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Sjögren's syndrome (SS), an autoimmune disease primarily affecting the exocrine glands, particularly the lacrimal and salivary glands, typically manifests as sicca symptoms (dry mouth and dry eyes). However, these symptoms are uncommon in pediatric patients. We present a case of a 13-year-old boy diagnosed with SS following the detection of bilateral parotid gland microcalcifications during a computed tomography scan for headache evaluation. The patient presented with a chief complaint of persistent headaches and malaise. However, he did not have sicca symptoms. A plain head computed tomography scan revealed multiple microcalcifications within the bilateral parotid glands. The fat-suppressed T2-weighted magnetic resonance imaging scan showed bilateral parotid gland enlargement and scattered areas of high intensity within the parotid glands. The patient was diagnosed with SS based on a serological examination and salivary and lacrimal gland disorders. Treatment with hydroxychloroquine improved headache and fatigue substantially. The patient can now participate in sports and daily life activities without difficulty. These findings stress the importance of considering SS in the differential diagnosis of children with chronic headaches and malaise. The presence of calcification within the parotid gland should raise suspicion for SS, and imaging studies can be a valuable tool for diagnosis, providing crucial information for informed decision-making., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sugiyama et al.)

n-3 Long-chain polyunsaturated fatty acids (n-3 LC-PUFAs), including eicosapentaenoic acid (EPA), are essential multifunctional nutrients in animals. Microorganisms such as microalgae are known to be n-3 LC-PUFA producers in aquatic environments. Various aquatic invertebrates, including Harpacticoida copepods, and a few terrestrial invertebrates, such as the nematode Caenorhabditis elegans, possess n-3 LC-PUFA biosynthetic enzymes. However, the capacity for n-3 LC-PUFA biosynthesis and the underlying molecular mechanisms in terrestrial insects are largely unclear. In this study, we investigated the fatty acid biosynthetic pathway in the silkworm Bombyx mori and found that EPA was present in silkworms throughout their development. Stable isotope tracing revealed that dietary α-linolenic acid (ALA) was metabolized to EPA in silkworm larvae. These results indicated that silkworms synthesize EPA from ALA. Given that EPA is enriched in the central nervous system, we propose that EPA confers optimal neuronal functions, similar to docosahexaenoic acid, in the mammalian nervous system., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Uridine diphosphate- N -acetylglucosamine (UDP-GlcNAc) is one of the major nucleotide sugars in living organisms and serves as the key donor substrate for the post-translational modification of protein O -GlcNAcylation. It undergoes interconversion to its epimer uridine diphosphate- N -acetylgalactosamine (UDP-GalNAc), which acts as a sugar donor initiating mucin-type O -linked glycosylation. The intracellular levels of the two differ between the cell lines and largely fluctuate in response to metabolic perturbations, and recent studies have focused on the details of their biosynthesis or turnover. However, due to their similar chemical properties, sufficient resolution for the two epimers required non-volatile mobile phases that cannot be applied directly to a mass spectrometer. In this study, to implement simple liquid chromatography-mass spectrometry for UDP-GlcNAc and UDP-GalNAc, we optimized a condition of hydrophilic interaction liquid chromatography-mass spectrometry. We found that the use of ammonium hydroxide and an amide column with an optimized water-acetonitrile ratio, flow rate, and column temperature, provided complete separation of the two. The method allowed the analysis of intracellular levels, a stable isotope-labeled target, and patterns of product ion spectra in a single run with fewer sample preparation steps. The new method can be widely used for mass spectrometric analysis of UDP-GlcNAc and UDP-GalNAc.

Endocytosis is an essential biological process for nutrient absorption and intercellular communication; it can also be used to accelerate the cellular internalization of drug delivery carriers. Clarifying the cellular uptake mechanisms of unidentified endogenous and exogenous molecules and designing new effective drug delivery systems require an accurate, specific endocytosis analysis methodology. Therefore, we developed a method to specifically evaluate cellular internalization via three main endocytic pathways: clathrin- and caveolae-mediated endocytosis, and macropinocytosis. We first revealed that most known endocytosis inhibitors had no specific inhibitory effect or were cytotoxic. Second, we successfully established an alternative method using small interfering RNA to knock down dynamin-2 and caveolin-1, which are necessary for clathrin- and caveolae-mediated endocytosis, in HeLa cells. Third, we established another method to specifically analyze macropinocytosis using rottlerin on A431 cells. Finally, we validated the proposed methods by testing the cellular internalization of a biological molecule (insulin) and carriers (nanoparticles and cell-penetrating peptides). Through this study, we established versatile methods to precisely and specifically evaluate endocytosis of newly developed biopharmaceuticals or drug delivery systems., (© 2023 Federation of American Societies for Experimental Biology.)

Aging-induced neuroinflammation, also known as neuroinflammaging, plays a pivotal role in emotional disturbances, including depression and anxiety, in older individuals, thereby leading to cognitive dysfunction. Although numerous studies have focused on therapeutic strategies for cognitive impairment in older individuals, little research has been performed on treating its preceding emotional disturbances. Here, we examined whether Kampo formulas (kososan [KS], nobiletin-rich kososan [NKS], and hachimijiogan [HJG]) can ameliorate aging-induced emotional disturbances and neuroinflammation in mice. The depression-like behaviors observed in SAMP8 mice, relative to normally aging SAMR1 mice, were significantly prevented by treatment with Kampo formulas for 13 weeks. Western blot analysis revealed that hippocampal neuroinflammation was significantly abrogated by Kampo formulas. KS and NKS also significantly attenuated the hippocampal neuroinflammatory priming induced by lipopolysaccharide (LPS, 0.33 mg/kg, i.p. ) challenge in SAMP8 mice. Hippocampal IL-1β, IL-6, and MCP-1 levels were significantly decreased in NKS-treated SAMP8 mice. KS and NKS showed significantly reduced tau accumulation in the brains of SAMP8 mice. RNA-sequencing revealed that each Kampo formula led to unique dynamics of hippocampal gene expression and appeared to abrogate hippocampal inflammatory responses. HJG significantly blocked the LPS-induced increase in serum IL-6 and MCP-1. These results suggest that Kampo formulas would be useful for treating aging-induced depression, in part by regulating neuroinflammatory pathways. This finding may pave the way for the development of therapeutic strategies for aging-related emotional disturbances, which may contribute to the prevention of cognitive dysfunction in older individuals.

Background: The education system can serve as a community-based resource to support the provision of long-term follow-up care after large-scale disasters. While school-based interventions conducted after a disaster have been confirmed to reduce symptoms of depression and posttraumatic stress disorder (PTSD), adolescents often exhibit low treatment motivation. Traditional methods used to encourage treatment motivation include fun activities, such as applied improv (AIM). This study evaluated the intervention effects and improved motivation of an intervention program combining AIM with the behavioral activation approach (BAA)., Methods: Participants were 253 tenth graders, who were in fifth grade at the time the Great East Japan Earthquake of 2011, and 239 students were included in the analyses. Participants were divided into two groups: the BAA and AIM + BAA groups. Students in each group participated in one class-wide intervention session, which lasted 60 min. Depression, PTSD symptoms, behavioral activation, avoidance, and resilience were evaluated using psychological scales. A participant's evaluations of the intervention were confirmed using the impression sheet consisting of six items that measure comprehension, difficulty, efficacy, generalization, confirmation of a specific situation, and motivation., Results: A two-way analysis of variance (ANOVA) conducted using data from the psychological scale did not reveal a significant effect from the intervention program. However, the Mann-Whitney U -test, which used data from the impression sheet, showed a significant effect on comprehension ( p = 0.001), generalization ( p = 0.023), and motivation ( p = 0.025)., Conclusion: This study did not confirm the effectiveness of the BAA in reducing symptoms of depression and PTSD in adolescents. Regarding treatment motivation, the AIM + BAA group reported higher motivation than the BAA group. Thus, one session of AIM may contribute to improved treatment motivation in adolescents. AIM creates a safe environment and encourages engagement and participation in interventions. Treatment motivation is an important issue in adolescent therapy, and AIM may help solve this problem., 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 © 2021 Sugiyama, Koseki, Niikawa, Ito, Takahashi and Ishikawa.)

Aging causes psychological dysfunction and neurodegeneration, and can lead to cognitive impairments. Although numerous studies have reported that neurodegeneration and subsequent cognitive impairments are involved in neuroinflammation, relationship between psychological disturbance and neuroinflammation with aging (neuroinflammaging) remains unclear. Here, to clarify the relationship, we examined whether neuroinflammaging affects emotional behaviors in senescence-accelerated mouse prone 8 (SAMP8) mice. Microglial inflammatory responses to a subsequent lipopolysaccharide (LPS) challenge were significantly enhanced in male SAMP8 mice relative to normal aging senescence-accelerated mouse resistant 1 (SAMR1) mice at 17 weeks, but not 8 weeks of age. LPS injection also significantly increased brain and systemic inflammation in SAMP8 mice at 17 weeks. In a battery of behavioral tests, SAMP8 mice at 17 weeks, but not 8 weeks, exhibited anxiety- and depression-like behaviors and circadian rhythm disruption. Taken together, SAMP8 mice at 17 weeks possess a brain microenvironment in which it is easier to trigger neuroinflammatory priming; this may lead to an emergence of anxiety- and depression-like behaviors and circadian rhythm disruption. These findings provide new insights into the temporal relationship between neuroinflammaging and emotion., (Copyright © 2020. Published by Elsevier Inc.)

In liver microsomes, selexipag (NS-304; ACT-293987) mainly undergoes hydrolytic removal of the sulfonamide moiety by carboxylesterase 1 (CES1) to yield the pharmacologically active metabolite MRE-269 (ACT-333679). However, it is not known how much CES in the liver and intestine contributes to the hydrolysis of selexipag or how selexipag is metabolized in the intestine, including by hydrolysis. To obtain a better understanding of selexipag metabolism in humans, we determined the percentage contribution of CES1 and carboxylesterase 2 (CES2) to the hydrolysis of selexipag and 7 of its analogs with different sulfonamide moieties and evaluated its nonhydrolytic metabolism in human liver microsomes and human intestinal microsomes (HIMS). For selexipag, the percentage contributions of CES1 and CES2 in human liver microsomes were 77.0% and 9.99%, respectively, while the percentage contribution of CES2 in HIMS was 100%. In HIMS, the rate of hydrolysis of selexipag was the lowest among the compounds tested, and no difference between the presence and absence of nicotinamide adenine dinucleotide phosphate was noted. We infer from these results that selexipag is likely to be hydrolyzed by CES2 as well as CES1, and only selexipag itself and the MRE-269 produced by hydrolysis in the intestine would be absorbed after oral administration., (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Visualization research often seeks designs that first establish an overview of the data, in accordance to the information seeking mantra: "Overview first, zoom and filter, then details on demand". However, in computational fluid dynamics (CFD), as well as in other domains, there are many situations where such a spatial overview is not relevant or practical for users, for example when the experts already have a good mental overview of the data, or when an analysis of a large overall structure may not be related to the specific, information-driven tasks of users. Using scientific workflow theory and, as a vehicle, the problem of viscous finger evolution, we advocate an alternative model that allows domain experts to explore features of interest first, then explore the context around those features, and finally move to a potentially unfamiliar summarization overview. In a model instantiation, we show how a computational back-end can identify and track over time low-level, small features, then be used to filter the context of those features while controlling the complexity of the visualization, and finally to summarize and compare simulations. We demonstrate the effectiveness of this approach with an online web-based exploration of a total volume of data approaching half a billion seven-dimensional data points, and report supportive feedback provided by domain experts with respect to both the instantiation and the theoretical model.

The relationship between Helicobacter pylori infection and gastric cancer associated with stomach lesions has been reported. Improvement of the adverse effects induced by H. pylori is required for human health. It has been reported that wasabi (Wasabiajaponica Matsum) leaves have various effects on bacteria and mammals. In this study, the effect was examined of wasabi leaf extract and allyl isothiocyanate (AIT), which is a main functional component of wasabi, on stomach lesions in Mongolian gerbils infected with H. pylori. After the gerbils infected with H. pylori were orally administrated with wasabi leaf extract and AIT for two weeks, colony forming units (CFU) of H. pylori, the degree of gastric mucosal erosion, and petechial hemorrhage in the stomachs of the gerbils were evaluated. Wasabi leaf extract and AIT exhibited a decreasing tendency of CFU in the stomachs. The degree of gastric mucosal erosion and petechial hemorrhage were significantly decreased by the intake of wasabi leaf extract and AIT. Wasabi leaf extract and AIT did not affect body weight, dietary intake, water intake, and the pH of the stomach. From these results, wasabi leaves and AIT may provide a natural remedy for stomach lesions induced by H. pylori.

In vitro estimating strategies for potential neurotoxicity are required to screen multiple substances. In a previous study, we showed that exposure to low-concentrations of some chemicals, such as organotin, decreased the expression of GluR2 protein, which is a subunit of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors, and led to neuronal vulnerability. This result suggested that GluR2 decreases as an index of neuronal cell sensitivity and vulnerability to various toxic insults. Accordingly, we developed a versatile method that is a large scale determination of GluR2 protein expression in the presence of environmental chemicals by means of AlphaLISA technology. Various analytical conditions were optimized, and then GluR2 protein amount was measured by the method using AlphaLISA. The GluR2 amounts were strongly correlated with that of measured by western blotting, which is currently used to determine GluR2 expression. An ideal standard curve could be written with the authentic GluR2 protein from 0 ng to 100 ng. Subsequently, twenty environmental chemicals were screened and nitenpyram was identified as a chemical which lead to decrease in GluR2 protein expression. This assay may provide a tool for detecting neurotoxic chemicals according to decreases in GluR2 protein expression.

The absolute optical power at 611 nm emitting from Eu doped Gd2O3 nano phosphors upon X-ray excitation from a microfocus X-ray source operated at 100 kV was measured with thin film photovoltaic cells (TFPCs), whose optical response was calibrated using an He-Ne laser at 632 nm. The same TFPCs were also used to determine the absorbed X-ray power by the nano phosphors. These measurements provided a convenient and inexpensive way to determine the absolute quantum efficiency of nano phosphors, normally a difficult task. The measured absolute X-ray-to-optical fluorescence efficiency of the nano phosphors annealed at 1100 °C was 3.2%. This is the first time such efficiency for Eu/Gd2O3 nano phosphors is determined, and the measured efficiency is a fraction of the theoretically predicted maximum efficiency of 10% reported in the literature.

Lignin modification has been a breeding target for the improvements of forage digestibility and energy yields in forage and bioenergy crops, but decreased lignin levels are often accompanied by reduced lodging resistance. The rice mutant gold hull and internode2 (gh2) has been identified to be lignin deficient. GH2 has been mapped to the short arm of chromosome 2 and encodes cinnamyl-alcohol dehydrogenase (CAD). We developed a long-culm variety, 'Leaf Star', with superior lodging resistance and a gh phenotype similar to one of its parents, 'Chugoku 117'. The gh loci in Leaf Star and Chugoku 117 were localized to the same region of chromosome 2 as the gh2 mutant. Leaf Star had culms with low lignin concentrations due to a natural mutation in OsCAD2 that was not present in Chugoku 117. However, this variety had high culm strength due to its strong, thick culms. Additionally, this variety had a thick layer of cortical fiber tissue with well-developed secondary cell walls. Our results suggest that rice can be improved for forage and bioenergy production by combining superior lodging resistance, which can be obtained by introducing thick and stiff culm traits, with low lignin concentrations, which can be obtained using the gh2 variety.

Objective: To clarify the effects of uterine myometrial suture techniques at prior caesarean section on the incidence of pathologically diagnosed placenta accreta in placenta praevia with prior caesarean section (PPPC)., Design: Case-control study., Setting: Eleven tertiary referral hospitals in central Japan., Population: A total of 98 cases of placenta praevia, a history of one or more prior caesarean sections, and a history of uterine transverse incision and usage of only absorbable thread for myometrial sutures at the prior caesarean section. Exclusions were a history of myomectomy or Strassmann's operation., Methods: Cases were grouped into a pathologically diagnosed placenta accreta group (38 cases) and a no accreta group (60 cases). Clinical characteristics including uterine suture methods at prior caesarean section were compared (single-layer versus double-layer closure; continuous versus interrupted sutures in the inner myometrial layer)., Main Outcome Measure: The incidence of placenta accreta., Results: No difference was found comparing single-layer with double-layer closure in the incidence of placenta accreta (37.1 versus 39.7%, P = 0.805); however, a significant difference was found comparing continuous with interrupted sutures (58.1 versus 29.9%, P = 0.008). Multivariable logistic regression analysis with stepwise selection for the eight factors meeting the criterion of P < 0.10 in univariate analysis was used, and four independent factors were selected, as follows: gravidity ≥ 3 (adjusted odds ratio, aOR, 3.4, 95% confidence interval, 95% CI, 0.99-11.6, P = 0.050); total praevia (versus non-total, aOR 18.4, 95% CI 3.2-107.0, P = 0.001); anterior/centre placenta (versus posterior, aOR 16.4, 95% CI 3.7-72.2, P < 0.001); and continuous sutures (versus interrupted, aOR 6.0, 95% CI 1.4-25.2, P = 0.015)., Conclusions: In this limited study, a history of continuous sutures on the inner side of the uterine wall showed potential to influence the development of placenta accreta in PPPC patients., (© 2014 Royal College of Obstetricians and Gynaecologists.)

Aim: To report our experience with pregnancy outcomes after emergent laparoscopic surgery for acute adnexal disorders at less than 10 weeks of gestation when surgical intervention could be more invasive to intrauterine pregnancy., Methods: Gasless multiport laparoscopic surgery or transumbilical laparoendoscopic single-site surgery was performed with securing of the surgical view by the abdominal wall-lift method. Intraoperative autologous blood salvage and donation was performed in cases associated with significant hemoperitoneum., Results: Six cases of ovarian bleeding with ruptured corpus luteal cyst, three cases of adnexal torsion with corpus luteal cyst, and one case each of ruptured heterotopic ampullary pregnancy and heterotopic tubal stump isthmic pregnancy after salpingectomy were managed. For ruptured corpus luteal cyst, hemostasis was achieved by removal of hematoma followed by suturing. For adnexal torsion, detorsion with cyst aspiration was performed in two cases and detorsion alone was performed in one case. For ruptured heterotopic ampullary pregnancy, unilateral salpingectomy was performed. For ruptured heterotopic tubal stump isthmic pregnancy after salpingectomy, removal of the expelled villous tissue followed by hemostatic coagulation was performed. In five cases associated with massive hemoperitoneum, intraoperative autologous blood salvage and donation were performed to avoid homologous blood transfusion. After surgery, seven live births were achieved, while two cases of biochemical pregnancy loss and a case of complete miscarriage were noted., Conclusion: Although miscarriage could be a significant concern in the perioperative period, gasless laparoscopic surgery appeared to be feasible for management of acute adnexal disorders at less than 10 weeks of gestation., (© 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.)

The present study was performed to investigate the histamine-induced airway effect of levocetirizine, an active enantiomer of cetirizine, by intranasal application using ddY mice. Nasal rubbing and sneezing after histamine application into the nasal cavity were used as an index of histamine-induced airway effect in mice. Intranasal application of levocetirizine inhibited both nasal rubbing and sneezing concentration-dependently, and the ED50 values were 0.62 (0.51-0.77) and 0.70 (0.51-1.02) %/site for nasal rubbing and sneezing, respectively. ED50 values of cetirizine were 1.24 (1.02-1.59) and 1.35 (1.02-2.08) %/site for nasal rubbing and sneezing, respectively. Levocetirizine also inhibited nasal rubbing and sneezing when administered orally. These results clearly indicate that levocetirizine was about two times more potent than cetirizine by intranasal application, similar to the findings of the former's affinity for human histamine H1 receptors. In addition, the present findings raise the expectation of the development of levocetirizine nasal drops.