Branch Thrombus after Endovascular Treatment with Arch Branched Devices for Aortic Arch Pathologies.

OBJECTIVE: The aim of this study was to describe the occurrence of branch thrombosis following endovascular treatment of aortic arch pathology using an arch branched device (ABD) and to determine whether this is influenced by clinical and geometric parameters. METHODS: In this retrospective observational study of patients treated with an ABD in three centres, the primary endpoint was thrombus formation within a branch during follow up. Secondary endpoints were technical success, serious adverse events (SAEs), early and late death, stroke, and re-interventions. Geometric measurements (tortuosity index and curvature) were determined on pre-operative and post-operative computed tomography angiographies. RESULTS: Thirty nine patients were treated and 68 antegrade branches were analysed (innominate artery, n = 27; common carotid artery [CCA], n = 40; left subclavian artery [LSA], n = 1). Thrombus was identified within seven branches (10%) on surveillance imaging (innominate artery, n = 6; CCA, n = 1; LSA, n = 0; p = .021) and was associated with a wider distal bridging stent diameter (median 14.0 mm [interquartile range {IQR} 2.0] vs. 8.7 mm [IQR 5.9]; p = .026), a higher degree of reversed tapering (4.3 mm [IQR 1.4] vs. 1.2 mm [IQR 2.8]; p = .023), use of polyethylene terephthalate (Dacron) covered (vs. expanded polytetrafluoroethylene) bridging stents (23% vs. 2%; p = .011), and higher body mass index (BMI) (32.1 kg/m2 [IQR 7.5] vs. 25.7 kg/m2 [IQR 5.4]; p = .029), but not with pre-operative or post-operative tortuosity index or curvature or alterations. Regarding secondary outcomes, the technical success rate was 97%, SAEs occurred in 15 patients (38%), early and late death rates were 8% and 23%, respectively, and early and late stroke rates were 5% and 23%, respectively. CONCLUSION: The risk of developing branch thrombosis after endovascular intervention with an ABD is considerable, especially of innominate artery branches, characterised by Dacron covered large diameter bridging stents, and in patients with a high BMI. Large prospective studies are required to analyse factors associated with branch thrombosis.

A new method for regionalization of the vertebral column in salmonids based on radiographic hallmarks.

Current procedures to establish vertebral column regionalization (e.g., histology) in fish are time consuming and difficult to apply. The aim of this study was to develop a more rapid and accurate radiology-based method for Atlantic salmon (Salmo salar). A detailed analysis of 90 animals (4 kg) led to the establishment of region-specific radiographic hallmarks. To elucidate its transferability to other salmonid species, radiography was carried out in brown trout (Salmo trutta), Arctic char (Salvelinus alpinus), rainbow trout (Oncorhynchus mykiss), pink salmon (Oncorhynchus gorbuscha), and Chinook salmon (Oncorhynchus tshawytscha). This method was also evaluated for whole ungutted fish. The vertebral column of Atlantic salmon can be subdivided into five regions (R1-R5) based on anatomy: postcranial (R1, V1, and V2), abdominal (R2, V3-V26), transitional (R3, V27-V36), caudal (R4, V37-V53), and ural (R5, V54-V59). The following specific radiographic hallmarks allow the identification of regions: (i) lack of ribs in R1, (ii) modified parapophysis of the first vertebra of R3, (iii) prominent hemal spine of the first vertebra of R4, and (iv) the separated hemal spine of the most cranial pre-ural vertebra of R5. These hallmarks were all transferable to the other salmonid species assessed. The results include a further description of various region-specific characteristics in Atlantic salmon. The method was found applicable for sedated/whole ungutted fish, verifying it as quick and easy compared to other regionalization methods. The regions defined by radiology in this study agree with the vertebral column regions recently defined for Chinook salmon (O. tshawytscha). Thus, and considering the results of this study on various salmonid species, the currently developed regionalization protocol can be generally used for salmonids.

Perihaematomal Oedema Evolution over 2 Weeks after Spontaneous Intracerebral Haemorrhage and Association with Outcome: A Prospective Cohort Study.

INTRODUCTION: We know little about the evolution of perihaematomal oedema (PHO) >24 h after ICH onset. We aimed to determine the trajectory of PHO after ICH onset and its association with outcome. METHODS: We did a prospective cohort study using a pre-specified scanning protocol in adults with first-ever spontaneous ICH and measured absolute PHO volumes on CT head scans at ICH diagnosis and 3 ± 2, 7 ± 2, and 14 ± 2 days after ICH onset. We used the largest ICH if ICHs were multiple. The primary outcomes were (a) the trajectory of PHO after ICH onset and (b) the association between PHO (absolute volume at the time when most repeat CT head scans were obtained, and change in PHO volume at this time compared with the first CT head scan) and poor functional outcome (modified Rankin scale 3-6 at 90 days). We pre-specified multivariable logistic regression models of this association adjusting analyses for potential confounders: age, GCS, infratentorial ICH location, and intraventricular extension. RESULTS: In 106 participants of whom 49 (46%) were female, with a median ICH volume 7 mL (interquartile range [IQR] 2-22 mL), the trajectory of median PHO volume increased from 14 mL (IQR: 7-26 mL) at diagnosis to 18 mL (IQR: 8-40 mL) at 3 ± 2 days (n = 87), 20 mL (IQR: 8-48 mL) at 7 ± 2 days (n = 93) and 21 mL (IQR: 10-54 mL) at 14 ± 2 days (n = 78) (p = <0.001). PHO volume at each time point was collinear with ICH volume at diagnosis (│r│ >0.7), but the change in PHO volume between diagnosis and each time point was not. Given collinearity, we used total lesion (i.e., ICH + PHO) volume instead of PHO volume in a logistic regression model of its association at each time point with outcome. Increasing total lesion (ICH + PHO) volume at day 7 ± 2 was associated with poor functional outcome (adjusted OR per mL 1.02, 95% CI: 1.00-1.03; p = 0.036), but the increase in PHO volume between diagnosis and day 7 ± 2 was not associated with poor functional outcome (adjusted OR per mL 1.03, 95% CI: 0.99-1.07; p = 0.132). CONCLUSION: PHO volume increases throughout the first 2 weeks after onset of mild to moderate ICH. Total lesion (ICH + PHO) volume at day 7 ± 2 was associated with poor functional outcome, but the change in PHO volume between diagnosis and day 7 ± 2 was not. Prospective cohort studies with larger sample sizes are needed to investigate these associations and their modifiers.

Responses to visual motion of neurons in the extrastriate visual cortex of macaque monkeys with experimental amblyopia.

Amblyopia is a developmental disorder that results from abnormal visual experience in early life. Amblyopia typically reduces visual performance in one eye. We studied the representation of visual motion information in area MT and nearby extrastriate visual areas in two monkeys made amblyopic by creating an artificial strabismus in early life, and in a single age-matched control monkey. Tested monocularly, cortical responses to moving dot patterns, gratings, and plaids were qualitatively normal in awake, fixating amblyopic monkeys, with primarily subtle differences between the eyes. However, the number of binocularly driven neurons was substantially lower than normal; of the neurons driven predominantly by one eye, the great majority responded only to stimuli presented to the fellow eye. The small population driven by the amblyopic eye showed reduced coherence sensitivity and a preference for faster speeds in much the same way as behavioral deficits. We conclude that, while we do find important differences between neurons driven by the two eyes, amblyopia does not lead to a large scale reorganization of visual receptive fields in the dorsal stream when tested through the amblyopic eye, but rather creates a substantial shift in eye preference toward the fellow eye.

Loss of bmp15 function in the seasonal spawner Atlantic salmon results in ovulatory failure.

Bone morphogenetic protein 15 (BMP15) is an oocyte-specific growth factor important for successful female reproduction in mammals. While mutations in BMP15/Bmp15 cause ovulatory deficiency and/or infertility in certain mammalian species, loss of bmp15 in zebrafish, a continuous spawner and the only bmp15 knockout model in fish to date, results in complete arrest of follicle development and later female-to-male sex reversal, preventing to examine effects on ovulation/fertilization. Here, we used Atlantic salmon, a seasonal spawner, and generated bmp15 mutants to investigate ovarian development and fertility. Histological and morphometric analyses revealed that in biallelic frameshift (bmp15 fs/fs) mutant ovaries, folliculogenesis started earlier, resulting in an advanced development compared to wild-type (WT) controls, accompanied by a weaker expression of the (early) oocyte-specific factor figla. This precocious ovarian development was followed in bmp15 fs/fs females by enhanced follicle atresia during vitellogenic stages. Although genes involved in steroid synthesis and signaling (star, cyp11b, cyp17a1 and esr1) were dramatically higher in late vitellogenic bmp15 fs/fs mutant ovaries, estradiol-17ß plasma levels were lower than in WT counterparts, potentially reflecting compensatory changes at the level of ovarian gene expression. At spawning, bmp15 fs/fs females displayed lower gonado-somatic index values and reduced oocyte diameter, and the majority (71.4%), showed mature non-ovulating ovaries with a high degree of atresia. The remaining (28.6%) females spawned eggs but they either could not be fertilized or, upon fertilization, showed severe malformations and embryonic mortality. Our results show that Bmp15 is required for proper follicle recruitment and growth and later ovulatory success in Atlantic salmon, providing an alternative candidate target to induce sterility in farmed salmon. Moreover, since loss of bmp15 in salmon, in contrast to zebrafish, does not result in female-to-male sex change, this is the first mutant model in fish allowing further investigations on Bmp15-mediated functions in the ovulatory period.

The Effect of the Menstrual Cycle on Energy Intake: A Systematic Review and Meta-analysis.

CONTEXT: Energy intake may differ across the menstrual cycle, with some studies identifying greater energy intake in the luteal phase (LP) compared with the follicular phase (FP) and others finding no clear differences. To date, no study has systematically synthesized the available data to draw more definite conclusions while considering any methodological inconsistencies between studies. OBJECTIVE: The aim was to conduct a systematic review/meta-analysis in an effort to determine if there are differences in energy intake between the FP and LP. DATA SOURCES: A systematic search strategy was developed and the search was conducted in 5 databases for studies that investigated any changes in energy intake across menstrual phases. DATA EXTRACTION: Using Covidence, studies were identified and included if they contained individuals between the ages of 18 and 45 years, maintained an average body mass index (BMI) of 18.5-25 kg/m2, had no history of disordered eating, and included energy intake and menstrual cycle measurements in the FP and LP. DATA ANALYSIS: Effect sizes were calculated for each study and a random-effects model was used to pool the results of each study. RESULTS: Fifteen datasets were included consisting of 330 female participants with a mean age of 26 ± 4 years and mean BMI of 22.4 ± 2.3 kg/m2. Overall, there was a statistically significant difference (standardized mean difference = 0.69; P = .039) with increased energy intake in the LP compared with the FP (crude 168 kcal⋅d-1 average difference between phases). CONCLUSION: Energy intake was found to be greater in the LP compared with the FP, providing insight into the effect of the menstrual cycle on energy intake. However, there were repeated methodological inconsistencies and future work should strive to utilize best practices for both energy intake measurement and menstrual phase specification.

RG7774 (Vicasinabin), an orally bioavailable cannabinoid receptor 2 (CB2R) agonist, decreases retinal vascular permeability, leukocyte adhesion, and ocular inflammation in animal models.

Introduction: Preclinical studies suggest that cannabinoid receptor type 2 (CB2R) activation has a therapeutic effect in animal models on chronic inflammation and vascular permeability, which are key pathological features of diabetic retinopathy (DR). A novel CB2R agonist, triazolopyrimidine RG7774, was generated through lead optimization of a high-throughput screening hit. The aim of this study was to characterize the pharmacology, absorption, distribution, metabolism, elimination, and toxicity (ADMET) profile of RG7774, and to explore its potential for managing the key pathological features associated with retinal disease in rodents. Methods: The in vitro pharmacology of RG7774 was investigated for CB2R binding and receptor activation using recombinant human and mouse CB2R expression in Chinese hamster ovary cells, and endogenous CB2R expression in human Jurkat cells, and rat and mouse spleen cells. The ADMET profile was evaluated and the effects of RG7774 on retinal permeability, leukocyte adhesion, and choroidal neovascularization (CNV) were investigated in rodent models of retinal disease. Pharmacokinetic (PK) parameters and the exposure-response relationship were characterized in healthy animals and in animals with laser-induced CNV. Results: RG7774 was found to be a potent (EC50: 2.8 nM and Ki: 51.3 nM), selective, and full CB2R agonist with no signs of cannabinoid receptor type 1 (CB1R) binding or activation. The ligand showed a favorable ADMET profile and exhibited systemic and ocular exposure after oral delivery. Functional potency in vitro translated from recombinant to endogenous expression systems. In vivo, orally administered RG7774 reduced retinal permeability and leukocyte adhesion in rodents with lipopolysaccharide (LPS)-induced uveitis and streptozotocin (STZ)-induced DR, and reduced lesion areas in rats with laser-induced CNV with an ED50 of 0.32 mg/kg. Anatomically, RG7774 reduced the migration of retinal microglia to retinal lesions. Discussion: RG7774 is a novel, highly selective, and orally bioavailable CB2R agonist, with an acceptable systemic and ocular PK profile, and beneficial effects on retinal vascular permeability, leukocyte adhesion, and ocular inflammation in rodent animal models. Results support the development of RG7774 as a potential treatment for retinal diseases with similar pathophysiologies as addressed by the animal models.

Effects of allopurinol and febuxostat on uric acid transport and transporter expression in human umbilical vein endothelial cells.

Uric acid induces radical oxygen species formation, endothelial inflammation, and endothelial dysfunction which contributes to the progression of atherosclerosis. Febuxostat inhibits BCRP- and allopurinol stimulates MRP4-mediated uric acid efflux in human embryonic kidney cells. We hypothesized that endothelial cells express uric acid transporters that regulate intracellular uric acid concentration and that modulation of these transporters by febuxostat and allopurinol contributes to their different impact on cardiovascular mortality. The aim of this study was to explore a potential difference between the effect of febuxostat and allopurinol on uric acid uptake by human umbilical vein endothelial cells. Febuxostat increased intracellular uric acid concentrations compared with control. In contrast, allopurinol did not affect intracellular uric acid concentration. In line with this observation, febuxostat increased mRNA expression of GLUT9 and reduced MRP4 expression, while allopurinol did not affect mRNA expression of these uric acid transporters. These findings provide a possible pathophysiological pathway which could explain the higher cardiovascular mortality for febuxostat compared to allopurinol but should be explored further.

Modulation of TMEM16B channel activity by the calcium-activated chloride channel regulator 4 (CLCA4) in human cells.

The Ca2+-activated Cl- channel regulator CLCA1 potentiates the activity of the Ca2+-activated Cl- channel (CaCC) TMEM16A by directly engaging the channel at the cell surface, inhibiting its reinternalization and increasing Ca2+-dependent Cl- current (ICaCC) density. We now present evidence of functional pairing between two other CLCA and TMEM16 protein family members, namely CLCA4 and the CaCC TMEM16B. Similar to CLCA1, (i) CLCA4 is a self-cleaving metalloprotease, and the N-terminal portion (N-CLCA4) is secreted; (ii) the von Willebrand factor type A (VWA) domain in N-CLCA4 is sufficient to potentiate ICaCC in HEK293T cells; and (iii) this is mediated by the metal ion-dependent adhesion site motif within VWA. The results indicate that, despite the conserved regulatory mechanism and homology between CLCA1 and CLCA4, CLCA4-dependent ICaCC are carried by TMEM16B, rather than TMEM16A. Our findings show specificity in CLCA/TMEM16 interactions and suggest broad physiological and pathophysiological links between these two protein families.

Alleviating nanostructural phase impurities enhances the optoelectronic properties, device performance and stability of cesium-formamidinium metal-halide perovskites.

The technique of alloying FA+ with Cs+ is often used to promote structural stabilization of the desirable α-FAPbI3 phase in halide perovskite devices. However, the precise mechanisms by which these alloying approaches improve the optoelectronic quality and enhance the stability have remained elusive. In this study, we advance that understanding by investigating the effect of cationic alloying in CsxFA1-xPbI3 perovskite thin-films and solar-cell devices. Selected-area electron diffraction patterns combined with microwave conductivity measurements reveal that fine Cs+ tuning (Cs0.15FA0.85PbI3) leads to a minimization of stacking faults and an increase in the photoconductivity of the perovskite films. Ultra-sensitive external quantum efficiency, kelvin-probe force microscopy and photoluminescence quantum yield measurements demonstrate similar Urbach energy values, comparable surface potential fluctuations and marginal impact on radiative emission yields, respectively, irrespective of Cs content. Despite this, these nanoscopic defects appear to have a detrimental impact on inter-grains'/domains' carrier transport, as evidenced by conductive-atomic force microscopy and corroborated by drastically reduced solar cell performance. Importantly, encapsulated Cs0.15FA0.85PbI3 devices show robust operational stability retaining 85% of the initial steady-state power conversion efficiency for 1400 hours under continuous 1 sun illumination at 35 °C, in open-circuit conditions. Our findings provide nuance to the famous defect tolerance of halide perovskites while providing solid evidence about the detrimental impact of these subtle structural imperfections on the long-term operational stability.

Clinical indications and protocol considerations for selecting initial body weight support levels in gait rehabilitation: a systematic review.

BACKGROUND: Body weight support (BWS) training devices are frequently used to improve gait in individuals with neurological impairments, but guidance in selecting an appropriate level of BWS is limited. Here, we aim to describe the initial BWS levels used during gait training, the rationale for this selection and the clinical goals aligned with BWS training for different diagnoses. METHOD: A systematic literature search was conducted in PubMed, Embase and Web of Science, including terms related to the population (individuals with neurological disorders), intervention (BWS training) and outcome (gait). Information on patient characteristics, type of BWS device, BWS level and training goals was extracted from the included articles. RESULTS: Thirty-three articles were included, which described outcomes using frame-based (stationary or mobile) and unidirectional ceiling-mounted devices on four diagnoses (multiple sclerosis (MS), spinal cord injury (SCI), stroke, traumatic brain injury (TBI)). The BWS levels were highest for individuals with MS (median: 75%, IQR: 6%), followed by SCI (median: 40%, IQR: 35%), stroke (median: 30%, IQR: 4.75%) and TBI (median: 15%, IQR: 0%). The included studies reported eleven different training goals. Reported BWS levels ranged between 30 and 75% for most of the training goals, without a clear relationship between BWS level, diagnosis, training goal and rationale for BWS selection. Training goals were achieved in all included studies. CONCLUSION: Initial BWS levels differ considerably between studies included in this review. The underlying rationale for these differences was not clearly motivated in the included studies. Variation in study designs and populations does not allow to draw a conclusion on the effectiveness of BWS levels. Hence, it remains difficult to formulate guidelines on optimal BWS settings for different diagnoses, BWS devices and training goals. Further efforts are required to establish clinical guidelines and to experimentally investigate which initial BWS levels are optimal for specific diagnoses and training goals.

Clinical management of liver cyst infections: an international, modified Delphi-based clinical decision framework.

Liver cyst infections often necessitate long-term hospital admission and are associated with considerable morbidity and mortality. We conducted a modified Delphi study to reach expert consensus for a clinical decision framework. The expert panel consisted of 24 medical specialists, including 12 hepatologists, from nine countries across Europe, North America, and Asia. The Delphi had three rounds. The first round (response rate 21/24 [88%]) was an online survey with questions constructed from literature review and expert opinion, in which experts were asked about their management preferences and rated possible management strategies for seven clinical scenarios. Experts also rated 14 clinical decision-making items for relevancy and defined treatment outcomes. During the second round (response rate 13/24 [54%]), items that did not reach consensus and newly suggested themes were discussed in an online panel meeting. In the third round (response rate 16/24 [67%]), experts voted on definitions and management strategies using an online survey based on previous answers. Consensus was predefined as a vote threshold of at least 75%. We identified five subclassifications of liver cyst infection according to cyst phenotypes and patient immune status and consensus on episode definitions (new, persistent, and recurrent) and criteria for treatment success or failure was reached. The experts agreed that fever and elevated C-reactive protein are pivotal decision-making items for initiating and evaluating the management of liver cyst infections. Consensus was reached on 26 management statements for patients with liver cyst infections across multiple clinical scenarios, including two treatment algorithms, which were merged into one after comments. We provide a clinical decision framework for physicians managing patients with liver cyst infections. This framework will facilitate uniformity in the management of liver cyst infections and can constitute the basis for the development of future guidelines.

Analysis of the Retinal and Choroidal Vasculature Using Ultrawidefield Fundus Imaging in Mild Cognitive Impairment and Normal Cognition.

Purpose: To utilize ultrawidefield (UWF) imaging to evaluate retinal and choroidal vasculature and structure in individuals with mild cognitive impairment (MCI) compared with that of controls with normal cognition. Design: Prospective cross sectional study. Participants: One hundred thirty-one eyes of 82 MCI patients and 230 eyes of 133 cognitively normal participants from the Eye Multimodal Imaging in Neurodegenerative Disease Study. Methods: A scanning laser ophthalmoscope (California, Optos Inc) was used to obtain UWF fundus color images. Images were analyzed with the Vasculature Assessment Platform for Images of the Retina UWF (VAMPIRE-UWF 2.0, Universities of Edinburgh and Dundee) software. Main outcome measures: Imaging parameters included vessel width gradient, vessel width intercept, large vessel choroidal vascular density, vessel tortuosity, and vessel fractal dimension. Results: Both retinal artery and vein width gradients were less negative in MCI patients compared with controls, demonstrating decreased rates of vessel thinning at the periphery (P < 0.001; P = 0.027). Retinal artery and vein width intercepts, a metric that extrapolates the width of the vessel at the center of the optic disc, were smaller in MCI patients compared with that of controls (P < 0.001; P = 0.017). The large vessel choroidal vascular density, which quantifies the vascular area versus the total choroidal area, was greater in MCI patients compared with controls (P = 0.025). Conclusions: When compared with controls with normal cognition, MCI patients had thinner retinal vasculature manifested in both the retinal arteries and the veins. In MCI, these thinner arteries and veins attenuated at a lower rate when traveling toward the periphery. MCI patients also had increased choroidal vascular density. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Somatostatin receptor 2A expression in von Hippel-Lindau-related hemangioblastomas.

BACKGROUND: Central nervous system hemangioblastomas are the most prevalent manifestation of von Hippel-Lindau (VHL) disease and remain the main cause of mortality. Surgical resection is the primary treatment strategy, but is not always possible, and should be used as restrictively as possible. There is an unmet need for less invasive treatment strategies, such as targeted therapy. Expression of somatostatin receptor 2A (SSTR2A) in VHL-related hemangioblastomas has been described earlier, but the extent of expression in a larger population has yet to be determined. The authors hypothesize that a substantial subset of VHL-related hemangioblastomas show SSTR2A expression, which may serve as a potential new treatment target. METHODS: Patients who were surgically treated for a VHL-related hemangioblastoma from 1990 until 2021 at the UMC Utrecht were included. Clinical data was derived from a clinical database. Tissue samples were histopathologically examined with use of hematoxylin and eosin staining, and immunohistochemical analysis of SSTR2A expression was performed. RESULTS: Forty-three tissue samples were obtained from 26 patients. Nine showed strong positivity for SSTR2A expression, whereas 13 showed moderate and 15 sparse expression. Three samples showed no expression of SSTR2A. The distribution showed right-skewedness favoring a strong expression. SSTR2A expression colocalized with endothelial markers and not with stromal cells. Additionally, within-patient variability for SSTR2A expression was described in 14 patients. CONCLUSION: SSTR2A is expressed in varying degrees in the majority of VHL-related hemangioblastomas. Future treatment with somatostatin analogues or even peptide receptor radionuclide treatment may be considered for SSTR2A-positive cases.

Upper Extremity Surgeon Recommendations for Imaging Do Not Correspond with Imaging Appropriateness Guidelines.

Background: Utilization of magnetic resonance imaging (MRI) and computed tomography (CT) increases annually, raising concerns about overuse. Imaging appropriateness guidelines have the potential to standardize decisions regarding imaging based on best evidence, which might reduce unhelpful or potentially misleading imaging. We studied expert use of advanced imaging for musculoskeletal illness compared to published appropriateness recommendations. Methods: First, 15 imaging guidelines with recommendations for advanced imaging of the upper extremity were collated. Next, members of the Science of Variation Group (SOVG) were invited to participate in a survey of 11 patient scenarios of common upper extremity illnesses and asked whether they would recommend MRI or CT. Guideline recommendations for imaging were compared with surgeon recommendations using Fisher's exact tests. We used Fleiss' kappa to measure the interobserver agreement among surgeons. Results: For the 11 scenarios, most imaging appropriateness guidelines suggested that MRI or CT is useful, while most surgeons (n = 108) felt it was not. There was no correlation between surgeons and guidelines recommendations for imaging (ρ = 0.28; p = 0.40). There was slight agreement among surgeons regarding imaging recommendations (kappa: 0.17; 95% confidence interval: 0.023-0.32). Conclusion: The available imaging appropriateness guidelines appear to be too permissive and therefore seem to have limited clinical utility for upper extremity surgeons. The notable surgeon-to-surgeon variation (unreliability) in recommendations for advanced imaging in this and other studies suggests a role for strategies to ensure that patient decisions about imaging are consistent with their values (what matters most to them) and not unduly influenced by patient misconceptions about imaging or by surgeon beliefs and habits. Level Of Evidence: II, diagnostic.

Squamate scavenging services: Heath goannas (Varanus rosenbergi) support carcass removal and may suppress agriculturally damaging blowflies.

Human-induced environmental change has caused widespread loss of species that support important functions for ecosystems and society. For example, vertebrate scavengers contribute to the functional health of ecosystems and provide services to agricultural landscapes by removing carcasses and associated pests. Widespread extirpation of native Australian mammals since the arrival of Europeans in Australia has removed many scavenging species from landscapes, while scavenging mammals such as European red foxes (Vulpes vulpes) have been introduced. In much of Australia, squamate reptiles are the largest native terrestrial scavengers remaining, where large native mammals are extinct and conservation management is being undertaken to remove invasive mammals. The contribution of reptiles to scavenging functions is not well understood. In this study, we investigated the ecosystem functions provided by large reptiles as scavengers to better understand how populations can be managed to support ecosystem services. We investigated the ecosystem services provided by vertebrate scavengers in Australian coastal mallee ecosystems, focusing on the heath goanna (Varanus rosenbergi), the only extant native terrestrial scavenger in the region. We carried out exclosure experiments, isolating the scavenging activity of different taxonomic groups to quantify the contribution of different taxa to scavenging services, specifically the removal of rat carcasses, and its impact on the occurrence of agriculturally damaging blowflies. We compared areas with different native and invasive scavenger communities to investigate the impact of invasive species removal and native species abundance on scavenging services. Our results indicated that vertebrate scavenging significantly contributes to carcass removal and limitation of necrophagous fly breeding in carcasses and that levels of removal are higher in areas associated with high densities of heath goannas and low densities of invasive mammals. Therefore, augmentation of heath goanna populations represents a promising management strategy to restore and maximize scavenging ecosystem services.

Genomic and Phenotypic Safety Assessment of Probiotic Bacillus coagulans Strain JBI-YZ6.3.

Spore-forming Bacillus coagulans has been widely recognized as an important probiotic, which is commonly used in products for human consumption and animal feeds. B. coagulans exhibits beneficial traits from both Bacillus and lactic acid-producing Lactobacillus. The present study evaluated the safety of the newly isolated B. coagulans strain JBI-YZ6.3, using combined genomic and phenotypic analysis approaches. The taxonomic classification based on genome sequence and biochemical tests identified strain JBI-YZ6.3 as B. coagulans. Comprehensive genome-based analyses established JBI-YZ6.3 as a novel strain of B. coagulans. Antibiotic susceptibility testing showed that the strain JBI-YZ6.3 was sensitive to a panel of fourteen antibiotics, and no genes related to antibiotic resistance were found in its genome. The spores of strain JBI-YZ6.3 exhibited tolerance to acid and bile salts, as well as stability at ambient and elevated conditions of temperature and relative humidity. There were no homologs of Bacillus toxin genes identified in the genome of JBI-YZ6.3, and the strain exhibited no cytotoxicity towards Vero cells and human peripheral blood mononuclear cells. In conclusion, findings from this study support the safety of B. coagulans strain JBI-YZ6.3, which can be developed into new probiotic products for preventive and therapeutic benefits in human and animal hosts.

INSPIRE, a publicly available research dataset for perioperative medicine.

We present the INSPIRE dataset, a publicly available research dataset in perioperative medicine, which includes approximately 130,000 surgical operations at an academic institution in South Korea over a ten-year period between 2011 and 2020. This comprehensive dataset includes patient characteristics such as age, sex, American Society of Anesthesiologists physical status classification, diagnosis, surgical procedure code, department, and type of anaesthesia. The dataset also includes vital signs in the operating theatre, general wards, and intensive care units (ICUs), laboratory results from six months before admission to six months after discharge, and medication during hospitalisation. Complications include total hospital and ICU length of stay and in-hospital death. We hope this dataset will inspire collaborative research and development in perioperative medicine and serve as a reproducible external validation dataset to improve surgical outcomes.

Paternal Inheritance of Mitochondrial DNA May Lead to Dioecy in Conifers.

In angiosperms cytoplasmic DNA is typically passed on maternally through ovules. Genes in the mtDNA may cause male sterility. When male-sterile (female) cytotypes produce more seeds than cosexuals, they pass on more copies of their mtDNA and will co-occur with cosexuals with a neutral cytotype. Cytoplasmic gynodioecy is a well-known phenomenon in angiosperms, both in wild and crop plants. In some conifer families (e.g. Pinaceae) mitochondria are also maternally inherited. However in some other families (e.g. Taxaceae and Cupressaceae) mtDNA is paternally inherited through the pollen. With paternal mtDNA inheritance, male cytotypes that produce more pollen than cosexuals are expected to co-occur with cosexuals. This is uncharted territory. An ESS model shows that the presence of male cytotypes selects for more female allocation in the cosexual, i.e. for sexual specialisation. An allele that switches sex from male to female can then invade. This leads to rapid loss of the neutral cytotype of the cosexual, fixation of the male cytotype and dioecy with 50% males and 50% females. The models suggest that paternal inheritance of mtDNA facilitates the evolution dioecy. Consistent with this hypothesis the Pinaceae are 100% monoecious, while dioecy is common in the Taxaceae family and in the genus Juniperus (Cupressaceae). However, no reliable data are yet available on both mode of inheritance of mtDNA and gender variation of the same species. When cosexuals benefit from reproductive assurance (high selfing rate, low inbreeding depression, low fertilisation) they maintain themselves next to males and females. This predicted pattern with three sex types present in the same population is observed in conifers in nature.

Sex-specific differences in the mechanisms for enhanced thromboxane A2-mediated vasoconstriction in adult offspring exposed to prenatal hypoxia.

BACKGROUND: Prenatal hypoxia, a common pregnancy complication, leads to impaired cardiovascular outcomes in the adult offspring. It results in impaired vasodilation in coronary and mesenteric arteries of the adult offspring, due to reduced nitric oxide (NO). Thromboxane A2 (TxA2) is a potent vasoconstrictor increased in cardiovascular diseases, but its role in the impact of prenatal hypoxia is unknown. To prevent the risk of cardiovascular disease by prenatal hypoxia, we have tested a maternal treatment using a nanoparticle-encapsulated mitochondrial antioxidant (nMitoQ). We hypothesized that prenatal hypoxia enhances vascular TxA2 responses in the adult offspring, due to decreased NO modulation, and that this might be prevented by maternal nMitoQ treatment. METHODS: Pregnant Sprague-Dawley rats received a single intravenous injection (100 µL) of vehicle (saline) or nMitoQ (125 µmol/L) on gestational day (GD)15 and were exposed to normoxia (21% O2) or hypoxia (11% O2) from GD15 to GD21 (term = 22 days). Coronary and mesenteric arteries were isolated from the 4-month-old female and male offspring, and vasoconstriction responses to U46619 (TxA2 analog) were evaluated using wire myography. In mesenteric arteries, L-NAME (pan-NO synthase (NOS) inhibitor) was used to assess NO modulation. Mesenteric artery endothelial (e)NOS, and TxA2 receptor expression, superoxide, and 3-nitrotyrosine levels were assessed by immunofluorescence. RESULTS: Prenatal hypoxia resulted in increased U46619 responsiveness in coronary and mesenteric arteries of the female offspring, and to a lesser extent in the male offspring, which was prevented by nMitoQ. In females, there was a reduced impact of L-NAME in mesenteric arteries of the prenatal hypoxia saline-treated females, and reduced 3-nitrotyrosine levels. In males, L-NAME increased U46619 responses in mesenteric artery to a similar extent, but TxA2 receptor expression was increased by prenatal hypoxia. There were no changes in eNOS or superoxide levels. CONCLUSIONS: Prenatal hypoxia increased TxA2 vasoconstrictor capacity in the adult offspring in a sex-specific manner, via reduced NO modulation in females and increased TP expression in males. Maternal placental antioxidant treatment prevented the impact of prenatal hypoxia. These findings increase our understanding of how complicated pregnancies can lead to a sex difference in the programming of cardiovascular disease in the adult offspring.

Prenatal hypoxia, when the fetus does not receive enough oxygen, is a common problem during pregnancy that impacts the developing fetus. It is associated with an increased risk of cardiovascular disease in the offspring in adulthood. While the mechanisms are not fully understood, the blood vessel function in the offspring may be impacted by prenatal hypoxia. We hypothesize that prenatal hypoxia increases the constriction of the blood vessels in the offspring. The placenta, an essential organ for fetal development, supplies oxygen and nutrients to the fetus. In prenatal hypoxia pregnancies, the placenta does not work properly. We have been studying a placental treatment (called nMitoQ) to improve placenta function and thereby the blood vessel function of the offspring. We used a rat model of prenatal hypoxia, where pregnant rats (dams) were placed in a low oxygen environment (hypoxia) during the last trimester of pregnancy. Control rats were kept in normal oxygen conditions. The dams were treated with nMitoQ, or with saline (control). Next, we studied the blood vessels of the offspring in adulthood. We found that prenatal hypoxia increases the constriction of the blood vessels, which was prevented by treating the dams with nMitoQ. Interestingly, this impact was more severe in females compared to males, and the mechanisms were different between the sexes. This study helps in the understanding of how complicated pregnancies can impair cardiovascular health in the offspring, and in a potential development of targeted and sex-specific therapies for those offspring at high risk for future cardiovascular disease.