Active vitamin D analog and SARS-CoV-2 IgG after BNT162b2 vaccination in patients with hemodialysis.

INTRODUCTION: Vaccination is the effective strategy for coronavirus disease 2019 (COVID-19). However, few studies have investigated the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin (Ig)G and vitamin D. METHODS: This study aimed to investigate the association between SARS-CoV-2 IgG and active vitamin D analogs in hemodialysis patients. Blood samples were collected four times: before vaccination and 30, 60, and 90 days after vaccination, BNT162b2 (Pfizer©). RESULTS: A total of 418 patients were enrolled. The mean age was 71.1 ± 12 years. Almost two thirds of the patients were prescribed active vitamin D analogs. The distribution of SARS-CoV-2 IgG before vaccination was 235 (93-454) AU/mL. After multiple regression analyses, active vitamin D analog use was found to be associated with higher SARS-CoV-2 IgG levels from prevaccination to 90 days postvaccination. CONCLUSION: This study demonstrated an association between higher SARS-CoV-2 IgG and active vitamin D analog use in hemodialysis patients. CLINICAL TRIAL REGISTRATION: The study information was registered in the UMIN-CTR (UMIN 000046906).

Shielding device for endoscopic procedures during lower gastrointestinal endoscopy.

Objectives: The coronavirus pandemic significantly impacted endoscopic practice. During lower gastrointestinal endoscopy, infectious substances disseminate; therefore, we developed an infection control device (STEP-L) for lower gastrointestinal endoscopy and examined its usefulness. Methods: STEP-L wraps around the patient's buttocks and covers the endoscope. Using lower endoscopy training models, three endoscopists performed 18 colonoscopies with STEP-L (group S) and without (group C). Endoscopic insertion time and pigmented areas of ​​gloves and diapers after the examination were compared between both groups. Results: Insertion of the endoscope up to the cecum was possible in all 18 examinations. The insertion time to the cecum was 52.4 ± 19.0 s in group S and 53.9 ± 13.3 s in group C. The pigmented areas of the ​​gloves measured 39,108.0 ± 16,155.3 pixels in group C, but were significantly reduced to 2610.5 ± 4333.8 pixels in group S (p < 0.05). The pigmented areas of the diapers measured 2280.9 ± 3285.2 pixels in group C, but were significantly reduced to 138.0 ± 82.9 pixels in group S (p < 0.05). Conclusions: Using STEP-L does not change the insertion time, and is technically feasible. STEP-L significantly reduces the adhesion of virtual pollutants to the surroundings, suggesting that this device is useful for infection control during lower gastrointestinal endoscopy.

Development of protective equipment for endoscopic treatment and surgery in otorhinolaryngology.

OBJECTIVE: The coronavirus disease pandemic has raised concerns regarding the transmission of infections to healthcare workers. We developed a new protective device to reduce the risk of aerosol diffusion and droplet infection among healthcare workers. Here, we report the results of a theoretical evaluation of the efficacy of this device. METHODS: We used suction-capable masks with and without rubber slits, sleeves for the insertion section of endoscopes and treatment tools, and a cover for the control section of the endoscope. To simulate droplet spread from patients, we created a droplet simulation model and an aerosol simulation model. The results with and without the devices attached and with and without the suction were compared. RESULTS: The droplet simulation model showed a 95% reduction in droplets with masks with rubber slits; furthermore, a reduction of 100% was observed when the insertion sleeve was used. Evaluation of aerosol simulation when suction was applied revealed an aerosol reduction of 98% and >99% with the use of the mask without rubber slits and with the combined use of the mask and insertion sleeve, respectively. The elimination of droplet emission upon instrument removal confirmed that the instrument sleeve prevented the diffusion of droplets. The elimination of droplets upon repeated pressing of the suction button confirmed that the cover prevented the diffusion of droplets. CONCLUSION: We developed a device for infection control, in collaboration with a gastrointestinal endoscopist and Olympus Medical Systems Corporation, that was effective in reducing droplet and aerosol diffusion in this initial theoretical assessment.

Caveolin-1 negatively regulates a metalloprotease-dependent epidermal growth factor receptor transactivation by angiotensin II.

A metalloprotease, ADAM17, mediates the generation of mature ligands for the epidermal growth factor receptor (EGFR). This is the key signaling step by which angiotensin II (AngII) induces EGFR transactivation leading to hypertrophy and migration of vascular smooth muscle cells (VSMCs). However, the regulatory mechanism of ADAM17 activity remains largely unclear. Here we hypothesized that caveolin-1 (Cav1), the major structural protein of a caveolae, a membrane microdomain, is involved in the regulation of ADAM17. In cultured VSMCs, infection of adenovirus encoding Cav1 markedly inhibited AngII-induced EGFR ligand shedding, EGFR transactivation, ERK activation, hypertrophy and migration, but not intracellular Ca(2+) elevation. Methyl-ß-cyclodextrin and filipin, reagents that disrupt raft structure, both stimulated an EGFR ligand shedding and EGFR transactivation in VSMCs. In addition, non-detergent sucrose gradient membrane fractionations revealed that ADAM17 cofractionated with Cav1 in lipid rafts. These results suggest that lipid rafts and perhaps caveolae provide a negative regulatory environment for EGFR transactivation linked to vascular remodeling induced by AngII. These novel findings may provide important information to target cardiovascular diseases under the enhanced renin angiotensin system.

Possibility of new shielding device for upper gastrointestinal endoscopy.

Background and study aims Infection control is essential when performing endoscopic procedures, especially during the COVID-19 pandemic. Therefore, we have developed a new shielding device called STEP for infection control in upper gastrointestinal endoscopy. Patients and methods STEP consists of a mask worn by the patient and a drape that is connected to the mask and covers the endoscope. A suction tube attached to the mask prevents aerosols from spreading. The endoscopist operates the endoscope through the drape. Three endoscopists performed a total of 18 examinations using an upper endoscopy training model with and without STEP. Endoscopic images were evaluated by three other endoscopists, using a visual analog scale. We also simulated contact, droplet, and aerosol infection and evaluated the utility of STEP. Results All examinations were conducted without a problem. Mean procedure time was 126.3 ±â€Š11.6 seconds with STEP and 122.3 ±â€Š10.0 seconds without STEP. The mean visual analog score was 90.7 ±â€Š10.1 with STEP and 90.4 ±â€Š10.0 without STEP. In the contact model, adherence of simulated contaminants was 4.9 ±â€Š1.4 % without STEP and 0 % with STEP. In the droplet model, the number of simulated contaminants attached to the paper was 338 273 ±â€Š90 735 pixels without STEP and 0 with STEP. In the aerosol model, the total number of particles was 346 837 ±â€Š9485 without STEP and was significantly reduced to 222 ±â€Š174 with STEP. Conclusions No effect on examination time or endoscopic image quality was observed when using STEP in upper gastrointestinal endoscopy. Using STEP reduced the diffusion of simulated contaminants in all three infection models.

Endothelial nitric oxide synthase inhibits G12/13 and rho-kinase activated by the angiotensin II type-1 receptor: implication in vascular migration.

BACKGROUND: Although, endothelial nitric oxide (NO) synthase (eNOS) is believed to antagonize vascular remodeling induced by the angiotensin II (AngII) type-1 receptor, the exact signaling mechanism remains unclear. METHODS AND RESULTS: By expressing eNOS to vascular smooth muscle cells (VSMCs) via adenovirus, we investigated a signal transduction mechanism of the eNOS gene transfer in preventing vascular remodeling induced by AngII. We found marked inhibition of AngII-induced Rho/Rho-kinase activation and subsequent VSMC migration by eNOS gene transfer whereas G(q)-dependent transactivation of the epidermal growth factor receptor by AngII remains intact. This could be explained by the specific inhibition of G(12/13) activation by eNOS-mediated G(12/13) phosphorylation. CONCLUSIONS: The eNOS/NO cascade specifically targets the Rho/Rho-kinase system via inhibition of G(12/13) to prevent vascular migration induced by AngII, representing a novel signal cross-talk in cardiovascular protection by NO.

GH-releasing peptide-2 does not stimulate arginine vasopressin secretion in healthy men.

Ghrelin has a stimulating effect on arginine vasopressin (AVP). However, it is not known whether GHRP-2, a synthetic ghrelin receptor agonist, also has a stimulating effect on AVP release in men. To determine whether the GHRP-2 test is useful for assessing AVP secretion, blood ACTH, GH, FSH, LH, PRL, TSH and AVP levels, as well as glucose, osmolality, sodium and hematocrit, were measured before and 15, 30, 45 and 60 min after an intravenous bolus of 100 microg GHRP-2 in 10 healthy men with and without fasting. Blood pressure was measured at 15-min intervals. AVP secretion was not stimulated by the GHRP-2 test with and without fasting. There were no significant differences in hematocrit, blood pressure and plasma osmolality before and after GFRP-2 injection, although significant (p<0.001) peak blood GH, and ACTH and PRL levels were observed 30 and 15 min after GHRP-2 injection with and without fasting, respectively, and the maximal peaks were significantly (p<0.05) higher with fasting than without fasting. These results suggest that AVP secretion is not stimulated by the GHRP-2 test both with and without fasting, though GH, ACTH and PRL levels were higher with than without fasting.

Dysfunction of the ER chaperone BiP accelerates the renal tubular injury.

Tubular-interstitial injury plays a key role in the progression of chronic kidney disease. Although endoplasmic reticulum (ER) stress plays significant roles in the development of chronic diseases such as neurodegenerative disease, cardiomyopathy and diabetes mellitus, its pathophysiological role in chronic renal tubular cell injury remains unknown. BiP is an essential chaperone molecule that helps with proper protein folding in the ER. Recently, we have produced a knock-in mouse that expresses a mutant-BiP in which the retrieval sequence to the ER is deleted in order to elucidate physiological processes that are sensitive to ER functions in adulthood. The heterozygous mutant-BiP mice showed significant tubular-interstitial lesions with aging. Furthermore, proteinuria induced by chronic protein overload accelerated the tubular-interstitial lesions in the mutant mice, accompanying caspase-12 activation and tubular cell apoptosis. These results suggest that the ER stress pathway is significantly involved in the pathophysiology of chronic renal tubular-interstitial injury in vivo.

Detection of tobacco smoke emanating from human skin surface of smokers employing passive flux sampler - GCMS system.

Cigarette smoking is a significant risk factor for higher incidences of numerous adverse health consequences. Related health disorders are also found in non-smokers exposed to secondhand smoke (SHS). To investigate the influence of cigarette smoking and exposure to SHS on the composition of human skin gas, a trace biogas emanating from human skin, dermal emissions of volatile compounds were semi-quantitatively measured for volunteers who smoke a cigarette and those exposed to SHS. This was performed using a passive flux sampler (PFS) coupled with gas chromatography mass spectrometry (GCMS). Numerous chemicals were detected, including acetaldehyde, toluene, 3-methyl furan (3-MF), 2,5-dimethyl furan (2,5-DMF), 3-ethenyl pyridine (3-EP), and nicotine, in the samples collected from the smokers after a smoking event, and a remarkable increase in the amount of chemicals collected was observed just after smoking. These chemicals were also found in the samples collected from volunteers exposed to SHS. Assessment of current smoking status is important for managing the negative effects of active and passive smoking, and for the development of public health policy. The tobacco specific chemicals such as 3-MF, 2,5-DMF, 3-EP, and nicotine, emanating from human skin surfaces, represent a potential non-invasive biomarker for monitoring current smoking status of active and passive smokers after establishing a more quantitative procedure.

Correction: The different pathogenesis of sporadic adenoma and adenocarcinoma in non-ampullary lesions of the proximal and distal duodenum.

[This corrects the article DOI: 10.18632/oncotarget.17051.].

Investigation of the influence of cell density of human fibroblasts cryopreserved inside collagen sponges at various cooling rates.

The influence of cell density of cells cryopreserved inside a collagen matrix at various cooling rates was investigated. Human fibroblasts were three-dimensionally cultured for 2 days in a collagen sponge (20 mm in diameter and 1 mm in thickness) as an extracellular matrix to imitate biological tissue (artificial tissue). Different cell densities for the artificial tissue were used, from 10(5) to 10(7) cells/cm(3). Four artificial tissues were first stacked in a test chamber, frozen at a cooling rate of 0.3 to 50 degrees C/min in a solution of Dulbecco's Modified Eagle Medium, 20% fetal bovine serum and 10% dimethylsulfoxide, kept frozen below -185 degrees C for 2 hours, and then finally thawed. Membrane integrity of fibroblasts using a trypan blue exclusion assay was evaluated as an index for post-thaw cellular viability. Results show that with increasing cell density, the post-thaw membrane integrity decreased. Therefore, in the cryopreservation of biological tissue, it seems high cell density is one factor which causes a decline in viability.

Simultaneous and multi-point measurement of ammonia emanating from human skin surface for the estimation of whole body dermal emission rate.

Ammonia is one of the members of odor gases and a possible source of odor in indoor environment. However, little has been known on the actual emission rate of ammonia from the human skin surface. Then, this study aimed to estimate the whole-body dermal emission rate of ammonia by simultaneous and multi-point measurement of emission fluxes of ammonia employing a passive flux sampler - ion chromatography system. Firstly, the emission fluxes of ammonia were non-invasively measured for ten volunteers at 13 sampling positions set in 13 anatomical regions classified by Kurazumi et al. The measured emission fluxes were then converted to partial emission rates using the surface body areas estimated by weights and heights of volunteers and partial rates of 13 body regions. Subsequent summation of the partial emission rates provided the whole body dermal emission rate of ammonia. The results ranged from 2.9 to 12mgh-1 with an average of 5.9±3.2mgh-1 per person for the ten healthy young volunteers. The values were much greater than those from human breath, and thus the dermal emission of ammonia was found more significant odor source than the breath exhalation in indoor environment.

The different pathogeneses of sporadic adenoma and adenocarcinoma in non-ampullary lesions of the proximal and distal duodenum.

Non-ampullary duodenal adenoma with activation of Wnt/ß-catenin signalling is common in familial adenomatous polyposis (FAP) patients, whereas sporadic non-ampullary adenoma is uncommon. The adenoma-carcinoma sequence similar to colon cancer is associated with duodenal tumors in FAP, but not always in sporadic tumors. We obtained 37 non-ampullary duodenal tumors, including 25 adenomas and 12 adenocarcinomas, were obtained from biopsies and endoscopic resections. We performed immunohistochemistry for ß-catenin, the hallmark of Wnt activation, and aldehyde dehydrogenase 1 (ALDH1), a putative cancer stem cell marker. In non-ampullary lesions, abnormal nuclear localization of ß-catenin was observed in 21 (84.0%) of 25 adenomas and 4 (33.3%) of 12 adenocarcinomas. In the proximal duodenum, nuclear ß-catenin was less frequent in both adenomas and adenocarcinomas. Gastric duodenal metaplasia (GDM) was observed only in the proximal duodenum. All adenomas with GDM were the gastric foveolar and pyloric gland types, and showed only membranous ß-catenin. The intestinal-type adenomas had nuclear ß-catenin in the proximal and distal duodenum. ALDH1-positive cells were more frequent in adenocarcinomas than adenomas. Nuclear ß-catenin accumulation frequently occurred in ALDH1-positive cells in adenoma, but not in adenocarcinoma. In the non-ampullary proximal duodenum, Wnt/ß-catenin pathway activation was more closely associated with adenomas than adenocarcinomas, and while it might cooperate with ALDH1 in adenoma, it does not in adenocarcinoma. The pathogenesis thus may differ between sporadic adenoma and adenocarcinoma of non-ampullary duodenal lesions, especially in the proximal and distal duodenum.

Measurement of 2-nonenal and diacetyl emanating from human skin surface employing passive flux sampler-GCMS system.

It is commonly said elderly persons have a characteristic body odor, and, at present, two chemical compounds have been found to vary with age in male Japanese: 2-nonenal and diacetyl. To investigate dermal emission flux of the ageing odor related compounds, we have developed a non-invasive sampling device based on a concept of passive flux sampler (PFS). The sampler was placed on the skin surface to create a headspace, and the gases emanating from skin moved toward a disk-type adsorbent. The trapped gases were then extracted with dichloromethane and determined by GCMS. The PFS was practically applied to healthy volunteers covering a wide range of age. Since emission fluxes of both compounds remarkably varied with sampling position, the nape of the neck was fixed as regular sampling position where there are dense networks of both sebaceous and eccrine glands which are potential sources of both compounds. The emission flux of 2-nonenal increased with age for both male and female volunteers, whilst the flux of diacetyl showed highest in 30s and decreased over 40s. Although diacetyl has been known as a middle-aged male odor, this study showed the odor caused by diacetyl was not specific to male.

Histopathological analysis of spontaneous large necrosis of adrenal pheochromocytoma manifested as acute attacks of alternating hypertension and hypotension: a case report.

BACKGROUND: Pheochromocytomas are rare catecholamine-producing neuroendocrine tumors. Hypertension secondary to pheochromocytoma is often paroxysmal, and patients occasionally present with sudden attacks of alternating hypertension and hypotension. Spontaneous, extensive necrosis within the tumor that is associated with catecholamine crisis is an infrequent complication of adrenal pheochromocytoma, but its pathogenesis remains unclear. CASE PRESENTATION: A 69-year-old Japanese man developed acute-onset episodic headaches, palpitations, and chest pains. During the episodes, both marked fluctuations in blood pressure (ranging from 40/25 to 300/160 mmHg) and high plasma levels of catecholamines were found simultaneously. Radiological findings indicated a 4-cm left adrenal pheochromocytoma. These episodic symptoms disappeared within 2 weeks with normalization of plasma catecholamine levels. Two months later, the patient underwent adrenalectomy. Microscopic examinations revealed pheocromocytoma with a large central area of coagulative necrosis. The necrotic material was immunohistochemically positive for chromogranin A. Granulation tissue was adjacent to the necrotic area, accompanied by numerous hemosiderin-laden macrophages and histiocytes with vascular proliferation. Viable tumor cells, detected along the periphery of the tumor, demonstrated pyknosis, and the Ki-67 labeling index was 2 % in the hot spot. No embolus or thrombus formation was found in the resected specimen harboring the whole tumor. The Pheochromocytoma of the Adrenal gland Scaled Score was 2 out of 20. The patient's postoperative course was unremarkable for > 7 years. CONCLUSIONS: Presumed causal factors for the extensive necrosis of adrenal pheochromocytoma in previously reported cases include hemorrhage into the tumor, hypotension induced by a phentolamine administration, embolic infarction, high intracapsular pressure due to malignant growth of the tumor, and catecholamine-induced vasoconstriction. In the present case, histopathological and clinical findings suggest that under conditions of chronic ischemia due to catecholamine-induced vasoconstriction, an acute infarction occurred after sudden attacks of alternating hypertension and hypotension. Over the subsequent 2 weeks, repetitive massive release of catecholamines from the infarcts into circulation likely accelerated infarction progression by causing repeated attacks of alternating hypertension and hypotension and resulted in the large necrosis. This case highlights the need for physicians to consider acute spontaneous tumor infarction accompanying episodic catecholamine crisis as a rare but severe complication of pheochromocytoma.

Functional analysis of transcriptional repressor Otx3/Dmbx1.

Otx3/Dmbx1 is a member of paired class homeodomain transcription factors. In this study, we found that Otx3/Dmbx1 represses the Otx2-mediated transactivation by forming heterodimer with Otx2 on the P3C (TAATCCGATTA) sequence in vitro. The 156 amino acid region (residues 1-156) of Otx3/Dmbx1 is required for its repressor activity, and interacts directly with Otx2. Co-localization of Otx3/Dmbx1 and Otx2 in brain sections was confirmed by in situ hybridization. These data suggest that Otx3/Dmbx1 represses Otx2-mediated transcription in the developing brain. We also identified the consensus binding sequence [TAATCCGATTA and TAATCC(N2-4)TAATCC] of Otx3/Dmbx1.

Constitutive stimulation of vascular smooth muscle cells by angiotensin II derived from an adenovirus encoding a furin-cleavable fusion protein.

BACKGROUND: To fill the gap between acute and chronic stimulation methods of angiotensin II (Ang II) and obtain relevant signaling information, we have made an adenovirus vector encoding a furin-cleavable Ang II fusion protein. METHODS: Vascular smooth muscle cells (VSMCs) were infected with adenovirus to evaluate Ang II production. Also, expression of early growth response-1 (Egr-1) and hypertrophic responses were examined in VSMCs. RESULTS: Acute stimulation of VSMCs with synthetic Ang II showed the peptide had a half-life of less than 1 h. Infection of VSMCs with Ang II adenovirus showed a time-dependent production of Ang II as early as 2 days and up to 7 days postinfection. The Ang II adenovirus induced VSMC hypertrophy, stimulated Egr-1 expression, and suppressed Ang II type 1 receptor mRNA expression. Chronic Ang II infusion in mice for 2 weeks markedly enhanced Egr-1 immunostaining in carotid artery compared with the control saline infusion. CONCLUSION: Application of the Ang II adenovirus vector to cultured cells will be useful to elucidate molecular and signaling mechanisms of cardiovascular diseases associated with enhanced Ang II production.