Effect of climatic environment on immunological features of rheumatoid arthritis.

The aim of this study was to clarify the effect of climatic environment on the immunological features of rheumatoid arthritis (RA). Blood samples were collected from patients with RA and healthy controls (HCs), matched by age and sex, living in two locations, Tsukuba and Karuizawa, which differ in their altitude and average air temperature and atmospheric pressure. Analysis of peripheral blood mononuclear cells (PBMCs) revealed that the proportion of T and B cell subpopulations in HCs and RA patients were significantly different between two sites. Inverse probability weighting adjustment with propensity scores was used to control for potential confounding factors. The results revealed that, in comparison with RA patients in Tsukuba, those in Karuizawa showed a significant increase in cTh1, cTfh1, and Tph cells, and significant decrease in cTh17, cTh17.1, and CD8+ Treg in T cell subpopulations, and a significant increase in DNB, DN1, DN2, and class-switched memory B cells, and a significant decrease in unswitched memory B, naïve B cells, and ABCs in B cell subpopulations. Our results suggest the possibility that climatic environment might have an effect on immune cell proportion and function, and be related to the pathogenic mechanism of RA.

Biological properties of Staphylococcus virus ΦSA012 for phage therapy.

Staphylococcus virus ΦSA012 has a wide host range and efficient lytic activity. Here, we assessed the biological stability of ΦSA012 against temperature, freeze-thawing, and pH to clinically apply the phage. In addition, inoculation of ΦSA012 through i.p. and i.v. injections into mice revealed that phages were reached the limit of detection in serum and accumulated notably spleens without inflammation at 48 h post-inoculation. Furthermore, inoculation of ΦSA012 through s.c. injections in mice significantly induced IgG, which possesses neutralizing activity against ΦSA012 and other Staphylococcus viruses, ΦSA039 and ΦMR003, but not Pseudomonas viruses ΦS12-3 and ΦR18 or Escherichia viruses T1, T4, and T7 in vitro. Immunoelectron microscopic analysis showed that purified anti-phage IgG recognizes the long-tail fiber of staphylococcus viruses. Although S. aureus inoculation resulted in a 25% survival rate in a mouse i.p. model, ΦSA012 inoculation (i.p.) improved the survival rate to 75%; however, the survival rate of ΦSA012-immunized mice decreased to less than non-immunized mice with phage i.v. injection at a MOI of 100. These results indicated that ΦSA012 possesses promise for use against staphylococcal infections but we should carefully address the appropriate dose and periods of phage administration. Our findings facilitate understandings of staphylococcus viruses for phage therapy.

Relationship between mortality and molecular epidemiology of methicillin-resistant Staphylococcus aureus bacteremia.

Staphylococcus aureus is the primary cause of bacteremia, and methicillin-resistant S. aureus bacteremia is associated with a high mortality rate. Methicillin-resistant S. aureus clones are widespread worldwide, and molecular epidemiological studies are important. Therefore, this study aimed to determine the characteristics of patients who died due to methicillin-resistant S. aureus bacteremia and microbiological characteristics of methicillin-resistant S. aureus strains in a tertiary teaching hospital. This single-center, retrospective study included patients with methicillin-resistant S. aureus isolated from blood bacterial culture performed at Kyoto Prefectural University of Medicine Hospital, from October 2016 to May 2019. The data analyzed included patient background, clinical strain characteristics, and molecular epidemiology. Of 41 patients with methicillin-resistant S. aureus bacteremia (median age, 60 [28-70] years; 24 (59%) were men), and 7 (17%) died due to methicillin-resistant S. aureus bacteremia. The median age of those who died in the methicillin-resistant S. aureus bacteremia group was predominantly higher than that of those in the alive group (p = 0.03). The most common cause of methicillin-resistant S. aureus bacteremia was endovascular devices, which occurred in 20 (49%), 18 (53%), and 2 (29%) patients in the total, alive, and died groups, respectively. Bacteriological characteristics showed that type IV Staphylococcal Cassette Chromosome mec genotype was most frequently detected in the total (n = 34 [83%]), alive (n = 29 [85%]), and died (n = 5 [71%]) groups. In the molecular cluster analysis, CC8, ST8, staphylococcal Cassette Chromosome mec type IV, and community-acquired-methicillin-resistant S. aureus formed the largest groups. The diversity of methicillin-resistant S. aureus clones is evident, and it is possible that clones with new virulence factors may still emerge. In the future, it will be crucial to monitor the epidemiological trends of methicillin-resistant S. aureus to respond quickly to changes in pathogenic and clonal factors, to clarify the gene expression network by identifying old and new virulence factors.

Surface translocation of Kir2.1 channel induces IL-1ß secretion in microglia.

One of the major properties of microglia is to secrete cytokines as a reaction to stress such as lipopolysaccharide (LPS) application. The mechanism of cytokine secretion from the microglia upon stress through the inflammasome-mediated release process is well studied, and the voltage-gated Kv1.3 channel is known to play an important role in this process. Most previous studies investigated long-term inflammasome-mediated cytokine release (at least over 4 h) and there are only a few studies on the acute reaction (within minutes order) of the microglia to stress and its cytokine secretion capacity. In this study, we found that LPS induced an increase in Kir2.1 current within 15 min after administration but had no effect on voltage-dependent outward currents. Moreover, cytological and western blot analysis revealed that the increase in the Kir2.1 channel current after LPS administration was induced by the translocation of Kir2.1 from the cytoplasm to the cell surface. From an experiment using the inhibitor and trafficking mutation of Kir2.1, an increase in Kir2.1 was found to contribute to the secretion of the inflammatory cytokine, IL-1ß. Although the physiological significance of this acute IL-1ß secretion remains unclear, our present data imply that Kir2.1 translocation functions as a regulator of IL-1ß secretion, and therefore becomes a potential target to control cytokine release from microglia.

Role of extracellular vesicles in severe pneumonia and sepsis.

INTRODUCTION: Extracellular vesicles (EV) released constitutively or following external stimuli from structural and immune cells are now recognized as important mediators of cell-to-cell communication. They are involved in the pathogenesis of pneumonia and sepsis, leading causes of acute respiratory distress syndrome (ARDS) where mortality rates remain up to 40%. Multiple investigators have demonstrated that one of the underlying mechanisms of the effects of EVs is through the transfer of EV content to host cells, resulting in apoptosis, inflammation, and permeability in target organs. AREAS COVERED: The current review focuses on preclinical research examining the role of EVs released into the plasma and injured alveolus during pneumonia and sepsis. EXPERT OPINION: Inflammation is associated with elevated levels of circulating EVs that are released by activated structural and immune cells and can have significant proinflammatory, procoagulant, and pro-permeability effects in critically ill patients with pneumonia and/or sepsis. However, clinical translation of the use of EVs as biomarkers or potential therapeutic targets may be limited by current methodologies used to identify and quantify EVs accurately (whether from host cells or infecting organisms) and lack of understanding of the role of EVs in the reparative phase during recovery from pneumonia and/or sepsis.

Efficacy of SGLT2 inhibitors as additional treatment in Japanese type 2 diabetic patients: second or third choice?

OBJECTIVES: Due to the increase of type 2 diabetes (T2D), the number of patients in treatment with multiple anti-diabetic agents is increased. According to the recent recommendation of treatment guidelines, sodium-glucose cotransporter 2 (SGLT2) inhibitors would be used as additional treatment to the currently administered anti-diabetic drugs for poorly controlled T2D patients. Here, we assessed the efficacy of SGLT2 inhibitors added to the current treatment with metformin, dipeptidyl peptidase-4 (DPP4) inhibitors, or both in Japanese T2D patients. RESULTS: Japanese T2D subjects with poor glucose control, who were treated with metformin (n = 10), DPP4 inhibitors (n = 11), or both (n = 28) and who were in need of additional treatment, were recruited. HbA1c levels before and 6 months after addition of SGLT2 inhibitor treatment were used to compare the effectiveness. The HbA1c levels after addition of SGLT2 inhibitors significantly decreased in all groups. The change in HbA1c levels (delta HbA1c) showed no significant difference between the three groups. The present data indicated that addition of SGLT2 inhibitors to metformin and/or DPP4 inhibitors is equally effective in the treatment of Japanese T2D patients.

Preoperative Left Ventricular Energy Loss in the Operating Theater Reflects Subjective Symptoms in Chronic Aortic Regurgitation.

BACKGROUND: There is currently no subjective, definitive evaluation method for therapeutic indication other than symptoms in aortic regurgitation. Energy loss, a novel parameter of cardiac workload, can be visualized and quantified using echocardiography vector flow mapping. The purpose of the present study was to evaluate whether energy loss in patients with chronic aortic regurgitation can quantify their subjective symptoms more clearly than other conventional metrics. METHODS: We studied 15 patients undergoing elective aortic valve surgery for aortic regurgitation. We divided the patients into symptomatic and asymptomatic groups using their admission records. We analyzed the mean energy loss in one cardiac cycle using transesophageal echocardiography during the preoperative period. The relationships between symptoms, energy loss, and other conventional metrics were statistically analyzed. RESULTS: There were seven and eight patients in the symptomatic and asymptomatic groups, respectively. The mean energy loss of one cardiac cycle was higher in the symptomatic group (121 mW/m [96-184]) than in the asymptomatic group (87 mW/m [80-103]) (p = 0.040), whereas the diastolic diameter was higher in the asymptomatic group (65 mm [59-78]) than in the symptomatic group (57 mm [51-57]) (p = 0.040). There was no significant difference between the symptomatic and asymptomatic groups in terms of other conventional metrics. CONCLUSIONS: An energy loss can quantify patients' subjective symptoms more clearly than other conventional metrics. The small sample size is the primary limitation of our study, further studies assessing larger cohort of patients are warranted to validate our findings.

RORγt+Foxp3+ regulatory T cells in the regulation of autoimmune arthritis.

RORγt+Foxp3+regulatory T (Treg) cells, known as T regulatory 17 cells (Tr17 cells), are a novel subset of Treg cells, which have the potential to regulate the development of experimental autoimmune encephalomyelitis (EAE) thorough a specific repression of T helper 17 (Th17) cell-mediated inflammation. However, the function of Tr17 cells the development of other autoimmune diseases such as autoimmune arthritis remains unclear. Collagen-induced arthritis (CIA) was found to be prolonged in Foxp3creRORγtfl/fl mice, in which Tr17 cells were deleted, compared with Foxp3wtRORγtfl/fl mice. Tr17 cells were significantly increased in ankle joints (AJ) compared with draining lymph nodes after the onset of arthritis. CC chemokine receptor 6 (CCR6) was up-regulated on Tr17 cells compared to RORγt negative Treg cells. CD25, cytotoxic T-lymphocyte antigen 4 (CTLA-4), glucocorticoid-induced TNF-receptor (GITR), and inducible T-cell co-stimulator (ICOS) expression was also up-regulated on Tr17 cells compared to RORγt negative Treg cells. IL-10-producing cells and Blimp-1+ and T-bet+ cells were increased in Tr17 cells compared to RORγt-negative Treg cells. Tr17-enriched Treg cells significantly suppressed proliferation of conventional T cells through IL-10 compared with CCR6-Treg cells. Tr17 cells increased during the clinical course of CIA and accumulated in inflamed joints. Taken together, it appears that Tr17 cells play a crucial role in the regulation of autoimmune arthritis.

Peripheral oxygen saturation to inspiratory oxygen fraction ratio-based identification of critically ill coronavirus disease patients for early therapeutic interventions.

BACKGROUND: Early identification of critically ill coronavirus disease (COVID-19) patients in clinical settings is crucial in reducing the mortality rate. Therefore, this study aimed to determine whether the saturation of peripheral oxygen (SpO2) to fraction of inspiratory oxygen (FiO2) ratio (SF ratio) at admission is useful for the early identification of severe COVID-19. METHODS: This single-center, retrospective, observational study conducted at the University Hospital, Kyoto, Japan, included 26 patients diagnosed with COVID-19 between January 24 and May 6, 2020. COVID-19 severity was classified into two groups based on the SF ratio: ≤ 235 (moderate to severe disease: low group) and > 235 (normal to mild disease: high group). The characteristics, laboratory data, and outcomes of the patients were examined retrospectively and compared between the groups. RESULTS: Of the 26 patients [median age 51.5 years, interquartile range 35.8-67.0], 6 were in the low group (23%) and 20 in the high group (77%). The low group had a higher respiratory rate than the high group (p < 0.05). Blood tests immediately after admission showed that the low group had significantly lower albumin (p < 0.01), and higher lactate dehydrogenase (p < 0.01), C-reactive protein (p < 0.01), and D-dimer (p < 0.01) levels than the high group. Moreover, all patients received antiviral agents; four received continuous renal replacement therapy and invasive positive pressure ventilation, one received extracorporeal membrane oxygenation, and two died in the low group. CONCLUSION: SF ratio measurement at admission could assist clinicians in the early identification of severe COVID-19, which in turn can lead to early therapeutic interventions.

Co-infection with Legionella and SARS-CoV-2: a case report.

INTRODUCTION: We report a case of COVID-19 with Legionella co-infection that was treated successfully. CASE REPORT: A 73-year-old man presented to the hospital with symptoms of fatigue that continued for the next 5 days. The patient was receiving docetaxel and prednisolone chemotherapy for prostate cancer. Laboratory findings on admission showed positive urine Legionella antigen test and SARS-CoV-2 test. He was administered antiviral and antibacterial agents, and a corticosteroid. Pneumonia exacerbated on day 2 of hospitalization. The patient underwent tracheal intubation and began receiving multidisciplinary care. On day 8 of hospitalization, his oxygenation improved, and the patient was extubated. He discharged on day 27 of hospitalization. CONCLUSIONS: The patient had a favorable outcome with early diagnosis and early treatment of both diseases. Patients with severe COVID-19 disease need to be evaluated for co-infection. Further, early diagnosis and early treatment of the microbial bacteria causing the co-infection are important.

Mapping of Supramolecular Chirality in Insect Wings by Microscopic Vibrational Circular Dichroism Spectroscopy: Heterogeneity in Protein Distribution.

The supramolecular chirality of the hindwing of Anomala albopilosa (male) was investigated using a microscopic vibrational circular dichroism (VCD) system, denoted as MultiD-VCD. The source of intense infrared (IR) light for the system was a quantum cascade laser. Two-dimensional maps of IR and VCD spectra were taken by scanning the surface area (ca. 2 mm × 2 mm) of the insect hindwing tissue. The spectra ranged from 1500 to 1700 cm-1, and the maps have a spatial resolution of 100 µm. The distribution of proteins, including their supramolecular structures, was analyzed from the location-dependent spectral shape of the VCD bands assigned to amides I and II. The results revealed that the hindwing consists of segregated domains of proteins with different secondary structures: an α-helix (in one part of the membrane), a hybrid of α-helix and ß-sheet (in another part of the membrane), and a coil (in a vein).

The deletion of glucagon-like peptide-1 receptors expressing neurons in the dorsomedial hypothalamic nucleus disrupts the diurnal feeding pattern and induces hyperphagia and obesity.

BACKGROUND: Feeding rhythm disruption contributes to the development of obesity. The receptors of glucagon-like peptide-1 (GLP-1) are distributed in the wide regions of the brain. Among these regions, GLP-1 receptors (GLP-1R) are expressed in the dorsomedial hypothalamic nucleus (DMH) which are known to be associated with thermogenesis and circadian rhythm development. However, the physiological roles of GLP-1R expressing neurons in the DMH remain elusive. METHODS: To examine the physiological role of GLP-1R expressing neurons in the DMH, saporin-conjugated exenatide4 was injected into rat brain DMH to delete GLP-1R-positive neurons. Subsequently, locomotor activity, diurnal feeding pattern, amount of food intake and body weight were measured. RESULTS: This deletion of GLP-1R-positive neurons in the DMH induced hyperphagia, the disruption of diurnal feeding pattern, and obesity. The deletion of GLP-1R expressing neurons also reduced glutamic acid decarboxylase 67 and cholecystokinin A receptor mRNA levels in the DMH. Also, it reduced the c-fos expression after refeeding in the suprachiasmatic nucleus (SCN). Thirty percent of DMH neurons projecting to the SCN expressed GLP-1R. Functionally, refeeding after fasting induced c-fos expression in the SCN projecting neurons in the DMH. As for the projection to the DMH, neurons in the nucleus tractus solitarius (NTS) were found to be projecting to the DMH, with 33% of those neurons being GLP-1-positive. Refeeding induced c-fos expression in the DMH projecting neurons in the NTS. CONCLUSION: These findings suggest that GLP-1R expressing neurons in the DMH may mediate feeding termination. In addition, this meal signal may be transmitted to SCN neurons and change the neural activities.

QTc interval prolongation in patients with systemic lupus erythematosus treated with hydroxychloroquine.

OBJECTIVES: The primary objective is to reveal the effect of hydroxychloroquine (HCQ) treatment on corrected QT (QTc) interval in patients with systemic lupus erythematosus (SLE). The secondary objective is to investigate factors that affect QTc prolongation. METHODS: SLE patients who had electrocardiograms between 2015 and 2020 were recruited and assigned to two groups based on whether they were treated with HCQ (HCQ group) or not (control group). Change of QTc before and after HCQ administration in the HCQ group was measured and compared with the control group. Patients treated with HCQ were further divided into two groups based on presence or absence of QTc prolongation and the characteristics were compared. RESULTS: In total, 126 patients were recruited, of whom 42 were treated with HCQ. In the HCQ group, the mean QTc significantly increased (p < .001), while there was no significant difference of mean QTc in the control group. Moreover, those in the HCQ group with QTc prolongation showed a significantly higher proportion of hypertension and longer SLE duration compared to those without QTc prolongation. However, the multiple logistic regression analysis showed that there were no significant differences among them. CONCLUSION: HCQ could induce QTc prolongation in SLE patients. It might be better that the possibility of QTc prolongation was taken into consideration when HCQ was administered in the patients with longer disease duration of SLE and coincidence of hypertension.

Multidimensional Vibrational Circular Dichroism Apparatus Equipped with Quantum Cascade Laser and Its Use for Investigating Some Peptide Systems Containing d-Amino Acids.

We developed a multidimensional vibrational circular dichroism system with a positional coordinate, making it possible to move in both x- and y-directions using an automatic stage. Quantum cascade laser (QCL) was used as a light source to achieve high intensity and narrow focusing. The QCL emitted light in the wavenumber range of 1500-1740 cm-1, which encompassed absorption bands assigned to the stretching vibrations of amides I and II. The operation of the instrument was analyzed for samples containing amide groups. An aqueous solution of Gly-l-Leu or Gly-d-Leu was measured under the background absorbance as high as 3.5 due to the water medium. The spectra were recorded by scanning at 1.0 cm-1 steps. The time required for performing measurement at each wavenumber was less than 1 s. The mirror-image relation was maintained between the optical antipodes. A peak assigned to amide II appeared clearly at around 1580 cm-1. In the case of KBr pellets containing the same compounds, peaks assigned to amide I and II were observed. For two-dimensional pattering, a KBr pellet comprising two domains of amino acids (or l-Ala and d-Ser) was investigated. The distribution of each component within the pellet was obtained under the two-dimensional alignment at the spatial interval of 2.5 mm.

Predictive Factors for Pneumomediastinum During Management of Connective Tissue Disease-related Interstitial Lung Disease: A Retrospective Study.

Objective To identify factors associated with pneumomediastinum during management of connective tissue disease (CTD)-related interstitial lung disease (ILD). Methods Patients diagnosed with pneumomediastinum after the initiation of corticosteroid therapy for their CTD-ILD were enrolled. The baseline characteristics of patients who developed pneumomediastinum after the initiation of corticosteroid therapy (n=13, all occurring within 120 days) were compared to those of patients who did not develop pneumomediastinum (n=49). A multivariate logistic regression analysis was performed to identify factors associated with pneumomediastinum. A receiver operating characteristic (ROC) curve analysis was also performed to assess the predictive performance. Results The body mass index (BMI) [odds ratio (OR) (95% confidence interval (CI)) 0.482 (0.272-0.853)] and serum lactate dehydrogenase (LDH) [OR (95% CI) 1.013 (1-1.025)] levels at baseline were identified as independent factors associated with pneumomediastinum after corticosteroid initiation. The optimal cut-off points of the BMI and LDH levels for predicting pneumomediastinum development, as estimated by the Youden index, were 20.2 kg/m2 and 378 U/L, respectively. LDH showed a sensitivity of 61.5% and the highest specificity of 87.8%. Importantly, combining these markers resulted in the highest sensitivity of 100% and a specificity of 71.4%. Conclusion A low BMI and high serum LDH levels at baseline are useful predictive factors for pneumomediastinum development in CTD-ILD patients.

T-bet represses collagen-induced arthritis by suppressing Th17 lineage commitment through inhibition of RORγt expression and function.

T-bet is a key transcription factor for the T helper 1 lineage and its expression level is negatively correlated to inflammation in patients with rheumatoid arthritis (RA). Our previous study using T-bet transgenic mice revealed over-expression of T-bet completely suppressed collagen-induced arthritis (CIA), a murine model of RA, indicating a potential suppressive role of T-bet in the pathogenesis of autoimmune arthritis. Here, we show T-bet-deficiency exacerbated CIA. T-bet in CD4 + T cells, but not in CD11c + dendritic cells, was critical for regulating the production of IL-17A, IL-17F, IL-22, and TNFα from CD4 + T cells. T-bet-deficient CD4 + T cells showed higher RORγt expression and increased IL-17A production in RORγt-positive cells after CII immunization. In addition, T-bet-deficient naïve CD4 + T cells showed accelerated Th17 differentiation in vitro. CIA induced in CD4-Cre T-betfl/fl (cKO) mice was more severe and T-bet-deficient CD4 + T cells in the arthritic joints of cKO mice showed higher RORγt expression and increased IL-17A production. Transcriptome analysis of T-bet-deficient CD4 + T cells revealed that expression levels of Th17-related genes were selectively increased. Our results indicate that T-bet in CD4 + T cells repressed RORγt expression and function resulting in suppression of arthritogenic Th17 cells and CIA.

Clinical features and prognosis of nocardiosis in patients with connective tissue diseases.

OBJECTIVES: To investigate the clinical features and prognosis of nocardiosis complicated by connective tissue diseases (CTDs). METHODS: We examined patients with CTDs who were diagnosed with nocardiosis from October 2004 to 2019. We retrospectively investigated patient characteristics and therapeutic outcomes. We then performed a comparison between survivors and non-survivors. RESULTS: Fourteen patients were examined. Underlying CTDs were systemic lupus erythematosus (28.6%), vasculitis syndrome (28.6%), rheumatoid arthritis (21.4%), adult Still disease (14.3%) and dermatomyositis (7.1%). Infected organs were lung (85.7%), brain (42.9%), skin/cutaneous lesions (28.6%) and muscle (7.1%). Disseminated infections were seen in nine patients (64.3%). At the onset of nocardiosis, all patients were given prednisolone (23.2 ± 11.9 mg/day). Only two patients (14.3%) were given TMP-SMX for prophylaxis of pneumocystis pneumonia. Relapse occurred in one patient (7.1%) and four patients (28.6%) died from nocardiosis for a cumulative survival rate at 52 weeks of 76.9%. In a comparison of survivors (71.4%) and non-survivors (28.6%), cutaneous lesions were significantly more frequent in the latter (10 vs 75%, p = .04) with an odds ratio of 27.0 (95% CI: 1.7-453.4). CONCLUSION: Cutaneous lesions as a result of dissemination might be a risk factor for nocardiosis mortality in patients with CTDs.

Myocardial injury in a patient with severe coronavirus disease: A case report.

INTRODUCTION: Coronavirus disease (COVID-19) can lead to severe disease or death and is characterized by a wide range of mild to severe symptoms. In addition to the lungs, studies have reported the involvement of the stomach, intestine, and angiotensin-converting enzyme 2 receptors in the heart. CASE REPORT: We present a case of a patient with COVID-19 who died soon after developing multi-organ failure and myocardial injury due to COVID-19-associated pneumonia. A 71-year-old man who contracted COVID-19 was admitted to the hospital after presenting with fever for 7 days and developed dyspnea. Following treatment, his respiratory status worsened. Thus, he was transferred to our hospital for intensive care on day 11. Physical examination revealed fever, dyspnea, respiratory distress, and no chest pain. Invasive positive pressure ventilation was initiated for acute respiratory distress syndrome on day 14. On day 15, we observed renal, liver, and coagulation dysfunction, indicating multi-organ failure. Chest radiography did not show clear signs of an increased cardiothoracic ratio or pulmonary congestion. An electrocardiogram (ECG) showed signs of myocardial infarction, which was confirmed by elevated troponin I and creatine kinase levels. The patient's circulatory dynamics did not improve on medication, and he died on day 16. CONCLUSIONS: We report the case of a patient with severe COVID-19 who died from an exacerbation of myocardial injury. Clinicians should not only evaluate respiration but also assess the heart by performing a 12-lead ECG, echocardiogram, and myocardial injury marker examination. Together, these tools can help predict which patients will develop severe COVID-19.

Detection of NUCB2/nesfatin-1 in cerebrospinal fluid of multiple sclerosis patients.

NUCB2/nesfatin-1 was originally discovered as an anorexigenic peptide. However, recent studies revealed various additional functions including the regulation of inflammation. However, there are no studies that investigated the involvement of NUCB2/nesfatin-1 in neuroinflammatory diseases. Here, we aimed to investigate the involvement of NUCB2/nesfatin-1 in a representative neuroinflammatory disease, multiple sclerosis (MS). Cerebrospinal fluids (CSF) were collected from 24 MS patients and 10 control subjects and NUCB2/nesfatin-1, proinflammatory cytokines (TNF-α, IL-1ß) and anti-inflammatory cytokines (IL-10, TGF-ß) levels were measured by using ELISA assay. Also the expression of NUCB2/nesfatin-1 in the CSF of MS patient was investigated by western blot analysis. Expression of NUCB2/nesfatin-1 was confirmed in the CSF of the MS patient by western blot analysis. NUCB2/nesfatin-1 levels were significantly higher in the CSF of the MS patients. Among the measured cytokines, only IL-1ß was lower in the CSF of the MS patients. We report for the first time increased NUCB2/nesfatin-1 levels in the CSF of MS patients.