Eosinophilic esophagitis (EoE) has emerged from a case-reportable illness in the early 1990s to a distinct clinicopathological entity. Increasing worldwide incidences have been observed, although due to various study designs estimates are inconsistent.

Workplace-based selective prevention of mental health problems currently relies on subjective evaluation of stress complaints. Hair cortisol captures chronic stress responses and could be a promising biomarker for the early identification of mental health problems. The objective was to provide an overview of the state-of-the-art knowledge on the practical value of hair cortisol in the occupational setting.

Skeletal muscle disuse results in rapid functional declines. Previous studies have typically been at least 1 week in duration and focused on the responsiveness of men. Herein, we report the timeline of initial impairments in strength, voluntary activation (VA), and motor unit control during 2 weeks of knee joint immobilization. Thirteen women (mean age =21 years) underwent 2 weeks of left knee joint immobilization via ambulation on crutches and use of a brace. Participants visited the laboratory for testing on seven occasions (two familiarization visits, pretest, 48 and 72 h, 1 and 2 weeks). Knee extensor isometric and concentric isokinetic strength at two velocities (180 and 360 degrees⋅s-1 ), VA, and submaximal vastus lateralis motor unit activity were evaluated. Moderate-to-large decreases in isometric and concentric strength at 180 degrees⋅s-1 and VA were observed within 48 hours. Isometric strength continued to decline beyond 72 h, whereas other variables plateaued. The B-term of the motor unit mean firing rate versus action potential amplitude relationship demonstrated a moderate increase 1 week into immobilization, suggesting that greater firing rates were necessary to maintain pretest torque levels. Concentric strength at a velocity of 360 degrees s-1 was not affected. Decreases in knee extensor strength occur within a matter of days after immobilization, although the time course and magnitude vary among assessment methods. These changes are mediated by the nervous system's capacity to activate skeletal muscle. Clinically appropriate interventions which target nervous system plasticity should be implemented early to minimize the rapid functional impairments associated with disuse.

Insulin-like growth factor-1 (IGF-1) is an important fetal growth factor. However, the role of fetal IGF-1 in increasing placental blood flow, nutrient transfer, and nutrient availability to support fetal growth and protein accretion is not well understood. Catheterized fetuses from late gestation pregnant sheep received an intravenous infusion of LR3 IGF-1 (LR3 IGF-1; n = 8) or saline (SAL; n = 8) for 1 wk. Sheep then underwent a metabolic study to measure uterine and umbilical blood flow, nutrient uptake rates, and fetal protein kinetic rates. By the end of the infusion, fetal weights were not statistically different between groups (SAL: 3.260 ± 0.211 kg, LR3 IGF-1: 3.682 ± 0.183; P = 0.15). Fetal heart, adrenal gland, and spleen weights were higher (P < 0.05), and insulin was lower in LR3 IGF-1 (P < 0.05). Uterine and umbilical blood flow and umbilical uptake rates of glucose, lactate, and oxygen were similar between groups. Umbilical amino acid uptake rates were lower in LR3 IGF-1 (P < 0.05) as were fetal concentrations of multiple amino acids. Fetal protein kinetic rates were similar. LR3 IGF-1 skeletal muscle had higher myoblast proliferation (P < 0.05). In summary, LR3 IGF-1 infusion for 1 wk into late gestation fetal sheep increased the weight of some fetal organs. However, because umbilical amino acid uptake rates and fetal plasma amino acid concentrations were lower in the LR3 IGF-1 group, we speculate that animals treated with LR3 IGF-1 can efficiently utilize available nutrients to support organ-specific growth in the fetus rather than by stimulating placental blood flow or nutrient transfer to the fetus.NEW & NOTEWORTHY After a 1-wk infusion of LR3 IGF-1, late gestation fetal sheep had lower umbilical uptake rates of amino acids, lower fetal arterial amino acid and insulin concentrations, and lower fetal oxygen content; however, LR-3 IGF-1-treated fetuses were still able to effectively utilize the available nutrients and oxygen to support organ growth and myoblast proliferation.

Investigating obstetric near misses (life-threatening obstetric complications) provides crucial information to prevent maternal mortality and morbidity.

This study aimed to assess whether the long-term effectiveness of the Melbourne Infant, Feeding, Activity and Nutrition Trial (INFANT) at 2 and 3·5 years post-intervention varied according to maternal education and age.

Plants are not only challenged by pathogenic organisms but also colonized by commensal microbes. The network of interactions these microbes establish with their host and among each other is suggested to contribute to the immune responses of plants against pathogens. In wild Arabidopsis thaliana populations, the oomycete pathogen Albugo laibachii plays an influential role in structuring the leaf phyllosphere. We show that the epiphytic yeast Moesziomyces bullatus ex Albugo on Arabidopsis, a close relative of pathogenic smut fungi, is an antagonistic member of the A. thaliana phyllosphere, which reduces infection of A. thaliana by A. laibachii. Combination of transcriptomics, reverse genetics, and protein characterization identified a GH25 hydrolase with lysozyme activity as a major effector of this microbial antagonism. Our findings broaden the understanding of microbial interactions within the phyllosphere, provide insights into the evolution of epiphytic basidiomycete yeasts, and pave the way for novel biocontrol strategies.

The CNS is regarded as an immunoprivileged organ, evading routine immune surveillance; however, the coordinated development of immune responses profoundly influences outcomes after brain injury. Innate lymphoid cells (ILCs) are cytokine-producing cells that are critical for the initiation, modulation, and resolution of inflammation, but the functional relevance and mechanistic regulation of ILCs are unexplored after acute brain injury. We demonstrate increased proliferation of all ILC subtypes within the meninges for up to 1 year after experimental traumatic brain injury (TBI) while ILCs were present within resected dura and elevated within cerebrospinal fluid (CSF) of moderate-to-severe TBI patients. In line with energetic derangements after TBI, inhibition of the metabolic regulator, AMPK, increased meningeal ILC expansion, whereas AMPK activation suppressed proinflammatory ILC1/ILC3 and increased the frequency of IL-10-expressing ILC2 after TBI. Moreover, intracisternal administration of IL-33 activated AMPK, expanded ILC2, and suppressed ILC1 and ILC3 within the meninges of WT and Rag1-/- mice, but not Rag1-/- IL2rg-/- mice. Taken together, we identify AMPK as a brake on the expansion of proinflammatory, CNS-resident ILCs after brain injury. These findings establish a mechanistic framework whereby immunometabolic modulation of ILCs may direct the specificity, timing, and magnitude of cerebral immunity.

Data regarding antibody responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in patients infected with COVID-19 are not yet available. In this study, we aimed to evaluate serum antibody responses in patients regardless of the outcome. We measured the circulating immunoglobulin G (IgG) antibody levels in 60 subjects with a certified history of SARS-CoV-2 infection by using immunoenzymatic, chemiluminescent, and Neutralization assays. Half patients had a severe infection, the other half were pauci-symptomatic. We analyzed their antibody response to see the trend of the humoral response. Our results showed a significant difference in circulating IgG level among the two groups. The neutralizing antibody response against SARS-CoV-2 was significantly higher among those who had severe disease. Furthermore, ten subjects from each group were screened twice, and a declining antibody trend was observed in pauci-symptomatic individuals. These findings provide evidence that humoral immunity against SARS-CoV-2 in pauci-symptomatic people is weak and may not be long-lasting. This may have implications for immunity strategy and prevention, since it is still not clear whether a time-dependent decrease of both circulating and neutralizing antibodies to nonprotective levels could occur in a longer time span and whether potential vaccines are able to induce a herd immunity and a durable response.

Viral infections remain a major cause of economic loss with an unmet need for novel therapeutic agents. Ivermectin is a putative antiviral compound; the proposed mechanism is the inhibition of nuclear translocation of viral proteins, facilitated by mammalian host importins, a necessary process for propagation of infections. We systematically reviewed the evidence for the applicability of ivermectin against viral infections including SARS-CoV-2 regarding efficacy, mechanisms and selective toxicity. The SARS-CoV-2 genome was mined to determine potential nuclear location signals for ivermectin and meta-analyses for in vivo studies included all comparators over time, dose range and viral replication in multiple organs. Ivermectin inhibited the replication of many viruses including those in Flaviviridae, Circoviridae and Coronaviridae families in vitro. Real and mock nuclear location signals were identified in SARS-CoV-2, a potential target for ivermectin and predicting a sequestration bait for importin β, stopping infected cells from reaching a virus-resistant state. While pharmacokinetic evaluations indicate that ivermectin could be toxic if applied based on in vitro studies, inhibition of viral replication in vivo was shown for Porcine circovirus in piglets and Suid herpesvirus in mice. Overall standardized mean differences and 95% confidence intervals for ivermectin versus controls were -4.43 (-5.81, -3.04), p < 0.00001. Based on current results, the potential for repurposing ivermectin as an antiviral agent is promising. However, further work is needed to reconcile in vitro studies with clinical efficacy. Developing ivermectin as an additional antiviral agent should be pursued with an emphasis on pre-clinical trials in validated models of infection.

Anticoagulant-related nephropathy (ARN), that was described in humans first as warfarin-related nephropathy, is characterized by acute kidney injury and red blood cell (RBC) tubular casts in the kidney. 5/6 nephrectomy (5/7NE) rats treated with warfarin or dabigatran show changes in kidney function and morphology that are similar to human disease. The role of glomerular filtration rate (GFR) in the pathogenesis of ARN is not clear. The aim of these studies was to elucidate the role of GFR in the pathogenesis of dabigatran-induced ARN in 5/6NE rats.

The outbreak of coronavirus disease 2019 (COVID-19) has led to substantial infections and mortality around the world. Fast screening and diagnosis are thus crucial for quick isolation and clinical intervention. In this work, we showed that attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FT-IR) can be a primary diagnostic tool for COVID-19 as a supplement to in-use techniques. It requires only a small volume (∼3 μL) of the serum sample and a shorter detection time (several minutes). The distinct spectral differences and the separability between normal control and COVID-19 were investigated using multivariate and statistical analysis. Results showed that ATR-FT-IR coupled with partial least squares discriminant analysis was effective to differentiate COVID-19 from normal controls and some common respiratory viral infections or inflammation, with the area under the receiver operating characteristic curve (AUROC) of 0.9561 (95% CI: 0.9071-0.9774). Several serum constituents including, but not just, antibodies and serum phospholipids could be reflected on the infrared spectra, serving as "chemical fingerprints" and accounting for good model performances.

P-glycoprotein (P-gp/ABCB1) and breast cancer resistance protein (BCRP/ABCG2) modulate the distribution of drugs and toxins across the blood-brain barrier (BBB). Animal studies reported that infection-induced disruption of these transporters in the developing BBB impairs fetal brain protection. However, the impact of infection mimics on P-gp/BCRP function in human brain endothelium is less well understood. We hypothesized that Toll-like receptor ligands mimicking bacterial and viral infection would modify the expression and function of P-gp and BCRP in human brain endothelial cells (BECs). Human cerebral microvascular endothelial cells (hCMEC/D3) were challenged with bacterial [Lipopolysaccharide (LPS)] and viral-mimics [polyinosinic:polycytidylic acid (PolyI:C) or single-stranded RNA (ssRNA)], or pro-inflammatory cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-α and interferon gamma (IFN)-ɣ. P-gp and BCRP function was assessed after 4 or 24 h, using Calcein-AM and Chlorin-6 assays, respectively. Western blot and qPCR quantified P-gp/ABCB1 and BCRP/ABCG2 expression following treatments. Infection mimics are potent modulators of drug transporters in human BECs in vitro. LPS and PolyI:C increased, while ssRNA exposure reduced P-gp activity. In contrast, LPS and PolyI:C decreased, while ssRNA increased BCRP activity (P < .05). There was little correlation between drug transporter function, gene expression and total protein level. Altered plasma membrane BCRP may suggest modified intracellular trafficking induced by infection in human BECs. Bacterial and viral infection mimics modify P-gp and BCRP transport function in human BECs, in vitro. This knowledge may contribute and have important implications for human brain protection and possible altered biodistribution of drugs and xenobiotics in the brain following exposure to TLR agonists.

Focus groups are useful to support HIV prevention research among US subpopulations, such as Black gay, Black bisexual, and other Black sexual minority men (BSMM). Virtual synchronous focus groups provide an electronic means to obtain qualitative data and are convenient to implement; however, the protocols and acceptability for conducting virtual synchronous focus groups in HIV prevention research among BSMM are lacking.

Medical professionals are exposed to multiple and often excessive demands in their work environment. Low-intensity internet interventions allow them to benefit from psychological support even when institutional help is not available. Focusing on enhancing psychological resources-self-efficacy and perceived social support-makes an intervention relevant for various occupations within the medical profession. Previously, these resources were found to operate both individually or sequentially with self-efficacy either preceding social support (cultivation process) or following it (enabling process).

Air pollution has been consistently linked with dementia and cognitive decline. However, it is unclear whether risk is accumulated through long-term exposure or whether there are sensitive/critical periods. A key barrier to clarifying this relationship is the dearth of historical air pollution data.

Electrocardiography (ECG) is an important tool to triage patients with out-of-hospital cardiac arrest (OHCA) after return of spontaneous circulation (ROSC). An immediate coronary angiography after ROSC is recommended only in patients with an ECG that is diagnostic of ST-segment elevation myocardial infarction (STEMI). To date, the benefit of this approach has not been demonstrated in patients with a post-ROSC ECG that is not diagnostic of STEMI.

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Understanding which children are at increased risk for poor outcome with COVID-19 is critical. In this study, we link pediatric population-based data from the US Center for Disease Control and Prevention to COVID-19 hospitalization and in-hospital death. In 27,045 US children with confirmed COVID-19, we demonstrate that African American [OR 2.28 (95% CI: 1.93, 2.70)] or mixed race [OR 2.95 (95% CI: 2.28, 3.82)] and an underlying medical condition [OR 3.55 (95% CI: 3.14, 4.01)] are strong predictors for hospitalization. Death occurred in 39 (0.19%) of 20,096 hospitalized children; children with a prior medical condition had an increased odd for death [OR 8.8 (95% CI: 3.7, 21.1)].Conclusion: Hospitalization and in-hospital death are rare in children diagnosed with COVID-19. However, children at higher risk for these outcomes include those with an underlying medical condition, as well as those of African American descent. What is Known: • Demographic factors are independent prognosticators of poor outcome in children with COVID-19. What is New: • Children with an underlying medical condition and those from an African American or mixed race/ethnicity are at high risk for COVID-19 hospitalization. • History of a comorbidity supersedes age, gender, and race/ethnicity as a risk factor for in-hospital pediatric COVID-19 death.