Permissive lung neutrophils facilitate tuberculosis immunopathogenesis in male phagocyte NADPH oxidase-deficient mice.

NADPH oxidase 2 (NOX2) is an enzyme responsible for generating reactive oxygen species, primarily found in phagocytes. Chronic Granulomatous Disease (CGD), along with bacterial infections such as Mycobacterium tuberculosis (Mtb), is a representative NOX2-deficient X-linked disease characterized by uncontrolled inflammation. However, the precise roles of host-derived factors that induce infection-mediated hyperinflammation in NOX2-deficient condition remain incompletely understood.

Adjunctive administration of parabiotic Lactobacillus sakei CVL-001 ameliorates drug-induced toxicity and pulmonary inflammation during antibiotic treatment for tuberculosis.

Tuberculosis (TB) treatment requires a long therapeutic duration and induces adverse effects such as hepatotoxicity, causing discontinuation of treatment. Reduced adherence to TB medications elevates the risk of recurrence and the development of drug resistance. Additionally, severe cavitary TB with a high burden of Mycobacterium tuberculosis (Mtb) and inflammation-mediated tissue damage may need an extended treatment duration, resulting in a higher tendency of drug-induced toxicity.

BCG-booster vaccination with HSP90-ESAT-6-HspX-RipA multivalent subunit vaccine confers durable protection against hypervirulent Mtb in mice.

The quest for effective and enhanced multiantigenic tuberculosis (TB) subunit vaccine necessitates the induction of a protective pathogen-specific immune response while circumventing detrimental inflammation within the lung milieu. In line with this goal, we engineered a modified iteration of the quadrivalent vaccine, namely HSP90-ESAT-6-HspX-RipA (HEHR), which was coupled with the TLR4 adjuvant, CIA09A. The ensuing formulation was subjected to comprehensive assessment to gauge its protective efficacy against the hypervirulent Mycobacterium tuberculosis (Mtb) Haarlem clinical strain M2, following a BCG-prime boost regimen.

Immunogenicity and protective efficacy of RipA, a peptidoglycan hydrolase, against Mycobacterium tuberculosis Beijing outbreak strains.

Given that individuals with latent tuberculosis (TB) infection represent the major reservoir of TB infection, latency-associated antigens may be promising options for development of improved multi-antigenic TB subunit vaccine. Thus, we selected RipA, a peptidoglycan hydrolase required for efficient cell division of Mycobacterium tuberculosis (Mtb), as vaccine candidate. We found that RipA elicited activation of dendritic cells (DCs) by induction of phenotypic maturation, increased production of inflammatory cytokines, and prompt stimulation of MAPK and NF-κB signaling pathways.

Vitamin C supplementation showed greater effects on systolic blood pressure in hypertensive and diabetic patients: an updated systematic review and meta-analysis of randomised clinical trials.

Results from randomised controlled trials (RCTs) testing the effect of vitamin C supplementation on blood pressure (BP) have been inconsistent. This systematic review evaluated the effects of vitamin C supplementation on BP and included RCTs testing the effects of vitamin C supplementation alone, on systolic and diastolic BP in adult participants (≥18 years). Random-effect models were conducted to estimate the pooled effects of vitamin C supplementation on BP.

Protective Efficacy and Immunogenicity of Rv0351/Rv3628 Subunit Vaccine Formulated in Different Adjuvants Against Infection.

Bacillus Calmette-Guerin (BCG) vaccine is the only licensed vaccine for tuberculosis (TB) prevention. Previously, our group demonstrated the vaccine potential of Rv0351 and Rv3628 against (Mtb) infection by directing Th1-biased CD4 T cells co-expressing IFN-γ, TNF-α, and IL-2 in the lungs. Here, we assessed immunogenicity and vaccine potential of the combined Ags (Rv0351/Rv3628) formulated in different adjuvants as subunit booster in BCG-primed mice against hypervirulent clinical Mtb strain K (Mtb K).

BCGΔBCG1419c increased memory CD8 T cell-associated immunogenicity and mitigated pulmonary inflammation compared with BCG in a model of chronic tuberculosis.

Previously, we reported that a hygromycin resistant version of the BCGΔBCG1419c vaccine candidate reduced tuberculosis (TB) disease in BALB/c, C57BL/6, and B6D2F1 mice infected with Mycobacterium tuberculosis (Mtb) H37Rv. Here, the second-generation version of BCGΔBCG1419c (based on BCG Pasteur ATCC 35734, without antibiotic resistance markers, and a complete deletion of BCG1419c) was compared to its parental BCG for immunogenicity and protective efficacy against the Mtb clinical isolate M2 in C57BL/6 mice. Both BCG and BCGΔBCG1419c induced production of IFN-γ, TNF-α, and/or IL-2 by effector memory (CD44CD62L), PPD-specific, CD4 T cells, and only BCGΔBCG1419c increased effector memory, PPD-specific CD8 T cell responses in the lungs and spleens compared with unvaccinated mice before challenge.

Novel Antibacterial Activity of Febuxostat, an FDA-Approved Antigout Drug against Mycobacterium tuberculosis Infection.

Accumulating evidence suggests that drug repurposing has drawn attention as an anticipative strategy for controlling tuberculosis (TB), considering the dwindling drug discovery and development pipeline. In this study, we explored the antigout drug febuxostat and evaluated its antibacterial activity against Mycobacterium species. Based on MIC evaluation, we found that febuxostat treatment significantly inhibited mycobacterial growth, especially that of Mycobacterium tuberculosis (Mtb) and its phylogenetically close neighbors, M.

Multilayer Perceptron-Based Real-Time Intradialytic Hypotension Prediction Using Patient Baseline Information and Heart-Rate Variation.

Intradialytic hypotension (IDH) is a common side effect that occurs during hemodialysis and poses a great risk for dialysis patients. Many studies have been conducted so far to predict IDH, but most of these could not be applied in real-time because they used only underlying patient information or static patient disease information. In this study, we propose a multilayer perceptron (MP)-based IDH prediction model using heart rate (HR) information corresponding to time-series information and static data of patients.

Viral coinfection promotes tuberculosis immunopathogenesis by type I IFN signaling-dependent impediment of Th1 cell pulmonary influx.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is often exacerbated upon coinfection, but the underlying immunological mechanisms remain unclear. Here, to elucidate these mechanisms, we use an Mtb and lymphocytic choriomeningitis virus coinfection model. Viral coinfection significantly suppresses Mtb-specific IFN-γ production, with elevated bacterial loads and hyperinflammation in the lungs.

Vaccination inducing durable and robust antigen-specific Th1/Th17 immune responses contributes to prophylactic protection against infection but is ineffective as an adjunct to antibiotic treatment in chronic disease.

complex (MAC) causing pulmonary disease in humanshas emerged worldwide. Thus, effective strategies simultaneously aiming to prevent MAC infection and accelerate therapeutic efficacy are required. To this end, subunit vaccine-induced protection against a well-defined virulent (Mav) isolate was assessed as a preventative and therapeutic modality in murine models.

Host-directed anti-mycobacterial activity of colchicine, an anti-gout drug, via strengthened host innate resistance reinforced by the IL-1β/PGE axis.

Background And Purpose: To diversify and expand possible tuberculosis (TB) drug candidates and maximize limited global resources, we investigated the effect of colchicine, an FDA-approved anti-gout drug, against Mycobacterium tuberculosis (Mtb) infection because of its immune-modulating effects.

Experimental Approach: We evaluated the intracellular anti-Mtb activity of different concentrations of colchicine in murine bone marrow-derived macrophages (BMDMs). To elucidate the underlying mechanism, RNA sequencing, biological and chemical inhibition assays, and Western blot, quantitative real-time PCR, enzyme-linked immunosorbent assay (ELISA), and immunohistochemical analyses were employed.

Exacerbation of pulmonary infection by comorbid allergic asthma is associated with diminished mycobacterium-specific Th17 responses.

Accumulating evidence suggests that two chronic respiratory diseases, nontuberculous mycobacterium (NTM)-pulmonary disease (PD) and allergic asthma, are frequently present together and that they likely influence the disease development and progression of each other. However, their precise interactions regarding the pathogenesis of comorbid diseases versus that of individual diseases are not well understood. In this study, comorbid diseases ( (Mav) pulmonary infection (PI) (Mav-PI) and ovalbumin-induced allergic asthma) were established in mice in different orders and at different time periods.

An Adaptive Median Filter Based on Sampling Rate for R-Peak Detection and Major-Arrhythmia Analysis.

With the advancement of the Internet of Medical Things technology, many vital sign-sensing devices are being developed. Among the diverse healthcare devices, portable electrocardiogram (ECG) measuring devices are being developed most actively with the recent development of sensor technology. These ECG measuring devices use different sampling rates according to the hardware conditions, which is the first variable to consider in the development of ECG analysis technology.

Mass Infection Analysis of COVID-19 Using the SEIRD Model in Daegu-Gyeongbuk of Korea from April to May, 2020.

Background: The novel coronavirus (coronavirus disease 2019 [COVID-19]) outbreak began in China in December last year, and confirmed cases began occurring in Korea in mid-February 2020. Since the end of February, the rate of infection has increased greatly due to mass (herd) infection within religious groups and nursing homes in the Daegu and Gyeongbuk regions. This mass infection has increased the number of infected people more rapidly than was initially expected; the epidemic model based on existing studies had predicted a much lower infection rate and faster recovery.

Antigen-Specific IFN-γ/IL-17-Co-Producing CD4 T-Cells Are the Determinants for Protective Efficacy of Tuberculosis Subunit Vaccine.

The antigen-specific Th17 responses in the lungs for improved immunity against (Mtb) infection are incompletely understood. Tuberculosis (TB) vaccine candidate HSP90-ESAT-6 (E6), given as a Bacillus Calmette-Guérin (BCG)-prime boost regimen, confers superior long-term protection against the hypervirulent Mtb HN878 infection, compared to BCG or BCG-E6. Taking advantage of protective efficacy lead-out, we found that ESAT-6-specific multifunctional CD4IFN-γIL-17 T-cells optimally correlated with protection level against Mtb infection both pre-and post-challenge.

Toll-like receptor 4 signaling-mediated responses are critically engaged in optimal host protection against highly virulent K infection.

Toll-like receptors (TLRs) play critical roles in the innate recognition of (Mtb) by host immune cells. However, controversy has arisen regarding the role of TLR4 in determining the outcomes of Mtb infection. To address this controversy, the function of TLR4 in the induction of an optimal protective immune response against the highly virulent Mtb K-infection was comparatively investigated in C3 H/HeJ (TLR4-deficient mutant) and C3 H/HeN (TLR4-competent wild-type) mice.

Primary amelanotic melanoma of the mandibular gingiva.

Oral mucosal melanoma is a very rare type of malignant melanoma, the characteristics of which differ from those of cutaneous melanoma. Primary amelanotic melanoma of the mandibular gingiva, which can invade the mandibular bone, is very rare worldwide. Here, we report a case in which we performed a reconstruction of the mandible and gingiva using the fibula osteocutaneous free flap procedure to treat a patient diagnosed with a primary amelanotic melanoma of the mandibular gingiva.

An Alternative Dendritic Cell-Induced Murine Model of Asthma Exhibiting a Robust Th2/Th17-Skewed Response.

Purpose: Simple and reliable animal models of human diseases contribute to the understanding of disease pathogenesis as well as the development of therapeutic interventions. Although several murine models to mimic human asthma have been established, most of them require anesthesia, resulting in variability among test individuals, and do not mimic asthmatic responses accompanied by T-helper (Th) 17 and neutrophils. As dendritic cells (DCs) are known to play an important role in initiating and maintaining asthmatic inflammation, we developed an asthma model via adoptive transfer of allergen-loaded DCs.

Intra-parotid lymph node metastasis in patients with non-cutaneous head and neck cancers: clinical and imaging features for differentiation from simultaneous parotid primary tumor.

Background: Although uncommon, intra-parotid lymph node (IPLN) metastasis should be considered in the differential diagnosis of parotid masses in patients with head and neck cancers.

Purpose: To compare the clinical and imaging features of IPLN metastases from head and neck cancers and simultaneous parotid primary tumors.

Material And Methods: A retrospective review of 2199 patients with non-parotid head and neck cancers revealed 63 patients who also underwent parotidectomy during curative resection of head and neck cancer.

Vital Block and Vital Sign Server for ECG and Vital Sign Monitoring in a Portable u-Vital System.

An important function in the future healthcare system involves measuring a patient's vital signs, transmitting the measured vital signs to a smart device or a management server, analyzing it in real-time, and informing the patient or medical staff. Internet of Medical Things (IoMT) incorporates information technology (IT) into patient monitoring device (PMD) and is developing traditional measurement devices into healthcare information systems. In the study, a portable ubiquitous-Vital (u-Vital) system is developed and consists of a Vital Block (VB), a small PMD, and Vital Sign Server (VSS), which stores and manages measured vital signs.

Long-term protective efficacy with a BCG-prime ID93/GLA-SE boost regimen against the hyper-virulent Mycobacterium tuberculosis strain K in a mouse model.

Since ID93/GLA-SE was developed as a targeted BCG-prime booster vaccine, in the present study, we evaluated the protective efficacy of ID93/GLA-SE as a boost to a BCG-prime against the hypervirulent Mycobacterium tuberculosis (Mtb) K challenge to provide further information on the development and application of this vaccine candidate. Boosting BCG with the ID93/GLA-SE vaccine significantly reduced bacterial burden at 16 weeks post-challenge while the BCG vaccine alone did not confer significant protection against Mtb K. The pathological analysis of the lung from the challenged mice also showed the remarkably protective boosting effect of ID93/GLA-SE on BCG-immunised animals.