GG in a chewable colonizes the nose and facilitates local immune benefits in allergic rhinoconjunctivitis patients.

Current treatments fall short in managing allergic rhinitis (AR), emphasizing the need for additional strategies. Beneficial bacteria application shows promise in AR; however, most studies focus on oral probiotic administration without monitoring the applied strains in the upper respiratory tract (URT) and their local effects. In this randomized, double-blind, placebo-controlled trial, the probiotic GG was administered via chewable tablets in seasonal AR patients, randomized to probiotic ( = 33) or placebo ( = 31) groups.

Drivers of quasispecies development in SARS-CoV-2 and implications for emergent variants and COVID-19.

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019, significant research has focused on SARS-CoV-2 evolution and transmission. Most transmission studies rely on RT-qPCR and consensus sequencing for SARS-CoV-2 characterization, often overlooking the collection of viable genetically linked genomes characterized by one or more intra-host single nucleotide variants (iSNVs) within the same sample, defined as "quasispecies" (QS), which could influence disease outcomes. QS are highly variable in genomic position and frequency and have been proven to impact viral evolution substantially.

Aquaporin 4 modulation drives amyloid burden and cognitive abilities in an APPPS1 mouse model of Alzheimer's disease.

Introduction: Deficiency in the aquaporin-4 (AQP4) water channel has been linked to impaired amyloid beta (Aβ) clearance. However, a detailed morphopathological analysis of amyloid deposition following AQP4 therapeutic modulation remains unexplored.

Methods: Two-month-old amyloid precursor protein presenilin 1 (APPPS1) mice were treated daily for 28 days with either the AQP4 facilitator N-(3-(Benzyloxy)pyridin-2-yl) benzene-sulfonamide (TGN-073) or the AQP4 inhibitor N-(1,3,4-thiadiazol-2-yl)pyridine-3-carboxamide dihydrochloride (TGN-020) (both at 200 mg/kg).

Quasi-species prevalence and clinical impact of evolving SARS-CoV-2 lineages in European COVID-19 cohorts, January 2020 to February 2022.

BackgroundEvolution of SARS-CoV-2 is continuous.AimBetween 01/2020 and 02/2022, we studied SARS-CoV-2 variant epidemiology, evolution and association with COVID-19 severity.MethodsIn nasopharyngeal swabs of COVID-19 patients (n = 1,762) from France, Italy, Spain, and the Netherlands, SARS-CoV-2 was investigated by reverse transcription-quantitative PCR and whole-genome sequencing, and the virus variant/lineage (NextStrain/Pangolin) was determined.

An Assessment of Smartphone Use on Brainstem Auditory Evoked Potentials in Healthy Young Adults in North India Short Title: Assessing BAEP Changes in Young Smartphone Users.

Background: A smartphone is an essential part of our daily existence. Smartphones are used by about 5.26 billion people.

Protocol for fecal microbiota transplantation: A microaerophilic approach for mice housed in a specific pathogen-free facility.

Recently, studies have emerged exploring the potential application of fecal microbiota transplantation (FMT) in pre-clinical settings. Here, we present a protocol for FMT for mice housed in a specific pathogen-free (SPF) facility. We describe steps for sample collection, microaerophilic processing of freshly collected fecal pellets, and administration through oral gavage.

Tracing carriage, acquisition, and transmission of ESBL-producing Escherichia coli over two years in a tertiary care hospital.

Background: The impact of community carriage on the influx of extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) into hospitals remains understudied. In this prospective 2-year single-centre study, we investigate the community ESBL-E influx and trace the colonisation, nosocomial acquisition, transmission, and infection dynamics of ESBL-producing Escherichia coli (ESBL-Ec) in non-ICU wards at a tertiary care hospital.

Methods: This study reports primary and post hoc outcomes of the clinical trial NCT01208519 in which hospitalised patients were screened for rectal carriage of ESBL-E.

Characteristics of Auditory Brainstem Response in Night-shift Health Workers.

Background: With technological advancement and economic competitiveness there is an exponential rise in the number of shift workers. Worldwide, healthcare workers constitute the single largest proportion of workers who work on shift duty in order to provide round-the-clock healthcare services to patients. Various studies have demonstrated an association between circadian cycle disturbance due to shift work and adverse health impacts.

Chemosensory assessment and impact on quality of life in neurosensorial cluster of the post COVID 19 syndrome.

COVID-19 pandemic brought chemosensory impairment to the forefront of medicine, revealing gaps in the knowledge of pathophysiological mechanisms, true prevalence and preventive/therapeutic alternatives. This is a sub-study of the ORCHESTRA cohort focusing on post-COVID-19 chemosensory symptoms. Risk factors for neurosensorial cluster of post-COVID-19 syndrome (NSc-PCS) were assessed through multivariable analysis.

Mrgprb2-dependent Mast Cell Activation Plays a Crucial Role in Acute Colitis.

Background & Aims: Mast cells (MCs) are typically found at mucosal surfaces, where their immunoglobulin E (IgE)-dependent activation plays a central role in allergic diseases. Over the past years, signaling through Mas-related G protein-coupled receptor b2 (Mrgprb2) in mice and MRGPRX2 in humans has gained a lot of interest as an alternative MC activation pathway with high therapeutic potential. The aim of this study was to explore the relevance of such IgE-independent, Mrgprb2-mediated signaling in colonic MCs in the healthy and acutely inflamed mouse colon.

Interleukin-2-mediated CD4 T-cell activation correlates highly with effective serological and T-cell responses to SARS-CoV-2 vaccination in people living with HIV.

People living with HIV (PLWH) despite having an appreciable depletion of CD4 T-cells show a good severe acute respiratory syndrome coronavirus 2 vaccination response. The underlying mechanism(s) are currently not understood. We studied serological and polyfunctional T-cell responses in PLWH receiving anti-retroviral therapy stratified on CD4 counts as PLWH-high (CD4 ≥ 500 cells/mm) and PLWH-low (<500 cells/mm).

Immunogenicity, reactogenicity, and safety of a second booster with BNT162b2 or full-dose mRNA-1273: A randomized VACCELERATE trial in adults aged ≥75 years (EU-COVAT-1-AGED Part B).

Objectives: To assess the safety and immunogenicity of a fourth vaccination (second booster) in individuals aged ≥75 years.

Methods: Participants were randomized to BNT162b2 (Comirnaty, 30 µg) or messenger RNA (mRNA)-1273 (Spikevax, 100 µg). The primary end point was the rate of two-fold antibody titer increase 14 days after vaccination, targeting the receptor binding domain (RBD) region of wild-type SARS-CoV-2.

Assessing the Brainstem Auditory Evoked Potentials in Subjects with Family History of Hypertension.

Background: Hypertension (HTN) has a genetic predisposition and it also impairs microcirculation, thereby, affecting the well vascularized structures like the brainstem and causing changes in Brainstem Auditory Evoked Potentials (BAEPs).

Purpose: To find out the usefulness of BAEPs as a screening tool in apparently healthy individuals with a family history of HTN.

Methods: One hundred and ten volunteers, aged 17 to 23 years, were enrolled in the study as participants with proper consent.

Fractal Analysis in Neurodegenerative Diseases.

Neurodegenerative diseases are defined by progressive nervous system dysfunction and death of neurons. The abnormal conformation and assembly of proteins is suggested to be the most probable cause for many of these neurodegenerative disorders, leading to the accumulation of abnormally aggregated proteins, for example, amyloid β (Aβ) (Alzheimer's disease and vascular dementia), tau protein (Alzheimer's disease and frontotemporal lobar degeneration), α-synuclein (Parkinson's disease and Lewy body dementia), polyglutamine expansion diseases (Huntington disease), or prion proteins (Creutzfeldt-Jakob disease). An aberrant gain-of-function mechanism toward excessive intraparenchymal accumulation thus represents a common pathogenic denominator in all these proteinopathies.

Cytokine Expression in Cancer Survivors Suffering From Chronic Pain: A Systematic Review.

Background: Chronic cancer-related pain remains underdiagnosed and undertreated, although it affects 40% of cancer survivors. Recent insights suggest that cytokine signaling between immune, neuro, and glial cells contributes to chronic pain.

Objectives: This study systematically reviewed cytokine levels and their relation to chronic cancer-related pain and, additionally, investigated differences in cytokine levels between cancer survivors with and without chronic pain.

Dissecting the role of the gut microbiome and fecal microbiota transplantation in radio- and immunotherapy treatment of colorectal cancer.

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and poses a major burden on the human health worldwide. At the moment, treatment of CRC consists of surgery in combination with (neo)adjuvant chemotherapy and/or radiotherapy. More recently, immune checkpoint blockers (ICBs) have also been approved for CRC treatment.

Immunogenicity and reactogenicity of a first booster with BNT162b2 or full-dose mRNA-1273: A randomised VACCELERATE trial in adults ≥75 years (EU-COVAT-1).

Background: Vaccination remains crucial for protection against severe SARS-CoV-2 infection, especially for people of advanced age, however, optimal dosing regimens are as yet lacking.

Methods: EU-COVAT-1-AGED Part A is a randomised controlled, adaptive, multicentre phase II trial evaluating safety and immunogenicity of a 3rd vaccination (1st booster) in individuals ≥75 years. Fifty-three participants were randomised to full-doses of either mRNA-1273 (Spikevax®, 100 µg) or BNT162b2 (Comirnaty®, 30 µg).

Clinical phenotypes and quality of life to define post-COVID-19 syndrome: a cluster analysis of the multinational, prospective ORCHESTRA cohort.

Background: Lack of specific definitions of clinical characteristics, disease severity, and risk and preventive factors of post-COVID-19 syndrome (PCS) severely impacts research and discovery of new preventive and therapeutics drugs.

Methods: This prospective multicenter cohort study was conducted from February 2020 to June 2022 in 5 countries, enrolling SARS-CoV-2 out- and in-patients followed at 3-, 6-, and 12-month from diagnosis, with assessment of clinical and biochemical features, antibody (Ab) response, Variant of Concern (VoC), and physical and mental quality of life (QoL). Outcome of interest was identification of risk and protective factors of PCS by clinical phenotype, setting, severity of disease, treatment, and vaccination status.

Using machine learning to predict antibody response to SARS-CoV-2 vaccination in solid organ transplant recipients: the multicentre ORCHESTRA cohort.

Objectives: The study aim was to assess predictors of negative antibody response (AbR) in solid organ transplant (SOT) recipients after the first booster of SARS-CoV-2 vaccination.

Methods: Solid organ transplant recipients receiving SARS-CoV-2 vaccination were prospectively enrolled (March 2021-January 2022) at six hospitals in Italy and Spain. AbR was assessed at first dose (t), second dose (t), 3 ± 1 month (t), and 1 month after third dose (t).

Host immunological responses facilitate development of SARS-CoV-2 mutations in patients receiving monoclonal antibody treatments.

BackgroundThe role of host immunity in emergence of evasive SARS-CoV-2 Spike mutations under therapeutic monoclonal antibody (mAb) pressure remains to be explored.MethodsIn a prospective, observational, monocentric ORCHESTRA cohort study, conducted between March 2021 and November 2022, mild-to-moderately ill COVID-19 patients (n = 204) receiving bamlanivimab, bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab were longitudinally studied over 28 days for viral loads, de novo Spike mutations, mAb kinetics, seroneutralization against infecting variants of concern, and T cell immunity. Additionally, a machine learning-based circulating immune-related biomarker (CIB) profile predictive of evasive Spike mutations was constructed and confirmed in an independent data set (n = 19) that included patients receiving sotrovimab or tixagevimab/cilgavimab.

Predictive model for BNT162b2 vaccine response in cancer patients based on blood cytokines and growth factors.

Background: Patients with cancer, especially hematological cancer, are at increased risk for breakthrough COVID-19 infection. So far, a predictive biomarker that can assess compromised vaccine-induced anti-SARS-CoV-2 immunity in cancer patients has not been proposed.

Methods: We employed machine learning approaches to identify a biomarker signature based on blood cytokines, chemokines, and immune- and non-immune-related growth factors linked to vaccine immunogenicity in 199 cancer patients receiving the BNT162b2 vaccine.

Gut to lung translocation and antibiotic mediated selection shape the dynamics of Pseudomonas aeruginosa in an ICU patient.

Bacteria have the potential to translocate between sites in the human body, but the dynamics and consequences of within-host bacterial migration remain poorly understood. Here we investigate the link between gut and lung Pseudomonas aeruginosa populations in an intensively sampled ICU patient using a combination of genomics, isolate phenotyping, host immunity profiling, and clinical data. Crucially, we show that lung colonization in the ICU was driven by the translocation of P.

Clinical Impact of Monoclonal Antibodies in the Treatment of High-Risk Patients with SARS-CoV-2 Breakthrough Infections: The ORCHESTRA Prospective Cohort Study.

The clinical impact of anti-spike monoclonal antibodies (mAb) in Coronavirus Disease 2019 (COVID-19) breakthrough infections is unclear. We present the results of an observational prospective cohort study assessing and comparing COVID-19 progression in high-risk outpatients receiving mAb according to primary or breakthrough infection. Clinical, serological and virological predictors associated with 28-day COVID-19-related hospitalization were identified using multivariate logistic regression and summarized with odds ratio (aOR) and 95% confidence interval (CI).