Search

We propose a new type of CNT hydrogel that has unique conductive and reversible characteristics. We found in previous studies that CNT dispersions became gelatinous without any gelators when a specific CNT was combined with a specific dispersant. This hydrogel has conductive properties derived mainly from the CNTs it contains; and even after gelation, it can be returned to a liquid state by ultrasonic irradiation. Furthermore, the liquid is gelable again. In this study, we prepared several types of CNTs and several types of dispersants, experimentally verified the possibility of gelation by combining them, and geometrically investigated the gelation mechanism to determine how this unique hydrogel is formed. As a result, we found that the experimental results and the theory examined in this study were consistent with the combination of materials that actually become hydrogels. We expect that this study will allow us to anticipate whether or not an unknown combination of CNTs and dispersants will also become gelatinous.

Kisspeptin is a peptide that plays an important role through its effects on the hypothalamus-pituitary-gonadal (HPG) axis. It has also been implicated in sexual behavior. The present study investigated whether the relationship between kisspeptin and sexual behavior is independent of the HPG axis, i.e., testosterone. Sexual behavior was examined after the administration of kisspeptin to gonadally intact male rats and gonadectomized male rats that received testosterone supplementation. Other male rats were also observed for sexual behavior once a week from 2 to 5 weeks after gonadectomy and receiving kisspeptin for the sixth postoperative week. Sexual behavior in female rats serving as the partner for each male was also observed. Female rats were not administered kisspeptin in the present study. The results obtained showed that the administration of kisspeptin increased precopulatory behavior in gonadally intact male rats and gonadectomized male rats that received testosterone supplementation and proceptive behavior in their female partners. Precopulatory behavior in males and receptive behavior in females increased, while copulatory behavior in males and receptive behavior in females remained unchanged. Furthermore, the administration of kisspeptin increased precopulatory behavior in gonadectomized males, but did not affect receptive behavior in females. These results suggest that kisspeptin affected males independently and/or supplementally to testosterone, and also that changes in the presence of testosterone in males had an impact on proceptive behavior in their female partners. In conclusion, kisspeptin may involve an as-yet-unidentified neural pathway in sexual desire independently of the HPG axis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Polycystic ovary syndrome (PCOS) is associated with an increased risk of psychological distress as well as enhanced responses to psychosocial stress. Recently, it was hypothesized that PCOS patients may be at high risk of novel COVID-19 infections and worse clinical presentations during such infections. Here, we evaluated the effects of PCOS on stress responses to bacterial and viral mimetics using dihydrotestosterone-induced PCOS model rats. Lipopolysaccharide (LPS; a bacterial mimetic) or polyinosinic-polycytidylic acid (Poly-IC; a viral mimetic) was injected into PCOS model rats (PCOS) and non-PCOS rats (control), and the rats' stress responses were evaluated. In the PCOS group, the rats' anorectic and febrile responses to LPS injection were enhanced, whereas their anorectic and febrile responses to Poly-IC injection were unaltered. The PCOS group also exhibited greater changes in peripheral cytokine levels in response to LPS, but not Poly-IC. On the contrary, after the injection of Poly-IC depressed locomotor activity was more evident in the PCOS group, whereas no such changes were observed after LPS injection. These findings indicate that although the stress responses of PCOS model rats to infection may be enhanced, the patterns of change in stress responses and their underlying mechanisms may differ between bacterial and viral infections., Competing Interests: There are no conflict of interest among all authors., (© 2024 The Authors.)

Aim: Medroxyprogesterone acetate (MPA) is one of the treatments of atypical endometrial hyperplasia (AEH) and endometrial cancer (EC) to preserve the fertility. Efficacy of MPA therapy and fertility and obstetric outcomes after remission were evaluated in EC or AEH patients., Methods: Among patients diagnosed with EC or AEH at Tokushima University Hospital between January 2002 and October 2020, we retrospectively analyzed patients, ages range from 26 to 40, who underwent conservative management using MPA (400-600 mg/day)., Results: In total, 19 patients underwent MPA therapy. The 18 (94%) patients achieved complete response (CR), and 1 (5%) patient achieved partial response (PR). Relapse occurred in 6 (32%) patients who had achieved CR. Of the patients who relapsed, 4 patients resumed MPA therapy and were in remission. Among 19 patients, 13 patients attempted pregnancy after CR. All of them underwent ovulation induction or assisted reproductive technology. As a result, 20 pregnancies in 10 (77%) patients and 12 live births in 9 (69%) patients were achieved. Rate of spontaneous abortion was 35% (7/20)., Conclusions: MPA therapy can produce a high remission rate, and be considered an effective treatment for patients who wish fertility preservation. Around 70% patients who attempt to pregnancy can have at least one baby by infertility treatments. Because recurrence rate after MPA therapy is high, it may be desirable to aim for early pregnancy by active intervention., (© 2023 Japan Society of Obstetrics and Gynecology.)

Secreted frizzled-related proteins (SFRPs) are involved in the development of various types of cancer and function by suppressing the Wnt signaling pathway. To elucidate the clinical implications of SFRPs in uterine sarcoma, SFRP expression levels and their effects on uterine leiomyosarcoma cells were examined. Immunostaining for SFRP4 was performed on uterine smooth muscle, uterine fibroid and uterine leiomyosarcoma tissues. Additionally, the effects of SFRP4 administration on cell viability, migration and adhesion were evaluated in uterine leiomyosarcoma SKN cells using the WST-1 assay (Roche Diagnostics) and the CytoSelect™ 24-well Cell Migration Assay Kit and the CytoSelect™ 48-well Cell Adhesion Assay Kit. The expression levels of SFRP4 in uterine leiomyosarcoma tissues were lower than those in normal smooth muscle and uterine fibroid tissues. In addition, SFRP4 suppressed the viability and migration, and increased the adhesion ability of uterine leiomyosarcoma cells compared with in the control group. In conclusion, SFRP4 may suppress the viability and migration, and enhance the adhesion of sarcoma cells. These results suggested that SFRP4 could be considered as a novel therapeutic target for uterine sarcoma., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2024, Spandidos Publications.)

While the effects of progesterone on body weight and appetite in pre-menopausal conditions have been well elucidated, its effects in post-menopausal conditions have not been clarified. On the contrary, the effects of estrogen on body weight and appetite in post-menopausal conditions have been well established. In this study, the effects of progesterone treatment on body weight, appetite, and fat mass in ovariectomized rats were evaluated. In addition, the central and/or peripheral levels of oxytocin (OT), leptin, and their receptors, which are potent anorectic factors, were examined. Female rats were ovariectomized and divided into control, progesterone-treated, and estrogen-treated groups. Body weight, food intake, and subcutaneous fat mass were lower in both the progesterone and estrogen groups than in the control group. The estrogen group exhibited higher serum OT levels than the control group, whereas the OT levels of the progesterone and control groups did not differ. The serum leptin levels of both the progesterone and estrogen groups were lower than those of the control group. Gene expression analysis of OT, leptin, and their receptors in the hypothalamus and adipose tissue found few significant differences among the groups. Hypothalamic neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) mRNA levels involved in appetite regulation were slightly altered in the progesterone and estrogen groups. These findings suggest that progesterone treatment may have favorable effects on body weight, appetite, and fat mass regulation in post-menopausal conditions and that the mechanisms underlying these effects of progesterone differ from those underlying the effects of estrogen., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This retrospective cohort study analyzes the presentation, diagnosis, and treatment outcomes of patients who developed drug rash with eosinophilia and systemic symptoms (DRESS) to tuberculosis (TB) therapy in a TB non-endemic region. Anti-TB agents represented 7.5% of all antimicrobial-induced DRESS cases, and rifampin was the most commonly implicated agent among drugs used to treat TB., Competing Interests: Dr. Haemel is a consultant to Guidepoint LLC and to CSL Behring., (© 2024 The Authors. Skin Health and Disease published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Introduction: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease that affects the function of exocrine glands, such as the lacrimal and the salivary glands. Extraglandular lesions and malignant lymphoma also occur during the progressive stage of pSS. We have, herein, focused on the pulmonary lesions of pSS and have aimed clarifying their pathophysiological mechanism by comparing the glandular with the extraglandular lesions observed in a mouse model of pSS., Results: The histopathological analysis of lung tissues obtained from NFS/ sld mice that have undergone neonatal thymectomy was performed. Moreover, in vivo and in vitro experiments were conducted along with immunological analyses in order to characterize the unique phenotypes of the pulmonary lesions identified in these pSS model mice. Inflammatory lesions with a bronchus-associated lymphoid tissue-like structure were identified in the lungs of pSS model mice. In addition, relative to salivary gland lesions, pulmonary lesions showed increased CD23 + follicular B (FB) cells. In vitro and pulmonary B cells were more readily driven to CD23 + FB cell phenotype than salivary gland B cells in pSS model mice. Furthermore, the CD23 + FB cell differentiation was found to be enhanced in a CD4 + T-cell-dependent manner under a Th2-type condition in the lungs of herein examined pSS model mice., Discussion: A Th2-type response in the pSS lung may promote the progression of autoimmune lesions through an enhanced abnormal differentiation of B cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sato-Fukuba, Arakaki, Ushio, Otsuka, Nagao, Matsuzawa, Tawara, Tsunematsu and Ishimaru.)

Importance: Scoring systems for Stevens-Johnson syndrome and epidermal necrolysis (EN) only estimate patient prognosis and are weighted toward comorbidities and systemic features; morphologic terminology for EN lesions is inconsistent., Objectives: To establish consensus among expert dermatologists on EN terminology, morphologic progression, and most-affected sites, and to build a framework for developing a skin-directed scoring system for EN., Evidence Review: A Delphi consensus using the RAND/UCLA appropriateness criteria was initiated with a core group from the Society of Dermatology Hospitalists to establish agreement on the optimal design for an EN cutaneous scoring instrument, terminology, morphologic traits, and sites of involvement., Findings: In round 1, the 54 participating dermatology hospitalists reached consensus on all 49 statements (30 appropriate, 3 inappropriate, 16 uncertain). In round 2, they agreed on another 15 statements (8 appropriate, 7 uncertain). There was consistent agreement on the need for a skin-specific instrument; on the most-often affected skin sites (head and neck, chest, upper back, ocular mucosa, oral mucosa); and that blanching erythema, dusky erythema, targetoid erythema, vesicles/bullae, desquamation, and erosions comprise the morphologic traits of EN and can be consistently differentiated., Conclusions and Relevance: This consensus exercise confirmed the need for an EN skin-directed scoring system, nomenclature, and differentiation of specific morphologic traits, and identified the sites most affected. It also established a baseline consensus for a standardized EN instrument with consistent terminology.

Sex steroid hormones are important for the maintenance of metabolism in both sexes. Oxytocin (OT) is a neuropeptide that is synthesized in hypothalamic regions, secreted from the posterior lobe of the pituitary gland, and is involved in the control of appetite, body weight, and metabolism. Estrogen and OT both play a role in the metabolism of nutrients, and OT has potential in the prevention of obesity. However, the relationship between testosterone and OT remains unclear. Therefore, the present study investigated the relationship between testosterone and OT in hypogonadal male rats and male rats receiving testosterone replacement therapy. The results obtained showed that testosterone increased serum OT levels and promoted the secretion of adiponectin from visceral fat, and reduced body fat directly and/or indirectly through OT and adiponectin. Testosterone also increased the expression of OT receptors in the hypothalamus to increase sensitivity to OT, and perhaps because of this, OT administration had the effect of reducing food intake and body weight gain in both normal and castrated rats, and this effect was stronger in normal rats. In other words, the preventative effects of OT on obesity may be synergistic with testosterone. Collectively, the present results indicate that testosterone exerts indirect effects to prevent obesity and atherosclerosis through OT and adiponectin. In conclusion, testosterone replacement therapy is useful for preventing obesity caused by hypogonadism, and OT has potential in supportive medicine to prevent obesity and adult diseases., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Changes in the activities of some metabolic factors have been suggested to increase the risk of conditions associated with the Developmental Origins of Health and Disease (DOHaD). We examined changes in oxytocin (OT), a metabolic factor, and OT receptor (OTR) mRNA levels throughout the developmental period in rats of intrauterine undernutrition. Pregnant rats were divided into two groups: a maternal normal nutrition (mNN) and maternal undernutrition (mUN) group. Serum OT concentrations and hypothalamic mRNA levels of OT and OTR were measured in both offspring at various postnatal stages. Both offspring showed significant increases in serum OT concentrations during the neonatal period, significant reductions around the pubertal period, and significant increases in adulthood. Hypothalamic OT mRNA expression levels gradually increased from the neonatal to pubertal period and decreased in adulthood in both offspring. In the pre-weaning period, hypothalamic OT mRNA expression levels were significantly lower in the mUN offspring than in the mNN offspring. In the mUN offspring, hypothalamic OTR mRNA expression levels transiently increased during the neonatal period, decreased around the pubertal period, and increased again in adulthood, whereas transient changes were not detected in mNN offspring. These changes could affect nutritional and metabolic regulation systems in later life and play a role in the mechanisms underlying DOHaD.

It recently has been reported that partial-epithelial-mesenchymal transition (p-EMT) program is associated with metastasis in head and neck squamous cell carcinoma (HNSCC). We previously have identified POSTN (which encodes periostin) as an invasion-promoting molecule in HNSCC. Interestingly, POSTN expression is frequently observed in cancer cells with higher p-EMT score by using a previous single-cell transcriptomic data of HNSCC cases. Although it is known that POSTN has 11 splicing variants, the role of them has not been determined in HNSCC. Here, we found that HNSCC cells with EMT features expressed POSTN isoforms, Iso3 (lacking exon 17 and 21) and Iso5 (lacking exon 17), whereas fibroblast expressed Iso3 and Iso4 (lacking exon 17, 18, and 21). The expression of POSTN Iso3 and Iso4 are known to be widely observed in various cell types including stromal cells. Therefore, we focused on the role of novel cancer cell-derived POSTN isoform, Iso5, in HNSCC. Single overexpression of POSTN Iso5 as well as Iso3 promoted invasion. Surprisingly, Iso5 synergistically promoted invasion together with Iso3. Notably, Iso5 as well as Iso3 upregulated p-EMT-related genes. We suggest that a novel cancer-specific POSTN isoform lacking exon 17 (Iso5) can be a useful marker for detecting cancer cells undergoing p-EMT. Moreover, a POSTN Iso5 can be a novel target for diagnosis and therapy in HNSCC., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Ultrasonography and computed tomography urography are two commonly used modalities to image the upper tracts for the evaluation of hematuria. This study evaluated the efficacy of ultrasonography for the detection of upper tract urothelial carcinoma compared to computed tomography urography as a standard reference., Methods: This retrospective study included patients with urothelial carcinoma of the renal pelvis and/or ureter who were diagnosed using computed tomography urography and underwent surgical treatment. We calculated the sensitivity of ultrasonography in upper tract urothelial carcinoma diagnosis, further classified the degree of hydronephrosis on ultrasonography, and analyzed the relationship between the sensitivity and the degree of hydronephrosis and tumor location. Additionally, the usefulness of the combination of the screening ultrasonography findings, the presence of gross hematuria, and/or urine cytology was analyzed., Results: This study included 136 patients with upper urothelial carcinoma. Ultrasonography in the diagnosis had 45.6% sensitivity, and ultrasonography findings, including the detection of hydronephrosis, were present in 72.8%. The presence of hydronephrosis and tumor location were associated with detection by ultrasonography. The tumor was identified in a total of 134 (98.5%) patients by combining tumor detection and hydronephrosis using ultrasonography with gross hematuria and positive urine cytology as screening., Conclusion: Ultrasonography showed acceptable sensitivity for upper tract urothelial carcinoma diagnosis. Considering the hydronephrosis findings, ultrasonography is a useful screening tool for upper tract urothelial carcinoma. Additionally, excessive computed tomography examinations can be reduced by adding gross hematuria and positive urine cytology., (© 2023. The Author(s), under exclusive licence to The Japan Society of Ultrasonics in Medicine.)

Sustainable Engineering education must provide cyber-physical and distributed systems competencies, such as the Internet of Things (IoT), to contribute to the Sustainable Development Goals (SDG). The COVID-19 pandemic caused profound impacts arising from a traditional on-site teaching model rupture and demanded distance learning for engineering students. In this context, we considered the following Research Questions (RQ): How can Project Based Learning (PjBL) be applied in hardware and software courses from the Engineering curriculum to foster practical activities during the COVID-19 pandemic? Is the student performance in the fully remote offering comparable to the face-to-face offering? (RQ1); Which Sustainable Development Goals are related to the Engineering students' project themes? (RQ2). Regarding RQ1, we present how PjBL was applied in first-, third- and fifth-year Computer Engineering Courses to support 31 projects of 81 future engineers during the COVID-19 pandemic. Student grades in a Software Engineering course indicate no relevant differences between student performance in remote and face-to-face offerings. Regarding RQ2, most Computer Engineering students from the Polytechnic School of the University of São Paulo in 2020 and 2021 decided to create projects related to SDG 3-Good Health and Well-being, SDG 8-Decent Work and Economic Growth and SDG 11-Sustainable Cities and Communities. Most projects were related to health and well-being, which was an expected behavior according to how health issues were brought into highlight during the pandemic.

Objective: To examine the safety and efficacy of ureteroscopy (URS) for urolithiasis in octogenarians, and identify preoperative risk factors for the incidence of postoperative complications., Methods: The patients who underwent URS for urolithiasis were divided into octogenarians and younger patients (age: <80 years), and the groups were compared regarding their clinical characteristics, intraoperative and postoperative complications, and stone-free rate. The predictors of postoperative complications were evaluated using logistic regression models., Results: A total of 1207 patients were included, 166 in the octogenarian patient group and 1041 in the younger patient group. The proportion of female patients (p < 0.001), American Society of Anesthesiologists (ASA) score (p < 0.001), rate of preoperative pyelonephritis (p < 0.001), and diabetes mellitus (p = 0.003) were higher in the octogenarian group. No statistically significant differences were found between the two groups regarding stone size, location, and intraoperative complications. Postoperative complications, which reached a significant difference, were observed in 34 (20.5%) octogenarians and 117 (11.2%) younger patients (p = 0.002). However, age itself was not significantly associated with postoperative fever, the most frequent postoperative complication, in multivariate analysis. Female sex, ASA score of ≥3, history of diabetes mellitus, and prolonged operative time (≥120 min) were the significant predictors of fever. The stone-free rate in the octogenarian group was superior to that in the younger patient group (80.1% vs. 70.6%, respectively; p = 0.035)., Conclusion: Our results suggest that URS for urolithiasis can be safely and effectively applied to octogenarians in selected cases., (© 2022 The Japanese Urological Association.)

It has been well established that undernutrition and low energy availability disturb female reproductive functions in humans and many animal species. These reproductive dysfunctions are mainly caused by alterations of some hypothalamic factors, and consequent reduction of gonadotrophin-releasing hormone (GnRH) secretion. Evidence from literature suggests that increased activity of orexigenic factors and decreased activity of anorexigenic/satiety-related factors in undernourished conditions attenuate GnRH secretion in an integrated manner. Likewise, the activity of kisspeptin neurons, which is a potent stimulator of GnRH, is also reduced in undernourished conditions. In addition, it has been suggested that gonadotrophin-inhibitory hormone, which has anti-GnRH and gonadotrophic effects, may be involved in reproductive dysfunctions under several kinds of stress conditions. It should be remembered that these alterations, i.e., promotion of feeding behavior and temporary suppression of reproductive functions, are induced to prioritize the survival of individual over that of species, and that improvements in metabolic and nutritional conditions should be considered with the highest priority.

Robust, fault tolerant, and available systems are fundamental for the adoption of Internet of Things (IoT) in critical domains, such as finance, health, and safety. The IoT infrastructure is often used to collect a large amount of data to meet the business demands of Smart Cities, Industry 4.0, and Smart Home, but there is a opportunity to use these data to intrinsically monitor an IoT system in an autonomous way. A Test Driven Development (TDD) approach for automatic module assessment for ESP32 and ESP8266 IoT development devices based on unsupervised Machine Learning (ML) is proposed to monitor IoT device status. A framework consisting of business drivers, non-functional requirements, engineering view, dynamic system evaluation, and recommendations phases is proposed to be used with the TDD development tool. The proposal is evaluated in academic and smart home study cases with 25 devices, consisting of 15 different firmware versions collected in one week, with a total of over 550,000 IoT status readings. The K-Means algorithm was applied to free memory available, internal temperature, and Wi-Fi level metrics to automatically monitor the IoT devices under development to identify device constraints violation and provide insights for monitoring frequency configuration of different firmware versions. To the best of the authors' knowledge, it is the first TDD approach for IoT module automatic assessment which uses machine learning based on the real testbed data. The IoT status monitoring and the Python scripts for model training and inference with K-Means algorithm are available under a Creative Commons license.

The toxicologic effects of nanomaterials, such as carbon nanotubes (CNTs), on the immune system are understood well. However, the precise relationship between long-term exposure to CNTs and chronic inflammation remains unclear. In this study, a mouse model of chronic peritonitis was established using i.p. injection of multiwalled CNTs treated by the Taquann method with high dispersion efficiency. Chronic peritonitis with fibrosis was observed in Taquann-treated multiwalled CNT (T-CNT)-injected mice, but not in Taquann-treated titanium dioxide-injected mice. In vivo and in vitro experiments showed that matrix metalloproteinase-12 (MMP-12) of macrophages was up-regulated by T-CNT to enhance fibroblast activation and profibrotic molecule expression in fibroblasts. In addition, T-CNT-induced peritonitis reduced MMP-12 expression in Nfκb1 -/- mice, suggesting that MMP-12-producing macrophages play a key role in chronic inflammation due to T-CNT exposure through NF-κB activation. The results of this study could be helpful in understanding the molecular toxicity of nanomaterial and chronic inflammation., (Copyright © 2022 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Objective: Innate lymphoid cells (ILCs), including natural killer (NK) cells, ILC1, ILC2, lymphoid tissue-inducer (LTi) cells, and ILC3 cell, play a key role in various immune responses. Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by chronic inflammation of exocrine glands, such as the lacrimal and salivary glands (SGs). The role of NK cells among ILCs in the pathogenesis of pSS is still unclear. In this study, the characteristics and subsets of NK cells in the salivary gland (SG) tissue were analyzed using a murine model of pSS., Methods: Multiple phenotypes and cytotoxic signature of the SG NK cells in control and pSS model mice were evaluated by flow cytometric analysis. Intracellular expression of interferon-γ (IFN-γ) among T cells and NK cells from the SG tissues was compared by in vitro experiments. In addition, pathological analysis was performed using anti-asialo-GM1 (ASGM1) antibody (Ab)-injected pSS model mice., Results: The number of conventional NK (cNK) cells in the SG of pSS model mice significantly increased compared with that in control mice at 6 weeks of age. The production level of IFN-γ was significantly higher in SG NK cells than in SG T cells. The depletion of NK cells by ASGM1 Ab altered the ratio of tissue resident NK (rNK) cells to cNK cells, which inhibited the injury to SG cells with the recovery of saliva secretion in pSS model mice., Conclusion: The results indicate that SG cNK cells may enhance the autoreactive response in the target organ by upregulating of IFN-γ, whereas SG rNK cells protect target cells against T cell cytotoxicity. Therefore, the activation process and multiple functions of NK cells in the target organ could be helpful to develop potential markers for determining autoimmune disease activity and target molecules for incurable immune disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sato, Arakaki, Tawara, Nagao, Tanaka, Tamura, Kawahito, Otsuka, Ushio, Tsunematsu and Ishimaru.)

Practical knowledge is essential for engineering education. With the COVID-19 pandemic, new challenges have arisen for remote practical learning (e.g., collaborations/experimentations with real equipment when face-to-face offerings are not possible). In this context, LabEAD is a remote lab project that aims to provide practical knowledge learning opportunities for Brazilian engineering students. This article describes how engineering project management methods consisting of application domains, requirement identification, technical solution specification, implementation, and delivery phases, were applied to the development of an Internet of Things (IoT) remote lab architecture. The distributed computing environment allows integration between students' smartphones and IoT devices deployed in campus labs and in student residences. The code is open-source for facilitated replication and reuse, and the remote lab was built in six months to enable six experiments for the digital electronics lab during the COVID-19 pandemic, covering all the experiments of the original face-to-face offering. More than 70% of the 32 students preferred remote labs over simulations, and only 2 were not approved in the digital electronics course offered remotely.Student perceptions collected by questionnaires showed that they could successfully specify, develop, and present their projects using the remote lab infrastructure in four weeks.

Polycystic ovary syndrome (PCOS) is frequently seen in females of reproductive age and is associated with metabolic disorders that are exacerbated by obesity. Although body weight reduction programs via diet and lifestyle changes are recommended for modifying reproductive and metabolic phenotypes, the drop-out rate is high. Thus, an efficacious, safe, and continuable treatment method is needed. Recent studies have shown that oxytocin (OT) reduces body weight gain and food intake, and promotes lipolysis in some mammals, including humans (especially obese individuals), without any adverse effects. In the present study, we evaluated the changes in endogenous OT levels, and the effects of acute and chronic OT administration on body weight changes, food intake, and fat mass using novel dihydrotestosterone-induced PCOS model rats. We found that the serum OT level was lower in PCOS model rats than in control rats, whereas the hypothalamic OT mRNA expression level did not differ between them. Acute intraperitoneal administration of OT during the dark phase reduced the body weight gain and food intake in PCOS model rats, but these effects were not observed in control rats. In contrast, chronic administration of OT decreased the food intake in both the PCOS model rats and control rats. These findings indicate that OT may be a candidate medicine that is efficacious, safe, and continuable for treating obese PCOS patients.

Competing Interests: Conflicts of interest None disclosed.

Background: The optimal treatment for aortic thrombus remains to be determined, but surgical treatment is indicated when there is a risk for thromboembolism., Case Presentation: A 47-year-old male presented with weakness in his left arm upon awakening. Contrast-enhanced computed tomography and transesophageal echocardiography revealed a mobile pedunculated object suggestive of a thrombus arising from the ascending aorta and extending to the left common carotid artery. It was removed under hypothermic circulatory arrest and direct cannulation of the left carotid artery to avoid carotid thromboembolism. Histopathological examination revealed that the object was a thrombus. The patient had an uneventful postoperative course and was discharged 9 days after surgery., Conclusion: When a thrombus in the aortic arch extends to the neck arteries, direct cannulation of the neck arteries with selective cerebral perfusion via cervical incision is a useful technique., (© 2022. The Author(s).)

Monascus spp. are filamentous fungi used in fermented foods. They are also natural colorants and food preservatives. Certain metabolites of Monascus spp. lower cholesterol and have other health-promoting effects in humans. In the present study, we demonstrated that the fermentation products of Monascus spp. inhibited ATP synthesis and motility in toxigenic Vibrio cholerae. Single-cell tracking and rotation assays on single flagella showed that Monascus fermentation extract (MFE) significantly impaired V. cholerae swimming by disrupting flagellar rotation. A membrane potential-sensitive carbocyanine dye revealed that MFE depolarized the V. cholerae cell membrane which, in turn, lowered the membrane potential and, by extension, restricted ATP synthesis and flagellar rotation. MFE also severely hindered the motility of other pathogenic bacteria such as V. parahaemolyticus, Pseudomonas aeruginosa, Salmonella enterica Typhimurium, and Leptospira interrogans. The foregoing findings indicate that Monascus fermentation extract could potentially preventing infection caused by multiple pathogenic bacteria as the conventional prophylaxes and slow their progression and lower mortality and morbidity., (Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Aim of the Study: We aimed to determine the outcomes of contemporary mitral valve replacement (MVR) in octogenarians, for rational treatment selection in a patient cohort., Methods: Between 2007 and 2018, 656 consecutive MVRs were performed. Among these cases, 109 patients were aged 80 years or older, and 547 patients were younger than 80 years. Isolated MVRs were performed in 211 patients, of whom 36 were aged 80 years or older. Perioperative mortality and complications were compared between the two groups, adjusted by propensity score., Results: In-hospital mortality of the entire MVR (<80: 26 [4.8%] vs. ≥80: 6 [5.5%], p = .81) and isolated MVR (<80: 6 [3.4%] vs. ≥80: 1 [2.8%], p > .99) groups were similar. Age >80 years did not influence in-hospital mortality (hazard ratio [HR], 1.07; 95% confidence interval [CI], 0.36-3.14, p = .9), stroke (HR, 1.12; 95% CI, 0.19-6.71, p = .9), hemodialysis (HR, 1.44; 95% CI, 0.45-4.66, p = .54), or prolonged ventilation (HR, 1.61; 95% CI, 0.81-3.23, p = .18), but influenced the incidence of reopening for bleeding (HR, 3.97; 95% CI, 1.11-14.19, p = .03). Cox proportional hazard model results showed that age >80 years did not affect cardiac death (HR, 1.45, 95% CI: 0.67-3.12, p = .35), bleeding events (HR, 1.89, 95% CI: 0.84-4.27, p = .13), or stroke (HR, 1.51, 95% CI: 0.54-4.21, p = .44) during the follow-up period., Conclusions: The perioperative and follow-up outcomes of MVR in octogenarians were not inferior to those of younger patients. We should not hesitate to conduct MVR on the grounds of old age., (© 2021 Wiley Periodicals LLC.)

Targeted blockade of the checkpoint molecule programmed cell death 1 (PD-1) can activate tumor-specific T cells to destroy tumors, whereas targeted potentiation of PD-1 is expected to suppress autoreactive T cells and alleviate autoimmune diseases. However, the development of methods to potentiate PD-1 remains challenging. Here we succeeded in eliciting PD-1 function by targeting the cis-PD-L1-CD80 duplex, formed by binding of CD80 to the PD-1 ligand PD-L1, that attenuates PD-L1-PD-1 binding and abrogates PD-1 function. By generating anti-CD80 antibodies that detach CD80 from the cis-PD-L1-CD80 duplex and enable PD-L1 to engage PD-1 in the presence of CD80, we demonstrate that the targeted dissociation of cis-PD-L1-CD80 duplex elicits PD-1 function in the condition where PD-1 function is otherwise restricted. We demonstrate using murine models that the removal of PD-1 restriction is effective in alleviating autoimmune disease symptoms. Our findings establish a method to potentiate PD-1 function and propose the removal of restraining mechanisms as an efficient strategy to potentiate the function of inhibitory molecules., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

It has been shown that biotin, a water-soluble vitamin (B7), plays roles in reproductive functions, such as oocyte maturation and embryo development, in experimental animals. On the other hand, little is known about the clinical effects of biotin on human reproduction. In this study, serum and follicular fluid biotin levels were measured in patients who underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), and their associations with reproductive outcomes were evaluated. As a result, biotin was detected in follicular fluid, as well as serum, and the biotin levels of follicular fluid were found to be positively correlated with those of serum. The biotin levels of serum were higher than those of follicular fluid, suggesting that biotin may be taken up into the follicular fluid from the blood. Although serum and follicular fluid biotin levels tended to be higher in pregnant patients than in non-pregnant patients, these data did not show the significant statistical difference. These findings indicate that biotin does not contribute to the maintenance of oocyte quality, and hence, it does not increase fertilization and pregnancy rates. J. Med. Invest. 69 : 65-69, February, 2022.

Background and Aim of the Study: Coronary artery fistula (CAF) is a relatively rare cardiac anomaly. We investigated long-term outcomes following surgical repair of CAF in adults., Methods: We retrospectively investigated 13 consecutive patients undergoing surgical repair of CAF in our institution between 2008 and 2019 (67.3 ± 10.4 years old, 38% male). CAF types were coronary artery-pulmonary artery fistula (77%), coronary artery-coronary sinus fistula (15%), and both (8%). CAFs originated from the left coronary artery (38%), right coronary artery (8%), and bilateral coronary arteries (38%). Pulmonary and systemic flow (Qp/Qs) was measured in seven patients (54%), with a mean value of 1.52. Seven patients underwent surgery for CAFs alone, and others simultaneously underwent surgery for comorbid cardiac diseases., Results: All procedures were conducted under cardiopulmonary bypass. Surgical procedures were direct epicardial ligation of fistula (92%), direct closure of CAF through pulmonary artery incision (38%), direct closure of CAF through coronary sinus incision (8%), or patch closure of CAF through coronary artery incision (8%). Myocardial perfusion scintigraphy showed asymptomatic myocardial ischemia in the right coronary area after surgery in one patient. There were no deaths perioperatively or during follow-up (mean: 66.6 months). There were no coronary or other CAF-related events., Conclusions: Several anatomical variations in CAF were observed which coexist with cardiac disease. Long-term outcomes following surgical repair were satisfactory, and the concurrent intervention of CAFs during surgery for comorbid cardiac disease is useful to prevent future complications related CAFs in adults., (© 2021 Wiley Periodicals LLC.)

Objectives: To determine the incidence of bioprosthetic structural valve deterioration in dialysis patients undergoing aortic valve replacement compared to that in patients without dialysis., Methods: This single-centre retrospective observational study included 1159 patients who underwent aortic valve replacement using bioprosthetic valves for aortic stenosis and/or regurgitation at our institution between 2007 and 2017 [patients with dialysis (group D, n = 134, 12%) or without dialysis (group N, n = 1025, 88%)]. To adjust for potential differences between groups in terms of initial preoperative characteristics or selection bias, a propensity score analysis was conducted. The final sample that was used in the comparison included 258 patients, as follows: 129 patients with dialysis (group D) and 129 patients without dialysis (group N). The cumulative incidences of all-cause death, cardiac death and moderate or severe structural valve deterioration were estimated using the Kaplan-Meier method., Results: Operative mortality was significantly higher in group D than group N (9% vs 0%, P = 0.001). Kaplan-Meier analysis revealed that in group D, the incidence was significantly higher for all-cause death (P < 0.001, 50% vs 18% at 5 years), cardiac death (P = 0.001, 18% vs 5% at 5 years) and moderate or severe structural valve deterioration (P < 0.001, 29% vs 5% at 5 years) compared with group N., Conclusions: The incidence of structural valve deterioration in dialysis patients undergoing aortic valve replacement was higher than that in patients without dialysis. Bioprosthetic valves should be carefully selected in dialysis patients undergoing aortic valve replacement., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: There are no reports of midterm outcomes after mitral valve replacement with a 25-mm bioprosthesis in a large series of patients. This study aimed to examine perioperative and midterm outcomes of bioprosthetic valve choice, porcine or bovine pericardial, in the mitral position, focusing on 25-mm valves., Methods: From 2007 to 2018, 467 patients received a mitral bioprosthesis, with or without concomitant procedures. Of these, 111 (23.8%) were porcine, and 356 (76.2%) were bovine pericardial, and 219 patients (46.9%) received a 25-mm valve. A propensity-matched cohort of 192 patients was used for outcome analyses. The influence of the valve type on midterm survival and incidence of cardiac death was assessed. Similarly, subanalysis stratified by valve size was conducted., Results: In matched patients, there were no differences in midterm survival and incidence of cardiac death between the two groups (log-rank test; p = .268 and p = .097, respectively). There were no differences in midterm survival and incidence of cardiac death between the 25-mm valve and larger valve (log-rank test; p = .563 and p = .597, respectively). The Cox proportional-hazards model revealed that the valve type and 25-mm valve did not affect midterm survival (p = .487 and p = .375, respectively) and incidence of cardiac death (p = .678 and p = .562, respectively)., Conclusions: The choice of a porcine or bovine pericardial bioprosthesis does not affect midterm survival and cardiac death. The 25-mm valves, whether bovine or porcine, could be an appropriate alternative when the patient's body size is small., (© 2021 Wiley Periodicals LLC.)

The effect of patient-prosthesis mismatch (PPM) on late outcomes after mitral valve replacement (MVR) remains unclear. We evaluated the impact of PPM after MVR on the late survival using propensity score matching analysis. From 2007 to 2018, 660 consecutive MVRs were performed. Effective orifice areas were obtained from a literature review of in vivo echocardiographic data, and mitral PPM was defined as an effective orifice area index of ≤1.2 cm 2 /m 2 . Propensity score matching yielded a cohort of 126 patients with PPM and 126 patients without PPM. Mitral PPM was found in 37.8% of the patients. In the whole matched patients, there were no differences in late survival (log-rank test, P = 0.629) between 2 groups. Patients aged ≤70 years and those aged >70 years had no differences in late survival (log-rank test, P = 0.073 and 0.572). The Cox proportional hazards model for the overall survival showed that mitral PPM tended to decrease survival in patients aged ≤70 years (P = 0.084, hazard ratio [HR] 2.647, 95% CI: 0.876-7.994). Mitral PPM did not adversely affect long-term survival. There may be a tendency of adverse impact on late survival in patients aged ≤70 years. Implanting a safe size rather than larger size prosthesis in mitral position may be an appropriate option in older patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Patient outcomes are improved when dermatologists provide inpatient consultations. Inpatient access to dermatologists is limited, illustrating an opportunity to use teledermatology. Little is known about the ability of dermatologists to accurately diagnose disease and manage inpatients with teledermatology, particularly when using nondermatologist-generated clinical data., Methods: This prospective study assessed the ability of teledermatology to diagnose disease and manage 41 dermatology consultations from a large urban tertiary care center, using internal medicine referral documentation and photographs. Twenty-seven dermatology hospitalists were surveyed. Interrater agreement was assessed by the κ statistic., Results: There was substantial agreement between in-person and teledermatology assessment of the diagnosis with differential diagnosis (median κ = 0.83), substantial agreement in laboratory evaluation decisions (median κ = 0.67), almost perfect agreement in imaging decisions (median κ = 1.0), and moderate agreement in biopsy decisions (median κ = 0.43). There was almost perfect agreement in treatment (median κ = 1.0), but no agreement in follow-up planning (median κ = 0.0). There was no association between raw photograph quality and the primary plus differential diagnosis or primary diagnosis alone., Limitations: Selection bias and single-center nature., Conclusions: Teledermatology may be effective in the inpatient setting, with concordant diagnosis, evaluation, and management decisions., (Copyright © 2020. Published by Elsevier Inc.)

The relationship between autoimmunity and changes in intestinal microbiota is not yet fully understood. In this study, the role of intestinal microbiota in the onset and progression of autoimmune lesions in non-obese diabetic (NOD) mice was evaluated by administering antibiotics to alter their intestinal microenvironment. Flow cytometric analysis of spleen cells showed that antibiotic administration did not change the proportion or number of T and B cells in NOD mice, and pathological analysis demonstrated that autoimmune lesions in the salivary glands and in the pancreas were also not affected by antibiotic administration. These results suggest that the onset and progression of autoimmunity may be independent of enteral microbiota changes. Our findings may be useful for determining the appropriate use of antibiotics in patients with autoimmune diseases who are prescribed drugs to maintain systemic immune function.

Immunosenescence is characterized by age-associated changes in immunological functions. Although age- and autoimmune-related sialadenitis cause dry mouth (xerostomia), the roles of immunosenescence and cellular senescence in the pathogenesis of sialadenitis remain unknown. We demonstrated that acquired immune cells rather than innate immune cells infiltrated the salivary glands (SG) of aged mice. An analysis of isolated epithelial cells from SG revealed that the expression levels of the chemokine CXCL13 were elevated in aged mice. Senescence-associated T cells (SA-Ts), which secrete large amounts of atypical pro-inflammatory cytokines, are involved in the pathogenesis of metabolic disorders and autoimmune diseases. The present results showed that SA-Ts and B cells, which express the CXCL13 receptor CXCR5, accumulated in the SG of aged mice, particularly females. CD4 + T cells derived from aged mice exhibited stronger in vitro migratory activity toward CXCL13 than those from young mice. In a mouse model of Sjögren's syndrome (SS), SA-Ts also accumulated in SG, presumably via CXCL12-CXCR4 signaling. Collectively, the present results indicate that SA-Ts accumulate in SG, contribute to the pathogenesis of age- and SS-related sialadenitis by up-regulating chemokines in epithelial cells, and have potential as therapeutic targets for the treatment of xerostomia caused by these types of sialadenitis.

Resistance to the mechanistic target of rapamycin (mTOR) inhibitors, which are a standard treatment for advanced clear cell renal cell carcinoma (ccRCC), eventually develops in most cases. In this study, we established a patient-derived xenograft (PDX) model which acquired resistance to the mTOR inhibitor temsirolimus, and explored the underlying mechanisms of resistance acquisition. Temsirolimus was administered to PDX model mice, and one cohort of PDX models acquired resistance after repeated passages. PDX tumors were genetically analyzed by whole-exome sequencing and detected several genetic alterations specific to resistant tumors. Among them, mutations in ANKRD12 and DNMT1 were already identified in the early passage of a resistant PDX model, and we focused on a DNMT1 mutation as a potential candidate for developing the resistant phenotype. While DNMT1 expression in temsirolimus-resistant tumors was comparable with the control tumors, DNMT enzyme activity was decreased in resistant tumors compared with controls. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9-mediated heterozygous knockdown of DNMT1 in the temsirolimus-sensitive ccRCC (786-O) cell line was shown to result in a temsirolimus-resistant phenotype in vitro and in vivo. Integrated gene profiles using methylation and microarray analyses of PDX tumors suggested a global shift for the hypomethylation status including promotor regions, and showed the upregulation of several molecules that regulate the mTOR pathway in temsirolimus-resistant tumors. Present study showed the feasibility of PDX model to explore the mechanisms of mTOR resistance acquisition and suggested that genetic alterations, including that of DNMT1, which alter the methylation status in cancer cells, are one of the potential mechanisms of developing resistance to temsirolimus., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Herein, we report the fluorination of α-branched β-ynone esters to afford their corresponding quaternary fluorinated products with good enantioselectivity (ee = 73-90%) using a cinchona-based phase-transfer catalyst. α-Branched β-ynone esters possess a highly acidic α-proton and form their corresponding enolate as a single isomer, which allows the enantioselective fluorination reaction to occur under standard cinchona-based phase-transfer catalyst conditions. Moreover, the obtained α-fluorinated product can be treated with [(SPhos)AuNTf 2 ] (1 mol %) to afford a fluorinated 3,5-diketo carboxylic acid.

During mitosis, the chromosomal passenger complex (CPC) ensures the faithful transmission of the genome. The CPC is composed of the enzymatic component Aurora B (AURKB) and the three regulatory and targeting components borealin, INCENP, and survivin (also known as BIRC5). Although the CPC is known to be involved in diverse mitotic events, it is still unclear how CPC function terminates after mitosis. Here we show that borealin is ubiquitylated by the anaphase promoting complex/cyclosome (APC/C) and its cofactor Cdh1 (also known as FZR1) and is subsequently degraded in G1 phase. Cdh1 binds to regions within the N terminus of borealin that act as a non-canonical degron. Aurora B has also been shown previously to be degraded by the APC/C Cdh1 from late mitosis to G1. Indeed, Cdh1 depletion sustains an Aurora B activity with stable levels of borealin and Aurora B throughout the cell cycle, and causes reduced efficiency of DNA replication after release from serum starvation. Notably, inhibition of Aurora B kinase activity improves the efficiency of DNA replication in Cdh1-depleted cells. We thus propose that APC/C Cdh1 terminates CPC activity upon mitotic exit and thereby contributes to proper control of DNA replication., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Objective: Recent studies have revealed that the ability of cancer cells to undergo intermediate state of epithelial-to-mesenchymal transition (EMT), partial EMT (p-EMT), poses a higher metastatic risk rather than complete EMT. Here, we examined the prognostic value of p-EMT-related genes in head and neck squamous cell carcinoma (HNSCC) by bioinformatic approaches., Materials and Methods: We used RNA-seq data of 519 primary HNSCC cases obtained from TCGA database. We compared the expression of p-EMT-related genes in HNSCC tissues with normal tissues. We evaluated the prognostic value of p-EMT-related genes in HNSCC cases by log-rank test. We examined the expression of p-EMT-, EMT-, and epithelial differentiation-related genes by qPCR., Results: Among p-EMT-related genes that were highly expressed in HNSCC cases, high expression of SERPINE1, ITGA5, TGFBI, P4HA2, CDH13, and LAMC2 was significantly correlated with poor survival of HNSCC patients. By gene expression pattern, HNSCC cell lines were classified into three groups: epithelial phenotype, EMT phenotype, and p-EMT phenotype., Conclusions: Our findings suggest that p-EMT program may be involved in poor prognosis of HNSCC. SERPINE1, ITGA5, TGFBI, P4HA2, CDH13, and LAMC2 can be used for a prognostic marker. Moreover, HNSCC cells with p-EMT phenotype can be a useful model for investigating a nature of p-EMT., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)

Activation of the trigeminal system causes the release of various neuropeptides, cytokines, and other immune mediators. Calcitonin gene-related peptide (CGRP), which is a potent algogenic mediator, is expressed in the peripheral sensory neurons of trigeminal ganglion (TG). It affects the inflammatory responses and pain sensitivity by modulating the activity of glial cells. The primary aim of this study was to use array analysis to investigate the effect of CGRP on the glial cells of TG in regulating nuclear factor kappa B (NF-κB) signaling genes and to further check if CGRP in the TG can affect neuron-glia activation in the spinal trigeminal nucleus caudalis. The glial cells of TG were stimulated with CGRP or Minocycline (Min) + CGRP. The effect on various genes involved in NF-κB signaling pathway was analyzed compared to no treatment control condition using a PCR array analysis. CGRP, Min + CGRP or saline was directly injected inside the TG and the effect on gene expression of Egr1 , Myd88 and Akt1 and protein expression of cleaved Caspase3 (cleav Casp3) in the TG, and c-Fos and glial fibrillary acidic protein (GFAP) in the spinal section containing trigeminal nucleus caudalis was analyzed. Results showed that CGRP stimulation resulted in the modulation of several genes involved in the interleukin 1 signaling pathway and some genes of the tumor necrosis factor pathway. Minocycline pre-treatment resulted in the modulation of several genes in the glial cells, including anti-inflammatory genes, and neuronal activation markers. A mild increase in cleav Casp3 expression in TG and c-Fos and GFAP in the spinal trigeminal nucleus of CGRP injected animals was observed. These data provide evidence that glial cells can participate in neuroimmune interaction due to CGRP in the TG via NF-κB signaling pathway.

Systemic dry syndrome affects quality of life, and various effective methods are being developed for its treatment. We recently found that rooibos (Aspalathus linearis) extract activates muscarinic M 3 receptor and improves dryness in mice and humans. We identified eriodictyol-6-C-β- D -glucoside (E6CG) as the active component affecting the secretory functions of exocrine glands; however, the pharmacokinetics and distribution of E6CG in exocrine glands have not been elucidated in mice receiving rooibos extract. We have developed a quantification method using LC-MS/MS to detect E6CG without an internal standard. Experiments on C57BL/6 mice administered rooibos extract showed that E6CG was transferred into blood plasma, with its concentration levels peaking 19.3 min after treatment. Substantial levels of E6CG were detected in the submandibular, sublingual, parotid, and lacrimal glands and in the sweat glands in palm skin. This study reports that rooibos extracts containing E6CG can be used as functional foods for improving systemic dryness., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Follicular helper T (Tfh) cells contribute to various immune responses as well as to the pathogenesis of several immune diseases. However, the precise mechanism underlying the onset or development of autoimmunity via Tfh cells remains unclear. Herein, the detailed relationship between autoimmune disease and Tfh cells was analyzed using a murine model for Sjögren syndrome (SS) wherein the mice underwent neonatal thymectomy. Germinal center (GC) development was promoted in this SS model along with an increase of Tfh cells and GC B cells. The severity of the autoimmune lesions was correlated with the number of Tfh cells detected in the spleen of the SS model mice. In addition, treatment with an anti-CD20 monoclonal antibody effectively suppressed the autoimmune lesions with a reduction of Tfh cells and GC B cells. Comprehensive gene analysis revealed that several genes associated with Tfh cell differentiation, including achaete-scute homologue 2 (Ascl2), were up-regulated in peripheral CD25 - CD4 + T cells in SS model mice compared with those in control mice. Moreover, an experiment using CD4 Cre Bcl6 fl/fl mice that received neonatal thymectomy treatment demonstrated that Ascl2 contributes to the Tfh cell differentiation associated with autoimmunity during the early stages, independent of Bcl6. In conclusion, our results indicate that abnormal Tfh cell differentiation via Ascl2 regulation might contribute to the pathogenesis of autoimmunity., (Copyright © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Objectives: Sicca syndrome is characterized by dry mouth and eyes and results in a reduction of the patient's quality of life. Various natural plants, including certain herbs, have long been employed to alleviate such symptoms. Rooibos grown in South Africa is one of the potent herbal plants used for the treating dry mouth. However, the precise mechanism of action by which rooibos alleviates symptoms of dryness remains unclear., Methods: The in vivo effects of rooibos extract (RE), which comprises eriodictyol-6-C-glucoside, on the secretory function of saliva and tears were analyzed after intraoral RE administration using wild-type C57BL/6 (B6) mice. In addition, the mechanisms of RE were investigated after administration of a muscarinic acetylcholine receptor 3 (M3R) antagonist., Results: Tear and saliva volumes in mice increased significantly and in a dose-dependent manner following intraoral RE administration compared to those in mice in the control group administered H 2 O. An experiment performed using darifenacin administration revealed that the effects of RE on secretory function were exerted via M3R., Conclusion: These results suggest that RE administration is an effective treatment for symptoms of dryness and may be used in clinical settings against sicca syndrome., (Copyright © 2019. Published by Elsevier B.V.)

Many trigeminal neuropathic pain patients suffer severe chronic pain. The neuropathic pain might be related with cross-excitation of the neighboring neurons and satellite glial cells (SGCs) in the sensory ganglia and increasing the pain signals from the peripheral tissue to the central nervous system. We induced trigeminal neuropathic pain by infraorbital nerve constriction injury (IONC) in Sprague-Dawley rats. We tested cytokine (CXCL2 and IL-10) levels in trigeminal ganglia (TGs) after trigeminal neuropathic pain induction, and the effect of direct injection of the anti-CXCL2 and recombinant IL-10 into TG. We found that IONC induced pain behavior. Additionally, IONC induced satellite glial cell activation in TG and cytokine levels of TGs were changed after IONC. CXCL2 levels increased on day 1 of neuropathic pain induction and decreased gradually, with IL-10 levels showing the opposite trend. Recombinant IL-10 or anti-CXCL2 injection into TG decreased pain behavior. Our results show that IL-10 or anti-CXCL2 are therapy options for neuropathic pain., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Neuron-glia interactions contribute to pain initiation and sustainment. Intra-ganglionic (IG) secretion of calcitonin gene-related peptide (CGRP) in the trigeminal ganglion (TG) modulates pain transmission through neuron-glia signaling, contributing to various orofacial pain conditions. The present study aimed to investigate the role of satellite glial cells (SGC) in TG in causing cytokine-related orofacial nociception in response to IG administration of CGRP. For that purpose, CGRP alone (10 μL of 10 -5 M), Minocycline (5 μL containing 10 μg) followed by CGRP with one hour gap (Min + CGRP) were administered directly inside the TG in independent experiments. Rats were evaluated for thermal hyperalgesia at 6 and 24 h post-injection using an operant orofacial pain assessment device (OPAD) at three temperatures (37, 45 and 10 °C). Quantitative real-time PCR was performed to evaluate the mRNA expression of IL-1β, IL-6, TNF-α, IL-1 receptor antagonist (IL-1RA), sodium channel 1.7 (NaV 1.7, for assessment of neuronal activation) and glial fibrillary acidic protein (GFAP, a marker of glial activation). The cytokines released in culture media from purified glial cells were evaluated using antibody cytokine array. IG CGRP caused heat hyperalgesia between 6⁻24 h (paired- t test, p < 0.05). Between 1 to 6 h the mRNA and protein expressions of GFAP was increased in parallel with an increase in the mRNA expression of pro-inflammatory cytokines IL-1β and anti-inflammatory cytokine IL-1RA and NaV1.7 (one-way ANOVA followed by Dunnett's post hoc test, p < 0.05). To investigate whether glial inhibition is useful to prevent nociception symptoms, Minocycline (glial inhibitor) was administered IG 1 h before CGRP injection. Minocycline reversed CGRP-induced thermal nociception, glial activity, and down-regulated IL-1β and IL-6 cytokines significantly at 6 h ( t -test, p < 0.05). Purified glial cells in culture showed an increase in release of 20 cytokines after stimulation with CGRP. Our findings demonstrate that SGCs in the sensory ganglia contribute to the occurrence of pain via cytokine expression and that glial inhibition can effectively control the development of nociception.

Macrophages (MΦs) are critical regulators of immune response and serve as a link between innate and acquired immunity. The precise mechanism of involvement of tissue-resident MΦs in the pathogenesis of autoimmune diseases is not clear. Here, using a murine model for Sjögren's syndrome (SS), we investigated the role of tissue-resident MΦs in the onset and development of autoimmunity. Two unique populations of CD11b high and CD11b low resident MΦs were observed in the target tissue of the SS model. Comprehensive gene expression analysis of chemokines revealed effective production of CCL22 by the CD11b high MΦs. CCL22 upregulated the migratory activity of CD4 + T cells by increasing CCR4, a receptor of CCL22, on T cells in the SS model. In addition, CCL22 enhanced IFN-γ production of T cells of the SS model, thereby suggesting that CCL22 may impair the local immune tolerance in the target organ of the SS model. Moreover, administration of anti-CCL22 antibody suppressed autoimmune lesions in the SS model. Finally, histopathological analysis revealed numerous CCL22-producing MΦs in the minor salivary gland tissue specimens of the SS patients. CCL22-producing tissue-resident MΦs may control autoimmune lesions by enhancing T cell response in the SS model. These results suggest that specific chemokines and their receptors may serve as novel therapeutic or diagnostic targets for SS.

Background: Nanomaterials are widely used in various fields. Although the toxicity of carbon nanotubes (CNTs) in pulmonary tissues has been demonstrated, the toxicological effect of CNTs on the immune system in the lung remains unclear., Methods and Finding: In this study, exposure to Taquann-treated multi-walled CNTs (T-CNTs) was performed using aerosols generated in an inhalation chamber. At 12 months after T-CNT exposure, alveolar inflammation with macrophage accumulation and hypertrophy of the alveolar walls were observed. In addition, fibrotic lesions were enhanced by T-CNT exposure. The macrophages in the bronchoalveolar lavage fluid of T-CNT-exposed mice were not largely shifted to any particular population, and were a mixed phenotype with M1 and M2 polarization. Moreover, the alveolar macrophages of T-CNT-exposed mice produced matrix metalloprotinase-12., Conclusions: These results suggest that T-CNT exposure promoted chronic inflammation and fibrotic lesion formation in profibrotic macrophages for prolonged periods., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Unilateral re-expansion pulmonary edema (RPE) is a rare but one of the most critical complications that may occur after re-expansion of a collapsed lung after minimally invasive cardiac surgery (MICS) with mini-thoracotomy., Methods: We performed a total of 40 consecutive patients with MICS by right mini-thoracotomy with single-lung ventilation between January 2013 and June 2016. We divided the patients into control group (n = 13) and neutrophil elastase inhibitor group (n = 27). Neutrophil elastase inhibitor group received continuous intravenous infusion of neutrophil elastase inhibitor at 0.2-0.25 mg/kg per hour from the start of anesthesia until extubation during the perioperative period., Results: There were no relations with operative time, cardiopulmonary bypass (CPB) time, aortic clamp time, and intraoperative water valances for postoperative mechanical ventilation support time. Compared with the neutrophil elastase inhibitor group, the control group had significantly higher initial alveolar-arterial oxygen gradient and significantly lower initial ratio of partial pressure of arterial oxygen to fraction of inspired oxygen at the intensive care unit (ICU). The control group had significantly longer postoperative mechanical ventilation support time and hospital stay compared with the neutrophil elastase inhibitor group., Conclusions: Neutrophil elastase inhibitor may have beneficial effects against RPE after MICS with mini-thoracotomy.

Objective: A total of 69 patients with Budd-Chiari syndrome (BCS) were operated by direct approach under cardiopulmonary bypass (CPB). To assess the operative procedure, the perioperative course of esophageal varices (EVs) was evaluated., Patients and Methods: Of the 69 patients, 59 (22 females) were enrolled in this study because they had complete follow-up data for endoscopic evaluation of EVs. Their mean age was 46.3 ± 13.0 years (range 21-73.3 years). EVs were found in 52 patients. Under partial cardiopulmonary bypass, the inferior vena cava (IVC) was incised. The obstruction of the IVC was excised, and the occluded hepatic veins were reopened. The incised IVC was reconstructed with an auto-pericardial patch., Results: Postoperatively, the repaired IVC was patent in all patients. The average number of patent hepatic veins (HVs) increased from 1.23 ± 0.81 to 2.21 ± 0.97/patient. The pressure gradient between the IVC and right atrium (RA) decreased from 12.4 ± 5.52 to 4.46 ± 3.21 mmHg. The indocyanine green clearance test (ICG) at 15 min decreased from 31.57 ± 17.44 to 22.27 ± 15.23%. EVs had disappeared in 13 patients at discharge and in 6 patients at late postoperative follow-up., Conclusion: Our operative procedure for BCS is useful for decreasing portal pressure, which is reflected by disappearance of EVs. Therefore, the high risk of EV rupture could be avoided by reopening the occluded HVs.