Lightning-induced relativistic electron precipitation from the inner radiation belt.

The Earth's radiation belts are maintained by a number of acceleration, loss and transport mechanisms, and the electron fluxes at any given time are highly variable. Microbursts, which are rapid (sub-second) bursts of energetic electrons entering the atmosphere from the magnetosphere, are one of the key loss mechanisms controlling radiation belt fluxes. Such rapid bursts are typically observed from the outer radiation belt and driven by interactions with whistler mode chorus waves, but they can also occur in the inner belt and slot region, driven by lightning-generated whistlers. This lightning-induced electron precipitation is typically observed at 10s-100s keV, but here we present direct observations of this phenomenon at MeV energies. This unveils a coupling between near-Earth processes, such as lightning, and radiation belt processes, such as relativistic electron microbursts, bridging the gap between Earth weather and space weather.

The Effect of Upright Posture on Left Atrial Strain in Competitive Athletes.

BACKGROUND: Left atrial strain (LAS) assessment by speckle tracking echocardiography (STE) has been shown to be a remarkable means of quantifying LA function as an early marker of LV pathology. As exercise testing is also performed on a treadmill, the aim of this study was to investigate the effect of upright posture on LAS in healthy athletes. METHODS: Fifty male athletes (mean age 25.7 ± 7.3 years) underwent transthoracic echocardiography (TTE) in the upright and left lateral positions. In addition to the conventional echocardiographic parameters, in all athletes, LA conduction strain (LAScd), contraction strain (LASct), reservoir strain (LASr), and maximum LA volume (LAVmax) were assessed by STE in both positions. RESULTS: Comparing upright posture and the left lateral position, LAScd (-14.0 ± 5.9% vs. -27.4 ± 7.1%; p < 0.001), LASct (-4.6 ± 3.5% vs. -11.3 ± 4.1%; p < 0.001), LASr (18.7 ± 7.6% vs. 38.7 ± 8.0%; p < 0.001), and LAVmax (24.4 ± 8.8% vs. 50.0 ± 14.2%) differed significantly. CONCLUSIONS: Upright posture has a significant effect on LA deformation, with decreased LAScd, LASct, and LASr. The results of this study contribute to the understanding of athletes' hearts and must be considered when performing echocardiography in healthy athletes on a treadmill.

Echocardiographic assessment of left ventricular volumes: a comparison of different methods in athletes.

BACKGROUND: Cardiac magnetic resonance imaging (cMRI) is considered the gold standard for the assessment of left ventricular (LV) systolic function. However, discrepancies have been reported in the literature between LV volumes assessed by transthoracic echocardiography (TTE) and cMRI. The objective of this study was to analyze the differences in LV volumes between different echocardiographic techniques and cMRI. METHODS AND RESULTS: In 64 male athletes (21.1 ± 4.9 years), LV volumes were measured by TTE using the following methods: Doppler echocardiography, anatomical M-Mode, biplane/triplane planimetry and 3D volumetry. In addition, LV end-diastolic (LVEDV), end-systolic (LVESV), and stroke volumes (LVSV) were assessed in 11 athletes by both TTE and cMRI. There was no significant difference between LVEDV and LVESV determined by biplane/triplane planimetry and 3D volumetry. LVEDV and LVESV measured by M-Mode were significantly lower compared to 3D volumetry. LVSV determined by Doppler with 3D planimetry of LV outflow tract was significantly higher than 2D planimetry and 3D volumetry, whereas none of the planimetric or volumetric methods for determining LVSV differed significantly. There were no significant differences for LVEDV, LVESV, LVSV and LVEF between cMRI and TTE determined by biplane planimetry in the subgroup of 11 athletes. CONCLUSION: The choice of echocardiographic method used has an impact on LVSV in athletes, so the LVSV should always be checked for plausibility. The same echocardiographic method should be used to assess LVSV at follow-ups to ensure good comparability. The data suggest that biplane LV planimetry by TTE is not inferior to cMRI.

Functional analysis of postural spinal and pelvic parameters using static and dynamic spinometry.

Background: Spinometry is a radiation-free method to three-dimensional spine imaging that provides additional information about the functional gait patterns related to the pelvis and lower extremities. This radiation-free technology uses the surface topography of the trunk to analyze surface asymmetry and identify bony landmarks, thereby aiding the assessment of spinal deformity and supporting long-term treatment regimes. Especially reliable dynamic spinometric data for spine and pelvis are necessary to evaluate the management of non-specific back pain. Research aim: This study aims to generate reliable dynamic spinometric data for spine and pelvis parameters that can serve as reference data for future studies and clinical practice. Methods: This study assessed 366 subjects (185 females) under static and 360 subjects (181 females) under dynamic (walking on a treadmill at 3 km/h and 5 km/h) conditions. The DIERS Formetric 4Dmotion® system uses stripes of light to detect the surface topography of the spine and pelvis and identifies specific landmarks to analyze the spine during standing and walking. Results: Relevant gender effects were calculated for lordotic angle (ηp2 = 0.22) and pelvic inclination (ηp2 = 0.26). Under static conditions, female subjects showed larger values for both parameters (lordotic angle: 41.6 ± 8.60°; pelvic inclination: 25.5 ± 7.49°). Regarding speed effects, three relevant changes were observed (sagittal imbalance: ηp2 = 0.74, kyphotic angle: ηp2 = 0.13, apical deviation: ηp2 = 0.11). The most considerable changes were observed between static condition and 3 km/h, especially for sagittal imbalance and lordotic angle. For these parameters, relevant effect sizes (d > 0.8) were calculated between static and 3 km/h for males and females. Concerning clinical vertebral parameters, only lordotic angle and pelvic inclination were correlated with each other (r = 0.722). Conclusion: This study generated a gender-specific reference database of asymptomatic individuals for static and dynamic spinometry. It demonstrated that the DIERS Formetric 4Dmotion® system could capture natural changes in static and dynamic situations and catalogue functional adaptations of spino-pelvic statics at different speeds. The lordotic angle is an indirect marker of pelvic inclination, allowing spinometry to identify individuals at risk even under dynamic conditions.

Rosuvastatin as a Supplemental Treatment for the Clinical Symptoms of Nephropathia Epidemica: A Pilot Clinical Study.

Nephropathis epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS), is an acute zoonotic disease endemic in the Republic of Tatarstan. This study aimed to assess the impact of rosuvastatin on the clinical and laboratory results of NE. A total of 61 NE patients and 30 controls were included in this study; 22 NE patients and 7 controls received a daily dose of rosuvastatin (10 mg) for ten consecutive days. Serum samples were collected on days 1, 5, and 10 after admission to the hospital. These samples were analyzed to determine the levels of lipids, cytokines, and kidney toxicity markers. Our findings indicate that rosuvastatin reduced the duration of the second wave of fever and alleviated back pain and headache symptoms. Additionally, low-density lipoprotein cholesterol (LDL-C) serum levels were significantly decreased on days 5 and 10 upon rosuvastatin treatment. Furthermore, rosuvastatin decreased the levels of cytokines in the serum, particularly proinflammatory cytokines IL-1ß and IL-8. NE patients had significantly altered levels of the kidney toxicity markers albumin and osteopontin. The data from our study provide evidence supporting the therapeutic potential of rosuvastatin in NE cases.

On the potential role of naturally occurring carboxylic organic acids as anti-infective agents: opportunities and challenges.

Carboxylic organic acids are intermediates of central carbon metabolic pathways (e.g. acetic, propionic, citric, and lactic acid) long known to have potent antimicrobial potential, mainly at acidic pHs. The food industry has been leveraging those properties for years, using many of these acids as preservatives to inhibit the growth of pathogenic and/or spoilage fungal and bacterial species. A few of these molecules (the most prominent being acetic acid) have been used as antiseptics since Hippocratic medicine, mainly to treat infected wounds in patients with burns. With the growth of antibiotic therapy, the use of carboxylic acids (and other chemical antiseptics) in clinical settings lost relevance; however, with the continuous emergence of multi-antibiotic/antifungal resistant strains, the search for alternatives has intensified. This prospective article raises awareness of the potential of carboxylic acids to control infections in clinical settings, considering not only their previous exploitation in this context (which we overview) but also the positive experience of their safe use in food preservation. At a time of great concern with antimicrobial resistance and the slow arrival of new antimicrobial therapeutics to the market, further exploration of organic acids as anti-infective molecules may pave the way to more sustainable prophylactic and therapeutic approaches.

PFAS adsorbent selection: The role of adsorbent use rate, water quality, and cost.

Per- and polyfluoroalkyl substance (PFAS) contamination in aqueous matrices has intensified the search for PFAS adsorbents with elevated capacity, selectivity, and cost effectiveness. A novel surface modified organoclay (SMC) adsorbent was evaluated for PFAS removal performance in parallel with granular activated carbon (GAC) and ion exchange resin (IX) for the treatment of five distinct PFAS impaired waters including groundwater, landfill leachate, membrane concentrate and wastewater effluent. Rapid small scale column tests (RSSCTs) and breakthrough modeling were coupled to provide insight on adsorbent performance and cost for multiple PFAS and water types. IX exhibited the best performance with respect to adsorbent use rates in treatment of all tested waters. IX was nearly four times more effective than GAC and two times more effective than SMC in the treatment of PFOA from water types excluding groundwater. Employed modeling strengthened the comparison of adsorbent performance and water quality to infer adsorption feasibility. Further, evaluation of adsorption was extended beyond PFAS breakthrough with the inclusion of unit adsorbent cost as a decision metric influencing adsorbent selection. An analysis of levelized media cost indicated treatment of landfill leachate and membrane concentrate was at least three times more expensive than groundwaters or wastewaters evaluated.

Differential Cytokine Responses and the Clinical Severity of Adult and Pediatric Nephropathia Epidemica.

Nephropathia epidemica (NE), caused by the hantavirus infection, is endemic in Tatarstan Russia. The majority of patients are adults, with infection rarely diagnosed in children. This limited number of pediatric NE cases means there is an inadequate understanding of disease pathogenesis in this age category. Here, we have analyzed clinical and laboratory data in adults and children with NE to establish whether and how the disease severity differs between the two age groups. Serum cytokines were analyzed in samples collected from 11 children and 129 adult NE patients during an outbreak in 2019. A kidney toxicity panel was also used to analyze urine samples from these patients. Additionally, serum and urine samples were analyzed from 11 control children and 26 control adults. Analysis of clinical and laboratory data revealed that NE was milder in children than in adults. A variation in serum cytokine activation could explain the differences in clinical presentation. Cytokines associated with activation of Th1 lymphocytes were prominent in adults, while they were obscured in sera from pediatric NE patients. In addition, a prolonged activation of kidney injury markers was found in adults with NE, whilst only a short-lasting activation of these markers was observed in children with NE. These findings support previous observations of age differences in NE severity, which should be considered when diagnosing the disease in children.

Interference of reversible redox compounds in enzyme catalysed assays - Electrochemical limitations.

BACKGROUND: Several commercial assay kits exist with limited explanation of the kit components and reagent constituents, which greatly increases potential incompatibility issues resulting in the loss of samples, time, and data. Herein we explore such issues via the redox ion [Fe(CN)6]3/4- in two commercial l-lactate and pyruvate assay kits. RESULTS: We clearly demonstrate significant interference from redox compounds with the l-lactate and pyruvate assays; a significance in signal inhibition/mechanism restriction, and false/mechanism exhaustion, respectively. Potential mechanisms are explored to explain interference. CONCLUSION: The need for transparency is crucial for consistency of assay kit performance from lab to lab. There is a need for suppliers to list the components of kits and/or list the potential for interference from specific agents to ensure that results obtained from these kits are reliable and reproducible.

A Test of Energetic Particle Precipitation Models Using Simultaneous Incoherent Scatter Radar and Van Allen Probes Observations.

Quantification of energetic electron precipitation caused by wave-particle interactions is fundamentally important to understand the cycle of particle energization and loss of the radiation belts. One important way to determine how well the wave-particle interaction models predict losses through pitch-angle scattering into the atmospheric loss cone is the direct comparison between the ionization altitude profiles expected in the atmosphere due to the precipitating fluxes and the ionization profiles actually measured with incoherent scatter radars. This paper reports such a comparison using a forward propagation of loss-cone electron fluxes, calculated with the electron pitch angle diffusion model applied to Van Allen Probes measurements, coupled with the Boulder Electron Radiation to Ionization model, which propagates the fluxes into the atmosphere. The density profiles measured with the Poker Flat Incoherent Scatter Radar operating in modes especially designed to optimize measurements in the D-region, show multiple instances of close quantitative agreement with predicted density profiles from precipitation of electrons caused by wave-particle interactions in the inner magnetosphere, alternated with intervals with large differences between observations and predictions. Several-minute long intervals of close prediction-observation approximation in the 65-93 km altitude range indicate that the whistler wave-electron interactions models are realistic and produce precipitation fluxes of electrons with energies between 10 keV and >100 keV that are consistent with observations. The alternation of close model-data agreement and poor agreement intervals indicates that the regions causing energetic electron precipitation are highly spatially localized.

Noncardiac inpatient has acute hypertension: Treat or not?

A retrospective study found more harm than benefit from treating elevated blood pressure in hospitalized noncardiac patients.

Can early introduction of gluten reduce risk of celiac disease?

This UK study revealed the benefits of introducing gluten at age 4 months.

COVID-19 in European Soccer: A Public 2-Year Comparison of COVID-19 Case Management and Case Characteristics between the 1st Bundesliga, La Liga, Serie A and the Premier League.

To evaluate the extent and characteristics of COVID-19 cases in relation to environmental COVID-19 incidences in the four best European soccer leagues (Bundesliga, Premier League, Serie A and La Liga) from the first of January 2020 until the end of January 2022. Methods: A retrospective evaluation of all publicly available COVID-19 cases in the studied cohorts was performed. The 14-day case incidences from epidemiological national data were used as reference values. The leagues studied are the Bundesliga (Germany), Premier League (Great Britain), Serie A (Italy) and La Liga (Spain). For all cases, the duration of time loss and date of case notification were recorded. Results: League-specific mean time loss due to disease or quarantine per COVID-19 case differs significantly between La Liga (11.45; ±5.21 days) and the other leagues studied (Bundesliga 20.41; ±33.87; p 0.0242; Premier League 17.12; ±10.39; p 0.0001; Serie A 17.61; ±12.71; p < 0.0001). A positive correlation between 14-day national incidence with COVID-19 disease occurrence in soccer leagues was found for all leagues studied. The correlations were strong in the Bundesliga (r 0.5911; CI 0.4249−0.7187; p < 0.0001), Serie A (r 0.5979; CI 0.4336−0.7238; p < 0.0001) and La Liga (r 0.5251; CI 0.3432−0.6690; p < 0.0001). A moderate correlation was found for the Premier League (r 0.3308; CI 0.1147−0.5169; p 0.0026). Odds ratios for altered environmental case risk in the cohorts studied could be calculated for four different national COVID-19 incidence levels (<50/100.000 to >500/100.000). A trend towards shorter COVID-19 case duration in the second half of 2021 was shown for all leagues studied. Conclusions: There was a significantly lower mean time-loss caused by a COVID-19 infection for cases occurred in La Liga compared with the other three leagues studied. For all four leagues studied, a positive, significant correlation of national environmental COVID-19 incidence level and the incidence of COVID-19 cases in the cohort of a football league was found.

Antibody and T Cell Immune Responses to SARS-CoV-2 Peptides in COVID-19 Convalescent Patients.

Identifying immunogenic targets of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is critical to advance diagnostic and disease control strategies. We analyzed humoral (ELISA) and T-cell (ELISpot) immune responses to spike (S) and nucleocapsid (N) SARS-CoV-2 proteins as well as to human endemic coronavirus (eCoV) peptides in serum from convalescent coronavirus disease 2019 (COVID-19) patients from Tatarstan, Russia. We identified multiple SARS-CoV-2 peptides that were reactive with serum antibodies and T cells from convalescent COVID-19. In addition, age and gender associated differences in the reactivity to S and N protein peptides were identified. Moreover, several SARS-CoV-2 peptides tested negatively correlated with disease severity and lung damage. Cross-reactivity to eCoV peptides was analyzed and found to be lower in COVID-19 compared to controls. In this study, we demonstrate the changing pattern of immunogenic peptide reactivity in COVID-19 serum based on age, gender and previous exposure to eCoVs. These data highlight how humoral immune responses and cytotoxic T cell responses to some of these peptides could contribute to SARS-CoV-2 pathogenesis.

Global longitudinal strain differentiates physiological hypertrophy from maladaptive remodeling.

Aims: Differentiation of left ventricular (LV) hypertrophy in healthy athletes from pathological LV hypertrophy in heart disease is often difficult. We explored whether extended echocardiographic measurements such as E/e' and global longitudinal strain (GLS) distinguish physiologic from maladaptive hypertrophy in hypertrophic cardiomyopathy, excessively trained athletes' hearts and normal hearts. Methods: Seventy-eight professional athletes (cyclists n = 37, soccer players n = 29, handball players n = 21) were compared with patients (n = 88) with pathological LV hypertrophy (hypertrophic obstructive cardiomyopathy (HOCM, n = 17), hypertensive heart disease (HHD, n = 36), severe aortic valve stenosis (AVS, n = 35) and with sedentary healthy individuals as controls (n = 37). Results: LV ejection fraction (LVEF) was ≥50% in all patients, athletes (median age 26 years, all male) and the controls (97% male, median age 32 years). LV mass index (LVMI) and septal wall thickness was in normal range in controls, but elevated in cyclists and patients with pathological hypertrophy (p < 0.001 for both). E/e' was elevated in all patients with maladaptive hypertrophy but normal in controls and athletes (p < 0.001 vs. pathological hypertrophy). Furthermore GLS was reduced in patients with pathological hypertrophy compared with athletes and controls (for both p < 0.001). In subjects with septal wall thickness >11 mm, GLS (≥-18%) has a specificity of 79% to distinguish between physiological and pathological hypertrophy. Conclusion: GLS and E/e' are reliable parameters unlike left ventricular mass or LV ejection fraction to distinguish pathological and physiological hypertrophy.

Alcohol abstinence reduces A-fib burden in drinkers.

A recent Australian study demonstrated a significant reduction in A-fib recurrence and burden among regular drinkers who abstained from alcohol.

Immunogenic SARS-CoV-2 S and N Protein Peptide and Cytokine Combinations as Biomarkers for Early Prediction of Fatal COVID-19.

Early indications of the likelihood of severe coronavirus disease 2019 COVID-19 can influence treatments and could improve clinical outcomes. However, knowledge on the prediction markers of COVID-19 fatality risks remains limited. Here, we analyzed and quantified the reactivity of serum samples from acute (non-fatal and fatal) and convalescent COVID-19 patients with the spike surface glycoprotein (S protein) and nucleocapsid phosphoprotein (N protein) SARS-CoV-2 peptide libraries. Cytokine activation was also analyzed. We demonstrated that IgM from fatal COVID-19 serum reacted with several N protein peptides. In contrast, IgM from non-fatal serum reacted more with S protein peptides. Further, higher levels of pro-inflammatory cytokines were found in fatal COVID-19 serum compared to non-fatal. Many of these cytokines were pro-inflammatory and chemokines. Differences in IgG reactivity from fatal and non-fatal COVID-19 sera were also demonstrated. Additionally, the longitudinal analysis of IgG reactivity with SARS-CoV-2 S and N protein identified peptides with the highest longevity in humoral immune response. Finally, using IgM antibody reactivity with S and N SARS-CoV-2 peptides and selected cytokines, we have identified a panel of biomarkers specific to patients with a higher risk of fatal COVID-19 compared with that of patients who survive. This panel could be used for the early prediction of COVID-19 fatality risk.

Inhibition of Arenavirus Entry and Replication by the Cell-Intrinsic Restriction Factor ZMPSTE24 Is Enhanced by IFITM Antiviral Activity.

In the absence of effective vaccines and treatments, annual outbreaks of severe human haemorrhagic fever caused by arenaviruses, such as Lassa virus, continue to pose a significant human health threat. Understanding the balance of cellular factors that inhibit or promote arenavirus infection may have important implications for the development of effective antiviral strategies. Here, we identified the cell-intrinsic zinc transmembrane metalloprotease, ZMPSTE24, as a restriction factor against arenaviruses. Notably, CRISPR-Cas9-mediated knockout of ZMPSTE24 in human alveolar epithelial A549 cells increased arenavirus glycoprotein-mediated viral entry in pseudoparticle assays and live virus infection models. As a barrier to viral entry and replication, ZMPSTE24 may act as a downstream effector of interferon-induced transmembrane protein (IFITM) antiviral function; though through a yet poorly understood mechanism. Overexpression of IFITM1, IFITM2, and IFITM3 proteins did not restrict the entry of pseudoparticles carrying arenavirus envelope glycoproteins and live virus infection. Furthermore, gain-of-function studies revealed that IFITMs augment the antiviral activity of ZMPSTE24 against arenaviruses, suggesting a cooperative effect of viral restriction. We show that ZMPSTE24 and IFITMs affect the kinetics of cellular endocytosis, suggesting that perturbation of membrane structure and stability is likely the mechanism of ZMPSTE24-mediated restriction and cooperative ZMPSTE24-IFITM antiviral activity. Collectively, our findings define the role of ZMPSTE24 host restriction activity in the early stages of arenavirus infection. Moreover, we provide insight into the importance of cellular membrane integrity for productive fusion of arenaviruses and highlight a novel avenue for therapeutic development.

Role of Creatine Supplementation in Conditions Involving Mitochondrial Dysfunction: A Narrative Review.

Creatine monohydrate (CrM) is one of the most widely used nutritional supplements among active individuals and athletes to improve high-intensity exercise performance and training adaptations. However, research suggests that CrM supplementation may also serve as a therapeutic tool in the management of some chronic and traumatic diseases. Creatine supplementation has been reported to improve high-energy phosphate availability as well as have antioxidative, neuroprotective, anti-lactatic, and calcium-homoeostatic effects. These characteristics may have a direct impact on mitochondrion's survival and health particularly during stressful conditions such as ischemia and injury. This narrative review discusses current scientific evidence for use or supplemental CrM as a therapeutic agent during conditions associated with mitochondrial dysfunction. Based on this analysis, it appears that CrM supplementation may have a role in improving cellular bioenergetics in several mitochondrial dysfunction-related diseases, ischemic conditions, and injury pathology and thereby could provide therapeutic benefit in the management of these conditions. However, larger clinical trials are needed to explore these potential therapeutic applications before definitive conclusions can be drawn.

Absence, loss-of-function, or inhibition of Escherichia coli AcrB does not increase expression of other efflux pump genes supporting the discovery of AcrB inhibitors as antibiotic adjuvants.

OBJECTIVES: To determine whether expression of efflux pumps and antibiotic susceptibility are altered in Escherichia coli in response to efflux inhibition. METHODS: The promoter regions of nine efflux pump genes (acrAB, acrD, acrEF, emrAB, macAB, cusCFBA, mdtK, mdtABC, mdfA) were fused to gfp in pMW82 and fluorescence from each reporter construct was used as a measure of the transcriptional response to conditions in which AcrB was inhibited, absent or made non-functional. Expression was also determined by RT-qPCR. Drug susceptibility of efflux pump mutants with missense mutations known or predicted to cause loss of function of the encoded efflux pump was investigated. RESULTS: Data from the GFP reporter constructs revealed that no increased expression of the tested efflux pump genes was observed when AcrB was absent, made non-functional, or inhibited by an efflux pump inhibitor/competitive substrate, such as PAßN or chlorpromazine. This was confirmed by RT-qPCR for PAßN and chlorpromazine; however, a small but significant increase in macB gene expression was seen when acrB is deleted. Efflux inhibitors only synergized with antibiotics in the presence of a functional AcrB. When AcrB was absent or non-functional, there was no impact on MICs when other efflux pumps were also made non-functional. CONCLUSIONS: Absence, loss-of-function, or inhibition of E. coli AcrB did not significantly increase expression of other efflux pump genes, which suggests there is no compensatory mechanism to overcome efflux inhibition and supports the discovery of inhibitors of AcrB as antibiotic adjuvants.