NLRP3 promotes allergic responses to birch pollen extract in a model of intranasal sensitization.

Introduction & Objective: Allergic sensitization is an essential step in the development of allergic airway inflammation to birch pollen (BP); however, this process remains to be fully elucidated. Recent scientific advances have highlighted the importance of the allergen context. In this regard, microbial patterns (PAMPs) present on BP have attracted increasing interest.

Artificial intelligence in histopathological image analysis of central nervous system tumours: A systematic review.

The convergence of digital pathology and artificial intelligence could assist histopathology image analysis by providing tools for rapid, automated morphological analysis. This systematic review explores the use of artificial intelligence for histopathological image analysis of digitised central nervous system (CNS) tumour slides. Comprehensive searches were conducted across EMBASE, Medline and the Cochrane Library up to June 2023 using relevant keywords.

Cerebrospinal fluid cytology findings in a case of diffuse leptomeningeal glioneuronal tumour.

This case report describes the cytological features of a rare tumour: diffuse leptomeningeal glioneuronal tumour. This case highlights the value of cerebrospinal fluid analysis when this type of tumour is suspected, both for aiding the preliminary morphological diagnosis and for enabling potential molecular testing.

Multisystem screening reveals SARS-CoV-2 in neurons of the myenteric plexus and in megakaryocytes.

SARS-CoV-2, the causative agent of COVID-19, typically manifests as a respiratory illness, although extrapulmonary involvement, such as in the gastrointestinal tract and nervous system, as well as frequent thrombotic events, are increasingly recognised. How this maps onto SARS-CoV-2 organ tropism at the histological level, however, remains unclear. Here, we perform a comprehensive validation of a monoclonal antibody against the SARS-CoV-2 nucleocapsid protein (NP) followed by systematic multisystem organ immunohistochemistry analysis of the viral cellular tropism in tissue from 36 patients, 16 postmortem cases and 16 biopsies with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 status from the peaks of the pandemic in 2020 and four pre-COVID postmortem controls.

A change point analysis protocol for comparing intracellular transport by different molecular motor combinations.

Intracellular transport by microtubule-based molecular motors is marked by qualitatively different behaviors. It is a long-standing and still-open challenge to accurately quantify the various individual-cargo behaviors and how they are affected by the presence or absence of particular motor families. In this work we introduce a protocol for analyzing change points in cargo trajectories that can be faithfully projected along the length of a (mostly) straight microtubule.

Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2.

Individuals with potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) do not necessarily develop PCR or antibody positivity, suggesting that some individuals may clear subclinical infection before seroconversion. T cells can contribute to the rapid clearance of SARS-CoV-2 and other coronavirus infections. Here we hypothesize that pre-existing memory T cell responses, with cross-protective potential against SARS-CoV-2 (refs.

T lymphocyte senescence is attenuated in Parkinson's disease.

Background: Immune involvement is well-described in Parkinson's disease (PD), including an adaptive T lymphocyte response. Given the increasing prevalence of Parkinson's disease in older age, age-related dysregulation of T lymphocytes may be relevant in this disorder, and we have previously observed changes in age-associated CD8 T cell subsets in mid-stage PD. This study aimed to further characterise T cell immunosenescence in newly diagnosed PD patients, including shifts in CD4 and CD8 subpopulations, and changes in markers of cellular ageing in CD8 T lymphocytes.

Unhealthy Behaviours and Risk of Parkinson's Disease: A Mendelian Randomisation Study.

Background: Tobacco smoking and alcohol intake have been identified in observational studies as potentially protective factors against developing Parkinson's disease (PD); the impact of body mass index (BMI) on PD risk is debated. Whether such epidemiological associations are causal remains unclear. Mendelian randomsation (MR) uses genetic variants to explore the effects of exposures on outcomes; potentially reducing bias from residual confounding and reverse causation.

Emerging spectrum of COVID-19-related cardiopulmonary pathology in adults.

COVID-19 is currently a major cause of morbidity and mortality in adults throughout the world. Given the high infection rate, it is increasingly likely that histopathologists will encounter this disease during their practice. Although COVID-19 is increasingly recognized as a multi-system disease, the lungs and, to a lesser degree, the heart remain the major sites of pathology.

Time series analysis and mechanistic modelling of heterogeneity and sero-reversion in antibody responses to mild SARS‑CoV-2 infection.

Background: SARS-CoV-2 serology is used to identify prior infection at individual and at population level. Extended longitudinal studies with multi-timepoint sampling to evaluate dynamic changes in antibody levels are required to identify the time horizon in which these applications of serology are valid, and to explore the longevity of protective humoral immunity.

Methods: Healthcare workers were recruited to a prospective cohort study from the first SARS-CoV-2 epidemic peak in London, undergoing weekly symptom screen, viral PCR and blood sampling over 16-21 weeks.

Healthcare Workers Bioresource: Study outline and baseline characteristics of a prospective healthcare worker cohort to study immune protection and pathogenesis in COVID-19.

: Most biomedical research has focused on sampling COVID-19 patients presenting to hospital with advanced disease, with less focus on the asymptomatic or paucisymptomatic. We established a bioresource with serial sampling of health care workers (HCWs) designed to obtain samples before and during mainly mild disease, with follow-up sampling to evaluate the quality and duration of immune memory. : We conducted a prospective study on HCWs from three hospital sites in London, initially at a single centre (recruited just prior to first peak community transmission in London), but then extended to multiple sites 3 weeks later (recruitment still ongoing, target n=1,000).

Lower Lymphocyte Count is Associated With Increased Risk of Parkinson's Disease.

Objectives: Patients with established Parkinson's disease (PD) display differences in peripheral blood markers of immune function, including leukocyte differential counts, compared with controls. These differences may be useful biomarkers to predict PD and may shed light on pathogenesis. We sought to identify whether peripheral immune dysregulation was associated with increased risk of subsequent PD diagnosis.

A case report of metastatic renal cell carcinoma causing corticobasal syndrome.

We present a case report of a patient with a history of renal cell carcinoma in which corticobasal syndrome had been diagnosed ante-mortem. However, distinguishing features of corticobasal degeneration pathology were absent at post-mortem. Instead, neuropathological examination revealed features consistent with the patient's history of renal cell carcinoma: micrometastatic renal cell carcinoma in cerebellar and cerebral white matter, including within the gyral white matter of the primary motor and somatosensory cortices.

Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection.

Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW.

Beyond dexamethasone, emerging immuno-thrombotic therapies for COVID-19.

Host immunity is required to clear SARS-CoV-2, and inability to clear the virus because of host or pathogen factors renders those infected at risk of poor outcomes. Estimates of those who are able to clear the virus with asymptomatic or paucisymptomatic COVID-19 remain unclear, and dependent on widespread testing. However, evidence is emerging that in severe cases, pathological mechanisms of hyperinflammation and coagulopathy ensue, the former supported by results from the RECOVERY trial demonstrating a reduction in mortality with dexamethasone in advanced COVID-19.

Clinicopathological co-occurrence of Fahr's disease and dementia with Lewy bodies.

We present the clinicopathological findings of a case of combined Fahr's disease (FD) and dementia with Lewy bodies (DLB), associated with a novel pathogenic mutation. The patient presented with visual hallucinations, fluctuating confusion and parkinsonism, leading to a presumptive diagnosis of DLB. CT scan showed extensive bilateral parenchymal calcifications, suggestive of FD.

Antibody-Mediated Immobilization of Virions in Mucus.

Antibodies have been shown to hinder the movement of herpes simplex virus virions in cervicovaginal mucus, as well as other viruses in other mucus secretions. However, it has not been possible to directly observe the mechanisms underlying this phenomenon, so the nature of virion-antibody-mucin interactions remain poorly understood. In this work, we analyzed thousands of virion traces from single particle tracking experiments to explicate how antibodies must cooperate to immobilize virions for relatively long time periods.

The impact of selective serotonin reuptake inhibitors on the risk of intracranial haemorrhage: A systematic review and meta-analysis.

Introduction: Observational studies have suggested increased risk of intracranial haemorrhage (ICrH) in patients receiving selective serotonin reuptake inhibitors (SSRIs). We sought to clarify the impact of SSRIs on ICrH, accounting for study methodology.

Patients And Methods: A comprehensive search of Medline, Embase and the Cochrane Library from 1960 to December 2017 identified studies comparing SSRIs with control.

Disease-Modification in Huntington's Disease: Moving Away from a Single-Target Approach.

To date, no candidate intervention has demonstrated a disease-modifying effect in Huntington's disease, despite promising results in preclinical studies. In this commentary we discuss disease-modifying therapies that have been trialled in Huntington's disease and speculate that these failures may be attributed, in part, to the assumption that a single drug selectively targeting one aspect of disease pathology will be universally effective, regardless of disease stage or "subtype". We therefore propose an alternative approach for effective disease-modification that uses 1) a combination approach rather than monotherapy, and 2) targets the disease process early on - before it is clinically manifest.

Designing Next-Generation Local Drug Delivery Vehicles for Glioblastoma Adjuvant Chemotherapy: Lessons from the Clinic.

To date, the clinical outcomes and survival rates for patients with glioblastoma (GB) remain poor. A promising approach to disease-modification involves local delivery of adjuvant chemotherapy into the resection cavity, thus circumventing the restrictions imposed by the blood-brain barrier. The clinical performance of the only FDA-approved local therapy for GB [carmustine (BCNU)-loaded polyanhydride wafers], however, has been disappointing.

Mechanisms of spinal cord stimulation for the treatment of pain: Still in the dark after 50 years.

Background And Objective: Despite the value of spinal cord stimulation (SCS) in treating some patients with focal neuropathic pain, technological advances in stimulator design and treatment protocols have not correlated with significant improvements in clinical outcomes. This may be because incomplete understanding of the mechanisms underlying SCS precludes improvement in clinical efficacy. In this brief review, we (a) review phenomenological effects of SCS, (b) review the literature on proposed spinal sites of action of SCS and (c) propose a novel hypothesis of mechanism of action.