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. A total of 20 studies with 890 participants were included. The median dose of vitamin C was 757.5 mg/d, the median duration was 6 weeks. Vitamin C supplementation was found to reduce systolic BP by -3.0 mmHg (95%CI: -4.7, -1.3 mmHg; p = 0.001). Subgroup analysis showed a more pronounced effect on systolic BP in patients with hypertension (-3.2 mmHg, 95%CI -5.2, -1.2 mmHg, p = 0.002) and diabetes (-4.6 mmHg, 95%CI -8.9, -0.3 mmHg, p = 0.03). Further research needs to evaluate the long-term effect of vitamin C on BP in populations with impaired cardio-metabolic health.

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. bovis, M. kansasii, and M. shinjukuense, but these microorganisms were not affected by allopurinol and topiroxostat, which belong to a similar category of antigout drugs. Febuxostat concentration-dependently affected Mtb and durably mediated inhibitory functions (duration, 10 weeks maximum), as evidenced by resazurin microtiter assay, time-kill curve analysis, phenotypic susceptibility test, and the Bactec MGIT 960 system. Based on these results, we determined whether the drug shows antimycobacterial activity against Mtb inside murine bone marrow-derived macrophages (BMDMs). Notably, febuxostat markedly suppressed the intracellular growth of Mtb in a dose-dependent manner without affecting the viability of BMDMs. Moreover, orally administered febuxostat was efficacious in a murine model of TB with reduced bacterial loads in both the lung and spleen without the exacerbation of lung inflammation, which highlights the drug potency. Taken together, unexpectedly, our data demonstrated that febuxostat has the potential for treating TB.

PPE39 of the Mycobacterium tuberculosis strain Beijing/K induces Th1-cell polarization through dendritic cell maturation.

In a previous study, we have identified MTBK_24820, the complete protein form of PPE39 in the hypervirulent Mycobacterium tuberculosis (Mtb) strain Beijing/K by using comparative genomic analysis. PPE39 exhibited vaccine potential against Mtb challenge in a murine model. Thus, in this present study, we characterize PPE39-induced immunological features by investigating the interaction of PPE39 with dendritic cells (DCs). PPE39-treated DCs display reduced dextran uptake and enhanced MHC-I, MHC-II, CD80 and CD86 expression, indicating that this PPE protein induces phenotypic DC maturation. In addition, PPE39-treated DCs produce TNF-α, IL-6 and IL-12p70 to a similar and/or greater extent than lipopolysaccharide-treated DCs in a dose-dependent manner. The activating effect of PPE39 on DCs was mediated by TLR4 through downstream MAPK and NF-κB signaling pathways. Moreover, PPE39-treated DCs promoted naïve CD4+ T-cell proliferation accompanied by remarkable increases of IFN-γ and IL-2 secretion levels, and an increase in the Th1-related transcription factor T-bet but not in Th2-associated expression of GATA-3, suggesting that PPE39 induces Th1-type T-cell responses through DC activation. Collectively, the results indicate that the complete form of PPE39 is a so-far-unknown TLR4 agonist that induces Th1-cell biased immune responses by interacting with DCs.This article has an associated First Person interview with the first author of the paper.

Vaccine efficacy of a Mycobacterium tuberculosis Beijing-specific proline-glutamic acid (PE) antigen against highly virulent outbreak isolates.

Bacillus Calmette-Guerin vaccine confers insufficient pulmonary protection against tuberculosis (TB), particularly the Mycobacterium tuberculosis (Mtb) Beijing strain infection. Identification of vaccine antigens (Ags) by considering Mtb genetic diversity is crucial for the development of improved TB vaccine. MTBK_20640, a new Beijing genotype-specific proline-glutamic acid-family Ag, was identified by comparative genomic analysis. Its immunologic features were characterized by evaluating interactions with dendritic cells (DCs), and immunogenicity and vaccine efficacy were determined against highly virulent Mtb Beijing outbreak Korean Beijing (K) strain and HN878 strain in murine infection model. MTBK_20640 induced DCs via TLR2 and downstream MAPK and NF-κB signaling pathways, effectively promoting naive CD4-positive (CD4+) T-cell proliferation and IFN-γ production. Different IFN-γ response was observed in mice infected with Mtb K or reference H37Rv strain. Significant induction of T helper type 1 cell-polarized Ag-specific multifunctional CD4+ T cells and a marked Ag-specific IgG2c response were observed in mice immunized with MTBK_20640/glucopyranosyl lipid adjuvant-stable emulsion. The immunization conferred long-term protection against 2 Mtb Beijing outbreak strains, as evidenced by a significant reduction in colony-forming units in the lung and spleen and reduced lung inflammation. MTBK_20640 vaccination conferred long-term protection against highly virulent Mtb Beijing strains. MTBK_20640 may be developed into a novel Ag component in multisubunit TB vaccines in the future.-Kwon, K. W., Choi, H.-H., Han, S. J., Kim, J.-S., Kim, W. S., Kim, H., Kim, L.-H., Kang, S. M., Park, J., Shin, S. J. Vaccine efficacy of a Mycobacterium tuberculosis Beijing-specific proline-glutamic acid (PE) antigen against highly virulent outbreak isolates.

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. After exclusion of direct extension to the parotid gland from adjacent primary tumors (n = 12) and IPLN metastases from skin cancer (n = 5), the final study group was composed of 46 patients, including 26 (1.2%) with 33 IPLN metastases and 20 (0.9%) with 24 simultaneous parotid primary tumors. We compared clinical features of patients (sex, age, site of primary tumor, histologic type, history of prior treatment for malignancy, TNM stages, side of parotid lesion, multiplicity, and metastasis in ipsilateral cervical LNs) and the CT (location in parotid gland, maximum dimension, margins, and central necrosis or cystic change) and 18F-FDG PET/CT (maximum standardized uptake value) findings. RESULTS: Ipsilateral level II LN metastasis was more frequent in the IPLN metastasis group than in the simultaneous parotid primary tumor group (73.1% vs. 35.0%, P < 0.05). Imaging features such as location in parotid gland, maximum dimension, margins, central necrosis or cystic change, and maximum standardized uptake value showed no significant differences between the two groups. CONCLUSION: CT and PET/CT findings of IPLN metastasis are indistinguishable from simultaneous parotid primary tumor in patients with head and neck cancers.

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. METHODS: The present study evaluated rapid infection spread by mass infection in Korea and the high mortality rate for the elderly and those with underlying diseases through the Susceptible-Exposed-Infected-Recovered-Dead (SEIRD) model. RESULTS: The present study demonstrated early infection peak occurrence (-6.3 days for Daegu and -5.3 days for Gyeongbuk) and slow recovery trend (= -1,486.6 persons for Daegu and -223.7 persons for Gyeongbuk) between the actual and the epidemic model for a mass infection region compared to a normal infection region. CONCLUSION: The analysis of the time difference between infection and recovery can help predict the epidemic peak due to mass (or normal) infection and can also be used as a time index to prepare medical resources.

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. Herein, we propose an R-point detection method using an adaptive median filter based on the sampling rate and analyze major arrhythmias using the signal characteristics. First, the sliding window and median filter size are determined according to the set sampling rate, and a wider median filter is applied to the QRS section with high variance within the sliding window. Then, the R point is detected by subtracting the filtered signal from the original signal. Methods for detecting major arrhythmias using the detected R point are proposed. Different types of ECG signals were used for a simulation, including ECG signals from the MIT-BIH arrhythmia database and MIT-BIH atrial fibrillation database, signals generated by a simulator, and actual measured signals with different sampling rates. The experimental results indicated the effectiveness of the proposed R-point detection method and arrhythmia analysis technique.

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. Specifically, VBs collect a patient's electrocardiogram (ECG), blood oxygen saturation (SpO2), non-invasive blood pressure (NiBP), body temperature (BT) in real-time, and the collected vital signs are transmitted to a VSS via wireless protocols such as WiFi and Bluetooth. Additionally, an efficient R-point detection algorithm was also proposed for real-time processing and long-term ECG analysis. Experiments demonstrated the effectiveness of measurement, transmission, and analysis of vital signs in the proposed portable u-Vital system.

Behavior Modeling for Charge Storage in Single-Poly Floating Gate Device.

Single-poly floating gate is an efficient device for charge storage due to low power program, and implemented in a standard CMOS process. In floating gate, charges are injected and removed through the thin gate oxide. Among the gate leakage current mechanisms, FN tunneling is significant in the high electric field, while PF emission in the low electric field. We extracted FN and PF components from the measured current and built an accurate model which include fringing field effect induced by the 3-dimensional structure. This model helps engineers reflect exact behaviors of charge storage device in their circuit design.

Power-Efficient Nonvolatile Ternary Content Addressable Memory with Flexible Search Scope Using Reconfigurable Match Line Segment and Selective Search Line.

This paper proposes a nonvolatile-based Ternary Content Addressable Memory (nvTCAM) with efficient dynamic power. The selective search line technique reduces the unnecessary power consumption by designating the search range according to the pattern of the stored data. The reconfigurable match line (ML) segment guarantees the optimal performance independent of the search pattern. Thanks to this technology, it shows a 21% reduction in data-driven power and a 46% reduction in ML-driven power. All those techniques are built in nvTCAM respectively. The test chip is fabricated using 180 nm CMOS technology, and functions are verified.

Vaccine potential of ESAT-6 protein fused with consensus CD4+ T-cell epitopes of PE/PPE proteins against highly pathogenic Mycobacterium tuberculosis strain HN878.

Pro-Glu/Pro-Pro-Glu (PE/PPE) family proteins in Mycobacterium tuberculosis (Mtb) are contributors to pathogenesis and immune evasion. These proteins have a unique structure in which the sequence is conserved. We investigated the vaccine potential of ESAT-6 fused with consensus CD4+ T-cell epitopes of PE/PPE proteins against highly pathogenic Mtb strain HN878 in a murine model. We selected consensus CD4+ T-cell epitopes of PE/PPE proteins by multiple alignments, investigated their IFN-γ response during Mtb infection, and produced their fused ESAT-6 vaccine antigens. Our results showed an increased immune response in PE/PPE peptide -ESAT-6 fusion protein immunization group compared to ESAT-6 only immunization group. After challenge with Mtb strain HN878, we observed that induced CD4+ T-cells secreted double-positive cytokine IL-2+/IFN-γ+, which is considered to be associated with protective T-cell immunity. Additionally, lower numbers of colony-forming units were observed in the spleen of fusion protein immunization groups than in those of single ESAT-6 group. Therefore, conjugation of consensus CD4+ T-cell epitopes in N terminus of PE/PPE to vaccine antigens could potentially increase the protective efficacy of subunit vaccine.

Clinical Significance of CUB and Sushi Multiple Domains 1 Inactivation in Head and Neck Squamous Cell Carcinoma.

Although the genetic alteration of CUB and Sushi multiple domains 1 (CSMD1) is known to be associated with poor prognosis in several cancers, there is a lack of clinical relevance in head and neck cancer. The aim of this study was to offer insight into the clinical significance of CSMD1, utilizing a multimodal approach that leverages publicly available independent genome-wide expression datasets. CSMD1-related genes were found and analyzed to examine the clinical significance of CSMD1 inactivation in the HNSCC cohort of publicly available databases. We analyzed the frequency of somatic mutations, clinicopathologic characteristics, association with immunotherapy-related gene signatures, and the pathways of gene signatures. We found 363 CSMD1-related genes. The prognosis of the CSMD1-inactivated subgroup was poor. FBXW7, HLA-A, MED1, NOTCH2, NOTCH3, and TP53 had higher mutation rates in the CSMD1-inactivated subgroups. The Interferon-gamma score and immune signature score were elevated in CSMD1-inactivated subgroups. We identified several CSMD1-related pathways, such as the phosphatidylinositol signaling system and inositol phosphate metabolism. Our study using three large and independent datasets suggests that CSMD1-related gene signatures are associated with the prognosis of HNSCC patients.

Virulence-dependent induction of interleukin-10-producing-tolerogenic dendritic cells by Mycobacterium tuberculosis impedes optimal T helper type 1 proliferation.

Mycobacterium tuberculosis inhibits optimal T helper type 1 (Th1) responses during infection. However, the precise mechanisms by which virulent M. tuberculosis limits Th1 responses remain unclear. Here, we infected dendritic cells (DCs) with the virulent M. tuberculosis strain H37Rv or the attenuated strain H37Ra to investigate the phenotypic and functional alterations in DCs and resultant T-cell responses. H37Rv-infected DCs suppressed Th1 responses more strongly than H37Ra-infected DCs. Interestingly, H37Rv, but not H37Ra, impaired DC surface molecule expression (CD80, CD86 and MHC class II) due to prominent interleukin-10 (IL-10) production while augmenting the expression of tolerogenic molecules including PD-L1, CD103, Tim-3 and indoleamine 2,3-dioxygenase on DCs in a multiplicity-of-infection (MOI) -dependent manner. These results indicate that virulent M. tuberculosis drives immature DCs toward a tolerogenic phenotype. Notably, the tolerogenic phenotype of H37Rv-infected DCs was blocked in DCs generated from IL-10-/- mice or DCs treated with an IL-10-neutralizing monoclonal antibody, leading to restoration of Th1 polarization. These findings suggest that IL-10 induces a tolerogenic DC phenotype. Interestingly, p38 mitogen-activated protein kinase (MAPK) activation predominantly mediates IL-10 production; hence, H37Rv tends to induce a tolerogenic DC phenotype through expression of tolerogenic molecules in the p38 MAPK-IL-10 axis. Therefore, suppressing the tolerogenic cascade in DCs is a novel strategy for stimulating optimal protective T-cell responses against M. tuberculosis infection.

A Novel Therapeutic Approach Using Mesenchymal Stem Cells to Protect Against Mycobacterium abscessus.

Recent studies have demonstrated the therapeutic potential of mesenchymal stem cells (MSCs) for the treatment of acute inflammatory injury and bacterial pneumonia, but their therapeutic applications in mycobacterial infections have not been investigated. In this study, we demonstrated the use of MSCs as a novel therapeutic strategy against Mycobacterium abscessus (M. abscessus), which is the most drug-resistant and difficult-to-treat mycobacterial pathogen. The systemic intravenous injection of MSCs not only improved mouse survival but also enhanced bacterial clearance in the lungs and spleen. Additionally, MSCs enhanced IFN-γ, TNF-α, IL-6, MCP-1, nitric oxide (NO) and PGE2 production and facilitated CD4(+) /CD8(+) T cell, CD11b(high) macrophage, and monocyte recruitment in the lungs of M. abscessus-infected mice. To precisely elucidate the functions of MSCs in M. abscessus infection, an in vitro macrophage infection system was used. MSCs caused markedly increased NO production via NF-κB activation in M. abscessus-infected macrophages cultured in the presence of IFN-γ. Inhibiting NO or NF-κB signaling using specific inhibitors reduced the antimycobacterial activity of MSCs. Furthermore, the cellular crosstalk between TNF-α released from IFN-γ-stimulated M. abscessus-infected macrophages and PGE2 produced by MSCs was necessary for the mycobacterial-killing activity of the macrophages. Finally, the importance of increased NO production in response to MSC administration was confirmed in the mouse M. abscessus infection model. Our results suggest that MSCs may offer a novel therapeutic strategy for treating this drug-resistant mycobacterial infection by enhancing the bacterial-killing power of macrophages. Stem Cells 2016;34:1957-1970.

Mycobacterium tuberculosis RpfE promotes simultaneous Th1- and Th17-type T-cell immunity via TLR4-dependent maturation of dendritic cells.

Reciprocal induction of the Th1 and Th17 immune responses is essential for optimal protection against Mycobacterium tuberculosis (Mtb); however, only a few Mtb antigens are known to fulfill this task. A functional role for resuscitation-promoting factor (Rpf) E, a latency-associated member of the Rpf family, in promoting naïve CD4(+) T-cell differentiation toward both Th1 and Th17 cell fates through interaction with dendritic cells (DCs) was identified in this study. RpfE induces DC maturation by increasing expression of surface molecules and the production of IL-6, IL-1ß, IL-23p19, IL-12p70, and TNF-α but not IL-10. This induction is mediated through TLR4 binding and subsequent activation of ERK, p38 MAPKs, and NF-κB signaling. RpfE-treated DCs effectively caused naïve CD4(+) T cells to secrete IFN-γ, IL-2, and IL-17A, which resulted in reciprocal expansions of the Th1 and Th17 cell response along with activation of T-bet and RORγt but not GATA-3. Furthermore, lung and spleen cells from Mtb-infected WT mice but not from TLR4(-/-) mice exhibited Th1 and Th17 polarization upon RpfE stimulation. Taken together, our data suggest that RpfE has the potential to be an effective Mtb vaccine because of its ability to activate DCs that simultaneously induce both Th1- and Th17-polarized T-cell expansion.

Essential engagement of Toll-like receptor 2 in initiation of early protective Th1 response against rough variants of Mycobacterium abscessus.

Although Mycobacterium abscessus (M. abscessus) is becoming more prevalent in patients without overt immunodeficiency, little is known about the factors that contribute to disease susceptibility. This study was undertaken to investigate how Toll-like receptor 2 (TLR2) functionally contributes to the generation of protective immunity against M. abscessus in a morphotype-specific manner. We found that Tlr2-/- mice were extremely susceptible to an intravenous (i.v.) model of infection by M. abscessus rough variants, displaying uncontrolled infection in the lungs and a significantly lower survival rate than with wild-type (WT) mice. This uncontrolled infection resulted from failures in the following processes: (i) production of the crucial cytokines gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin 12p70 (IL-12p70); (ii) early infiltration of neutrophils, monocytes, and dendritic cells (DCs) in the lungs of Tlr2-/- mice; (iii) rapid influx of CD4+ and CD8+ T cells; and (iv) the expansion of memory/effector T cells. Notably, systemic administration of M. abscessus culture filtrate-treated syngeneic DCs from WT mice greatly strengthened immune priming in vivo, resulting in a dramatic reduction in bacterial growth and improved long-term survival in Tlr2-/- mice, with a recovery of protective immunity. Our findings demonstrate that TLR2 is an essential contributor to instructive and effector immunity during M. abscessus infection in a morphotype-specific manner.

Mycobacterium tuberculosis MmsA, a novel immunostimulatory antigen, induces dendritic cell activation and promotes Th1 cell-type immune responses.

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is an outstanding pathogen that modulates the host immune response. This inconvenient truth drives the continual identification of antigens that generate protective immunity, including Th1-type T cell immunity. Here, the contribution of methylmalonate semialdehyde dehydrogenase (MmsA, Rv0753c) of Mtb to immune responses was examined in the context of dendritic cell (DC) activation and T cell immunity both in vitro and in vivo. The results showed that MmsA induced DC activation by activating the MAPK and NF-κB signaling pathways. Additionally, MmsA-treated DCs activated naïve T cells, effectively polarized CD4(+) and CD8(+) T cells to secrete IFN-γ and IL-2, and induced T cell proliferation. These results indicate that MmsA is a novel DC maturation-inducing antigen that drives the Th1 immune response. Thus, MmsA was found to potentially regulate immune responses via DC activation toward Th1-type T cell immunity, enhancing our understanding of Mtb pathogenesis.

Incidental focal FDG uptake in the parotid glands on PET/CT in patients with head and neck malignancy.

OBJECTIVES: To evaluate the prevalence and clinical significance of focal parotid lesions identified by (18)F- FDG PET/CT in patients with nonparotid head and neck malignancies. METHODS: From 3,638 PET/CT examinations using (18)F-FDG conducted on 1,342 patients with nonparotid head and neck malignancies, we retrospectively identified patients showing incidental focal FDG uptake in the parotid glands. The diagnosis of parotid lesions was confirmed histopathologically or on imaging follow-up. Patient demographics, clinical features, maximum standardized uptake value (SUV(max)) on PET images, size and attenuation on corresponding contrast-enhanced CT images were assessed and correlated with the final diagnosis. RESULTS: The prevalence of incidental focal parotid FDG uptake on PET/CT was 2.1% (95% CI 1.4 - 3.0%). Among 21 patients with focal parotid lesions confirmed histologically or on imaging follow-up, 7 (33.3%) had malignant lesions (all metastases) and 14 (66.7%) had benign lesions (four pleomorphic adenomas, two Warthin's tumours, one benign lymph node, one granulomatous lesion, six lesions without histopathological confirmation). There were no significant differences in age, sex, SUV(max) or CT findings between patients with benign and those with malignant lesions. CONCLUSION: Focal parotid FDG uptake on PET/CT in patients with head and neck malignancy warrants further investigations to ensure adequate therapy for incidental parotid lesions. KEY POINTS: • The prevalence of parotid incidentaloma on PET in head and neck malignancy was 2.1% • The malignancy rate of incidental focal parotid FDG uptake was 33.3% • SUV max could not reliably differentiate malignant from benign incidental parotid lesions.

Posterosuperior lesion has a high risk of lateral and central nodal metastasis in solitary papillary thyroid cancer.

BACKGROUND: Preoperative nodal assessment of papillary thyroid cancer (PTC) is very important because 60 to 70 % of all disease recurrence in the neck can occur in the lymph nodes. This study explored the association between ultrasonographic intrathyroidal location and the nodal metastasis pattern in solitary PTC. METHODS: Data from 218 patients who underwent total thyroidectomy with or without neck dissection for previously untreated PTC between 2006 and 2010 were retrospectively analyzed. Only patient data for which both preoperative ultrasound findings and postoperative pathologic reports were available were included. Multifocal cases, cases with extrathyroidal extension, and distant metastasis were excluded. The association between nodal metastasis pattern and clinical or pathologic features of solitary PTCs was analyzed, as was the association between ultrasonographic intrathyroidal location and central or lateral nodal metastasis in solitary PTC. RESULTS: Mass size larger than 2 cm (p < 0.001, Odds ratio (OR) 4.117) and central nodal metastasis (p < 0.001, OR 3.984) were related with lateral neck metastasis in multivariate analysis. Male sex (p = 0.001, OR 3.012) and capsular invasion (p < 0.001, OR 4.720) were related with central neck metastasis in multivariate analysis. When analyzing ultrasonographic location of intrathyroidal solitary lesion, posterosuperiorly located lesion was strongly associated with both lateral and central neck metastasis. (p < 0.001 and p = 0.002, respectively). CONCLUSIONS: Posterosuperior location of intrathyroidal solitary PTC has a high risk of lateral and central nodal metastasis when compared to other locations. For such patients, careful preoperative evaluation of nodal status should be done.

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. We previously reported that the administration of Lactobacillus sakei CVL-001 (L. sakei CVL-001) regulates inflammation and improves mucosal barrier function in a murine colitis model. Since accumulating evidence has reported the functional roles of probiotics in drug-induced liver injury and pulmonary inflammation, we employed a parabiotic form of the L. sakei CVL-001 to investigate whether this supplement may provide beneficial effects on the reduction in drug-induced liver damage and pulmonary inflammation during chemotherapy. Intriguingly, L. sakei CVL-001 administration slightly reduced Mtb burden without affecting lung inflammation and weight loss in both Mtb-resistant and -susceptible mice. Moreover, L. sakei CVL-001 decreased T cell-mediated inflammatory responses and increased regulatory T cells along with an elevated antigen-specific IL-10 production, suggesting that this parabiotic may restrain excessive inflammation during antibiotic treatment. Furthermore, the parabiotic intervention significantly reduced levels of alanine aminotransferase, an indicator of hepatotoxicity, and cell death in liver tissues. Collectively, our data suggest that L. sakei CVL-001 administration has the potential to be an adjunctive therapy by reducing pulmonary inflammation and liver damage during anti-TB drug treatment and may benefit adherence to TB medication in lengthy treatment.