Neuroinflammation in comorbid depression in Alzheimer's disease: A pilot study using post-mortem brain tissue.

Comorbid depression and Alzheimer's disease (AD) is associated with poorer prognosis than either condition alone. Neuroinflammation has been implicated in the pathogenesis and progression of both depression and AD, but much of the existing research has been based on peripheral blood immune markers. Relatively little is known about the neuroinflammatory environment when these conditions occur simultaneously and using immune measures directly in the brain tissue.

Cerebrospinal fluid neurofilament light chain in acute optic neuritis and its predictive ability of multiple sclerosis.

Background: Studies on the capability of cerebrospinal fluid neurofilament light chain (cNfL) to predict multiple sclerosis (MS) conversion in clinically isolated syndromes have yielded varying results.

Objectives: To expand our understanding of cNfL in optic neuritis (ON) and investigate whether incorporating cNfL into the 2017 McDonald criteria could accelerate the diagnosis of MS in patients with ON.

Methods: cNfL was measured in diagnostic samples from 74 patients with verified ON.

Changes in the locus coeruleus during the course of Alzheimer's disease and their relationship to cortical pathology.

Aims: In Alzheimer's disease (AD), the locus coeruleus (LC) undergoes early and extensive neuronal loss, preceded by abnormal intracellular tau aggregation, decades before the onset of clinical disease. Neuromelanin-sensitive MRI has been proposed as a method to image these changes during life. Surprisingly, human post-mortem studies have not examined how changes in LC during the course of the disease relate to cerebral pathology following the loss of the LC projection to the cortex.

Cytotoxic CD4 tissue-resident memory T cells are associated with asthma severity.

Background: Patients with severe uncontrolled asthma represent a distinct endotype with persistent airway inflammation and remodeling that is refractory to corticosteroid treatment. CD4 T2 cells play a central role in orchestrating asthma pathogenesis, and biologic therapies targeting their cytokine pathways have had promising outcomes. However, not all patients respond well to such treatment, and their effects are not always durable nor reverse airway remodeling.

Glial reactivity and T cell infiltration in frontotemporal lobar degeneration with tau pathology.

Frontotemporal lobar degeneration with tau (FTLD-tau) is a group of tauopathies that underlie ∼50% of FTLD cases. Identification of genetic risk variants related to innate/adaptive immunity have highlighted a role for neuroinflammation and neuroimmune interactions in FTLD. Studies have shown microglial and astrocyte activation together with T cell infiltration in the brain of THY-Tau22 tauopathy mice.

The mitochondrial protein TSPO in Alzheimer's disease: relation to the severity of AD pathology and the neuroinflammatory environment.

The 18kD translocator protein (TSPO) is used as a positron emission tomography (PET) target to quantify neuroinflammation in patients. In Alzheimer's disease (AD), the cerebellum is the pseudo-reference region for comparison with the cerebral cortex due to the absence of AD pathology and lower levels of TSPO. However, using the cerebellum as a pseudo-reference region is debated, with other brain regions suggested as more suitable.

Perioperative redox changes in patients undergoing hepato-pancreatico-biliary cancer surgery.

Background: Tissue injury induces inflammation and the surgical stress response, which are thought to be central to the orchestration of recovery or deterioration after surgery. Enhanced formation of reactive oxygen and nitrogen species accompanies the inflammatory response and triggers separate but integrated reduction/oxidation (redox) pathways that lead to oxidative and/or nitrosative stress (ONS). Quantitative information on ONS in the perioperative period is scarce.

Sputum processing by mechanical dissociation: A rapid alternative to traditional sputum assessment approaches.

Background: Sputum cytology is currently the gold standard to evaluate cellular inflammation in the airways and phenotyping patients with airways diseases. Sputum eosinophil proportions have been used to guide treatment for moderate to severe asthma. Furthermore, raised sputum neutrophils are associated with poor disease control and impaired lung function in both asthma and COPD and small airways disease in cystic fibrosis.

Peripheral airways type 2 inflammation, neutrophilia and microbial dysbiosis in severe asthma.

Background: IL-13 is considered an archetypal T2 cytokine central to the clinical disease expression of asthma. The IL-13 response genes, which are upregulated in central airway bronchial epithelial of asthma patients, can be normalized by high-dose inhaled steroid therapy in severe asthma. However, this is not the case within the peripheral airways.

Hair cortisol concentration in anxiety disorders: exploration of relationships with symptom severity and inflammatory markers.

Background: Hair cortisol concentration (HCC) can be used to periodically assess hypothalamic-pituitary-adrenal (HPA) axis function, and appears correlated with prolonged exposure to stress.

Methods: Serial assessment (at Baseline, Week 6 and Week 12) of participants (n = 35) with anxiety disorders by psychopathological rating scales, with assays of HCC and levels of peripheral anti- and pro-inflammatory cytokines. Patients underwent antidepressant treatment for an initial 6 weeks, followed by cyclo-oxygenase inhibitor-2 (COX-2) inhibitor (celecoxib) augmentation or 'treatment as usual' for a further 6 weeks.

Peripheral immunophenotype in dementia with Lewy bodies and Alzheimer's disease: an observational clinical study.

Background: Inflammation plays a key role in the aetiology and progression of Alzheimer's disease (AD). However, the immunophenotype of the second most common neurodegenerative cause of dementia, dementia with Lewy bodies (DLB), remains unclear. To date there have been no studies examining peripheral inflammation in DLB using multiplex immunoassay and flow cytometry concomitantly.

Early Oxidative Stress Response in Patients with Severe Aortic Stenosis Undergoing Transcatheter and Surgical Aortic Valve Replacement: A Transatlantic Study.

Myocardial ischemia/reperfusion-related oxidative stress as a result of cardiopulmonary bypass is thought to contribute to the adverse clinical outcomes following surgical aortic valve replacement (SAVR). Although the acute response following this procedure has been well characterized, much less is known about the nature and extent of oxidative stress induced by the transcatheter aortic valve replacement (TAVR) procedure. We therefore sought to examine and directly compare the oxidative stress response in patients undergoing TAVR and SAVR.

Microglial motility in Alzheimer's disease and after Aβ42 immunotherapy: a human post-mortem study.

Microglial function is highly dependent on cell motility, with baseline motility required for homeostatic surveillance activity and directed motility to migrate towards a source of injury. Experimental evidence suggests impaired microglial motility in Alzheimer's disease (AD) and therefore we have investigated whether the expression of proteins associated with motility is altered in AD and affected by the Aβ immunotherapy using post-mortem brain tissue of 32 controls, 44 AD cases, and 16 AD cases from our unique group of patients immunised against Aβ42 (iAD).Sections of brain were immunolabelled and quantified for (i) the motility-related microglial proteins Iba1, cofilin 1 (CFL1), coronin-1a (CORO1A) and P2RY12, and (ii) pan-Aβ, Aβ42 and phosphorylated tau (ptau).

Small RNA Species and microRNA Profiles are Altered in Severe Asthma Nanovesicles from Broncho Alveolar Lavage and Associate with Impaired Lung Function and Inflammation.

MicroRNAs are known to regulate important pathways in asthma pathology including the IL-6 and IFN pathways. MicroRNAs have been found not only within cells but also within extracellular vesicles such as exosomes. In this study, we particularly focused on microRNA cargo of nanovesicles in bronchoalveolar lavage of severe asthmatic patients.

Reactive Species Interactome Alterations in Oocyte Donation Pregnancies in the Absence and Presence of Pre-Eclampsia.

In pregnancy, maternal physiology is subject to considerable adaptations, including alterations in cardiovascular and metabolic function as well as development of immunological tolerance towards the fetus. In an oocyte donation pregnancy, the fetus is fully allogeneic towards the mother, since it carries both oocyte donor antigens and paternal antigens. Therefore, oocyte donation pregnancies result in an immunologically challenging pregnancy, which is reflected by a higher-than-normal risk to develop pre-eclampsia.

Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation.

Background: Although several studies link high levels of IL-6 and soluble IL-6 receptor (sIL-6R) to asthma severity and decreased lung function, the role of IL-6 trans-signaling (IL-6TS) in asthmatic patients is unclear.

Objective: We sought to explore the association between epithelial IL-6TS pathway activation and molecular and clinical phenotypes in asthmatic patients.

Methods: An IL-6TS gene signature obtained from air-liquid interface cultures of human bronchial epithelial cells stimulated with IL-6 and sIL-6R was used to stratify lung epithelial transcriptomic data (Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes [U-BIOPRED] cohorts) by means of hierarchical clustering.

Primary ciliary dyskinesia ciliated airway cells show increased susceptibility to biofilm formation.

Non-typeable (NTHi) is the most common pathogen in primary ciliary dyskinesia (PCD) patients. We hypothesised that abnormal ciliary motility and low airway nitric oxide (NO) levels on airway epithelial cells from PCD patients might be permissive for NTHi colonisation and biofilm development.We used a primary epithelial cell co-culture model to investigate NTHi infection.

Honey is potentially effective in the treatment of atopic dermatitis: Clinical and mechanistic studies.

Introduction: As manuka honey (MH) exhibits immunoregulatory and anti-staphylococcal activities, we aimed to investigate if it could be effective in the treatment of atopic dermatitis (AD).

Methods: Adult volunteers with bilateral AD lesions were asked to apply MH on one site overnight for seven consecutive days and leave the contralateral site untreated as possible. Three Item Severity score was used to evaluate the response.

Peripheral inflammatory cytokines and immune balance in Generalised Anxiety Disorder: Case-controlled study.

Introduction: Previous investigations have demonstrated that major depression is associated with particular patterns of cytokine signalling. The primary aim of this study was to examine peripheral pro-inflammatory and anti-inflammatory cytokines and immune balance in Generalised Anxiety Disorder (GAD).

Methods: A case-controlled cross-sectional study design was employed: 54 patients with GAD and 64 healthy controls were recruited.

Multidimensional endotyping in patients with severe asthma reveals inflammatory heterogeneity in matrix metalloproteinases and chitinase 3-like protein 1.

Background: Disease heterogeneity in patients with severe asthma and its relationship to inflammatory mechanisms remain poorly understood.

Objective: We aimed to identify and replicate clinicopathologic endotypes based on analysis of blood and sputum parameters in asthmatic patients.

Methods: One hundred ninety-four asthmatic patients and 21 control subjects recruited from 2 separate centers underwent detailed clinical assessment, sputum induction, and phlebotomy.

Airway Surfactant Protein D Deficiency in Adults With Severe Asthma.

Background: Surfactant protein D (SP-D) is an essential component of the innate immune defense against pathogens within the airways. SP-D also regulates allergic inflammation and promotes the removal of apoptotic cells. SP-D dysregulation is evident in several pulmonary diseases.