Prevention of alloimmune rejection using XBP1-deleted bone marrow-derived dendritic cells in heart transplantation

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CD19 + CD21lo/neg cells are increased in systemic sclerosis-associated interstitial lung disease

Interstitial lung disease (ILD) represents a significant cause of morbidity and mortality in systemic sclerosis (SSc). The purpose of this study was to examine recirculating lymphocytes from SSc patients for potential biomarkers of interstitial lung disease (ILD). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SSc and healthy controls enrolled in the Vanderbilt University Myositis and Scleroderma Treatment Initiative Center cohort between 9/2017–6/2019. Clinical phenotyping was performed by chart abstraction. Immunophenotyping was performed using both mass cytometry and fluorescence cytometry combined with t-distributed stochastic neighbor embedding analysis and traditional biaxial gating. This study included 34 patients with SSc-ILD, 14 patients without SSc-ILD, and 25 healthy controls. CD21^lo/neg cells are significantly increased in SSc-ILD but not in SSc without ILD (15.4 ± 13.3% vs. 5.8 ± 0.9%, p = 0.002) or healthy controls (5.0 ± 0.5%, p < 0.0001). While CD21^lo/neg B cells can be identified from a single biaxial gate, tSNE analysis reveals that the biaxial gate is comprised of multiple distinct subsets, all of which are increased in SSc-ILD. CD21^lo/neg cells in both healthy controls and SSc-ILD are predominantly tBET positive and do not have intracellular CD21. Immunohistochemistry staining demonstrated that CD21^lo/neg B cells diffusely infiltrate the lung parenchyma of an SSc-ILD patient. Additional work is needed to validate this biomarker in larger cohorts and longitudinal studies and to understand the role of these cells in SSc-ILD.

     

Adjunctive therapies for in vitro carious lesions: Antimicrobial activity,activation of dentin metalloproteinases and effects on dental pulp cells

BackgroundAdjunctive therapies used before dental restorative procedures may encourage carious tissue removal. Beyond promising antimicrobial properties, treatments could positively modulate the dentin-pulp complex while not interfering with restoration survival. Herein, we evaluated a set of substances and their effects on carious lesions and the underlying dentin or pulp cells.MethodsArtificial caries lesions were developed in bovine teeth cavities immersed in Streptococcus mutans and Lactobacillus casei co-cultures. The cavities were treated according to the following groups: Phosphate Buffer Saline (PBS), Chlorhexidine (CHX), Papacárie® (Papain gel), Ozone (O₃), and antimicrobial Photodynamic Therapy (aPDT). After treatments, samples were cultivated to count isolated microbial colonies. The zymography assay evaluated the activity of dentin metalloproteinases (MMP-2 and MMP-9). Cell viability was indirectly assessed on human dental pulp cells after 24, 72, or 120 h, whereas the odontodifferentiation potential was evaluated after ten days of cell culture.ResultsCHX and aPDT led to around 1 log bacterial load reduction. PBS, CHX, and aPDT showed the eventual expression of MMP-2 and MMP-9. Cell viability was reduced (< 30%) after 120 h for all groups compared to the control. CHX, O3, and aPDT induced greater odontodifferentiation (≈ 20% higher) than PBS and papain gel.ConclusionAdjunctive therapies presented little or no biological significance in reducing bacterial load in artificial carious lesions. Although the activation of endogenous metalloproteinases may represent a possible concern for adhesive restorations, some of these treatments may have a positive role in dental pulp tissue repair.     

Single-dose replicating poxvirus vector-based RBD vaccine drives robust humoral and T cell immune response against SARS-CoV-2 infection

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The usefulness of measuring n-butyric acid concentration as a new indicator of blood decomposition in forensic autopsy

In forensic medicine, although various alcohols have been reported as indicators of decomposition in collected blood, no studies have examined short-chain fatty acids as indicators. In this study, the blood n-butyric acid concentration was quantified, and the association between n-butyric acid and decomposition was investigated to determine whether the detection of n-butyric acid could be a new indicator of decomposition. Among the forensic autopsies performed from 2016 to 2018 in our laboratory, the cases were divided into decomposed (n = 20) and non-decomposed (n = 20) groups based on macroscopic findings. Blood samples collected at the time of autopsy were derivatized with 3-nitrophenylhydrazine hydrochloride after solid-phase extraction. The n-butyric acid concentration was measured using liquid chromatography–tandem mass spectrometry. In addition, ethanol and n-propanol were measured using a gas chromatography-flame ionization detector. There was a significant difference (p < 0.01) in the concentrations of n-butyric acid between the decomposed and non-decomposed groups (0.343 ± 0.259 [0.030–0.973] and 0.003 ± 0.002 [0.001–0.007] mg/mL, respectively). In the decomposed group, n-butyric acid was detected at high concentrations, even in cases where n-propanol was low. These results suggest that n-butyric acid is more likely to be an indicator of blood decomposition than n-propanol.     

Seronegative autoimmune diseases: A challenging diagnosis

Autoimmune diseases (AID) are increasingly prevalent conditions which comprise more than 100 distinct clinical entities that are responsible for a great disease burden worldwide. The early recognition of these diseases is key for preventing their complications and for tailoring proper management. In most cases, autoantibodies, regardless of their potential pathogenetic role, can be detected in the serum of patients with AID, helping clinicians in making a definitive diagnosis and allowing screening strategies for early -and sometimes pre-clinical- diagnosis. Despite their undoubted crucial role, in a minority of cases, patients with AID may not show any autoantibody, a condition that is referred to as seronegative AID. Suboptimal accuracy of the available laboratory tests, antibody absorption, immunosuppressive therapy, immunodeficiencies, antigen exhaustion, and immunosenescence are the main possible determinants of seronegative AID. Indeed, in seronegative AID, the diagnosis is more challenging and must rely on clinical features and on other available tests, often including histopathological evaluation and radiological diagnostic tests. In this review, we critically dissect, in a narrative fashion, the possible causes of seronegativity, as well as the diagnostic and management implications, in several AID including autoimmune gastritis, celiac disease, autoimmune liver disease, rheumatoid arthritis, autoimmune encephalitis, myasthenia gravis, Sjögren’s syndrome, antiphospholipid syndrome, and autoimmune thyroid diseases.     

Echocardiographic Evaluation of Left and Right Ventricular Function in Patients with Coronary Slow Flow Syndrome: A Comparative Study

The Coronary Slow Flow Phenomenon is a syndrome of normal coronary anatomy and delayed progression of contrast medium through the coronary vessels. This research attempts to analyze and compare the systolic and diastolic function of the left and right ventricle in primary Slow Flow and Normal Coronary Flow.Two groups of primary Slow Coronary Flow (33 people) and Normal Coronary Flow (11 people) were included and the systolic and diastolic function of the ventricles was analyzed and compared between them.In the control group 18% of patients had mild and in the case group 24.2% mild, and 3.1% had moderate left ventricular diastolic dysfunction (P >0.05). The frequency distribution of the left and right ventricular systolic dysfunction was similar in the two groups.There was no statistically significant difference between two groups and in the association of cardiac dysfunction, it may be reasonable to investigate other causes.