PROTECTION OF MICE AGAINST CECAL LIGATION AND PUNCTURE-INDUCED POLYMICROBIAL SEPSIS BY A FASCIOLA HEPATICA HELMINTH DEFENSE MOLECULE.

Sepsis results from a dysregulated host immune response to infection and is responsible for ~11 million deaths each year. In the laboratory, many aspects of sepsis can be replicated using a cecal ligation and puncture model, which is considered the most clinically relevant rodent model of sepsis. In the present study, histological and biomarker multiplex analyses revealed that the cecal ligation and puncture model initiated a large-scale inflammatory response in mice by 24 h, with evidence of acute organ damage by 48-72 h.

Digital wearable insole-based identification of knee arthropathies and gait signatures using machine learning.

Gait is impaired in musculoskeletal conditions, such as knee arthropathy. Gait analysis is used in clinical practice to inform diagnosis and monitor disease progression or intervention response. However, clinical gait analysis relies on subjective visual observation of walking as objective gait analysis has not been possible within clinical settings due to the expensive equipment, large-scale facilities, and highly trained staff required.

Physicochemical Stability Study of the Morphine-Bupivacaine-Ziconotide Association.

Objective: The aim of this study was to investigate the physicochemical stability of morphine-bupivacaine-ziconotide mixtures used in intrathecal analgesia in polypropylene syringes and intrathecal pumps.

Materials And Methods: The stability study method was conceived according to International Council for Harmonisation guidelines. For propylene syringes, six different mixtures of morphine-bupivacaine and ziconotide were assessed over seven days.

Differential modulation of allergic rhinitis nasal transcriptome by dupilumab and allergy immunotherapy.

Background: Nasal epithelial cells are important regulators of barrier function and immune signaling; however, in allergic rhinitis (AR) these functions can be disrupted by inflammatory mediators. We aimed to better discern AR disease mechanisms using transcriptome data from nasal brushing samples from individuals with and without AR.

Methods: Data were drawn from a feasibility study of individuals with and without AR to Timothy grass and from a clinical trial evaluating 16 weeks of treatment with the following: dupilumab, a monoclonal antibody that binds interleukin (IL)-4Rα and inhibits type 2 inflammation by blocking signaling of both IL-4/IL-13; subcutaneous immunotherapy with Timothy grass (SCIT), which inhibits allergic responses through pleiotropic effects; SCIT + dupilumab; or placebo.

Maintaining glucose integrity ex-vivo: Impact of preanalytical specimen handling.

Background: Adopting the WHO protocol for glucose analysis is arguably impractical in the routine clinical setting. Deviations may develop due to a lack of understanding regarding the impact of glycolysis on the accuracy of results.

Aim: We sought to assess the stability of glucose in two different blood collection tubes (BCT), BD Vacutainer® FX 'Fl-Ox' and Greiner Vacuette® FC-Mix 'FC-Mix' stored at room temperature (RT:18-22°C) and 4°C over 8.

Identifying Persons with Special Healthcare Needs in Dentistry-Development and Validation of the French Case Mix Tool.

Providing dental care for certain patient groups is complicated due to difficulties with cooperation, communication, health conditions, and social context, amongst others. The majority of dentists in France work within a public fee-per-item system. A new measure has been introduced providing a financial supplement to dentists for each episode of care for a patient with a severe disability.

A pilot study of the Earable device to measure facial muscle and eye movement tasks among healthy volunteers.

The Earable device is a behind-the-ear wearable originally developed to measure cognitive function. Since Earable measures electroencephalography (EEG), electromyography (EMG), and electrooculography (EOG), it may also have the potential to objectively quantify facial muscle and eye movement activities relevant in the assessment of neuromuscular disorders. As an initial step to developing a digital assessment in neuromuscular disorders, a pilot study was conducted to determine whether the Earable device could be utilized to objectively measure facial muscle and eye movements intended to be representative of Performance Outcome Assessments, (PerfOs) with tasks designed to model clinical PerfOs, referred to as mock-PerfO activities.

Association of complement pathways with COVID-19 severity and outcomes.

Objectives: Complement activation has been implicated in COVID-19 pathogenesis. This study aimed to assess the levels of complement activation products and full-length proteins in hospitalized patients with COVID-19, and evaluated whether complement pathway markers are associated with outcomes.

Methods: Longitudinal measurements of complement biomarkers from 89 hospitalized adult patients, grouped by baseline disease severity, enrolled in an adaptive, phase 2/3, randomized, double-blind, placebo-controlled trial and treated with intravenous sarilumab (200 mg or 400 mg) or placebo (NCT04315298), were performed.

Use of Whole-Genome Sequencing to Estimate the Contribution of Immune Evasion and Waning Immunity on Decreasing COVID-19 Vaccine Effectiveness.

Background: The impact variant-specific immune evasion and waning protection have on declining coronavirus disease 2019 (COVID-19) vaccine effectiveness (VE) remains unclear. Using whole-genome sequencing (WGS), we examined the contribution these factors had on the decline that followed the introduction of the Delta variant. Furthermore, we evaluated calendar-period-based classification as a WGS alternative.

CD22-targeted CD28 bispecific antibody enhances antitumor efficacy of odronextamab in refractory diffuse large B cell lymphoma models.

Although many patients with diffuse large B cell lymphoma (DLBCL) may achieve a complete response to frontline chemoimmunotherapy, patients with relapsed/refractory disease typically have poor outcomes. Odronextamab, a CD20xCD3 bispecific antibody that provides "signal 1" through the activation of the T cell receptor/CD3 complex, has exhibited early, promising activity for patients with highly refractory DLBCL in phase 1 trials. However, not all patients achieve complete responses, and many relapse, thus representing a high unmet medical need.

Stability of Morphine Sulfate-Clonidine and Sufentanil-Clonidine Mixtures.

Background: Spinal analgesia is recommended for intractable cancer pain. Morphine-clonidine and sufentanil-clonidine are often used in association in intrathecal drug delivery systems, injected by intraabdominal pumps. To refill these pumps and to limit patient transport, it may be necessary to ship the mixtures in polypropylene syringes to peripheral establishments located near patient homes.

Moderation of buprenorphine therapy for cocaine dependence efficacy by variation of the Prodynorphin gene.

Purpose: The aim of this secondary analysis was to identify prodynorphin (PDYN) genetic markers moderating the therapeutic response to treatment of cocaine dependence with buprenorphine/naloxone (Suboxone®; BUP).

Methods: Cocaine-dependent participants (N = 302) were randomly assigned to a platform of injectable, extended-release naltrexone (XR-NTX) and one of three daily medication arms: 4 mg BUP (BUP4), 16 mg BUP (BUP16), or placebo (PLB) for 8 weeks (Parent Trial Registration: Protocol ID: NIDA-CTN-0048, Clinical Trials.gov ID: NCT01402492).

UGT1A1 genetic variants are associated with increases in bilirubin levels in rheumatoid arthritis patients treated with sarilumab.

Sarilumab is a human monoclonal antibody against interleukin (IL)-6Rα that has been approved for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) and an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs). Mild liver function test abnormalities have been observed in patients treated with sarilumab. We describe a genome-wide association study of bilirubin elevations in RA patients treated with sarilumab.

Neoadjuvant cemiplimab for resectable hepatocellular carcinoma: a single-arm, open-label, phase 2 trial.

Background: Surgical resection of early stage hepatocellular carcinoma is standard clinical practice; however, most tumours recur despite surgery, and no perioperative intervention has shown a survival benefit. Neoadjuvant immunotherapy has induced pathological responses in multiple tumour types and might decrease the risk of postoperative recurrence in hepatocellular carcinoma. We aimed to evaluate the clinical activity of neoadjuvant cemiplimab (an anti-PD-1) in patients with resectable hepatocellular carcinoma.

The Activin/FLRG Pathway Associates with Poor COVID-19 Outcomes in Hospitalized Patients.

A subset of hospitalized COVID-19 patients, particularly the aged and those with comorbidities, develop the most severe form of the disease, characterized by acute respiratory disease syndrome (ARDS), coincident with experiencing a "cytokine storm." Here, we demonstrate that cytokines which activate the NF-κB pathway can induce activin A. Patients with elevated activin A, activin B, and FLRG at hospital admission were associated with the most severe outcomes of COVID-19, including the requirement for mechanical ventilation, and all-cause mortality.

Pathogenicity and virulence of the liver flukes and that cause the zoonosis Fasciolosis.

Fasciolosis caused by the liver flukes and is one of the most important neglected parasitic diseases of humans and animals. The ability of the parasites to infect and multiply in their intermediate snail hosts, and their adaptation to a wide variety of mammalian definitive hosts contribute to their high transmissibility and distribution. Within the mammalian host, the trauma caused by the immature flukes burrowing through the liver parenchyma is associated with most of the pathogenesis.

Anti-SARS-CoV-2 IgA Identifies Asymptomatic Infection in First Responders.

Background: Immunoglobulin A (IgA) is an important component of the early immune response to SARS-CoV-2. Prior serosurveys in high-risk groups employing IgG testing alone have provided discordant estimates. The potential added benefit of IgA in serosurveys has not been established.

Baseline Severe Acute Respiratory Syndrome Viral Load Is Associated With Coronavirus Disease 2019 Severity and Clinical Outcomes: Post Hoc Analyses of a Phase 2/3 Trial.

Background: Elucidating the relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and clinical outcomes is critical for understanding coronavirus disease 2019 (COVID-19).

Methods: The SARS-CoV-2 levels were analyzed by quantitative real-time polymerase chain reaction (RT-qPCR) of nasopharyngeal or oropharyngeal swab specimens collected at baseline, and clinical outcomes were recorded over 60 days from 1362 COVID-19 hospitalized patients enrolled in a multicenter, randomized, placebo-controlled phase 2/3 trial of sarilumab for COVID-19 (ClinicalTrials.gov NCT04315298).

The monoclonal antibody combination REGEN-COV protects against SARS-CoV-2 mutational escape in preclinical and human studies.

Monoclonal antibodies against SARS-CoV-2 are a clinically validated therapeutic option against COVID-19. Because rapidly emerging virus mutants are becoming the next major concern in the fight against the global pandemic, it is imperative that these therapeutic treatments provide coverage against circulating variants and do not contribute to development of treatment-induced emergent resistance. To this end, we investigated the sequence diversity of the spike protein and monitored emergence of virus variants in SARS-COV-2 isolates found in COVID-19 patients treated with the two-antibody combination REGEN-COV, as well as in preclinical in vitro studies using single, dual, or triple antibody combinations, and in hamster in vivo studies using REGEN-COV or single monoclonal antibody treatments.

Autonomous Non Antioxidant Roles for Secreted Thioredoxin-1 and Peroxiredoxin-1.

Trematode parasites of the genus are the cause of liver fluke disease (fasciolosis) in humans and their livestock. Infection of the host involves invasion through the intestinal wall followed by migration in the liver that results in extensive damage, before the parasite settles as a mature egg-laying adult in the bile ducts. Genomic and transcriptomic studies revealed that increased metabolic stress during the rapid growth and development of is balanced with the up-regulation of the thiol-independent antioxidant system.

The OPRD1 rs678849 variant influences outcome of disulfiram treatment for cocaine dependency in methadone-maintained patients.

Objective: Prior research demonstrated that the δ-opioid receptor (OPRD1) rs678849 variant influences opioid use in African Americans treated with methadone. We examined whether this variant moderated cocaine and opioid use in our clinical cohort of methadone and disulfiram treated recipients.

Methods: Cocaine and opioid codependent patients were stabilized for 2 weeks on methadone and subsequently randomized into groups treated with either methadone + placebo (n = 37) or methadone + disulfiram (250 mg/day; n = 33) for 12 weeks.

Preventing Post Dural Puncture Headache after Intrathecal Drug Delivery System Implantation Through Preventive Fibrin Glue Application: A Retrospective Study.

Background: Cerebrospinal fluid (CSF) leakage resulting in post dural puncture headache (PDPH) is a frequent adverse effect observed after intrathecal drug delivery system (IDDS) implantation. CSF leakage symptoms negatively affect patient quality of life and can result in additional complications. Fibrin glue was used to treat CSF leakage syndrome.

Reference intervals for commonly requested biochemical and haematological parameters in a healthy Irish adult Caucasian population.

Introduction: In laboratory medicine, reference intervals (RIs) are key decision support tools used to guide the clinical interpretation of numerical test results. Best practice suggests each laboratory establishes RIs in the local population prior to introducing an assay into routine clinical practice.

Aim: The aim of this study was to define RIs for frequently requested biochemical/haematological parameters in a healthy adult Irish Caucasian population.