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Droplet microfluidics has become a powerful tool in precision medicine, green biotechnology, and cell therapy for single-cell analysis and selection by virtue of its ability to effectively confine cells. However, there remains a fundamental trade-off between droplet volume and sorting throughput, limiting the advantages of droplet microfluidics to small droplets (

Background: Non-esophageal eosinophilic gastrointestinal disorders (non-EoE EGIDs) are chronic inflammatory disorders with massive infiltration of eosinophils into the gastrointestinal tract. Food elimination diets are potentially effective treatments. But the existing dietary therapies have various weak points. We developed a new regimen to compensate for the shortcomings of the elemental diet and 6-food elimination diet. The new regimen consists of an amino-acid-based formula, potatoes, vegetables, fruits and restricted seasonings. We named it the “Rainbow Elimination Diet (ED).” The aims of this study were to evaluate the tolerability and safety of this diet. Methods: A retrospective medical record examination was conducted at the National Center for Child Health and Development covering the period from January 2010 through December 2018. The medical records of patients (age 2–17 y) with histologically diagnosed non-EoE EGIDs were reviewed. The tolerability, nutritional intake, symptoms, and blood test findings were evaluated. Results: Nineteen patients were offered several kinds of food-elimination diets. Seven patients (eosinophilic gastritis: 5; gastroenteritis: 1; duodenitis: 1) were treated with Rainbow ED. Six patients were compliant with this diet. The median duration of the diet induction phase was 15 days (range 14–30). All 5 patients who had had symptoms just before the induction phase became symptom-free. The body weight decreased in 5 patients (median −0.6 kg), probably because the serum protein increased, resulting in reduced edema. All 5 patients with hypoproteinemia had elevated serum albumin (median 2.9–3.5 g/dL). The ingested nutritional elements were calculated, and most of them were sufficient, except for fat and selenium. Conclusions: The Rainbow ED was well-tolerated and safe for pediatric non-EoE EGIDs.

This study aimed to characterize calyculin A (CL-A)-induced and thimerosal-induced hyperactivation of cryopreserved bovine spermatozoa. Hyperactivation was effectively induced by treating with 10 nM CL-A for 60 min in the presence of cyclic AMP analogs, extracellular Ca2+, and albumin or with 12.5 µM thimerosal briefly in the absence of these capacitation-supporting factors. Majority of the spermatozoa exhibiting CL-A-induced hyperactivation were characterized by the 3-dimensional helical movement with head rotation, higher degree of flagellar curvature, and faster beating of the flagella than those exhibiting thimerosal-induced hyperactivation of the 2-dimensional planar movement without head rotation. The CL-A-induced hyperactivation was linked to the activation of cAMP/protein phosphorylation-dependent signaling cascades and to the decreased activity of glycogen synthase kinase-3α (GSK-3α). In contrast, the thimerosal-induced hyperactivation was suppressed by pretreatment with CL-A and cyclic AMP analogs in the absence of CaCl2 to activate cAMP/protein phosphorylation-dependent signaling cascades. Additionally, the intracellular Ca2+ level in live sperm flagella was significantly higher in the CL-A-treated samples than in the thimerosal-treated samples. These results indicate that CL-A-induced hyperactivation of cryopreserved bovine spermatozoa is an extracellular Ca2+-dependent type with the 3-dimensional helical movement, which can be regulated not only by the activation of cAMP/protein phosphorylation-dependent signaling cascades, leading to a large enhancement of the intracellular Ca2+ level, but also by the reduction in GSK-3α activity. Considering the different characteristics of thimerosal-induced hyperactivation, our results suggest that the diversity of sperm hyperactivation arises from different combinations of flagellar bending and head rotation.

Purpose: An inspiratory muscle warm-up (IMW) improves inspiratory muscle function, but the effects of high-intensity exercise are inconsistent. We aimed to determine the effects of high-intensity IMW on high-intensity exercise performance and muscle oxygenation. Methods: Ten healthy men (maximal oxygen uptake [ V ˙ O 2 max ] 52.2 [5.0] mL·kg–1·min–1) performed constant-load exercise to exhaustion on a cycle ergometer at V ˙ O 2 max under 2 IMW conditions: a placebo condition (PLA) and a high-intensity IMW condition (HIGH). The inspiratory loads were set at 15% and 80% of maximal inspiratory pressure, respectively. Maximal inspiratory pressure was measured before and after IMW. Oxyhemoglobin was measured in the vastus lateralis by near-infrared spectroscopy during exercise. Rating of perceived exertion (RPE) for a leg was measured after 1 and 2 minutes of exercise. Results: Exercise tolerance was significantly higher under HIGH than PLA (228 [49] s vs 218 [49] s, P =.003). Maximal inspiratory pressure was significantly increased by IMW under HIGH (from 125 [20] to 136 [25] cm H2O, P =.031). Oxyhemoglobin was significantly higher under HIGH than PLA at 80% of the total duration of exercise (P =.048). RPE for the leg was significantly lower under HIGH than PLA after 2 minutes of exercise (P =.019). Conclusions: Given that oxyhemoglobin is an index of local oxygen supply, the results of this study suggest that high-intensity IMW increases the oxygen supply to active limbs. It may also reflect a reduction in RPE in the leg. In addition, high-intensity IMW may improve exercise performance. [ABSTRACT FROM AUTHOR]

Background: Eczema patients are commonly immunoglobulin (Ig)E polysensitized. Although atopic dermatitis (AD) phenotypes have been recognized, IgE sensitization patterns based on AD phenotypes have not been well illustrated. We aimed to investigate how eczema phenotypes impact IgE component sensitization patterns. Methods: This birth cohort study investigated a general population in the Tokyo Children's Health, Illness, and Development Study (T-Child Study) until children reached the age of 13 years. Eczema was assessed using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Allergen component specific IgE antibody titers were measured using a multiplex array ImmunoCAP ISAC. Results: Persistent eczema phenotype until adolescence was strongly associated with allergic march symptoms, such as wheezing and hay fever, and oral allergy symptoms, and IgE component sensitizations of airborne (Japanese cedar, house dust mite, Timothy, cat, and dog) and cross-reactive allergens (Bet v 1 family) compared to early-remission and late-onset eczema. On the other hand, late-onset eczema did not show any strong associations with allergic symptoms and IgE sensitization. Adolescents with persistent eczema have high comorbidity of symptoms of pollen-food allergy syndrome. Conclusions: Early-onset eczema is deeply connected with the later allergic march, and late-onset eczema differs from the phenotype of allergic march. Early-onset eczema characterizing IgE sensitization was likely to be an extrinsic type, and late-onset eczema, which was not related to IgE sensitization, was likely an intrinsic type. Pollen-Food Allergy Syndrome is one of the allergic features in allergic march.

Masafumi Seki,1,2 Kosuke Hashimoto,2 Nami Kondo,2 Yoshitaka Ohya,2 Futoshi Kotajima,2 Kotaro Mitsutake1,2 1Division of Infectious Diseases and Infection Control, International Medical Center, Saitama Medical University, Hidaka City, Saitama, Japan; 2COVID-19 Management Team, International Medical Center, Saitama Medical University, Hidaka City, Saitama, JapanCorrespondence: Masafumi Seki, Division of Infectious Diseases and Infection Control, International Medical Center, Saitama Medical University, Yamane 1397-1, Hidaka City, Saitama, 350-1298, Japan, Tel +81-42-984-4392, Fax +81-42-984-0280, Email sekimm@saitama-med.ac.jpBackground: The detailed treatment regimen of COVID-19 patients with hematological malignancies has been unclear, and some fatalities have occurred, although combination therapy with antiviral agents and corticosteroids has been established for moderate to severe COVID-19 patients.Case Series: Case 1 was a 57-year-old woman who had malignant lymphoma and received CHOP therapy with obinutuzumab, and case 2 was a 70-year-old-man who had myeloma and received molecular targeted therapy with weekly corticosteroid. In both cases, SARS-CoV-2 genes and antigens were detected from their nasal swabs, and treatment was started for moderate to severe COVID-19. Case 1 received antiviral agents with high doses of corticosteroids for a long term simultaneously, but the high titer of viral antigens in her nasal swabs persisted. Ground-glass opacities and interstitial shadows also worsened in both lungs, and she finally died on day 60. In contrast, in case 2, antiviral agents were started first, and restarted the immunosuppressive agents, such as gamma globulin and corticosteroids after no titer of SARS-CoV-2 antigens was confirmed. The patient survived, and his abnormal chest shadows showed gradual improvement. Both of the patients received two vaccinations, but showed the low antibody titers for SARS-CoV-2.Conclusion: Administration of both antiviral agents and corticosteroids has been recommended for moderate to severe COVID-19 patients, but in patients with hematological malignancies, it might be better to use antiviral agents first to reduce the viral titers, and then add steroid and related immunosuppressive agents later appropriately to inhibit the excessive inflammatory state. The dose, timing, and order of the antivirals and immunosuppressive agents for COVID-19 should be considered carefully in the patients with hematological malignancies who showed low vaccine effectiveness.Keywords: SARS-CoV-2, B cell depleting agents, corticosteroid, obinutuzumab, rituximab

Abstract Laser thermal therapy is one of the treatments for malignant tumors. We developed a thermal endoscope using an ultra-compact thermo-sensor and established a new laparoscopic laser thermal therapy system to heat cancer tissue at an appropriate temperature, focusing on the fact that thermographic cameras are capable of two-dimensional temperature mapping. Hepatocellular carcinoma (N1S1) cells were implanted into the livers of Sprague–Dawley rats (n = 13) to create orthotopic hepatocellular carcinoma. Six of the rats underwent laparoscopic laser thermotherapy (70 °C, 5 min) using the newly developed system, and the others underwent laparoscopic insertion only. Lesion volume measurement and histological evaluation were performed in all of the rats. The laparoscopic laser thermal therapy system provided stable temperature control. When a temperature of 70 °C was used for the set temperature, the temperature of the target cancer was maintained within the range of 68–72 °C for 93.2% of the irradiation time (5 min). The median volume of the tumors that were thermally treated was significantly smaller than that of the untreated tumors. The newly developed laparoscopic laser thermal therapy system was capable of maintaining the temperature of the tumor surface at any desired temperature and was proven to be effective in treatment of the rat hepatocellular carcinoma model.

This article covers the salient and updated themes of the Japanese Pediatric Guidelines for the Treatment and Management of Asthma (JPGL) 2020 published by the Japanese Society of Pediatric Allergy and Clinical Immunology. In the 2020 guidelines, five new clinical questions (CQs) have been added to address the 12 CQs regarding the treatment of childhood asthma. “Infant and preschool asthma” is diagnosed when young children (

This is an abridged edition of English version of the Clinical Practice Guidelines for the Management of Atopic Dermatitis 2021. Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. In Japan, from the perspective of evidence-based medicine, the current strategies for the treatment of AD consist of three primary measures: (i) use of topical corticosteroids, tacrolimus ointment, and delgocitinib ointment as the main treatment of the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling, and advice about daily life. In the present revised guidelines, the description about three new drugs, namely, dupilumab, delgocitinib, and baricitinib, has been added. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice.

Abstract High-mobility two-dimensional carriers originating from surface Fermi arcs in magnetic Weyl semimetals are highly desired for accessing exotic quantum transport phenomena and for topological electronics applications. Here, we demonstrate high-mobility two-dimensional carriers that show quantum oscillations in magnetic Weyl semimetal SrRuO3 epitaxial films by systematic angle-dependent, high-magnetic field magnetotransport experiments. The exceptionally high-quality SrRuO3 films were grown by state-of-the-art oxide thin film growth technologies driven by machine-learning algorithm. The quantum oscillations for the 10-nm SrRuO3 film show a high quantum mobility of 3.5 × 103 cm2/Vs, a light cyclotron mass, and two-dimensional angular dependence, which possibly come from the surface Fermi arcs. The linear thickness dependence of the phase shift of the quantum oscillations provides evidence for the non-trivial nature of the quantum oscillations mediated by the surface Fermi arcs. In addition, at low temperatures and under magnetic fields of up to 52 T, the quantum limit of SrRuO3 manifests the chiral anomaly of the Weyl nodes. Emergence of the hitherto hidden two-dimensional Weyl states in a ferromagnetic oxide paves the way to explore quantum transport phenomena for topological oxide electronics.

Study Design Clinical case series. Purpose This study aimed to report dynamization–posterior lumbar interbody fusion (PLIF), our surgical treatment for hemodialysis-related spondyloarthropathy (HSA), and investigate patients’ postoperative course within 2 years. Overview of Literature HSA often requires lumbar fusion surgery. Conventional PLIF for HSA may cause progressive destructive changes in the vertebral endplate, leading to progressive cage subsidence, pedicle screw loosening, and pseudoarthrosis. A dynamic stabilization system might be effective in patients with a poor bone quality. Thus, we performed “dynamization–PLIF” in hemodialysis patients with destructive vertebral endplate changes. Methods We retrospectively examined patients with HSA who underwent dynamization–PLIF at our hospital between April 2010 and March 2018. The radiographic measurements included lumbar lordosis and local lordosis in the fused segment. The evaluation points were before surgery, immediately after surgery, 1 year after surgery, and 2 years after surgery. The preoperative and postoperative radiographic findings were compared using a paired t-test. A p-value of less than 0.05 was considered significant. Results We included 50 patients (28 males, 22 females). Lumbar lordosis and local lordosis were significantly improved through dynamization–PLIF (lumbar lordosis, 28.4°–35.5°; local lordosis, 2.7°–12.8°; p

While many companies have actively implemented human resource initiatives to promote employee work-life balance (WLB), some workplaces still maintain old workplace norms against WLB, making it difficult for employees to utilize such benefits. Previous literature has attributed this issue in part to a phenomenon known as pluralistic ignorance, where unpopular norms are maintained due to misperceptions of each other’s beliefs. Existing studies have confirmed that pluralistic ignorance undermines employee WLB, but how to attenuate pluralistic ignorance has not yet been fully examined. Therefore, this study uses agent-based simulation and examines how to resolve pluralistic ignorance. The model also incorporates differences in the nature of norms, particularly the degree of sanction expectations that are assumed to be related to the resolution of pluralistic ignorance. Our analysis confirmed that pluralistic ignorance about the norms with weak expected sanctions is more likely to be resolved by employees’ honest display of their true beliefs. The results also showed that pluralistic ignorance could take various forms, indicating the need to be aware of its different forms when considering intervention strategies in future research.