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Keicho, N., Y. Higashimoto, G. P. Bondy, W. M. Elliott, J. C. Hogg, and S. Hayashi. Endotoxin-specific NF-[Kappa]B activation in pulmonary epithelial cells harboring adenovirus E1A. Am. J. Physiol. 277 (Lung Cell. Mol. Physiol. 21): L523-L532, 1999.--Adenovirus E1A DNA and proteins are detected in lung epithelial cells of patients with chronic obstructive pulmonary disease. In investigating E1A regulation of inflammatory mediator expression in human lung epithelial cells, we found increased intercellular adhesion molecule-1 (ICAM-1) and interleukin-8 expression after lipopolysaccharide (LPS) stimulation of A549 cells stably transfected with adenovirus 5 E1A. We now show that E1A-dependent induction of interleukin-8 expression is specific to LPS, superinduced by cycloheximide, and not observed after tumor necrosis factor or phorbol 12-myristate 13-acetate stimulation. Electrophoretic mobility shift assays revealed that tumor necrosis factor or phorbol 12-myristate 13-acetate induced nuclear factor-[Kappa]B binding complexes of Rel A and p50 in E1A and control transfectants, whereas LPS was effective only in E1A transfectants. Similarly, LPS-induced nuclear translocation of nuclear factor-[Kappa]B was observed only in E1A transfectants. CCAAT-enhancer binding protein binding was undetected and activator protein-1 binding was unaffected by LPS in either cell type, whereas basal mRNA levels of c-jun were unchanged by E1A. We conclude that E1A enhances the expression of these inflammatory mediator genes by modulating events specific to LPS-triggered nuclear factor-[Kappa]B induction in these cells. A549 cells; lipopolysaccharide response; regulation of infiammatory mediator expression; nuclear factor-[Kappa]B

Pigment epithelium-derived factor (PEDF) is a glycoprotein with complex neuroprotective, anti-angiogenic, and anti-inflammatory properties, all of which could potentially be exploited as a therapeutic option for vascular complications in diabetes. We have previously shown that PEDF-derived synthetic peptide, P5-3 (FIFVLRD) has a comparable ability with full PEDF protein to inhibit rat corneal neovascularization induced by chemical cauterization. However, the effects of PEDF peptide on experimental diabetic nephropathy remain unknown. To address the issue, we modified P5-3 to stabilize and administered the modified peptide (d-Lys-d-Lys-d-Lys-Gln-d-Pro- P5-3-Cys-amide, 0.2 nmol/day) or vehicle to streptozotocin-induced diabetic rats (STZ-rats) intraperitoneally by an osmotic mini pump for 2 weeks. We further examined the effects of modified peptide on human proximal tubular cells. Renal PEDF expression was decreased in STZrats. Although the peptide administration did not affect blood glucose or blood pressure, it decreased urinary excretion levels of 8-hydroxy- 2′-deoxyguanosine, an oxidative stress marker, and reduced plasminogen activator inhibitor-1 (PAI-1) gene expression, and suppressed glomerular expansion in the diabetic kidneys. High glucose or advanced glycation end products stimulated oxidative stress generation and PAI-1 gene expression in tubular cells, all of which were significantly suppressed by 10 nM modified P5-3 peptide. Our present study suggests that PEDF-derived synthetic modified peptide could protect against experimental diabetic nephropathy and inhibit tubular cell damage under diabetes- like conditions through its anti-oxidative properties. Supplementation of modified P5-3 peptide may be a novel therapeutic strategy for diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Advanced glycation end products ( AGEs) decrease adiponectin expression and suppress insulin signaling in cultured adipocytes through the interaction with a receptor for AGEs (RAGE) via oxidative stress generation. We have recently found that high-affinity DNA aptamer directed against AGE (AGE-aptamer) prevents the progression of experimental diabetic nephropathy by blocking the harmful actions of AGEs in the kidney. This study examined the effects of AGE-aptamer on adipocyte remodeling, AGE-RAGE oxidative stress axis, and adiponectin expression in fructose-fed rats. Although AGE-aptamer treatment by an osmotic mini pump for 8 weeks did not affect serum insulin levels, it significantly decreased average fasting blood glucose and had a tendency to inhibit body weight gain in fructose- fed rats. Furthermore, AGE-aptamer significantly suppressed the increase in adipocyte size and prevented the elevation in AGEs, RAGE, and an oxidative stress marker, 8-hydroxydeoxyguanosine (8-OHdG), levels in adipose tissues of fructose-fed rats at 14-week-old, while it restored the decrease in adiponectin mRNA levels. Our present study suggests that AGE-aptamer could improve glycemic control and prevent adipocyte remodeling in fructose-fed rats partly by suppressing the AGE-RAGE-mediated oxidative stress generation. AGE-aptamer might be a novel therapeutic strategy for fructose-induced metabolic derangements. [ABSTRACT FROM AUTHOR]

Presents information on a study which detected a type of adenovirus DNA and proteins in lung epithelial cells of patients with chronic obstructive pulmonary disease. Methodology and materials; Results; Conclusion.

Background: Although acute kidney injury (AKI) is associated with an increased risk of chronic kidney disease (CKD), the underlying mechanisms remain unclear. High mobility group box-1 (HMGB1), one of the ligands for the receptor for advanced glycation end products (RAGE), is elevated in patients with AKI. We recently demonstrated that the mineralocorticoid receptor (MR) is activated by the RAGE/Rac1 pathway, contributing to chronic renal damage in hypertensive mice. Therefore, this study investigated the role of the HMGB1/RAGE/MR pathway in AKI and progression to CKD., Methods: We performed a mouse model of renal ischemia-reperfusion (I/R) with or without MR antagonist (MRA). In vitro experiments were conducted using cultured endothelial cells to examine the interaction between the HMGB1/RAGE and Rac1/MR pathways., Results: In renal I/R injury mice, renal MR activation was associated with elevated serum HMGB1, renal RAGE, and activated Rac1, all of which were suppressed by MRA. Renal I/R injury led to renal dysfunction, tubulointerstitial injury, and increased expressions of inflammation and fibrosis mediators, which were ameliorated by MRA. In vitro, RAGE-aptamer or MRA inhibited HMGB1-induced Rac1/MR activation and upregulation of MCP-1 and NF-κB expressions. 7 days following I/R injury, renal I/R injury mice developed CKD, whereas MRA prevented renal injury progression and decreased mortality rate. Furthermore, in case of MRA treatment even after I/R injury, attenuated renal dysfunction compared to untreated mice was also observed., Conclusions: Our findings suggest that HMGB1 may play a crucial role in AKI and CKD development by activating the Rac1/MR pathway through interactions with RAGE., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology.)

An increase in the number of herpes zoster patients has been reported since universal varicella immunization was introduced, perhaps because of reduced opportunities for varicella patients to experience the natural booster effect caused by reexposure. We investigated recent trends of varicella zoster virus (VZV)-related central nervous system (CNS) infections at a university hospital in Japan. We enrolled patients with suspected CNS infection during 2013-2022 and tested cerebrospinal fluid samples by real-time PCR for DNA from 7 human herpesviruses. VZV DNA was the most commonly detected in 62 (10.2%) of 615 patients. Kulldorff's circular spatial scan statistics demonstrated a significant temporal cluster of patients with VZV-related CNS infections during 2019-2022 (p = 0.008). Among persons with such infections, the percentage with aseptic meningitis was significantly higher during 2019-2022 (86.8%), when the temporal cluster of cases occurred, than during 2013-2018 (50.0%) (p = 0.0029).

Background: Inspiratory muscle training (IMT) has preventive effects against postoperative pulmonary complications (PPCs) after upper abdominal surgery. However, its impact on diaphragmatic function has not been evaluated. This study investigated the effect of preoperative IMT on diaphragmatic excursion (DE) and prevention of PPCs for patients with esophageal cancer., Methods: This study was an unblinded, parallel, randomized controlled trial. Patients with thoracic or abdominal esophageal cancer scheduled for esophagectomy were randomized into the incentive spirometry (IS) or IMT group. During preoperative neoadjuvant chemotherapy, IS or IMT intervention was performed. The inspiratory resistance of the IMT group was consistently set at 50% maximal inspiratory pressure. The primary outcome was the amount of change in DE evaluated with ultrasonography, and the secondary outcome was the incidence of Clavien-Dindo grade II or higher PPCs., Results: This study recruited 42 patients. Among these patients 21 were randomized into the IS or IMT group, and 2 patients dropped out from the study. Finally, 40 patients were included in this analysis. The DE of the IMT group increased significantly after the intervention. The IMT group had significantly larger DE changes than the IS group. Of the 39 patients analyzed for postoperative outcome, 5 experienced grade II PPCs. The IMT group had a lower incidence of PPCs than the IS group., Conclusions: Patients with thoracic and abdominal esophageal cancer scheduled for surgery who had preoperative IMT have increased DE, which may have an important role in prevention of PPCs., (© 2024. Society of Surgical Oncology.)

Objective: Inspiratory muscle training (IMT) is used to improve inspiratory muscle strength in patients with COPD. However, the effect of IMT on diaphragmatic function has not yet been thoroughly evaluated. This study aimed to evaluate the effect of IMT on maximum diaphragmatic excursion (DE max ) using ultrasonography in patients with COPD., Methods: This was a single-centre, randomised, prospective, parallel-group, unblinded controlled trial involving 38 participants with stable COPD. Participants underwent a standardised 12-week pulmonary rehabilitation (PR) programme followed by a 12-week IMT programme, consisting of home-based IMT and low-frequency outpatient PR sessions supervised by physiotherapists (once every 2 weeks), versus low-frequency outpatient PR alone as a control. The DE max and exercise tolerance were measured., Results: Out of the 38 patients initially enrolled in the PR programme, 33 successfully completed it and were subsequently randomised to the IMT programme. Finally, 15 (94%) and 14 (88%) patients from the IMT and control groups, respectively, completed the study. Following the IMT programme, DE max increased in the IMT group (mean±sd 50.1±7.6 mm to 60.6±8.0 mm, p<0.001), but not in the control group (47.4±7.9 mm to 46.9±8.3 mm, p=0.10). Changes in DE max and exercise tolerance (peak oxygen uptake) were greater in the IMT group than in the control group (both p<0.01)., Conclusions: IMT following the PR programme improved DE max and exercise tolerance. Therefore, DE max may be an important outcome of IMT., Competing Interests: Conflict of interest: The authors have nothing to disclose., (Copyright ©The authors 2024.)

To elucidate the seroprevalence and rate of asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Japanese children, serological analysis was performed using serum samples collected from March 2020 to February 2023. A total of 1493 serum samples were collected during the first study period (March 2020 to February 2021). None of the serum samples was positive for SARS-CoV-2 antibody. In the second period (March 2021 to February 2022), seven of the 1055 patients (0.7%) experienced SARS-CoV-2 infection. The third period (March 2022 to February 2023) was divided into three terms: from March to June 30, 2022; from July to October 2022; and from November 2022 to February 2023. The seroprevalence gradually increased throughout this period, with rates of 6.0%, 18.6%, and 30.4% in the three terms, respectively. Pediatric cases of asymptomatic SARS-CoV-2 infection occurred after the surge of Omicron variants. Since none of the SARS-CoV-2 antibody-positive patients had a previous history of coronavirus disease 2019, the seroprevalence rate in this study may represent the rate of asymptomatic infection., (© 2024 Wiley Periodicals LLC.)

The live attenuated human rotavirus vaccine strain RIX4414 (Rotarix ® ) is used worldwide to prevent severe rotavirus-induced diarrhea in infants. This strain was attenuated through the cell culture passaging of its predecessor, human strain 89-12, which resulted in multiple genomic mutations. However, the specific molecular reasons underlying its attenuation have remained elusive, primarily due to the absence of a suitable reverse genetics system enabling precise genetic manipulations. Therefore, we first completed the sequencing of its genome and then developed a reverse genetics system for the authentic RIX4414 virus. Our experimental results demonstrate that the rescued recombinant RIX4414 virus exhibits biological characteristics similar to those of the parental RIX4414 virus, both in vitro and in vivo. This novel reverse genetics system provides a powerful tool for investigating the molecular basis of RIX4414 attenuation and may facilitate the rational design of safer and more effective human rotavirus vaccines.

Idiopathic pleuroparenchymal fibroelastosis (iPPFE) is a rare form of idiopathic interstitial pneumonia. We report a case of a patient with iPPFE in whom postural changes improved diaphragmatic excursion (DE) and exercise tolerance. Chest radiography showed a greater elevation of the diaphragm at maximum expiration in the supine position than the standing position. DE measured by ultrasonography was higher in the supine position than the standing position. The findings may suggest greater diaphragm movement in the supine position, leading to successful rehabilitation and improved exercise endurance. There is no effective treatment for iPPFE; therefore, an innovative treatment strategy is warranted., Competing Interests: No conflict., (© 2024 The Authors.)

Notably, certain nutrients are effective in preventing migraine. Nonetheless, zinc replacement therapy for migraine treatment has yet to be explored. We herein report four patients with migraine who were refractory to prophylactic therapy and whose headache frequency and severity improved with zinc supplementation. Zinc administration may be an option for treating patients with prophylaxis-refractory migraine. Further investigation is required to determine the efficacy of zinc replacement therapy as a treatment option for migraine.

Type 2 diabetes mellitus (T2DM) is a risk factor for male infertility, but the underlying molecular mechanisms remain unclear. Advanced glycation end products (AGEs) are pathogenic molecules for diabetic vascular complications. Here, we investigated the effects of the DNA aptamer raised against AGEs (AGE-Apt) on testicular and sperm abnormalities in a T2DM mouse model. KK-Ay (DM) and wild-type (non-DM) 4- and 7-week-old male mice were sacrificed to collect the testes and spermatozoa for immunofluorescence, RT-PCR, and histological analyses. DM and non-DM 7-week-old mice were subcutaneously infused with the AGE-Apt or control-aptamer for 6 weeks and were then sacrificed. Plasma glucose, testicular AGEs, and Rage gene expression in 4-week-old DM mice and plasma glucose, testicular AGEs, oxidative stress, and pro-inflammatory gene expressions in 7-week-old DM mice were higher than those in age-matched non-DM mice, the latter of which was associated with seminiferous tubular dilation. AGE-Apt did not affect glycemic parameters, but it inhibited seminiferous tubular dilation, reduced the number of testicular macrophages and apoptotic cells, and restored the decrease in sperm concentration, motility, and viability of 13-week-old DM mice. Our findings suggest that AGEs-Apt may improve sperm abnormality by suppressing AGE-RAGE-induced oxidative stress and inflammation in the testes of DM mice.

Background: Decreased respiratory muscle strength and muscle mass is key in diagnosing respiratory sarcopenia. However, the role of reduced diaphragm activity, expressed as the maximal level of diaphragmatic excursion (DEmax), in diagnosing respiratory sarcopenia in patients with chronic obstructive pulmonary disease (COPD) remains unclear. This study aimed to characterize patients with COPD and low DEmax and maximal inspiratory pressure (MIP), a measure of inspiratory muscle strength, and assess the role of DEmax in respiratory sarcopenia., Methods: Patients with COPD underwent spirometry, exercise tolerance (VO 2peak ) test, and MIP measurement. DEmax and sternocleidomastoid thickness at the maximal inspiratory level (TscmMIL) were assessed using ultrasound sonography., Results: Overall, 58 patients with COPD (median age, 76 years; median %FEV 1 , 51.3 %) were included, 28 of whom showed a %MIP of ≥80 %, defined as having preserved MIP. Based on the %MIP of 80 % and median value of DEmax (48.0 mm) as thresholds, the patients were stratified into four groups: both-high (n = 18), %MIP-alone low (n = 11), DEmax-alone low (n = 10), and both-low (n = 19) groups. The both-low group exhibited the lowest %FEV 1 , Δinspiratory capacity, VO 2peak , and TscmMIL, and these values were significantly lower than those of the both-high group. Except for %FEV 1 , these values were significantly lower in the both-low group than in the %MIP-alone low group despite adjusting DEmax level for body mass index., Conclusion: Measuring DEmax along with MIP can characterize patients with COPD, reduced exercise capacity, and decreased accessory respiratory muscle mass and can help diagnose respiratory sarcopenia., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

We encountered a previously healthy 3-year-old girl with interstitial pneumonitis that initially developed due to human adenovirus type 2 infection and exacerbated by primary human herpesvirus 7 infection. A comprehensive serum biomarker analysis showed patterns that differed by viral infection, suggesting that respiratory and lymphotropic viral infections might have different pathophysiology in interstitial pneumonitis., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This study aimed to investigate the association between the level of tissue oxygen saturation (StO 2 ) and quadriceps/skeletal muscle dysfunction, measured using the Medical Research Council (MRC) scale and ultrasonography, in critically ill patients. Thirty-four patients hospitalized at the Critical Care Medicine Center of Kindai University Hospital, between January 2022 and March 2023, were enrolled in this study. The StO 2 of the quadriceps muscle was measured via near-infrared spectroscopy. Muscle atrophy was measured by the thickness, cross-sectional area (CSA), and echo intensity of the rectus femoris (RF). These values were evaluated every alternate day until 13 days after admission or until discharge, whichever occurred first. Muscle weakness was assessed using the sum score of the MRC scale (MRC-SS), with the patient sitting at bedside. The mean age of the patients was 67.3 ± 15.3 years, and 20 (59%) were men. Seven patients (21%) were admitted for trauma, and 27 (79%) were admitted for medical emergencies or others. The mean score for the MRC-SS was 51.0 ± 7.9 points. RF thickness and CSA significantly decreased after day 7 (p < 0.05). There were no significant changes in StO 2 levels during hospitalization. However, there were positive correlations between the nadir StO 2 during hospitalization and MRC-SS, and changes in RF thickness and CSA at discharge (r = 0.41, p = 0.03; r = 0.37, p = 0.03; and r = 0.35, p = 0.05, respectively). StO 2 in the quadriceps muscle may be useful for predicting muscle atrophy and dysfunction in patients with critical illnesses., (© 2024. The Author(s).)

We have developed DNA aptamers that can inhibit the toxic effects of advanced glycation end products (AGE-Apts). We herein evaluated the effects of AGE-Apts on muscle mass and strength in senescence-accelerated mouse prone 8 (SAMP8) mice. Eight-month-old male SAMP8 mice received subcutaneous infusion of control DNA aptamers (CTR-Apts) or AGE-Apts. Mice in an age-matched senescence-accelerated mouse resistant strain 1 (SAMR1) group were treated with CTR-Apts as controls. The soleus muscles were collected after the 8-week intervention for weight measurement and histological, RT-PCR, and immunofluorescence analyses. Grip strength was measured before and after the 8-week intervention. AGE-Apt treatment inhibited the progressive decrease in the grip strength of SAMP8 mice. SAMP8 mice had lower soleus muscle weight and fiber size than SAMR1 mice, which was partly restored by AGE-Apt treatment. Furthermore, AGE-Apt-treated SAMP8 mice had a lower interstitial fibrosis area of the soleus muscle than CTR-Apt-treated SAMP8 mice. The soleus muscle levels of AGEs, oxidative stress, receptor for AGEs, and muscle ring-finger protein-1 were increased in the CTR-Apt-treated mice, all of which, except for AGEs, were inhibited by AGE-Apt treatment. Our present findings suggest that the subcutaneous delivery of AGE-Apts may be a novel therapeutic strategy for aging-related decrease in skeletal muscle mass and strength.

The low attenuation area percentage (LAA%) is gaining popularity. LAA% is an index of quantitative emphysema on computed tomography (CT) imaging of the chest. This study aims to retrospectively investigate whether preoperative LAA% is associated with postoperative prognosis in patients with esophageal cancer who were scheduled for esophagectomy. From January 2016 to March 2020, 105 patients with esophageal cancer underwent esophagectomy via right thoracotomy and neoadjuvant chemotherapy. A Synapse Vincent volume analyzer (Fujifilm Medical, Tokyo, Japan) was used for measurement. The software automatically quantified LAA% using a threshold of less than - 950 Hounsfield units on CT images of lung regions. Cox proportional hazard analyses were performed in univariable and multivariable forms. Estimates of the receiver operating curve are used to determine the cutoff value for death of LAA%, and the binary value is then inserted into Cox proportional hazard analyses. The preoperative LAA% cutoff value was ≥ 6.3%. Patients with a preoperative LAA% ≥6.3% had a significantly worse prognosis than those with a preoperative LAA% of < 6.3%. LAA% ≥6.3% (hazard ratio: 6.76; 95% confidence interval: 2.56-17.90, P < .001) was the most influential preoperative factor for overall survival after esophagectomy in multivariate Cox proportional hazard analyses. LAA% is one of the preoperative risk factors for survival after esophagectomy and an indicator of lung condition using routinely performed preoperative CT images. We quantified the extent of preoperative emphysema in patients with esophageal cancer, who were scheduled for surgery, and for the first time, reported LAA% as one of the preoperative risk factors for survival after esophagectomy., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Intestinal rotavirus (RV) vaccine replication and host immune response are suggested to be affected by several factors, including maternal antibodies, breastfeeding history, and gut microbiome, which are thought to be similar in pairs of twins. The aim of this study was to determine whether viral shedding from the fecal RV vaccine strain Rotarix ® (RV1) and IgG and IgA responses to RV show similarity in pairs of twins., Methods: Quantitative reverse transcription polymerase chain reaction specific to RV vaccine strain RV1 was used to monitor fecal RV1 viral shedding. RV IgG and IgA titers were measured using an in-house enzyme-linked immunosorbent assay. Fecal RV1 viral shedding and immune responses were compared between twins and singletons with mixed effects and fixed effects models., Results: A total of 347 stool and 54 blood samples were collected from four pairs of twins and twelve singletons during the observation period. Although the kinetics of fecal RV1 viral shedding and immune responses differed among vaccinated individuals, they appeared to be similar within twin pairs. RV shedding after the first dose ( P =0.049) and RV IgG titers during the entire observation period ( P =0.015) had a significantly better fit in the fixed effect model that assumed that twins have the same response versus the model that assumed that twins have a different response., Conclusions: The similarity of RV vaccine viral replication in intestine and host immune responses in twin pairs was demonstrated using statistical analysis., Competing Interests: The authors have no conflicts of interest directly relevant to the content of this article.

Nonpharmaceutical interventions (NPIs) to control COVID-19 have decreased the incidence of many pediatric infectious diseases. The epidemiology of β- and γ-herpesvirus infections might have been affected by NPIs. The aim of this study was to elucidate changes in trends in β- and γ-herpesvirus infections and complex febrile seizures (cFS) of viral etiology before and during the COVID-19 pandemic. Between April 2017 and March 2021, febrile children aged ≤5 years were enrolled. Detection of EBV, CMV, HHV-6B, and HHV-7 DNA in serum was performed using real-time PCR. The epidemiology of viral infections and cFS were compared between the prepandemic and pandemic periods. During the observation period, 1432 serum samples were collected. The mean number of febrile children decreased during the pandemic period, but the number of patients with HHV-6B infection increased from 35 (9.3% of all febrile children) per year before the pandemic to 43 (15.5%) during the pandemic. The change in the proportion of patients with primary HHV-6B infection was 6.50% (95% confidence interval [CI], 2.05%-11.3%; p = 0.0047). The mean number of patients with cFS decreased during the pandemic period, but the number of patients with HHV-6B-associated cFS was stable throughout the observation period. Therefore, the change in proportion of patients with cFS caused by primary HHV-6B infection was 49.5% (95% CI, 12.2%-60.5%; p = 0.0048). The disease burden of primary HHV-6B infection among patients in the emergency room remained unchanged, with a significant increase in the relative proportion after the COVID-19 pandemic began., (© 2023 Wiley Periodicals LLC.)

Background and Objective: Dynamic lung hyperinflation (DLH) can play a central role in exertional dyspnoea in patients with COPD. Chest radiography is the basic tool for assessing static lung hyperinflation in COPD. However, the predictive capacity of DLH using chest radiography remains unknown. This study was conducted to determine whether DLH can be predicted by measuring the height of the right diaphragm (dome height) on chest radiography., Methods: This single-centre, retrospective cohort study included patients with stable COPD with pulmonary function test, cardiopulmonary exercise test, constant load test and pulmonary images. They were divided into two groups according to the median of changes of inspiratory capacity (ΔIC=IC lowest - IC at rest). The right diaphragm dome height and lung height were measured on plain chest radiography., Results: Of the 48 patients included, 24 were classified as having higher DLH (ΔIC ≤-0.59 L from rest; -0.59 L, median of all) and 24 as having lower DLH. Dome height correlated with ΔIC (r=0.66, p<0.001). Multivariate analysis revealed that dome height was associated with higher DLH independent of % low attenuation area on chest computed tomography and forced expiratory volume in 1 s (FEV 1 ) % predicted. Furthermore, the area under the receiver operating characteristic curve of dome height to predict higher DLH was 0.86, with sensitivity and specificity of 83% and 75%, respectively, at a cut-off of 20.5 mm. Lung height was unrelated to ΔIC., Conclusion: Diaphragm dome height on chest radiography may adequately predict higher DLH in patients with COPD., Competing Interests: Conflict of interest: None declared., (Copyright ©The authors 2023.)

Objectives: To establish a point-of-care test for coronavirus disease 2019 (COVID-19), we developed a dry loop-mediated isothermal amplification (LAMP) method to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA., Methods: We carried out reverse transcription (RT)-LAMP using the Loopamp SARS-CoV-2 Detection kit (Eiken Chemical, Tokyo, Japan). The entire mixture, except for the primers, is dried and immobilized inside the tube lid., Results: To determine the specificity of the kit, 22 viruses associated with respiratory infections, including SARS-CoV-2, were tested. The sensitivity of this assay, determined by either a real-time turbidity assay or colorimetric change of the reaction mixture, as evaluated by the naked eye or under illumination with ultraviolet light, was 10 copies/reaction. No LAMP product was detected in reactions performed with RNA from any pathogens other than SARS-CoV-2. After completing an initial validation analysis, we analyzed 24 nasopharyngeal swab specimens collected from patients suspected to have COVID-19. Of the 24 samples, 19 (79.2%) were determined by real-time RT-PCR analysis as being positive for SARS-CoV-2 RNA. Using the Loopamp SARS-CoV-2 Detection kit, we detected SARS-CoV-2 RNA in 15 (62.5%) of the 24 samples. Thus, the sensitivity, specificity, positive predictive value, and negative predictive values of the Loopamp 2019-CoV-2 detection reagent kit were 78.9%, 100%, 100%, and 55.6%, respectively., Conclusions: The dry LAMP method for detecting SARS-CoV-2 RNA is fast and easy to use, and its reagents can be stored at 4°C, solving the cold chain problem; thus, it represents a promising tool for COVID-19 diagnosis in developing countries., Competing Interests: All authors declare no conflict of interest with regard to this work.

Objectives: Fetal human cytomegalovirus (HCMV) infection might be involved in fetal growth restriction (FGR). Maternal serostatus and the prevalence of congenital HCMV infection are affected by various factors, such as socioeconomic status and ethnicity. Therefore, the prevalence of congenital HCMV-related FGR should be examined in each region., Methods: Seventy-eight cases of FGR with delivery between January 2012 and January 2017 at Fujita Health University Hospital were studied. Twenty-one non-FGR cases were also included as a control group. Placental sections obtained from the FGR and control cases were immunostained with two primary antibodies for detecting immediate early antigens., Results: Nineteen placental samples from FGR cases with another etiology were excluded. Finally, 59 placental samples from FGR cases of unknown etiology were included in the pathological analysis. Four of 59 (6.8%) placental samples were positive for HCMV antigen. All four positive cases were stained with the M0854 antibody, and there were no positive case with the MAB810R antibody. Neither maternal nor infantile clinical features were different between the HCMV-positive and -negative FGR cases. A pathological examination showed a hematoma in three of four cases and infarction in two of four cases., Conclusions: HCMV antigen was detected in 6.8% of placental samples obtained from FGR cases without an obvious etiology. No remarkable maternal or neonatal clinical features discriminated HCMV-related FGR from FGR due to other causes. Vasculitis and inflammation might play important roles in the pathogenesis of HCMV-related FGR., Competing Interests: The authors have no conflicts of interest relevant to this article to disclose. This work was supported by the Japan Agency for Medical Research and Development (AMED) (Grant number: 20gk0110037s0302).

SMTP-44D has been reported to have anti-oxidative and anti-inflammatory reactions, including reduced expression of receptor for advanced glycation end products (RAGE) in experimental diabetic neuropathy. Although activation of RAGE with its ligands, and advanced glycation end products (AGEs), play a crucial role in atherosclerotic cardiovascular disease, a leading cause of death in diabetic patients, it remains unclear whether SMTP-44D could inhibit experimental atherosclerosis by suppressing the AGEs-RAGE axis. In this study, we investigated the effects of SMTP-44D on atherosclerotic plaque formation and expression of AGEs in apolipoprotein-E null ( Apoe -/- ) mice. We further studied here whether and how SMTP-44D inhibited foam cell formation of macrophages isolated from Apoe -/- mice ex vivo. Although administration of SMTP-44D to Apoe -/- mice did not affect clinical or biochemical parameters, it significantly decreased the surface area of atherosclerotic lesions and reduced the atheromatous plaque size, macrophage infiltration, and AGEs accumulation in the aortic roots. SMTP-44D bound to immobilized RAGE and subsequently attenuated the interaction of AGEs with RAGE in vitro. Furthermore, foam cell formation evaluated by Dil-oxidized low-density lipoprotein (ox-LDL) uptake, and gene expression of RAGE, cyclin-dependent kinase 5 ( Cdk5 ) and CD36 in macrophages isolated from SMTP-44D-treated Apoe -/- mice were significantly decreased compared with those from saline-treated mice. Gene expression levels of RAGE and Cdk5 were highly correlated with each other, the latter of which was also positively associated with that of CD36 . The present study suggests that SMTP-44D may inhibit atherosclerotic plaque formation in Apoe -/- mice partly by blocking the AGEs-RAGE-induced ox-LDL uptake into macrophages via the suppression of Cdk5-CD36 pathway.

In the era of universal varicella vaccination, diagnosis of varicella is challenging, especially for breakthrough cases. We sought to clarify the reliability of direct varicella-zoster virus (VZV) loop-mediated isothermal amplification (LAMP) and DermaQuick® VZV using the immunochromatography technique as rapid diagnostic tests for varicella. In addition, the usefulness of saliva as a sample type for direct LAMP was investigated. Among the 46 enrolled patients with suspected VZV infection, 31 patients (67.3%) were positive for the nucleic acid test based on real-time PCR from skin swab samples. Direct LAMP of skin swabs was positive in 29 (63.0%) of 46 patients. DermaQuick® VZV was positive in 25 (54.3%) of 46 patients. VZV DNA was detected in only 48.4% of oral swabs with the direct LAMP method. With real-time polymerase chain reaction (PCR) as the standard for diagnosing varicella, the sensitivity and specificity of DermaQuick® VZV were 80.7% and 100%, respectively. The sensitivity and specificity of direct LAMP from skin swabs were 93.6% and 100%, respectively. The sensitivity and specificity of real-time PCR for DNA extracted from oral swabs were 74.2% and 93.3%, respectively. Thus, oral swab samples are not suitable for breakthrough varicella diagnosis. Although DermaQuick® VZV is considered the most convenient point-of-care test for varicella, its sensitivity and specificity were lower than those of direct VZV LAMP., (© 2023 Wiley Periodicals LLC.)

Background: Patients with chronic obstructive pulmonary disease (COPD) have difficulties inhaling as the diaphragm becomes flattened and weakened due to lung hyperinflation. This weakened respiratory function is compensated for by the increased activity of the accessory respiratory muscles, such as the sternocleidomastoid muscle (SCM)., Objectives: This study aimed to evaluate the difference in the SCM thickening fraction (SCM TF) of each respiratory phase (end-expiration, resting inspiration, and end-inspiration), as measured using ultrasonography (US), between patients with COPD and control subjects. We also evaluate the correlation between the SCM TF of each respiratory phase and exercise tolerance in patients with COPD., Methods: Patients with COPD (n = 44) and age-matched controls (n = 20) underwent US for determination of the SCM TF. Ventilation parameters, including the peak oxygen uptake (peak VO2) and the change in the inspiratory capacity, were measured during cardiopulmonary exercise testing. The SCM thickness and TF was measured during end-expiration, resting breathing, and end-inspiration., Results: The SCM was significantly thinner in patients with COPD than in controls at end-expiration. The increase in the SCM TF from end-expiration to end-inspiration in patients with COPD did not differ significantly from that in control subjects. In contrast, the SCM TF from end-expiration to resting inspiration was significantly greater in patients with COPD than in control subjects. The peak VO2 was strongly positively correlated with the SCM TF from end-expiration to end-inspiration in patients with COPD (r = 0.71, p < 0.01)., Conclusions: The SCM may be thinner in patients with COPD than in controls. The SCM TF may also be associated with exercise tolerance., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Rotavirus (RV) is a leading cause of gastroenteritis in children. In Japan, Rotarix (RV1; GlaxoSmithKline), which is a monovalent vaccine derived from human RV (G1P[8]), has been introduced since November 2011, and RotaTeq (RV5; MSD) which is an pentavalent, human-bovine mono-reassortant vaccine (G1, G2, G3, G4, and P1A[8]), has been introduced since July 2012. Long-term follow-up on vaccine efficacy and RV genotypical change should be carried out in order to control RV infection. The RV gastroenteritis (RVGE) outbreak occurred during the 2018/2019 season in Aichi prefecture, Japan. Therefore, the molecular epidemiology of RV among three different groups of RVGE, which were outpatients who received RV1, those who received RV5, and those without vaccination, was explored. Clinical features of RVGE patients were compared among the three patient groups. Children less than 15 years of age with gastroenteritis who visited any of seven pediatric practices between January and June 2019 were enrolled in the study. G, P, and E genotypes were determined by direct sequencing of reverse transcription-polymerase chain reaction products amplified from stool samples. Among 110 patients, there were 27, 28, and 55 in the RV1-vaccinated, RV5-vaccinated, and unvaccinated groups, respectively. The most frequent genotype was G8P[8] (92/110 patients, 83.6%). Genotype distributions did not significantly differ among the three patient groups ( P  = .125). Mean Vesikari score was significantly lower among RV1-vaccinated (7.1) and RV5-vaccinated patients (6.4) than among unvaccinated patients (10.2) ( P  < .001). Even in RVGE patients treated in an outpatient clinic, RV vaccine reduced the severity of the disease in this cohort.

Competing Interests: The authors have no conflicts of interest.

We analyzed serially collected serum samples from healthy adults who underwent BNT162b2 vaccination to elucidate the association between spike (S)-IgG antibody titers determined by ELISA using the WHO international standard (NIBSC code 20/136) and neutralizing antibody titers against three live SARS-CoV-2 variants. This study included 53 health care workers who received two doses of the BNT162b2 vaccine. S-IgG and nucleocapsid (N)-IgG antibody titers were measured by ELISA. Neutralizing (NT) antibody responses against three variants (Wuhan D614 G: KUH003, Alpha, and Delta) were evaluated before and after the first and second vaccination. N -IgG were not detected in any serum samples. S-IgG antibody titers remarkably increased after two BNT162b2 vaccine doses in all participants. S-IgG antibody titers were strongly correlated with NT titers against three variants of live viruses: KUH003 (r = 0.86), Alpha (r = 0.72), and Delta (r = 0.84). Serum samples from participants after one dose of BNT162b2 neutralized Alpha efficiently (median titer, 113.0), but median NT titers against KUH003 and Delta variants were lower, 57.0 and 28.0, respectively ( p  < .01). Two doses of the BNT162b2 vaccine elicited a strong immune response in this study. The second dose was required for induction of a strong booster effect. Serum collected from BNT162b2 vaccine recipients contained significantly lower neutralizing activity against Delta than that of against KUH003 ( p  < .0001) and Alpha ( p  < .0001). If a new variant emerges, live virus-based NT titers should be examined in serum obtained from vaccine recipients to evaluate vaccine efficacy for protection against infection.