Dynamics of neutrophil migration in lymph nodes during infection

Although the signals that control neutrophil migration from the blood to sites of infection have been well characterized, little is known about their migration patterns within lymph nodes or the strategies that neutrophils use to find their local sites of action. To address these questions, we used two-photon scanning-laser microscopy to examine neutrophil migration in intact lymph nodes during infection with an intracellular parasite, Toxoplasma gondii. We found that neutrophils formed both small, transient and large, persistent swarms via a coordinated migration pattern. We provided evidence that cooperative action of neutrophils and parasite egress from host cells could trigger swarm formation. Neutrophil swarm formation coincided in space and time with the removal of macrophages that line the subcapsular sinus of the lymph node. Our data provide insights into the cellular mechanisms underlying neutrophil swarming and suggest new roles for neutrophils in shaping immune responses.     

Fungal-specific humoral response in eosinophilic mucus chronic rhinosinusitis

OBJECTIVES/HYPOTHESIS: An immunoglobulin (Ig)E-mediated allergic pathogenesis is presumed in allergic fungal sinusitis (AFS), yet extensive polyps and eosinophilic mucus (EM) in the paranasal sinuses may also occur in the absence of allergy. Although a noninvasive fungal pathogenesis is presumed in all chronic rhinosinusitis with EM (EMCRS), fungal-specific nonallergic immune responses have not been thoroughly investigated. We tested the hypothesis that there is a fungal-specific humoral response in EMCRS and that it is not confined to IgE. STUDY DESIGN: EMCRS patients were prospectively stratified into subgroups based on the presence or absence of fungi within EM and of fungal-specific systemic IgE. There were 12 AFS, 5 AFS-like, 8 nonallergic fungal eosinophilic sinusitis (NAFES), and 5 nonallergic, nonfungal eosinophilic sinusitis (NANFES) patients. METHODS: Alternaria alternata and Aspergillus fumigatus-specific serum IgE, IgG, IgM, and IgA was measured by enzyme-linked immunosorbent assay and compared with strictly defined healthy and disease-control groups. RESULTS: Fungal-specific IgG (Alternaria alternata P = .0002; Aspergillus fumigatus P = .004), and IgA levels (Alternaria alternata P = .0016; Aspergillus fumigatus P = .002) were higher in EMCRS compared with healthy volunteers but not with disease controls. Fungal-specific IgG3 levels were significantly elevated in all the EMCRS subgroups compared with controls for either fungal antigen (P < .0001). Importantly, fungal-specific IgE levels were not significantly different between fungal-allergic EMCRS and disease controls. CONCLUSIONS: Fungal-specific immunity characterized by serum IgG3 and not IgE, distinguished the EMCRS subgroups from control groups regardless of the presence of fungus within EM or of systemic fungal allergy. Fungal-specific IgE responses in fungal-allergic EMCRS were no different to those in fungal-allergic controls, thus challenging the presumption of a unique pathogenic role of fungal allergy in "allergic fungal sinusitis."     

Serum and organ-associated anti-hemoglobin humoral autoreactivity: association with anti-Sm responses and inflammation

The release of hemoglobin (Hb) occurs in some infectious and autoimmune diseases characterized by inflammation. As levels of haptoglobin (Hp) fall, free Hb can cause pathology. Humoral autoreactivity to human Hb was demonstrated in the sera of systemic lupus erythematosus (SLE), leishmania and malaria patients. Serum anti-murine Hb antibody levels in lupus-prone mice also exhibited an age-dependent increase, with progressive organ sequestration; significant isotypic correlation was observed with anti-dsDNA antibodies. A suggestive link between anti-Hb and anti-Sm responses was observed: Human lupus sera expressing anti-Sm antibody reactivity preferentially contained heightened levels of anti-Hb autoantibodies, and immunization of lupus-prone mice with Sm led to enhanced anti-murine Hb reactivity. Human and murine anti-Hb monoclonal antibodies were generated, some of which were preferentially reactive toward disease-associated methemoglobin. Epitope-mapping studies revealed evidence of intra-molecular cross-reactivity. One such autoantibody synergized with Hb to enhance the secretion of pro-inflammatory cytokines while eliciting the increased production of monocyte migratory signals from endothelial cells. Preferential usage of specific variable region gene segments was not observed, although somatic mutations were documented. These studies reveal that, while the etiology, specificity and sequences of anti-Hb autoreactive antibodies can vary, they occur quite frequently and can have inflammatory consequences.     

An unusual presentation of hemolytic anemia in a patient with prosthetic mitral valve

Although rare, periprosthetic valvular regurgitation can cause hemolytic anemia. We present the case of a 63-year-old man who had an unusual presentation of hemolytic anemia due to periprosthetic mitral valve regurgitation (PMVR) in the presence of cold agglutinins. Due to high surgical risk, PMVR was percutaneously closed with three Amplatzer devices under the guidance of three-dimensional transesophageal echocardiography.     

Lipid-based nanoformulations in the treatment of neurological disorders

Abstract

The neurological disorders affect millions of people worldwide, and are bracketed as the foremost basis of disability-adjusted life years (DALYs). The treatment options are symptomatic and often the movement of drugs is restricted by a specialized network of endothelial cell layers (adjoined by tight cell-to-cell junction proteins; occludin, claudins, and junctional adhesion molecules), pericytes and astroglial foot processes. In recent years, advances in nanomedicine have led to therapies that target central nervous system (CNS) pathobiology via altering signaling mechanisms such as activation of PI3K/Akt pathway in ischemic stroke arrests apoptosis, interruption of α-synuclein aggregation prevents neuronal degeneration in Parkinson’s. Often such interactions are limited by insufficient concentrations of drugs reaching neuronal tissues and/or insufficient residence time of drug/s with the receptor. Hence, lipid nanoformulations, SLNs (solid lipid nanoparticles) and NLCs (nanostructured lipid carriers) emerged to overcome these challenges by utilizing physiological transport mechanisms across blood–brain barrier, such as drug-loaded SLN/NLCs adsorb apolipoproteins from the systemic circulation and are taken up by endothelial cells via low-density lipoprotein (LDL)-receptor mediated endocytosis and subsequently unload drugs at target site (neuronal tissue), which imparts selectivity, target ability, and reduction in toxicity. This paper reviews the utilization of SLN/NLCs as carriers for targeted delivery of novel CNS drugs to improve the clinical course of neurological disorders, placing some additional discussion on the metabolism of lipid-based formulations.     

Patients’ anxiety around incidental brain tumors: a qualitative study

Background

Incidental findings are common on MRI. Our study examined how patients are told about their incidental finding as well as anxiety until the neurosurgical consultation and afterward.

Methods

Qualitative research methodology was used. Thirty-two participants were interviewed using open-ended questions. Answers were transcribed and analyzed for themes.

Results

The level of patient satisfaction for the initial breaking of the news averaged 4.1 (range 1–5). Four themes were identified: (1) emotional stress over incidental findings are partially dependent on how the news was communicated; (2) breaking worrisome news is best done in person, but telephone communication can sometimes be acceptable; (3) patients are divided about how much information they wish to get about incidental findings before going for an MRI; (4) waiting for the neurosurgical consultation is a stressful time without adequate support.

Conclusions

When dealing with an unexpected MRI finding, patients are anxious about the situation. Our study exposes ways the experience could be made more comfortable for patients right from the start, from being told the news in a calm and sympathetic manner, to providing support for patients while they wait for a meeting with a neurosurgeon, to expediting the neurosurgical consultation.     

Minimally Invasive Approaches Do Not Compromise Outcomes for Pneumonectomy: A Comparison Using the National Cancer Database

Introduction

Minimally invasive approaches are increasingly being used for the conduct of complex surgical procedures. Whether the benefits of minimally invasive approaches compared to thoracotomy for sublobar and lobar lung resection for NSCLC are realized for patients undergoing pneumonectomy is not clear.

A Review of Adsorbents for Heavy Metal Decontamination: Growing Approach to Wastewater Treatment

Heavy metal is released from many industries into water. Before the industrial wastewater is discharged, the contamination level should be reduced to meet the recommended level as prescribed by the local laws of a country. They may be poisonous or cancerous in origin. Their presence does not only damage people, but also animals and vegetation because of their mobility, toxicity, and non-biodegradability into aquatic ecosystems. The review comprehensively discusses the progress made by various adsorbents such as natural materials, synthetic, agricultural, biopolymers, and commercial for extraction of the metal ions such as Ni²⁺, Cu²⁺, Pb²⁺, Cd²⁺, As²⁺ and Zn²⁺ along with their adsorption mechanisms. The adsorption isotherm indicates the relation between the amount adsorbed by the adsorbent and the concentration. The Freundlich isotherm explains the effective physical adsorption of the solute particle from the solution on the adsorbent and Langmuir isotherm gives an idea about the effect of various factors on the adsorption process. The adsorption kinetics data provide valuable insights into the reaction pathways, the mechanism of the sorption reaction, and solute uptake. The pseudo-first-order and pseudo-second-order models were applied to describe the sorption kinetics. The presented information can be used for the development of bio-based water treatment strategies.     

Pleural “drop metastases” 21 years after resection of a thymoma

Introduction: We describe an unusual case of pleural drop metastases 21 years after complete resection of an encapsulated thymoma in a Southeast Asian patient with myasthenia gravis (MG). Methods: This investigation includes a case report and brief review of the literature. Results: The patient presented in 2015 with generalized weakness, fatigue, and shortness of breath, but no diplopia, ptosis, dysphagia, or dysarthria. Because these symptoms were atypical for an MG exacerbation, a de‐novo work‐up was performed. Chest computed tomography (CT) showed numerous pleural nodules (“drop metastases”), and CT‐guided biopsy revealed metastatic thymoma. Conclusions: The average disease‐free interval for thymoma ranges from 68 to 86 months. Pleural and mediastinal recurrence are more common than distant hematogenous recurrence. Adverse prognostic factors include an initial higher Masaoka stage, incomplete resection, older age, and pleural or pericardial involvement. Despite apparent complete resection of thymoma, clinicians should remain vigilant for recurrence for as long as 20 years after initial management. Long‐term follow‐up with radiologic surveillance is recommended. Muscle Nerve 56 : 171–175, 2017