Search

An abdominal aortic aneurysm (AAA) is a pathological local dilatation of the abdominal aorta that may develop from a variety of causes. With a 80% mortality rate, it is mainly linked to male gender, age above 65 years, smoking, and a family history of AAA. Ultrasonography is an effective method for screening males who are 65 or older for AAA. Endovascular aneurysm repair (EVAR) procedure reduces 30-day operative mortality and hospital stay, becoming a global standard. Both open and endovascular surgery aim to cut off the aneurysm's circulation, preventing it from rupturing. Diabetes mellitus (DM) may provide protection against regrowth and the need for additional intervention after endovascular AAA repair, thereby limiting the enlargement and rupture of AAAs. Hyperglycemia thickens the aortic walls and reduces wall stress in diabetic patients' abdominal aortas. It stabilizes collagen structure and promotes the synthesis of collagen type IV. Anti-diabetic drugs like metformin, thiazolidinedione, and dipeptidyl peptidase 4 inhibitors (DPP-4i) have been shown in both animal and human studies to protect against aortic aneurysms. In a dose-response pattern, these antidiabetic drugs may lower the prevalence, incidence, and enlargement rate of AAA. [ABSTRACT FROM AUTHOR]

Meningiomas are the most common neoplasms of the central nervous system, accounting for approximately 40% of all brain tumors. Surgical resection represents the mainstay of management for symptomatic lesions. Preoperative planning is largely informed by neuroimaging, which allows for evaluation of anatomy, degree of parenchymal invasion, and extent of peritumoral edema. Recent advances in imaging technology have expanded the purview of neuroradiologists, who play an increasingly important role in meningioma diagnosis and management. Tumor vascularity can now be determined using arterial spin labeling and dynamic susceptibility contrast‐enhanced sequences, allowing the neurosurgeon or neurointerventionalist to assess patient candidacy for preoperative embolization. Meningioma consistency can be inferred based on signal intensity; emerging machine learning technologies may soon allow radiologists to predict consistency long before the patient enters the operating room. Perfusion imaging coupled with magnetic resonance spectroscopy can be used to distinguish meningiomas from malignant meningioma mimics. In this comprehensive review, we describe key features of meningiomas that can be established through neuroimaging, including size, location, vascularity, consistency, and, in some cases, histologic grade. We also summarize the role of advanced imaging techniques, including magnetic resonance perfusion and spectroscopy, for the preoperative evaluation of meningiomas. In addition, we describe the potential impact of emerging technologies, such as artificial intelligence and machine learning, on meningioma diagnosis and management. A strong foundation of knowledge in the latest meningioma imaging techniques will allow the neuroradiologist to help optimize preoperative planning and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Signals emanating from the T-cell receptor (TCR), co-stimulatory receptors, and cytokine receptors each influence CD8 T-cell fate. Understanding how these signals respond to homeostatic and microenvironmental cues can reveal new ways to therapeutically direct T-cell function. Through forward genetic screening in mice, we discover that loss-of-function mutations in LDL receptor-related protein 10 (Lrp10) cause naive and central memory CD8 T cells to accumulate in peripheral lymphoid organs. Lrp10 encodes a conserved cell surface protein of unknown immunological function. T-cell activation induces Lrp10 expression, which post-translationally suppresses IL7 receptor (IL7R) levels. Accordingly, Lrp10 deletion enhances T-cell homeostatic expansion through IL7R signaling. Lrp10 -deficient mice are also intrinsically resistant to syngeneic tumors. This phenotype depends on dense tumor infiltration of CD8 T cells, which display increased memory cell characteristics, reduced terminal exhaustion, and augmented responses to immune checkpoint inhibition. Here, we present Lrp10 as a new negative regulator of CD8 T-cell homeostasis and a host factor that controls tumor resistance with implications for immunotherapy. Synopsis: Lrp10 is a putative cell surface receptor with unknown functions in immunity. This study shows that Lrp10 prevents accumulation of peripheral CD8 T cells, suppresses IL7R expression to limit homeostatic expansion, and impairs anti-tumor immune responses. Genetic deletion of Lrp10 causes an increased number of peripheral CD8 T cells in mice. Lrp10 is induced upon T cell activation and post-translationally suppresses IL7R expression. Lrp10 reduces CD8 central memory differentiation, T cell homeostatic expansion, and IL7 responsiveness. Lrp10 deletion promotes CD8 T cell infiltration, resulting in enhanced anti-tumor immunity and susceptibility to immune checkpoint inhibition. Lrp10 is a putative cell surface receptor with unknown functions in immunity. This study shows that Lrp10 prevents accumulation of peripheral CD8 T cells, suppresses IL7R expression to limit homeostatic expansion, and impairs anti-tumor immune responses. [ABSTRACT FROM AUTHOR]

We use angular clustering of luminous red galaxies from the Dark Energy Spectroscopic Instrument (DESI) imaging surveys to constrain the local primordial non-Gaussianity parameter f NL. Our sample comprises over 12 million targets, covering 14 000 deg2 of the sky, with redshifts in the range 0.2 < z < 1.35. We identify Galactic extinction, survey depth, and astronomical seeing as the primary sources of systematic error, and employ linear regression and artificial neural networks to alleviate non-cosmological excess clustering on large scales. Our methods are tested against simulations with and without f NL and systematics, showing superior performance of the neural network treatment. The neural network with a set of nine imaging property maps passes our systematic null test criteria, and is chosen as the fiducial treatment. Assuming the universality relation, we find |$f_{\rm NL} = 34^{+24(+50)}_{-44(-73)}$| at 68 per cent (95 per cent) confidence. We apply a series of robustness tests (e.g. cuts on imaging, declination, or scales used) that show consistency in the obtained constraints. We study how the regression method biases the measured angular power spectrum and degrades the f NL constraining power. The use of the nine maps more than doubles the uncertainty compared to using only the three primary maps in the regression. Our results thus motivate the development of more efficient methods that avoid overcorrection, protect large-scale clustering information, and preserve constraining power. Additionally, our results encourage further studies of f NL with DESI spectroscopic samples, where the inclusion of 3D clustering modes should help separate imaging systematics and lessen the degradation in the f NL uncertainty. [ABSTRACT FROM AUTHOR]

Despite the availability of life-extending treatments for B cell leukemias and lymphomas, many of these cancers remain incurable. Thus, the development of new molecular targets and therapeutics is needed to expand treatment options. To identify new molecular targets, we used a forward genetic screen in mice to identify genes required for development or survival of lymphocytes. Here, we describe Zfp574, an essential gene encoding a zinc finger protein necessary for normal and malignant lymphocyte survival. We show that ZFP574 interacts with zinc finger protein THAP12 and promotes the G1-to-S-phase transition during cell cycle progression. Mutation of ZFP574 impairs nuclear localization of the ZFP574-THAP12 complex. ZFP574 or THAP12 deficiency results in cell cycle arrest and impaired lymphoproliferation. Germline mutation, acute gene deletion, or targeted degradation of ZFP574 suppressed Myc-driven B cell leukemia in mice, but normal B cells were largely spared, permitting long-term survival, whereas complete lethality was observed in control animals. Our findings support the identification of drugs targeting ZFP574-THAP12 as a unique strategy to treat B cell malignancies. [ABSTRACT FROM AUTHOR]

Gilbert's syndrome is the most common inherited jaundice worldwide. It affects 5-10% of the population. It is caused by a mutation of the UGT1A1 gene, which results in impaired bilirubin metabolism. It is a benign disease and does not affect the life expectancy of patients. Patients with Gilbert's syndrome should be alert to factors that exacerbate the course of the disease, interactions with medications taken and possible comorbidities such as hemolytic anemia, cholelithiasis or schizophrenia. However, it is the responsibility of physicians with such patients under their care to properly educate patients. Gilbert's syndrome carries not only the consequences associated with the mutation, but also has many benefits that patients may not be fully aware of. Mildly elevated bilirubin levels have an antioxidant and anti-inflammatory effect, which prevents the development of lifestyle diseases and cancer. Ongoing clinical trials suggest that this could be a great step toward new treatments for diseases affecting the entire human population. PURPOSE OF THE WORK: This review paper aims to show Gilbert's syndrome as a multifaceted disease and to sensitize doctors' attention to patients with the described mutation. MATERIALS AND METHODS: An analysis of papers available in PubMed and Google Scholar was performed using the following key words: Gilbert's syndrome, bilirubin, UDPglucuronosyltransferase, Gilbert's syndrome harmful and protective aspects, iatrogenic Gilbert's syndrome. RESULTS: The result of the work is to present Gilbert's syndrome as a disease that carries medical problems directly related to the mutation, but also, in some cases, has a protective effect on affected individuals. The work highlights the complexity of the problem. [ABSTRACT FROM AUTHOR]

Genetic mouse models of skeletal abnormalities have demonstrated promise in the identification of phenotypes relevant to human skeletal diseases. Traditionally, phenotypes are assessed by manually examining radiographs, a tedious and potentially error-prone process. In response, this study developed a deep learning-based model that streamlines the measurement of murine bone lengths from radiographs in an accurate and reproducible manner. A bone detection and measurement pipeline utilizing the Keypoint R-CNN algorithm with an EfficientNet-B3 feature extraction backbone was developed to detect murine bone positions and measure their lengths. The pipeline was developed utilizing 94 X-ray images with expert annotations on the start and end position of each murine bone. The accuracy of our pipeline was evaluated on an independent dataset test with 592 images, and further validated on a previously published dataset of 21,300 mouse radiographs. The results showed that our model performed comparably to humans in measuring tibia and femur lengths (R2 > 0.92, p-value = 0) and significantly outperformed humans in measuring pelvic lengths in terms of precision and consistency. Furthermore, the model improved the precision and consistency of genetic association mapping results, identifying significant associations between genetic mutations and skeletal phenotypes with reduced variability. This study demonstrates the feasibility and efficiency of automated murine bone length measurement in the identification of mouse models of abnormal skeletal phenotypes. [ABSTRACT FROM AUTHOR]

Combining galaxy clustering information from regions of different environmental densities can help break cosmological parameter degeneracies and access non-Gaussian information from the density field that is not readily captured by the standard two-point correlation function (2PCF) analyses. However, modelling these density-dependent statistics down to the non-linear regime has so far remained challenging. We present a simulation-based model that is able to capture the cosmological dependence of the full shape of the density-split clustering (DSC) statistics down to intra-halo scales. Our models are based on neural-network emulators that are trained on high-fidelity mock galaxy catalogues within an extended-ΛCDM framework, incorporating the effects of redshift-space, Alcock–Paczynski distortions, and models of the halo–galaxy connection. Our models reach sub-per cent level accuracy down to |$1 \, h^{-1}\text{Mpc}$| and are robust against different choices of galaxy–halo connection modelling. When combined with the galaxy 2PCF, DSC can tighten the constraints on ωcdm, σ8, and ns by factors of 2.9, 1.9, and 2.1, respectively, compared to a 2PCF-only analysis. DSC additionally puts strong constraints on environment-based assembly bias parameters. [ABSTRACT FROM AUTHOR]

We present a clustering analysis of the BOSS DR12 CMASS galaxy sample, combining measurements of the galaxy two-point correlation function and density-split clustering down to a scale of |$1 \, h^{-1}\, \text{Mpc}$|⁠. Our theoretical framework is based on emulators trained on high-fidelity mock galaxy catalogues that forward model the cosmological dependence of the clustering statistics within an extended-ΛCDM framework, including redshift-space and Alcock–Paczynski distortions. Our base-ΛCDM analysis finds ωcdm = 0.1201 ± 0.0022, σ8 = 0.792 ± 0.034, and ns  = 0.970 ± 0.018, corresponding to f σ8 = 0.462 ± 0.020 at z ≈ 0.525, which is in agreement with Planck 2018 predictions and various clustering studies in the literature. We test single-parameter extensions to base-ΛCDM, varying the running of the spectral index, the dark energy equation of state, and the density of mass-less relic neutrinos, finding no compelling evidence for deviations from the base model. We model the galaxy–halo connection using a halo occupation distribution framework, finding signatures of environment-based assembly bias in the data. We validate our pipeline against mock catalogues that match the clustering and selection properties of CMASS, showing that we can recover unbiased cosmological constraints even with a volume 84 times larger than the one used in this study. [ABSTRACT FROM AUTHOR]

Evolution depends upon genetic variations that influence physiology. As defined in a genetic screen, phenotypic performance may be enhanced or degraded by such mutations. We set out to detect mutations that influence motor function, including motor learning. Thus, we tested the motor effects of 36,444 non‐synonymous coding/splicing mutations induced in the germline of C57BL/6J mice with N‐ethyl–N‐nitrosourea by measuring changes in the performance of repetitive rotarod trials while blinded to genotype. Automated meiotic mapping was used to implicate individual mutations in causation. In total, 32,726 mice bearing all the variant alleles were screened. This was complemented with the simultaneous testing of 1408 normal mice for reference. In total, 16.3% of autosomal genes were thus rendered detectably hypomorphic or nullified by mutations in homozygosity and motor tested in at least three mice. This approach allowed us to identify superperformance mutations in Rif1, Tk1, Fan1 and Mn1. These genes are primarily related, among other less well‐characterized functions, to nucleic acid biology. We also associated distinct motor learning patterns with groups of functionally related genes. These functional sets included, preferentially, histone H3 methyltransferase activity for mice that learnt at an accelerated rate relative to the remaining mutant mice. The results allow for an estimation of the fraction of mutations that can modify a behaviour influential for evolution such as locomotion. They may also enable, once the loci are further validated and the mechanisms elucidated, the harnessing of the activity of the newly identified genes to enhance motor ability or to counterbalance disability or disease. Key points: We studied the effect of chemically induced random mutations on mouse motor performance.An array of mutations influenced the rate of motor learning.DNA regulation genes predominated among these mutant loci.Several mutations in unsuspected genes led to superperformance.Assuming little‐biased mutagenicity, the results allow for an estimation of the probability for any spontaneous mutation to influence a behaviour such as motor learning and ultimate performance. [ABSTRACT FROM AUTHOR]

Background: Mechanical thrombectomy represents a mainstay of management for acute ischemic stroke in the setting of large vessel occlusion. However, there are no clinical practice guidelines defining the role of thrombectomy at the extremes of age. In this scoping review, we aimed to summarize the existing medical and neurosurgical literature pertaining to mechanical thrombectomy in nonagenarians. The PubMed database was queried using the following terms and relevant citations assessed: "thrombectomy nonagenarian," "thrombectomy age 90," "stroke nonagenarian," and "ischemic stroke thrombectomy." Common measurable outcomes, including mortality, modified Rankin scale (mRS) score, and thrombolysis in cerebral infarction (TICI) scale score, were utilized to compare results. Summary: Thrombectomy was shown to improve functional outcomes in all eight of the studies included in the analysis. Mortality was assessed in only two reported studies, and thrombectomy was shown to provide a mortality benefit in 1 study among patients for whom first-pass reperfusion was achieved. Other outcomes of reported interest included greater early neurologic recovery at discharge and improved functional outcomes at 90 days among nonagenarians who underwent thrombectomy as compared to those who received thrombolytic therapy alone. Nonagenarians with good functional status at baseline were the most likely to have favorable outcomes. Key Messages: Mechanical thrombectomy improves outcomes among nonagenarians presenting with acute ischemic stroke due to large vessel occlusion. Further large-scale prospective studies are warranted to optimize patient selection and develop clinical practice guidelines specific to this important patient demographic. [ABSTRACT FROM AUTHOR]

Aesthetic medicine is a rapidly developing branch of modern medicine. Its main procedures include needle-based procedures such as mesotherapy, botulinum toxin injections and filler injections. Each of them may result in unwanted complications. In the case of mesotherapy, the complications are usually local, while in the case of the usage of botulinum toxin, there have been reports of deaths, whereas filler injections have been reported to cause stroke and loss of vision. It is of the highest importance for the professional to properly prepare for the procedure. In Poland, there is no such thing as a specialization in aesthetic medicine. The lack of precise regulations contributes to an increased number of complications caused by people without appropriate qualifications and offences defined in law as damage to health. It is especially important in cases when the procedure is carried out by people, who are underqualified and do not have appropriate permissions. [ABSTRACT FROM AUTHOR]

Background: Survival differences between left‐sided colon cancer (LSCC) and right‐sided colon cancer (RSCC) has been previously reported with mixed results, with various study periods not accounting for other causes of mortality. Purpose: We sought to assess the trends in colon cancer cause‐ specific survival (CSS) and overall survival (OS) based on sidedness. Method: Fine‐Gray competing risk and Cox models were used to analyze Surveillance, Epidemiology, and End Results (SEER) population‐based cohort from 1975 to 2019. Various interval periods were identified based on the timeline of clinical adoption of modern chemotherapy (1975–1989, interval period A; 1990–2004, B; and 2005–2019, C). Results: Of the 227,637 patients, 50.1% were female and 46.2% were RSCC. RSCC was more common for African Americans (51.5%), older patients (age ≥65; 51.4%), females (50.4%), while LSCC was more common among Whites (53.1%; p < 0.001), younger patients (age 18–49, 64.6%; 50–64, 62.3%; p < 0.001), males (58.1%; p < 0.001). The Median CSS for LSCC and RCC were 19.3 and 16.7 years respectively for interval period A (1975–1989). Median CSS for interval periods B and C were not reached (more than half of the cohort was still living at the end of the follow‐up period). Adjusted CSS was superior for LSCC versus RSCC for the most recent interval period C (HR 0.89; 0.86–0.92; p < 0.001). LSCC consistently showed superior OS for all study periods. Stage stratification showed worse CSS for localized and regional LSCC in the earlier study periods, but the risk attenuated over time. However, left sided distant disease had superior CSS per stage for all interval periods. OS was better for LSCC irrespective of stage, with gradual improvement over time. Conclusion: LSCC was associated with superior survival compared to right sided tumors. With the adoption of modern chemotherapy regimens, prognosis between LSCC and RSCC became more divergent in favor of LSCC. Colon cancer clinical trials should strongly consider tumor sidedness as an enrollment factor. [ABSTRACT FROM AUTHOR]

About 80 % of the precipitation at the Colorado River's headwaters is snow, and the resulting snowmelt-driven hydrograph is a crucial water source for about 40 million people. Snowmelt from alpine and subalpine snowpack contributes substantially to groundwater recharge and river flow. However, the dynamics of snowmelt progression are not well understood because observations of the high-elevation snowpack are difficult due to challenging access in complex mountainous terrain as well as the cost and labor intensity of currently available methods. We present a novel approach to infer the processes and dynamics of high-elevation snowmelt contributions predicated upon stable hydrogen and oxygen isotope ratios observed in streamflow. We show that deuterium-excess (d-excess) values of stream water could serve as a comparatively cost-effective proxy for a catchment-integrated signal of high-elevation snowmelt contributions to catchment runoff. We sampled stable hydrogen and oxygen isotope ratios of the precipitation, snowpack, and stream water in the East River, a headwater catchment of the Colorado River, and the stream water of larger catchments at sites on the Gunnison River and Colorado River. The d-excess of snowpack increased with elevation; the upper subalpine and alpine snowpack (> 3200 m) had substantially higher d-excess compared to lower elevations (< 3200 m) in the study area. The d-excess values of stream water reflected this because d-excess values increased as the higher-elevation snowpack contributed more to stream water generation later in the snowmelt/runoff season. End-member mixing analyses based on the d-excess data showed that the share of high-elevation snowmelt contributions within the snowmelt hydrograph was on average 44 % and generally increased during melt period progression, up to 70 %. The observed pattern was consistent during 6 years for the East River, and a similar relation was found for the larger catchments on the Gunnison and Colorado rivers. High-elevation snowpack contributions were found to be higher for years with lower snowpack and warmer spring temperatures. Thus, we conclude that the d-excess of stream water is a viable proxy to observe changes in high-elevation snowmelt contributions in catchments at various scales. Inter-catchment comparisons and temporal trends of the d-excess of stream water could therefore serve as a catchment-integrated measure to monitor if mountain systems rely on high-elevation water inputs more during snow drought compared to years of average snowpack depths. [ABSTRACT FROM AUTHOR]

Background: In patients with end-stage heart failure, durable Left Ventricular Assist Devices (LVADs) can be used as a bridge to transplant or destination therapy. LVADs have been shown to improve survival for patients with heart failure (HF). HF is associated with electrolyte abnormalities and the development of sustained arrhythmias. However, data on the influence of arrhythmias and electrolyte imbalances on inpatient outcomes in LVAD patients are lacking. Furthermore, previous works assessing inpatient outcomes focused mainly on the role of chronic comorbidities in those outcomes. Methods: In this cross-sectional study, we used discharge data from the National Inpatient Sample from 2019 to 2020 to assess the influence of acute arrhythmias on inpatient mortality in patients with LVADs. We also investigated the relationship between acute medical conditions and mortality. Results: There were 9418 (not survey-adjusted) hospitalizations with LVAD, among which 2539 (27%) died during the hospitalization. Univariate analysis of arrhythmias showed that ventricular arrhythmias (VAs)—ventricular fibrillation/flutter and ventricular tachycardia—as well as complete heart block were associated with significantly higher odds of mortality. Follow-up multivariable logistic analysis showed that these arrhythmias retain their increased association with death. Hyperkalemia and acidosis had increased adjusted odds of death (1.54 (95% confidence interval: 1.28–1.85) (p < 0.001) and 2.44 (CI: 2.14–2.77) (p < 0.001), respectively). Conclusions: VAs, complete heart block, hyperkalemia, and acidosis were associated with increased odds of all-cause mortality. Females had higher odds of inpatient mortality. These findings suggest that electrolyte management, maintenance of optimal acid–base balance, and interventions to treat sustained ventricular arrhythmias may be suitable therapeutic targets to reduce mortality in hospitalized patients with LVADs. [ABSTRACT FROM AUTHOR]

Dementia is a significant global health issue that is exacerbated by an aging population. Imaging plays an established role in the evaluation of patients with neurocognitive disorders such as dementia. In current clinical practice, magnetic resonance imaging (MRI) and positron emission tomography (PET) are primary imaging modalities used separately but in concert to help diagnose and classify dementia. The clinical applications of PET/MRI hybrid imaging in dementia are an active area of research, particularly given the continued emergence of functional MRI (fMRI) and amyloid PET tracers. This narrative review provides a comprehensive overview of the rationale and current evidence for PET/MRI hybrid dementia imaging from 2018 to 2023. Hybrid imaging offers advantages in the accuracy of characterizing neurodegenerative disorders, and future research will need to address the cost of integrated PET/MRI systems compared to stand-alone scanners, the development of new biomarkers, and image correction techniques. [ABSTRACT FROM AUTHOR]

Mountainous watersheds are characterized by variability in functional traits, including vegetation, topography, geology, and geomorphology, which determine nitrogen (N) retention, and release. Coal Creek and East River are two contrasting catchments within the Upper Colorado River Basin that differ markedly in total nitrate (NO3−) export. The East River has a diverse vegetation cover, and sinuous floodplains, and is underlain by N‐rich marine shale. At 0.21 ± 0.14 kg ha−1 yr−1, the East River exports ∼3.5 times more NO3− relative to the conifer‐dominated Coal Creek (0.06 ± 0.02 kg ha−1 yr−1). While this can partly be explained by the larger size of the East River, the distinct watershed traits of these two catchments imply different mechanisms controlling the aggregate N‐export signal. A causality analysis shows physical and biogenic processes were critical in determining NO3− export from the East River catchment. Stable isotope ratios of NO3− (δ15NNO3 and δ18ONO3) show the East River catchment is a strong hotspot for biogeochemical processing of NO3− at the hillslope soil‐saprolite. By contrast, the conifer‐dominated Coal Creek retained nearly all atmospherically deposited NO3−, and its export was controlled by catchment hydrological traits (i.e., snowmelt periods and water table depth). The conservative N‐cycle within Coal Creek is likely due to the abundance of conifer trees, and smaller riparian regions, retaining more NO3− overall and reduced processing prior to export. This study highlights the value of integrating isotope systematics to link watershed functional traits to mechanisms of watershed element retention and release. Plain Language Summary: The role different functional traits play in the retention and release of nitrogen remains uncertain. Here we describe how two neighboring catchments in the Upper Colorado River Basin, characterized by contrasting vegetation, geology, and geomorphology, cycle and export nitrogen. The East River catchment, which is underlain by nitrogen‐rich shale, and has a diverse vegetation cover, releases over three times as much nitrate (NO3−) than the conifer‐dominated Coal Creek, which is underlain by granitic rock. However, a suite of analyses show that the distinct watershed traits of these two catchments lead to diverse pathways of nitrogen cycling. Biogenic processes, critical to determining NO3− export in East River, impart strong biogeochemical processing prior to export. By contrast, Coal Creek retains almost all of the atmospherically deposited NO3−, likely due to uptake by conifers, and a small riparian region. This study highlights the use of nitrate isotope systematics to parse different mechanisms leading to NO3− export. Key Points: Comparing and contrasting neighboring catchments identifies watershed traits regulating the cycling, retention and release of nitrogenConifer forest‐dominated catchments show a conservative nitrogen cycling, retaining ∼97% of atmospherically dominated nitrateBy contrast, meadow‐dominated catchments underlain Mancos shale are biogeochemical hotspots for N‐cycling, and export higher nitrate loads [ABSTRACT FROM AUTHOR]

Introduction Anemia and iron deficiency are common comorbidities in population with heart failure. Their association with unfavorable prognostic outcomes and diminished quality of life underscores the imperative need for accurate diagnosis and efficacious treatment interventions. In recent years numerous treatment options have been explored in clinical trials, aimed at addressing the multifaced aspects of these concurrent conditions. Purpose of work The aim of these review is to delineate potential therapeutic interventions for anemia and iron deficiency in patients with heart failure. Materials and methods Literature review in database PubMed, Google Scholar, MDPI using keywords: heart failure, anemia, iron deficiency, ferric carboxymaltose. Summary In patients with heart failure effective treatment of anemia and iron deficiency has demonstrated enhancements in quality of life and exercise capacity. Findings from IRONMAN clinical study have prompted revisions in the latest guidelines from the European Society of Cardiology. The imminent release of results from two ongoing trials holds the potential to reshape the therapeutic landscape for treating individuals with heart failure and iron deficiency. Nevertheless, there is no explicit evidence that studied interventions could improve morbidity or risk of hospitalizations. [ABSTRACT FROM AUTHOR]

In clinical practice among cardiac patients, symptoms of palpitations diagnosed as premature beats or episodes of atrial fibrillation (AF) are very frequently reported. One of the most common diseases in the field of gastroenterology is gastroesophageal reflux disease (GERD). However, it may happen that the coincidence of the above-mentioned disease entities may predispose to the development of arrhythmias. In this article we describe the case of a 65-year-old man, without previously diagnosed diseases, in whom a clear association of arrhythmias with gastrointestinal complaints was observed. The presence of a burning sensation in the lower sternal region and typical symptoms resulting from esophagitis aggravated by triggers allows us to suspect esophageal reflux disease. Diagnostic tests performed for concomitant cardiac diseases did not reveal an organic cause of the arrhythmia. The recurrent course of symptoms observed in the present case and the analysis of the cause-effect course made us to diagnose gastrointestinal syndrome, also referred to as Romheld's Syndrome. [ABSTRACT FROM AUTHOR]

Introduction: A rapid outbreak of SARS-CoV-2 in the past few years caused a significant increase in the number of upper respiratory tract infections throughout the world. Numerous public health institutions tried to control the COVID-19 pandemic, including mandatory mask wearing, vaccinations, increased frequency of using disinfectants or compulsory lockdowns. Lockdown interventions were necessary, although they lead to insufficient, comparing to the international recommendations, levels of physical activity, which could trigger an elevated susceptibility to diseases of affluence. Purpose: Regular aerobic exercise may suppress inflammation, boost innate immunity and result in enhanced protection against viral infections. This review aims to show the relationship between level of physical activity and the risk and severity of COVID-19 infection. Material and methods: In December 2023, the Medline (PubMed) and Google Scholar databases were searched using following keywords: physical activity, exercise, COVID-19, SARS-CoV-2, infection, mortality. Records published in 2020 - 2023 in English were selected. Brief description of the state of knowledge: SARS-CoV-2 virus infection occurs through respiratory droplet. The most common symptoms of the disease include fever, dry cough, shortness of breath, fatigue and muscle pain. Laboratory tests show elevated inflammation factors and abnormal coagulation factors among people with SARS-CoV-2 infection. Limited physical activity promotes the development of various diseases, such as diabetes and obesity, which were the main causes of death during the SARS-CoV-2 pandemic. Regular physical exercises activate cells of the immune system, i.e. leukocytes, lymphocytes and NK cells, such process is associated with a better cellular response to infection. Patients who regularly undertook physical activity of at least moderate intensity had better respiratory capacity and reserve, higher haemoglobin oxygen saturation levels, and were therefore less susceptible to hypoxemia. People who were more athletic before SARS-CoV-2 infection were less often hospitalized, admitted to the intensive care unit and had a lower risk of death compared to people leading a sedentary lifestyle. Due to its anti-inflammatory and anti-metabolic effects, obese patients also benefit from it. The least susceptible to SARS-CoV-2 infection were people who performed vigorous, high-intensity exercise. Conclusions: Physical activity has a protective effect against severe SARS-CoV-2 infection. It is worth to consider, whether limiting physical activity and a sedentary lifestyle effectively fight viral infection. A recommendation to perform regular physical activity might be a simple way of protection against the high risk of mortality during the coming waves of the pandemic. [ABSTRACT FROM AUTHOR]

Globally, tuberculosis (TB) remains the deadliest bacterial infectious disease, and spreading antibiotic resistances is the biggest challenge for combatting the disease. Rapid and comprehensive diagnostics including drug susceptibility testing (DST) would assure early treatment, reduction of morbidity and the interruption of transmission chains. To date, rapid genetic resistance testing addresses only one to four drug groups while complete DST is done phenotypically and takes several weeks. To overcome these limitations, we developed a two-stage workflow for rapid TB diagnostics including DST from a single sputum sample that can be completed within three days. The first stage is qPCR detection of M. tuberculosis complex (MTBC) including antibiotic resistance testing against the first-line antibiotics, isoniazid (Inh) and rifampicin (Rif). The test is automated by centrifugal microfluidics and designed for point of care (PoC). Furthermore, enriched MTBC DNA is provided in a detachable sample tube to enable the second stage: if the PCR detects MTBC and resistance to either Inh or Rif, the MTBC DNA is shipped to specialized facilities and analyzed by targeted next generation sequencing (tNGS) to assess the complete resistance profile. Proof-of-concept testing of the PoC test revealed an analytical sensitivity of 44.2 CFU ml−1, a diagnostic sensitivity of 96%, and a diagnostic specificity of 100% for MTBC detection. Coupled tNGS successfully provided resistance profiles, demonstrated for samples from 17 patients. To the best of our knowledge, the presented combination of PoC qPCR with tNGS allows for the fastest comprehensive TB diagnostics comprising decentralized pathogen detection with subsequent resistance profiling in a facility specialized in tNGS. [ABSTRACT FROM AUTHOR]

Introduction Chronic coronary syndrome is predominantly related to the atherosclerotic obstruction of the coronary artery or arteries. However, this phenomenon is not the only causative factor in this disease. It is usually forgotten, that there is a possibility of ischemia of the cardiac muscle with no obstruction found in the main vessel. The trigger of such pathology might be underlying in the microcirculatory system and the inappropriate dilation or constriction of those small vessels, which results in insufficient blood supply to the cardiomyocytes, similarly to the typical obstructive coronary artery disease. In this article we are willing to show that such dysfunction poses a great danger to the health and life and therefore we should be able to properly diagnose and treat it. Purpose of the work The aim of this review of up-to-date literature is to raise awareness among both doctors and patients about the phenomenon of coronary artery disease but with no significant obstruction in the vessels supplying the cardiac muscle. The common cause of such condition is coronary microvascular dysfunction, that leads to a disease called microvascular angina. Our purpose was to reveal, how dangerous to the health of the patients this could be and therefore how essential it is to provide a proper diagnose and management. In addition, we have noticed a need for a summary of what has already been discovered on this topic, available therapeutic methods and future perspectives. Materials and methods The search of English and Polish language literature up to December 2023 has been done using the PubMed database, Google Scholar database and several international guidelines. The search regarded the topics of microvascular angina, coronary microvascular dysfunction, cardiac syndrome X and chronic coronary syndrome. Summary Microvascular angina, like any chronic coronary syndrome, means a chest pain developed when the cardiac muscle is insufficiently supplied with blood, although in this case the symptoms usually occur untypically, since there is no obstruction in the main epicardial arteries. The pathology arises in the smallest of vessels: arterioles, capillaries and venules. They might be minuscule, but they play a crucial role in the distribution of local blood flow and an exchange between cardiomyocytes and red blood cells or plasma. We must be aware of that and stop underestimating the implications that it brings. The diagnosis of the impaired microcirculation is challenging but not impossible. There still a lot to develop in this field, we especially should keep seeking new methods of targeted treatment for this condition. Doctors must be able to properly care about their patients suffering from microvascular angina. It is essential to stratify their cardiovascular risk, propose different therapeutic strategies, since the treatment may frequently be fruitless, and to monitor their mental health. [ABSTRACT FROM AUTHOR]

INTRODUCTION: One of the primary health issues bringing patients to hospital emergency rooms is pain. It is often treated inadequately. Doctors working in the emergency department have the option of using a number of drugs for analgesia. The three main groups include non-steroidal antiinflammatory drugs, non-opioid analgesics and opioid analgesics. In order to properly exploit their potential, it is necessary to properly classify the pain, know the basic action of the available drugs, choose the right dose, and know how to combine drugs from different groups to achieve balanced analgesia. By acting in this way, the patient in the hospital emergency department will be properly provided with medication, and this will have a positive effect on his overall health. PURPOSE OF THE WORK: This review paper aims to present the possible and available treatments for pain in a hospital emergency department. MATERIALS AND METHODS: An analysis of papers available in PubMed and Google Scholar was performed using the following key words: pain in the emergency department, opioids in the ED, non-opioid drugs in the ED, oligoanalgesia. RESULTS: The result of the review paper is to show the wide range of drugs used in the emergency department for pain management and their potential, and to demonstrate that the problem of oligoanalgesia is avoidable. [ABSTRACT FROM AUTHOR]

The intricate development and physiological dynamics of the mammary glands, orchestrated by a delicate interplay of hormones, are crucial for reproductive function and lactation. Beginning with intrauterine clusters evolving into mature glands, hormonal fluctuations throughout puberty and the menstrual cycle finely tune mammary tissue growth. Oestrogens stimulate the proliferation of epithelial cells, while progesterone orchestrates the formation of lactiferous glands. During pregnancy, oestrogen and progesterone induces hyperplasia of lobules and ducts, preparing the breast for lactation. Prolactin is vital for lactation and stimulates milk production during pregnancy and postpar- tum. As shown by ultrasonography, physiological changes during lactation reflect glandular tissue transformation for milk secretion. Clinical and physiological changes, including increased blood flow, contribute to mammary growth and firmness, complicating clinical examination. Ultrasonographic findings reveal variability in women’s glandular and fat tissue distribution, suggesting that milk production is not solely determined by anatomical factors. Though not directly linked to milk production, blood flow dynamics hint at a threshold for optimal lactation. Understand- ing these complex hormonal and physiological mechanisms is crucial for comprehending mammary development, function, and clinical assessment. [ABSTRACT FROM AUTHOR]

The ability of nanophotonic cavities to confine and store light to nanoscale dimensions has important implications for enhancing molecular, excitonic, phononic, and plasmonic optical responses. Spectroscopic signatures of processes that are ordinarily exceedingly weak such as pure absorption and Raman scattering have been brought to the single-particle limit of detection, while new emergent polaritonic states of optical matter have been realized through coupling material and photonic cavity degrees of freedom across a wide range of experimentally accessible interaction strengths. In this review, we discuss both optical and electron beam spectroscopies of cavity-coupled material systems in weak, strong, and ultrastrong coupling regimes, providing a theoretical basis for understanding the physics inherent to each while highlighting recent experimental advances and exciting future directions. [ABSTRACT FROM AUTHOR]

Case: A 61-year-old woman with recurrent left L5 radiculopathy underwent revision L4-5 decompression complicated by incidental durotomy requiring primary repair. Postoperative course was complicated by wound drainage and headache. Repeat magnetic resonance imaging demonstrated cerebrospinal fluid dissecting a plane deep to the dura mater but superficial to the arachnoid, with the collection compressing the cauda equina in an atypical horizontal and linear fashion. Nonoperative treatment was ineffective, and she required revision decompression and dural repair. Conclusion: Spine surgeons should recognize this finding on postoperative imaging as a potential sign of an incomplete dural repair necessitating return to the operating room. [ABSTRACT FROM AUTHOR]

We present a series of full-shape analyses of galaxy power spectrum multipole measurements from the 6dFGS, BOSS, and eBOSS galaxy surveys. We use an emulated effective field theory of large-scale structure (EFTofLSS) model to conduct these analyses. We exploit the accelerated prediction speed of the neural-network-based emulator to explore various analysis setups for our cosmological inference pipeline. Via a set of mock full-shape analyses of synthetic power spectrum multipoles, designed to approximate measurements from the surveys above, we demonstrate that the use of alternative priors on nuisance parameters and restricted model complexity reduces many of the biases previously observed in marginalized cosmological constraints coming from EFTofLSS analyses. The alternative priors take the form of a Jeffreys prior; a non-informative prior that can mitigate against biases induced by marginalizing over poorly constrained nuisance parameters. When performing a joint analysis of all synthetic multipoles, we see an improvement in the level of agreement between the marginalized ln (1010 As) constraints and the truth; from ∼2.0σ to ∼0.42σ. Using our pipeline to analyse the measured multipoles, we find an improvement in the level of agreement with cosmic microwave background (CMB) results; from ∼2.4σ to ∼0.5σ. Therefore, we conclude that the spectroscopic galaxy survey data sets listed above are consistent with constraints obtained from the CMB. [ABSTRACT FROM AUTHOR]

We detected ENU-induced alleles of Mfsd1 (encoding the major facilitator superfamily domain containing 1 protein) that caused lymphopenia, splenomegaly, progressive liver pathology, and extramedullary hematopoiesis (EMH). MFSD1 is a lysosomal membrane-bound solute carrier protein with no previously described function in immunity. By proteomic analysis, we identified association between MFSD1 and both GLMP (glycosylated lysosomal membrane protein) and GIMAP5 (GTPase of immunity-associated protein 5). Germline knockout alleles of Mfsd1, Glmp, and Gimap5 each caused lymphopenia, liver pathology, EMH, and lipid deposition in the bone marrow and liver. We found that the interactions of MFSD1 and GLMP with GIMAP5 are essential to maintain normal GIMAP5 expression, which in turn is critical to support lymphocyte development and liver homeostasis that suppresses EMH. These findings identify the protein complex MFSD1-GLMP-GIMAP5 operating in hematopoietic and extrahematopoietic tissues to regulate immunity and liver homeostasis. [ABSTRACT FROM AUTHOR]

In a forward genetic screen of mice with N-ethyl-N-nitrosourea-induced mutations for aberrant immune function, we identified animals with low percentages of B220+ cells in the peripheral blood. The causative mutation was in Ier3ip1, encoding immediate early response 3 interacting protein 1 (IER3IP1), an endoplasmic reticulum membrane protein mutated in an autosomal recessive neurodevelopmental disorder termed Microcephaly with simplified gyration, Epilepsy and permanent neonatal Diabetes Syndrome (MEDS) in humans. However, no immune function for IER3IP1 had previously been reported. The viable hypomorphic Ier3ip1 allele uncovered in this study, identical to a reported IER3IP1 variant in a MEDS patient, reveals an essential hematopoietic-intrinsic role for IER3IP1 in B cell development and function. We show that IER3IP1 forms a complex with the Golgi transmembrane protein 167A and limits activation of the unfolded protein response mediated by inositol-requiring enzyme-1a and X-box binding protein 1 in B cells. Our findings suggest that B cell deficiency may be a feature of MEDS. [ABSTRACT FROM AUTHOR]

Copyright of European Journal of Psychotraumatology is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We present, for the first time, an observational test of the consistency relation for the large-scale structure (LSS) of the Universe through a joint analysis of the anisotropic two- and three-point correlation functions (2PCF and 3PCF) of galaxies. We parameterize the breakdown of the LSS consistency relation in the squeezed limit by E s, which represents the ratio of the coefficients of the shift terms in the second-order density and velocity fluctuations. E s ≠ 1 is a sufficient condition under which the LSS consistency relation is violated. A novel aspect of this work is that we constrain E s by obtaining information about the non-linear velocity field from the quadrupole component of the 3PCF without taking the squeezed limit. Using the galaxy catalogues in the Baryon Oscillation Spectroscopic Survey (BOSS) Data Release 12, we obtain |$E_{\rm s} = -0.92_{-3.26}^{+3.13}$|⁠ , indicating that there is no violation of the LSS consistency relation in our analysis within the statistical errors. Our parameterization is general enough that our constraint can be applied to a wide range of theories, such as multicomponent fluids, modified gravity theories, and their associated galaxy bias effects. Our analysis opens a new observational window to test the fundamental physics using the anisotropic higher-order correlation functions of galaxy clustering. [ABSTRACT FROM AUTHOR]

About 80 % of the precipitation in the Colorado River's headwaters is snow, and the resulting snowmelt-driven hydrograph is a crucial water source for about 40 million people. Snowmelt from alpine and subalpine snowpack contributes substantially to groundwater recharge and river flow. However, the dynamics of snowmelt progression are not well understood because observations of the high elevation snowpack are difficult due to challenging access in complex mountainous terrain as well as the cost- and labor-intensity of methods. We present a novel approach to infer the processes and dynamics of high elevation snowmelt contributions predicated upon stable hydrogen and oxygen isotope ratios observed in stream discharge. We show that d-excess values of stream water can serve as a comparatively cost-effective proxy for a catchment integrated signal of high elevation snow melt contributions to catchment runoff. We sampled stable hydrogen and oxygen isotope ratios of the precipitation, snowpack, and stream water in the East River, a headwater catchment of the Colorado River and the stream water of larger catchments at sites on the Gunnison River and Colorado River. The d-excess of snowpack increased with elevation; the upper subalpine and alpine snowpack (>3200 m) and had a substantially higher d-excess compared to lower elevations (<3200 m) in the study area. The d-excess values of stream water reflected this because d-excess values increased as the higher elevation snowpack contributed more to stream water generation later in the snowmelt/runoff season. Endmember mixing analyses based on the d-excess data showed that the share of high elevation snowmelt contributions within the snowmelt hydrograph was on average 44 % and generally increased during melt period progression, up to 70 %. The observed pattern was consistent during six years for the East River, and a similar relation was found for the larger catchments on the Gunnison and Colorado Rivers. High elevation snowpack contributions were found to be higher for years with lower snowpack and warmer spring temperatures. Thus, we conclude that the d-excess of stream water is a viable proxy to observe changes in high elevation snowmelt contributions in catchments at various scales. Inter-catchment comparisons and temporal trends of the d-excess of stream water could therefore serve as a catchment-integrated measure to monitor if mountain systems increasingly rely on high elevation water inputs during snow drought. [ABSTRACT FROM AUTHOR]