Commonly disrupted pathways in brain and kidney in a pig model of systemic endotoxemia.

Sepsis is a life-threatening state that arises due to a hyperactive inflammatory response stimulated by infection and rarely other insults (e.g., non-infections tissue injury). Although changes in several proinflammatory cytokines and signals are documented in humans and small animal models, far less is known about responses within affected tissues of large animal models. We sought to understand the changes that occur during the initial stages of inflammation by administering intravenous lipopolysaccharide (LPS) to Yorkshire pigs and assessing transcriptomic alterations in the brain, kidney, and whole blood. Robust transcriptional alterations were found in the brain, with upregulated responses enriched in inflammatory pathways and downregulated responses enriched in tight junction and blood vessel functions. Comparison of the inflammatory response in the pig brain to a similar mouse model demonstrated some overlapping changes but also numerous differences, including oppositely dysregulated genes between species. Substantial changes also occurred in the kidneys following LPS with several enriched upregulated pathways (cytokines, lipids, unfolded protein response, etc.) and downregulated gene sets (tube morphogenesis, glomerulus development, GTPase signal transduction, etc.). We also found significant dysregulation of genes in whole blood that fell into several gene ontology categories (cytokines, cell cycle, neutrophil degranulation, etc.). We observed a strong correlation between the brain and kidney responses, with significantly shared upregulated pathways (cytokine signaling, cell death, VEGFA pathways) and downregulated pathways (vasculature and RAC1 GTPases). In summary, we have identified a core set of shared genes and pathways in a pig model of systemic inflammation.

Atopic dermatitis (eczema) guidelines: 2023 American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters GRADE- and Institute of Medicine-based recommendations.

BACKGROUND: Guidance addressing atopic dermatitis (AD) management, last issued in 2012 by the American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force, requires updating as a result of new treatments and improved guideline and evidence synthesis methodology. OBJECTIVE: To produce evidence-based guidelines that support patients, clinicians, and other decision-makers in the optimal treatment of AD. METHODS: A multidisciplinary guideline panel consisting of patients and caregivers, AD experts (dermatology and allergy/immunology), primary care practitioners (family medicine, pediatrics, internal medicine), and allied health professionals (psychology, pharmacy, nursing) convened, prioritized equity, diversity, and inclusiveness, and implemented management strategies to minimize influence of conflicts of interest. The Evidence in Allergy Group supported guideline development by performing systematic evidence reviews, facilitating guideline processes, and holding focus groups with patient and family partners. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach informed rating the certainty of evidence and strength of recommendations. Evidence-to-decision frameworks, subjected to public comment, translated evidence to recommendations using trustworthy guideline principles. RESULTS: The panel agreed on 25 recommendations to gain and maintain control of AD for patients with mild, moderate, and severe AD. The eAppendix provides practical information and implementation considerations in 1-2 page patient-friendly handouts. CONCLUSION: These evidence-based recommendations address optimal use of (1) topical treatments (barrier moisturization devices, corticosteroids, calcineurin inhibitors, PDE4 inhibitors [crisaborole], topical JAK inhibitors, occlusive [wet wrap] therapy, adjunctive antimicrobials, application frequency, maintenance therapy), (2) dilute bleach baths, (3) dietary avoidance/elimination, (4) allergen immunotherapy, and (5) systemic treatments (biologics/monoclonal antibodies, small molecule immunosuppressants [cyclosporine, methotrexate, azathioprine, mycophenolate, JAK inhibitors], and systemic corticosteroids) and UV phototherapy (light therapy).

Systemic treatments for atopic dermatitis (eczema): Systematic review and network meta-analysis of randomized trials.

BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes. OBJECTIVE: We sought to systematically synthesize the benefits and harms of AD systemic treatments. METHODS: For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, Web of Science, and GREAT databases from inception to November 29, 2022, for randomized trials addressing systemic treatments and phototherapy for AD. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. This review is registered in the Open Science Framework (https://osf.io/e5sna). RESULTS: The 149 included trials (28,686 patients with moderate-to-severe AD) evaluated 75 interventions. With high-certainty evidence, high-dose upadacitinib was among the most effective for 5 of 6 patient-important outcomes; high-dose abrocitinib and low-dose upadacitinib were among the most effective for 2 outcomes. These Janus kinase inhibitors were among the most harmful in increasing adverse events. With high-certainty evidence, dupilumab, lebrikizumab, and tralokinumab were of intermediate effectiveness and among the safest, modestly increasing conjunctivitis. Low-dose baricitinib was among the least effective. Efficacy and safety of azathioprine, oral corticosteroids, cyclosporine, methotrexate, mycophenolate, phototherapy, and many novel agents are less certain. CONCLUSIONS: Among individuals with moderate-to-severe AD, high-certainty evidence demonstrates that high-dose upadacitinib is among the most effective in addressing multiple patient-important outcomes, but also is among the most harmful. High-dose abrocitinib and low-dose upadacitinib are effective, but also among the most harmful. Dupilumab, lebrikizumab, and tralokinumab are of intermediate effectiveness and have favorable safety.

Allergen immunotherapy for atopic dermatitis: Systematic review and meta-analysis of benefits and harms.

BACKGROUND: Atopic dermatitis (AD, eczema) is driven by a combination of skin barrier defects, immune dysregulation, and extrinsic stimuli such as allergens, irritants, and microbes. The role of environmental allergens (aeroallergens) in triggering AD remains unclear. OBJECTIVE: We systematically synthesized evidence regarding the benefits and harms of allergen immunotherapy (AIT) for AD. METHODS: As part of the 2022 American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters AD Guideline update, we searched the MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Global Resource for Eczema Trials, and Web of Science databases from inception to December 2021 for randomized controlled trials comparing subcutaneous immunotherapy (SCIT), sublingual immunotherapy (SLIT), and/or no AIT (placebo or standard care) for guideline panel-defined patient-important outcomes: AD severity, itch, AD-related quality of life (QoL), flares, and adverse events. Raters independently screened, extracted data, and assessed risk of bias in duplicate. We synthesized intervention effects using frequentist and Bayesian random-effects models. The GRADE approach determined the quality of evidence. RESULTS: Twenty-three randomized controlled trials including 1957 adult and pediatric patients sensitized primarily to house dust mite showed that add-on SCIT and SLIT have similar relative and absolute effects and likely result in important improvements in AD severity, defined as a 50% reduction in SCORing Atopic Dermatitis (risk ratio [95% confidence interval] 1.53 [1.31-1.78]; 26% vs 40%, absolute difference 14%) and QoL, defined as an improvement in Dermatology Life Quality Index by 4 points or more (risk ratio [95% confidence interval] 1.44 [1.03-2.01]; 39% vs 56%, absolute difference 17%; both outcomes moderate certainty). Both routes of AIT increased adverse events (risk ratio [95% confidence interval] 1.61 [1.44-1.79]; 66% with SCIT vs 41% with placebo; 13% with SLIT vs 8% with placebo; high certainty). AIT's effect on sleep disturbance and eczema flares was very uncertain. Subgroup and sensitivity analyses were consistent with the main findings. CONCLUSIONS: SCIT and SLIT to aeroallergens, particularly house dust mite, can similarly and importantly improve AD severity and QoL. SCIT increases adverse effects more than SLIT. These findings support a multidisciplinary and shared decision-making approach to optimally managing AD.

Threshold-Responsive Colorimetric Sensing System for the Continuous Monitoring of Gases.

Colorimetric sensors are widely used because of their inherent advantages including accuracy, rapid response, ease-of-use, and low costs; however, they usually lack reusability, which precludes the continuous use of a single sensor. We have developed a threshold-responsive colorimetric system that enables repeated analyte measurements by a single colorimetric sensor. The threshold responsive algorithm automatically adjusts the sensor exposure time to the analyte and measurement frequency according to the sensor response. The system registers the colorimetric sensor signal change rate, prevents the colorimetric sensor from reaching saturation, and allows the sensor to fully regenerate before the next measurement is started. The system also addresses issues common to colorimetric sensors, including the response time and range of detection. We demonstrate the benefits and feasibility of this novel system, using colorimetric sensors for ammonia and carbon dioxide gases for continuous monitoring of up to (at least) 60 detection cycles without signs of analytical performance degradation of the sensors.

Correlating the Role of Nanofillers with Active Layer Properties and Performance of Thin-Film Nanocomposite Membranes.

Thin-film nanocomposite (TFN) membranes are emerging water-purification membranes that could provide enhanced water permeance with similar solute removal over traditional thin-film composite (TFC) membranes. However, the effects of nanofiller incorporation on active layer physico-chemical properties have not been comprehensively studied. Accordingly, we aimed to understand the correlation between nanofillers, active layer physico-chemical properties, and membrane performance by investigating whether observed performance differences between TFN and control TFC membranes correlated with observed differences in physico-chemical properties. The effects of nanofiller loading, surface area, and size on membrane performance, along with active layer physico-chemical properties, were characterized in TFN membranes incorporated with Linde Type A (LTA) zeolite and zeolitic imidazole framework-8 (ZIF-8). Results show that nanofiller incorporation up to ~0.15 wt% resulted in higher water permeance and unchanged salt rejection, above which salt rejection decreased 0.9-25.6% and 26.1-48.3% for LTA-TFN and ZIF-8-TFN membranes, respectively. Observed changes in active layer physico-chemical properties were generally unsubstantial and did not explain observed changes in TFN membrane performance. Therefore, increased water permeance in TFN membranes could be due to preferential water transport through porous structures of nanofillers or along polymer-nanofiller interfaces. These findings offer new insights into the development of high-performance TFN membranes for water/ion separations.

Bleach baths for atopic dermatitis: A systematic review and meta-analysis including unpublished data, Bayesian interpretation, and GRADE.

BACKGROUND: Bleach bathing is frequently recommended to treat atopic dermatitis (AD), but its efficacy and safety are uncertain. OBJECTIVE: To systematically synthesize randomized controlled trials (RCTs) addressing bleach baths for AD. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and GREAT from inception to December 29, 2021, for RCTs assigning patients with AD to bleach vs no bleach baths. Paired reviewers independently and in duplicate screened records, extracted data, and assessed risk of bias (Cochrane version 2) and GRADE quality of evidence. We obtained unpublished data, harmonized individual patient data and did Frequentist and Bayesian random-effects meta-analyses. RESULTS: There were 10 RCTs that enrolled 307 participants (median of mean age 7.2 years, Eczema Area Severity Index baseline mean of means 27.57 [median SD, 10.74]) for a median of 6 weeks (range, 4-10). We confirmed that other trials registered globally were terminated. Bleach baths probably improve AD severity (22% vs 32% improved Eczema Area Severity Index by 50% [ratio of means 0.78, 95% credible interval 0.59-0.99]; moderate certainty) and may slightly reduce skin Staphylococcal aureus colonization (risk ratio, 0.89 [95% confidence interval, 0.73-1.09]; low certainty). Adverse events, mostly dry skin and irritation, along with itch, patient-reported disease severity, sleep quality, quality of life, and risk of AD flares were not clearly different between groups and of low to very low certainty. CONCLUSION: In patients with moderate-to-severe AD, bleach baths probably improve clinician-reported severity by a relative 22%. One in 10 will likely improve severity by 50%. Changes in other patient-important outcomes are uncertain. These findings support optimal eczema care and the need for additional large clinical trials. TRIAL REGISTRATION: PROSPERO Identifier: CRD42021238486.

Latex barrier thin film formation on porous substrates.

Here we present the formation of thin layers of barrier polymers onto mesoporous and macroporous substrates via dip coating of latex solutions. We investigated four commercially available latex solutions: polytetrafluoroethylene (PTFE), perfluoroalkoxy fluorothermoplastic (PFA), polyvinylidene chloride (PVDC), and polyolefin-based latex (Hypod). We examined the latex film formation on porous polymeric and ceramic substrates with a broad range of pore sizes from 10 to 200 nm. Our results show that both characteristics of the latex solution [glass transition temperature (Tg), particle size, and crystallinity] and the characteristics of the porous substrate (pore size and hydrophobicity) impact the film formation. We confirmed the defect-free, barrier nature of our latex thin films through scanning electron microscopy (SEM), atomic force microscopy (AFM), and hydraulically driven water permeation tests. Additionally, we found that latex concentration (not dipping time) is the most important parameter determining ultimate latex film thickness. We obtained defect-free films from PVDC and Hypod, which are "soft" polymers (Tg < room temperature), on mesoporous substrates under the conditions of slow evaporation rate of the solvent from these latex solutions. PTFE and PFA, which are "hard" polymers (Tg > room temperature), did not form continuous films on porous substrates.

Designing metallic glass matrix composites with high toughness and tensile ductility.

The selection and design of modern high-performance structural engineering materials is driven by optimizing combinations of mechanical properties such as strength, ductility, toughness, elasticity and requirements for predictable and graceful (non-catastrophic) failure in service. Highly processable bulk metallic glasses (BMGs) are a new class of engineering materials and have attracted significant technological interest. Although many BMGs exhibit high strength and show substantial fracture toughness, they lack ductility and fail in an apparently brittle manner in unconstrained loading geometries. For instance, some BMGs exhibit significant plastic deformation in compression or bending tests, but all exhibit negligible plasticity (<0.5% strain) in uniaxial tension. To overcome brittle failure in tension, BMG-matrix composites have been introduced. The inhomogeneous microstructure with isolated dendrites in a BMG matrix stabilizes the glass against the catastrophic failure associated with unlimited extension of a shear band and results in enhanced global plasticity and more graceful failure. Tensile strengths of approximately 1 GPa, tensile ductility of approximately 2-3 per cent, and an enhanced mode I fracture toughness of K(1C) approximately 40 MPa m(1/2) were reported. Building on this approach, we have developed 'designed composites' by matching fundamental mechanical and microstructural length scales. Here, we report titanium-zirconium-based BMG composites with room-temperature tensile ductility exceeding 10 per cent, yield strengths of 1.2-1.5 GPa, K(1C) up to approximately 170 MPa m(1/2), and fracture energies for crack propagation as high as G(1C) approximately 340 kJ m(-2). The K(1C) and G(1C) values equal or surpass those achievable in the toughest titanium or steel alloys, placing BMG composites among the toughest known materials.

Zwitterionic Copolymers for Anti-Scaling Applications in Simulated Spaceflight Wastewater Scenarios.

Water reclamation in spaceflight applications, such as those encountered on the International Space Station (ISS), requires complex engineering solutions to ensure maximum water recovery. Current vapor compression distillation (VCD) technologies are effective but produce highly concentrated brines and often cause scaling within a separation system. This work evaluates initial steps toward integrating pervaporation, a membrane separation process, as a brine management strategy for ISS wastewaters. Pervaporation performs separations driven by a chemical potential difference across the membrane created by either a sweep gas or a vacuum pull. Pervaporation membranes, as with most membrane processes, can be subject to scaling. Therefore, this work studies the anti-scaling properties of zwitterions (polymeric molecules with covalently tethered positive and negative ions) coated onto sulfonated pentablock terpolymer block polymer (Nexar) pervaporation membrane surfaces. We report a method for applying zwitterions to the surface of pervaporation membranes and the effect on performance parameters such as flux and scaling resistance. Membranes with zwitterions had up to 53% reduction in permeance but reduced scaling. The highest amount of scaling occurred in the samples exposed to calcium chloride, and uncoated membranes had weight percent increases as high as 1617 ± 241%, whereas zwitterion-coated membranes experienced only about 317 ± 87% weight increase in the presence of the same scalant.

Values and Preferences of Patients and Caregivers Regarding Treatment of Atopic Dermatitis (Eczema): A Systematic Review.

Importance: Patient values and preferences can inform atopic dermatitis (AD) care. Systematic summaries of evidence addressing patient values and preferences have not previously been available. Objective: To inform American Academy of Allergy, Asthma & Immunology (AAAAI)/American College of Allergy, Asthma and Immunology (ACAAI) Joint Task Force on Practice Parameters AD guideline development, patient and caregiver values and preferences in the management of AD were systematically synthesized. Evidence Review: Paired reviewers independently screened MEDLINE, Embase, PsycINFO, and CINAHL databases from inception until March 20, 2022, for studies of patients with AD or their caregivers, eliciting values and preferences about treatment, rated risk of bias, and extracted data. Thematic and inductive content analysis to qualitatively synthesize the findings was used. Patients, caregivers, and clinical experts provided triangulation. The GRADE-CERQual (Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative Research) informed rating of the quality of evidence. Findings: A total of 7780 studies were identified, of which 62 proved eligible (n = 19 442; median age across studies [range], 15 years [3-44]; 59% female participants). High certainty evidence showed that patients and caregivers preferred to start with nonmedical treatments and to step up therapy with increasing AD severity. Moderate certainty evidence showed that adverse effects from treatment were a substantial concern. Low certainty evidence showed that patients and caregivers preferred odorless treatments that are not visible and have a minimal effect on daily life. Patients valued treatments capable of relieving itching and burning skin and preferred to apply topical corticosteroids sparingly. Patients valued a strong patient-clinician relationship. Some studies presented varied perspectives and 18 were at high risk for industry sponsorship bias. Conclusions and Relevance: In the first systematic review to address patient values and preferences in management of AD to our knowledge, 6 key themes that may inform optimal clinical care, practice guidelines, and future research have been identified.

Development of tough, low-density titanium-based bulk metallic glass matrix composites with tensile ductility.

The mechanical properties of bulk metallic glasses (BMGs) and their composites have been under intense investigation for many years, owing to their unique combination of high strength and elastic limit. However, because of their highly localized deformation mechanism, BMGs are typically considered to be brittle materials and are not suitable for structural applications. Recently, highly-toughened BMG composites have been created in a Zr-Ti-based system with mechanical properties comparable with high-performance crystalline alloys. In this work, we present a series of low-density, Ti-based BMG composites with combinations of high strength, tensile ductility, and excellent fracture toughness.

Tailoring the structure of thin film nanocomposite membranes to achieve seawater RO membrane performance.

Herein we report on the formation and characterization of pure polyamide thin film composite (TFC) and zeolite-polyamide thin film nanocomposite (TFN) reverse osmosis (RO) membranes. Four different physical-chemical post-treatment combinations were applied after the interfacial polymerization reaction to change the molecular structure of polyamide and zeolite-polyamide thin films. Both TFC and TFN hand-cast membranes were more permeable, hydrophilic, and rough than a commercial seawater RO membrane. Salt rejection by TFN membranes was consistently below that of hand-cast TFC membranes; however, two TFN membranes exhibited 32 g/L NaCl rejections above 99.4%, which was better than the commercial membrane under the test conditions employed. The nearly defect-free TFN films that produced such high rejections were achieved only with wet curing, regardless of other post-treatments. Polyamide films formed in the presence of zeolite nanoparticles were less cross-linked than similarly cast pure polyamide films. At the very low nanoparticle loadings evaluated, differences between pure polyamide and zeolite-polyamide membrane water and salt permeability correlated weakly with extent of cross-linking of the polyamide film, which suggests that defects and molecular-sieving largely govern transport through zeolite-polyamide thin film nanocomposite membranes.

Removal of pesticide toxicity by cysteine-capped Ag nanoparticles and study of their adsorption kinetics.

A new method has been developed for one-step synthesis of cysteine-capped Ag nanoparticles. The particles have been characterized by several techniques, including ultraviolet-visible spectroscopy, infrared spectroscopy, X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. The interaction of these nanoparticles has been seen with two pesticides, namely, chlorpyrifos and malathion, which are major water pollutants.

A Handheld, Colorimetric Optoelectronic Dynamics Analyzer for Measuring Total Ammonia of Biological Samples.

This paper introduces a wireless, solid-state, portable, and automated device capable of measuring the total ammonia [ammonia (NH3) and ammonium (NH4+)] levels of fluids, including biological samples. This device reliably measures the total ammonia of biological samples (e.g., urine) faster than the current ammonia quantification techniques. Medical professionals typically estimate NH4+ levels using error-prone indirect measurement techniques (i.e., urine anion gap), which are time-consuming and are seldom suitable for periodic measurements. Several instantaneous measurements of total ammonia levels in a patient urine could be utilized as an early warning for both acid-base and/or potassium disturbances. Given the device's operation mechanism, it is able to quantify the total ammonia concentration within a biological sample in only 5 s and can simultaneously transmit data to other devices via Bluetooth. The analytical operation demonstrated high sensitivity, high specificity, fast reversibility, rapid response time, and has enabled the accurate determination of total ammonia concentration in urine samples produced by subjects who had consumed diets of variable protein compositions.

Isoconfigurational elastic constants and liquid fragility of a bulk metallic glass forming alloy.

Samples of Zr(46.25)Ti(8.25)Cu(7.5)Ni(10)Be(27.5) were isothermally annealed and quenched near the glass transition temperature and studied by the pulse-echo overlap technique. The shear modulus G of the samples shows a strong reversible dependence on annealing temperatures and, thus, on the specific configurational potential energy of the equilibrium liquid. The low-T dependence of G of the configurationally frozen glasses shows linear temperature dependence as expected by Debye-Grüneisen theory. The T dependence of G in the liquid state is directly related to the viscosity and fragility of the liquid.