation of RyR1 by S100A1.

S100A1, a small homodimeric EF-hand Ca2+-binding protein (~21 kDa), plays an important regulatory role in Ca2+ signaling pathways involved in various biological functions including Ca2+ cycling and contractile performance in skeletal and cardiac myocytes. One key target of the S100A1 interactome is the ryanodine receptor (RyR), a huge homotetrameric Ca2+ release channel (~2.3 MDa) of the sarcoplasmic reticulum. Here, we report cryoelectron microscopy structures of S100A1 bound to RyR1, the skeletal muscle isoform, in absence and presence of Ca2+. Ca2+-free apo-S100A1 binds beneath the bridging solenoid (BSol) and forms contacts with the junctional solenoid and the shell-core linker of RyR1. Upon Ca2+-binding, S100A1 undergoes a conformational change resulting in the exposure of the hydrophobic pocket known to serve as a major interaction site of S100A1. Through interactions of the hydrophobic pocket with RyR1, Ca2+-bound S100A1 intrudes deeper into the RyR1 structure beneath BSol than the apo-form and induces sideways motions of the C-terminal BSol region toward the adjacent RyR1 protomer resulting in tighter interprotomer contacts. Interestingly, the second hydrophobic pocket of the S100A1-dimer is largely exposed at the hydrophilic surface making it prone to interactions with the local environment, suggesting that S100A1 could be involved in forming larger heterocomplexes of RyRs with other protein partners. Since S100A1 interactions stabilizing BSol are implicated in the regulation of RyR-mediated Ca2+ release, the characterization of the S100A1 binding site conserved between RyR isoforms may provide the structural basis for the development of therapeutic strategies regarding treatments of RyR-related disorders.

DESCRIPTION OF ESOPHAGOSTOMY TUBE PLACEMENT IN TWO GIANT ANTEATER (MYRMECOPHAGA TRIDACTYLA) CADAVERS.

Feeding of managed populations of giant anteater (Myrmecophaga tridactyla) is challenging in injured patients that present with anorexia. This report describes an approach for esophagostomy tube placement in this species. Cadavers of two adult giant anteaters were used for technique development. The animal was positioned in dorsal recumbency, and a guide feeding tube was inserted orally into the esophagus. A ventral midline incision in the midcervical region was made to access the esophagus and to protect submandibular salivary glands. The cervical musculature was dissected and retracted laterally to the right, the vagosympathetic nerve trunk was identified and preserved, and the esophagus was incised over the guide tube. The guide tube was removed to facilitate placement of the definitive tube, which was premeasured from its insertion point in the midcervical area to the level of the seventh-ninth intercostal space. The tube was secured to the cervical skin on the left side with a finger-trap suture.

Why Do People Watch Pornography? Cross-Cultural Validation of the Pornography Use Motivations Scale (PUMS) and Its Short Form (PUMS-8).

Motivations for pornography use may vary across gender identities, sexual orientations, and geographical regions, warranting examination to promote individual and public health. The aims of this study were to validate the Pornography Use Motivations Scale (PUMS) in a diverse, multicultural sample, and develop a short form (PUMS-8) that can assess a wide range of pornography use motivations. Using data from 42 countries (N = 75,117; Mage = 32.07; SDage = 12.37), enabled us to thoroughly evaluate the dimensionality, validity, and reliability of the Pornography Use Motivations Scale (PUMS), leading to the development of the more concise PUMS-8 short scale. Additionally, language-, nationality-, gender-, and sexual-orientation-based measurement invariance tests were conducted to test the comparability across groups. Both the PUMS and the PUMS-8 assess eight pornography use motivations, and both demonstrated excellent psychometric properties. Sexual Pleasure emerged as the most frequent motivation for pornography use across countries, genders, and sexual orientations, while differences were observed concerning other motivations (e.g. self-exploration was more prevalent among gender-diverse individuals than men or women). The motivational background of pornography use showed high similarity in the examined countries. Both the PUMS and the PUMS-8 are reliable and valid measurement tools to assess different types of motivations for pornography use across countries, genders, and sexual orientations. Both scales are recommended for use in research and clinical settings.

Epicapsular Stars in an Asymptomatic Patient.

This case report discusses a diagnosis of epicapsular stars during a routine ophthalmologic examination in an asymptomatic female patient aged 14 years.

Locus coeruleus noradrenaline depletion and its differential impact on CO2-induced panic and hyperventilation in male and female mice.

CO2 exposure has been used to investigate the panicogenic response in patients with panic disorder. These patients are more sensitive to CO2, and more likely to experience the "false suffocation alarm" which triggers panic attacks. Imbalances in locus coeruleus noradrenergic (LC-NA) neurotransmission are responsible for psychiatric disorders, including panic disorder. These neurons are sensitive to changes in CO2/pH. Therefore, we investigated if LC-NA neurons are differentially activated after severe hypercapnia in mice. Further, we evaluated the participation of LC-NA neurons in ventilatory and panic-like escape responses induced by 20% CO2 in male and female wild type mice and two mouse models of altered LC-NA synthesis. Hypercapnia activates the LC-NA neurons, with males presenting a heightened level of activation. Mutant males lacking or with reduced LC-NA synthesis showed hypoventilation, while animals lacking LC noradrenaline present an increased metabolic rate compared to wild type in normocapnia. When exposed to CO2, males lacking LC noradrenaline showed a lower respiratory frequency compared to control animals. On the other hand, females lacking LC noradrenaline presented a higher tidal volume. Nevertheless, no change in ventilation was observed in either sex. CO2 evoked an active escape response. Mice lacking LC noradrenaline had a blunted jumping response and an increased freezing duration compared to the other groups. They also presented fewer racing episodes compared to wild type animals, but not different from mice with reduced LC noradrenaline. These findings suggest that LC-NA has an important role in ventilatory and panic-like escape responses elicited by CO2 exposure in mice.

Revealing complex interdependencies in surgical instrument reprocessing using SEIPS 101 tools.

Sterile Processing Departments (SPDs) must clean, maintain, store, and organize surgical instruments which are then delivered to Operating Rooms (ORs) using a Courier Network, with regular coordination occurring across departmental boundaries. To represent these relationships, we utilized the Systems Engineering Initiative for Patient Safety (SEIPS) 101 Toolkit, which helps model how health-related outcomes are affected by healthcare work systems. Through observations and interviews which built on prior work system analyses, we developed a SEIPS 101 journey map, PETT scan, and tasks matrices to represent the instrument reprocessing work system, revealing complex interdependencies between the people, tools, and tasks occurring within it. The SPD, OR and Courier teams are found to have overlapping responsibilities and a clear co-dependence, with critical implications for the successful functioning of the whole hospital system.

Polycyclic aromatic hydrocarbons in seawater after the mysterious oil spill of 2019 on the Pernambuco coast, northeast Brazil.

In 2019, one of Brazil's most significant environmental disasters occurred, involving an oil spill that directly affected Pernambuco state. Contamination along the coast was evaluated by the quantification of polycyclic aromatic hydrocarbons (PAHs) in fifty seawater samples collected in the summer and winter of 2021. Analysis using fluorescence spectroscopy revealed that for all the samples, levels of dissolved/dispersed petroleum hydrocarbons (DDPHs) were higher than the regional baseline for tropical western shores of the Atlantic Ocean. GC-MS analyses quantified 17 PAHs in the samples, with highest total PAHs concentrations of 234 ng L-1 in summer and 33.3 ng L-1 in winter, which were consistent with the highest risks observed in ecotoxicity assays. The use of diagnostic ratios showed that the coast was impacted by a mixture of PAHs from petrogenic and pyrolytic sources. The results indicated the need for continuous monitoring of the regions affected by the 2019 spill.

Troubleshooting the influence of trace chemical impurities on nanoparticle growth kinetics via electrochemical measurements.

Reproducibility issues resulting from particle growth solutions made with cetyltrimethylammonium bromide (CTAB) surfactant from different lots and product lines in a newly developed synthesis of monometallic palladium (Pd) tetrahexahedra (THH) nanoparticles are investigated via a multi-pronged approach. Time-resolved electrochemical measurements of solution potential, variation of chemical parameters in colloidal synthesis, and correlation to electrodeposition syntheses are used together to uncover the effects of the unknown contaminants on the chemical reducing environment during nanoparticle growth. Iodide-a known impurity in commercial CTAB-is identified as one of the required components for equalizing the reducing environment across multiple CTAB sources. However, an additional component-acetone-is critical to establishing the growth kinetics necessary to enable the reproducible synthesis of THH in each of the CTAB formulations. In one CTAB variety, the powdered surfactant contains too much acetone, and drying of the as-received surfactant and re-addition of solvent is necessary for successful Pd THH synthesis. The relevance of solvent impurities to the reducing environment in aqueous nanoparticle synthesis is confirmed via electrochemical measurement approaches and solvent addition experiments. This work highlights the utility of real-time electrochemical potential measurements as a tool for benchmarking of nanoparticle syntheses and troubleshooting of reproducibility issues. The results additionally emphasize the importance of considering organic solvent impurities in powdered commercial reagents as a possible shape-determining factor during shaped nanomaterials synthesis.