Evaluation of PLGA, lipid-PLGA hybrid nanoparticles, and cationic pH-sensitive liposomes as tuberculosis vaccine delivery systems in a Mycobacterium tuberculosis challenge mouse model - A comparison.

Tuberculosis (TB) continues to pose a global threat for millennia, currently affecting over 2 billion people and causing 10.6 million new cases and 1.3 million deaths annually.

Longitudinal soluble marker profiles reveal strong association between cytokine storms resulting from macrophage activation and disease severity in COVID-19 disease.

SARS-CoV2 infection results in a range of disease severities, but the underlying differential pathogenesis is still not completely understood. At presentation it remains difficult to estimate and predict severity, in particular, identify individuals at greatest risk of progression towards the most severe disease-states. Here we used advanced models with circulating serum analytes as variables in combination with daily assessment of disease severity using the SCODA-score, not only at single time points but also during the course of disease, to correlate analyte levels and disease severity.

Positive mood induction does not reduce return of fear: A virtual reality exposure study for public speaking anxiety.

Previous laboratory work has shown that induction of positive mood prior to fear extinction decreases the negative valence of the conditional stimulus (CS) and reduces reinstatement of fear. Before translating these insights to clinical practice, it is important to test this strategy in anxious individuals. Students with a high fear of public speaking (N = 62) were randomized to either a positive mood induction, a negative mood induction, or no induction control group.

Global blood miRNA profiling unravels early signatures of immunogenicity of Ebola vaccine rVSVΔG-ZEBOV-GP.

The vectored Ebola vaccine rVSVΔG-ZEBOV-GP elicits protection against Ebola Virus Disease (EVD). In a study of forty-eight healthy adult volunteers who received either the rVSVΔG-ZEBOV-GP vaccine or placebo, we profiled intracellular microRNAs (miRNAs) from whole blood cells (WB) and circulating miRNAs from serum-derived extracellular vesicles (EV) at baseline and longitudinally following vaccination. Further, we identified early miRNA signatures associated with ZEBOV-specific IgG antibody responses at baseline and up to one year post-vaccination, and pinpointed target mRNA transcripts and pathways correlated to miRNAs whose expression was altered after vaccination by using systems biology approaches.

Airway epithelial cells mount an early response to mycobacterial infection.

Lung epithelial cells represent the first line of host defence against foreign inhaled components, including respiratory pathogens. Their responses to these exposures may direct subsequent immune activation to these pathogens. The epithelial response to mycobacterial infections is not well characterized and may provide clues to why some mycobacterial infections are cleared, while others are persistent and pathogenic.

Omitting continuous memory recall from dual-task interventions does not reduce intervention effectiveness.

In Eye Movement Desensitization and Reprocessing a patient recalls a traumatic memory, while simultaneously performing a dual-task (e.g., making horizontal eye movements, tapping a pattern).

Differences in Inflammatory Pathways Between Dutch South Asians vs Dutch Europids With Type 2 Diabetes.

Context: South Asian individuals are more prone to develop type 2 diabetes (T2D) coinciding with earlier complications than Europids. While inflammation plays a central role in the development and progression of T2D, this factor is still underexplored in South Asians.

Objective: This work aimed to study whether circulating messenger RNA (mRNA) transcripts of immune genes are different between South Asian compared with Europid patients with T2D.

Blood transcriptional profiles distinguish different clinical stages of cutaneous leishmaniasis in humans.

Cutaneous leishmaniasis (CL) is a neglected tropical disease with severe morbidity and socioeconomic sequelae. A better understanding of underlying immune mechanisms that lead to different clinical outcomes of CL could inform the rational design of intervention measures. While transcriptomic analyses of CL lesions were recently reported by us and others, there is a dearth of information on the expression of immune-related genes in the blood of CL patients.

Transcriptional profiles predict treatment outcome in patients with tuberculosis and diabetes at diagnosis and at two weeks after initiation of anti-tuberculosis treatment.

Background: Globally, the tuberculosis (TB) treatment success rate is approximately 85%, with treatment failure, relapse and death occurring in a significant proportion of pulmonary TB patients. Treatment success is lower among people with diabetes mellitus (DM). Predicting treatment outcome early after diagnosis, especially in TB-DM patients, would allow early treatment adaptation for individuals and may improve global TB control.

Recombinant BCG-LTAK63 Vaccine Candidate for Tuberculosis Induces an Inflammatory Profile in Human Macrophages.

Tuberculosis (TB) is one of the top 10 leading causes of death worldwide. The recombinant BCG strain expressing the genetically detoxified A subunit of the thermolabile toxin from (LTAK63) adjuvant (rBCG-LTAK63) has previously been shown to confer superior protection and immunogenicity compared to BCG in a murine TB infection model. To further investigate the immunological mechanisms induced by rBCG-LTAK63, we evaluated the immune responses induced by rBCG-LTAK63, BCG, and () H37Rv strains in experimental infections of primary human M1 and M2 macrophages at the transcriptomic and cytokine secretion levels.

The effect of cold exposure on circulating transcript levels of immune genes in Dutch South Asian and Dutch Europid men.

Objectives: Although cold exposure is commonly believed to be causally related to acute viral respiratory infections, its effect on the immune system is largely unexplored. In this study, we determined transcript levels of a large panel of immune genes in blood before and after cold exposure. We included both Dutch Europid and Dutch South Asian men to address whether the immune system is differently regulated in the metabolically vulnerable South Asian population.

Transcriptomic signatures induced by the Ebola virus vaccine rVSVΔG-ZEBOV-GP in adult cohorts in Europe, Africa, and North America: a molecular biomarker study.

Background: A recombinant vesicular stomatitis virus vector expressing the Zaire Ebola virus glycoprotein (rVSVΔG-ZEBOV-GP) vaccine has been reported as safe, immunogenic, and highly protective in a ring vaccination trial. We aimed to identify transcriptomic immune response biomarker signatures induced by vaccination and associated signatures with its immunogenicity and reactogenicity to better understand the potential mechanisms of action of the vaccine.

Methods: 354 healthy adult volunteers were vaccinated in randomised, double-blind, placebo-controlled trials in Europe (Geneva, Switzerland [November, 2014, to January, 2015]) and North America (USA [Dec 5, 2014, to June 23, 2015]), and dose-escalation trials in Africa (Lambaréné, Gabon [November, 2014, to January, 2015], and Kilifi, Kenya [December, 2014, to January, 2015]) using different doses of the recombinant vesicular stomatitis virus vector expressing the Zaire Ebola virus glycoprotein (rVSVΔG-ZEBOV-GP; 3 × 10 to 1 × 10 plaque-forming units [pfu]).

Stratification of COVID-19 patients based on quantitative immune-related gene expression in whole blood.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes mild symptoms in the majority of infected individuals, yet in some cases it leads to a life-threatening condition. Determination of early predictive biomarkers enabling risk stratification for coronavirus disease 2019 (COVID-19) patients can inform treatment and intervention strategies. Herein, we analyzed whole blood samples obtained from individuals infected with SARS-CoV-2, varying from mild to critical symptoms, approximately one week after symptom onset.

[A man with currant jelly sputum].

A 40-year-old man presented with acute respiratory distress and a productive cough in the past three days with 'currant jelly' sputum. X-ray showed a right upper lobe infiltrate. Culture of sputum showed Klebsiella pneumoniae, consistent with 'Friedländer' pneumonia.

Pyruvate Dehydrogenase Kinase Inhibitor Dichloroacetate Improves Host Control of Serovar Typhimurium Infection in Human Macrophages.

Global increases in the prevalence of antimicrobial resistance highlight the urgent need for novel strategies to combat infectious diseases. Recent studies suggest that host metabolic pathways play a key role in host control of intracellular bacterial pathogens. In this study we explored the potential of targeting host metabolic pathways for innovative host-directed therapy (HDT) against intracellular bacterial infections.

Bioorthogonal Correlative Light-Electron Microscopy of in Macrophages Reveals the Effect of Antituberculosis Drugs on Subcellular Bacterial Distribution.

Bioorthogonal correlative light-electron microscopy (B-CLEM) can give a detailed overview of multicomponent biological systems. It can provide information on the ultrastructural context of bioorthogonal handles and other fluorescent signals, as well as information about subcellular organization. We have here applied B-CLEM to the study of the intracellular pathogen () by generating a triply labeled through combined metabolic labeling of the cell wall and the proteome of a DsRed-expressing strain.

Functional Inhibition of Host Histone Deacetylases (HDACs) Enhances and Anti-mycobacterial Activity in Human Macrophages and in Zebrafish.

The rapid and persistent increase of drug-resistant () infections poses increasing global problems in combatting tuberculosis (TB), prompting for the development of alternative strategies including host-directed therapy (HDT). Since is an intracellular pathogen with a remarkable ability to manipulate host intracellular signaling pathways to escape from host defense, pharmacological reprogramming of the immune system represents a novel, potentially powerful therapeutic strategy that should be effective also against drug-resistant . Here, we found that host-pathogen interactions in -infected primary human macrophages affected host epigenetic features by modifying histone deacetylase (HDAC) transcriptomic levels.

Linguistic dual tasking reduces emotionality, vividness and credibility of voice memories in voice-hearing individuals: Results from a controlled trial.

Dual taxation of the working memory during recall is an effective strategy to reduce the emotionality and vividness of visual intrusive memories and potentially changes dysfunctional beliefs associated with the memories. This study tested the hypothesis that dual tasking decreases emotionality, vividness and credibility of auditory intrusive images (i.e.

Long-term Outcomes of Cognitive Behavioral Therapy for Anxiety-Related Disorders: A Systematic Review and Meta-analysis.

Importance: Cognitive behavioral therapy is recommended for anxiety-related disorders, but evidence for its long-term outcome is limited.

Objective: This systematic review and meta-analysis aimed to assess the long-term outcomes after cognitive behavioral therapy (compared with care as usual, relaxation, psychoeducation, pill placebo, supportive therapy, or waiting list) for anxiety disorders, posttraumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD).

Data Sources: English-language publications were identified from PubMed, PsycINFO, Embase, Cochrane, OpenGrey (1980 to January 2019), and recent reviews.

On EMDR: Measuring the working memory taxation of various types of eye (non-)movement conditions.

Background And Objective: A recent, large randomized controlled trial employing different forms of eye (non-)movements in eye movement desensitization and reprocessing (EMDR) showed that fixating the eyes either on a therapist's moving or non-moving hand led to equal reductions in symptoms of post-traumatic stress disorder (PTSD). However, numerous EMDR lab analogue studies found that eye movements produce larger memory effects than eyes stationary. These beneficial effects are typically explained by differences in working memory (WM) taxation.

The effects of dual-tasks on intrusive memories following analogue trauma.

Patients with post-traumatic stress disorder frequently and involuntarily experience intrusions, which are strongly linked to the trauma hotspot. Voluntary memory characteristics (i.e.

Making eye movements during imaginal exposure leads to short-lived memory effects compared to imaginal exposure alone.

Background And Objectives: A plethora of eye movement desensitization and reprocessing (EMDR) analogue studies has shown that, in the short term, making eye movements (EM) during brief imaginal exposure ("recall + EM") blurs memories more than just imaginal exposure ("recall only"). Yet, results of the few studies that included a follow-up test are inconsistent. We improved this paradigm's ecological validity by including an extended intervention phase and multiple assessments per phase.