Docosahexaenoic acid and vitamin E can reduce human monocytic U937 cell apoptosis induced by tumor necrosis factor

The effects of polyunsaturated fatty acids and vitamin E on tumor necrosis factor (TNF)-induced apoptosis of human monocytic U937 cells was explored to assess to what extent these nutrients could attenuate apoptosis. Preincubation of U937 cells with arachidonic acid for 24 h did not affect TNF-induced apoptosis. Eicosapentaenoic acid slightly but significantly reduced the proportion of apoptotic cells only when apoptosis was induced by TNF without cycloheximide (CHI). In contrast, preincubation with docosahexaenoic acid (DHA) greatly (40 approximately 70%) attenuated apoptosis induced by stimulation with either TNF or TNF + CHI for 3 h. The inhibition of apoptosis was accompanied by enrichment of DHA in membrane phospholipids, indicating that DHA probably exerted its inhibitory activity after being incorporated into the phospholipids. Vitamin E also played a role as a partial inhibitor of apoptosis 3 h after TNF addition. This vitamin could further reduce the apoptosis of DHA-treated cells, and such an additive effect was obvious when apoptosis was induced at a low frequency. Longer-range stimulation of U937 cells with TNF showed that inhibition of apoptosis by preincubating cells with either DHA or vitamin E was not significant 9 h after TNF addition, but that preincubation with both DHA and vitamin E could reduce the proportion of apoptotic cells even at this time point. Our findings suggested that ingestion of nutrients such as DHA and vitamin E might exert beneficial effects on organ dysfunction associated with various TNF-related diseases.     

Neurodevelopmental delay up to the age of 4 years in infants born to women with gestational diabetes mellitus: The Japan Environment and Children's Study

Aims/IntroductionThis study aimed to investigate the neurodevelopment of infants born to women with gestational diabetes mellitus (GDM).Materials and MethodsData from the National Birth Cohort in the Japan Environment and Children''s Study from 2011 to 2014 (n = 81,705) were used. Japan uses the GDM guidelines of the International Association of Diabetes and Pregnancy Study Groups. The Japanese translation of the Ages and Stages Questionnaires, third Edition, was used to assess neurodevelopment in the following domains: communication skills, gross motor skills, fine motor skills, problem‐solving ability, and personal and social skills. The survey was carried out every 6 months from the age of 6 months to 4 years (total of eight times). Generalized estimating equations were used to evaluate the association between maternal GDM and neurodevelopmental delay based on odds ratios (ORs) and 95% confidence intervals (95% CIs).ResultsNeurodevelopmental delays, particularly in problem‐solving ability, fine motor skills, and personal and social skills, were significantly higher in infants born to women with GDM than in those born to women without GDM (adjusted OR 1.24, 95% CI 1.12–1.36; adjusted OR 1.15, 95% CI 1.03–1.27; and adjusted OR 1.18, 95% CI 1.04–1.33). Furthermore, stratification showed no significant increase in the adjusted ORs (95% CIs) of girls.ConclusionsNeurodevelopment was significantly delayed up to 4 years‐of‐age among boys born to women with GDM.     

Exacerbation of Secondary Pulmonary Hypertension by Flat Chest after Lung Transplantation

A 40-year-old woman with idiopathic pleuroparenchymal fibroelastosis (IPPFE) and flat chest underwent left single lung transplantation (SLT). Although she had developed over-systemic pulmonary arterial pressure (PAP) at transplantation, it was alleviated. However, her PAP gradually increased again. Her transplanted lung was well-inflated, but progression of fibrosis in her right native lung appeared to have caused a mediastinal shift, and her flat chest caused obstruction of the outflow tract of the pulmonary vein. She died of heart failure and associated infection 1.5 years after transplantation. An autopsy confirmed irreversible pulmonary arterial and venous changes in the transplanted lung, suggestive of chronic pressure overload. The flat chest associated with IPPFE can affect pulmonary circulation after SLT.     

Antimicrobial second skin using copper nanomesh

The functional support and advancement of our body while preserving inherent naturalness is one of the ultimate goals of bioengineering. Skin protection against infectious pathogens is an application that requires common and long-term wear without discomfort or distortion of the skin functions. However, no antimicrobial method has been introduced to prevent cross-infection while preserving intrinsic skin conditions. Here, we propose an antimicrobial skin protection platform copper nanomesh, which prevents cross-infectionmorphology, temperature change rate, and skin humidity. Copper nanomesh exhibited an inactivation rate of 99.99% for Escherichia coli bacteria and influenza virus A within 1 and 10 min, respectively. The thin and porous nanomesh allows for conformal coating on the fingertips, without significant interference with the rate of skin temperature change and humidity. Efficient cross-infection prevention and thermal transfer of copper nanomesh were demonstrated using direct on-hand experiments.

The functional support and advancement of our body while preserving the inherent naturalness is one of the ultimate goals of bioengineering (1–4). A functional layer is placed on the skin to complement the intrinsic biological and interactive functions (5, 6) and to add functions that do not yet exist (7–9). During use, the second skin layer should completely exploit its function and underlay skin functions without deforming the skin or interfering with the skin’s external interaction. Materials and structures need to be conformal and mechanically similar to the skin to minimize the distortion of natural sensations and movements. In addition, the air and heat transfer on the skin must be unimpeded to obtain a natural and comfortable wear fit (10).Body protection that requires common and long-term wear is an application in which both functionality and naturalness are important. As the outermost layer connecting our body to the environment, the skin is exposed to physical damage, hazardous chemicals, and infectious pathogens (11, 12). Therefore, we add a protective layer on the skin that blocks or filters out external contaminants. This entails the isolation and accumulation of biochemical compounds, which can lead to self-contamination and the subsequent cross-contamination/infection by interacting with other objects. In contrast to chemical contamination, which is not self-reproductive, the biological contamination of infectious microbes, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a considerable issue to be addressed.By containing an antimicrobial material on the surface of the skin protective layer, cross-infection can be prevented in the long term. Unlike temporary rinsing or disinfection, the use of antibacterial or antiviral substances such as chemical or natural disinfectants and metal nanomaterials inhibits the growth of microorganisms on the surface (13–17). These materials are embedded in a complete covering polymer layer, such as gloves (18, 19), to isolate and protect both the inner and outer surfaces from the infection. To add breathability to the textile especially for the mask (13, 20, 21), many antibacterial fibers have been developed based on these materials. Moreover, various skin-attachable platforms with antimicrobial properties have been developed for convenient usage in daily lives. Antimicrobial nanofibers with conformal attachment to the skin have been developed for drug delivery, wound healing (22, 23), and electrophysiology (24, 25). In addition, stretchable and antibacterial hydrogels have been developed to allow more natural skin movement in wound-healing applications (26–28).However, there has been no practical skin protective solution to prevent cross-infection while preserving intrinsic skin conditions such as surface morphology, thermal transfer, and skin humidity. The thickening of the additional skin layer frequently results in a significant modification of the surface morphology, heat transfer, and the corresponding sensation. Thin layers have limited performance in terms of antimicrobial duration and speed. The skin coverage of polymer or hydrogel film blocks the transfer of air, moisture, and heat. In addition, the antimicrobial performance is focused on the skin side rather than the external side that affects cross-infection. Voids owing to the stiffness of the film or fiber and morphological differences compared to the skin further limit conformality, heat transfer, and water/air permeability (29).Here, we propose an antimicrobial skin protection platform copper nanomesh, which prevents cross-infection while minimizing modification of intrinsic skin properties such as interfacial morphology, temperature change rate, and skin humidity. The thin thickness and porous structure of the nanomesh allow conformal attachment to the fingertips, regardless of the mechanical and structural variations of the fingerprints, nails, and interfaces. To impart antimicrobial properties, copper, one of the most well-known antimicrobial (nano)materials (30–33), was coated with maintaining the nanomesh structure (copper nanomesh, from here onward). The measured inactivation rates of copper nanomesh against Escherichia coli bacteria and influenza virus A (H1N1) were 99.99% within 1 min and 10 min, respectively. It was found that the nanomesh structure contributed to the acceleration of bacterial inactivation compared to the copper film. Furthermore, it exhibited high biocompatibility with the skin cells and stable antibacterial performance even after long-term use (more than 6 h), including water immersion (more than 1 h).In addition, we investigated the naturalness of the copper nanomesh compared to that of the copper film and conventional gloves. As confirmed using the artificial skin and fingerprint recognition, the proposed copper nanomesh exhibited a higher conformability compared to that of the copper film. The copper nanomesh showed a high hydrophobicity to block external contaminants in solution while having high gas permeability and maintaining the skin humidity in a safe range. Additionally, the insertion of copper nanomesh did not affect the temperature change rate, which is important to maintain the sensation and comfort fit of the skin. Finally, the copper nanomesh was compared to the glove by wearing on our hands and interacting with various real-life objects. Using the proposed copper nanomesh, we successfully achieved an effective prevention of cross-infection and less-hindered thermal recognition of objects.     

Acquired hemophilia A associated with Epstein–Barr-virus-associated T/natural killer-cell lymphoproliferative disease: A case report

Introduction:Acquired hemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies against factor VIII (FVIII). Hematological malignancies, especially lymphoid malignancies, are known to be underlying causes of AHA; however, thus far, there is no report of AHA associated with Epstein–Barr-virus-associated T/natural killer-cell lymphoproliferative disease (EBV-T/NK-LPD). Here, we present a case of AHA that developed during treatment for EBV-T/NK-LPD.History:A 69-year-old man visited our hospital because of general fatigue. Blood examination showed pancytopenia, and computed tomography revealed whole-body lymphadenopathy, but there were no findings indicating hematological malignancy from bone marrow aspiration and cervical lymph node biopsy. The level of EBV DNA in peripheral blood was extremely high, and he was diagnosed with EBV-T/NK-LPD. EBV-T/NK-LPD improved with prednisolone (PSL) administration. Seventeen months after starting treatment, the patient complained of back and right leg pain. At that time, he had been treated with low-dose PSL, and EBV-T/NK-LPD was well controlled. Imaging revealed hematoma of the right iliopsoas muscle. Prolonged activated partial thromboplastin time (APTT) was the only abnormal finding in a screening coagulation test. FVIII coagulant activity was below detection limit, and FVIII inhibitor level was increased. From these results, he was diagnosed with AHA.A higher dose of PSL was administered, and, after 1 month of treatment, FVIII activity gradually increased, and FVIII inhibitor level became undetectable. APTT also normalized, and complete remission was achieved and maintained for 13 months with low-dose PSL. During treatment, EBV-T/NK-LPD was well controlled.Conclusion:It is speculated that proliferating lymphocytes interfere with normal immune functions and that abnormal autoantibodies are produced from those lymphocytes in patients with LPD. Therefore, we speculate that EBV-infected and proliferating monoclonal NK cells might have modulated the immune system and produced autoantibodies against FVIII, thus causing AHA in this patient with EBV-T/NK-LPD.     

Effect of sarpogrelate on cardiovascular disorders

The present article, dedicated to Dr NS Dhalla on the occasion of the jubilee of his life’s work, is a brief review of articles based on the authors’ studies of sarpogrelate conducted in collaboration with Dr NS Dhalla. These studies on the effects of sarpogrelate on cardiovascular disorders have been ongoing for more than 10 years, and 10 articles have been published to date.     

Poor responses to tyrosine kinase inhibitors in a child with precursor B‐cell acute lymphoblastic leukemia with SNX2‐ABL1 chimeric transcript

In addition to BCR, various rare fusion partners for the ABL1 gene have been reported in leukemia. We have identified the fusion gene SNX2‐ABL1 in a pediatric case of acute lymphoblastic leukemia (ALL), which has only once previously been reported in an adult patient. Cytogenetic analysis detected this fusion gene arising from a t(5;9)(q22;q34) translocation. ALL cells carrying a SNX2‐ABL1 fusion exhibited a BCR‐ABL1+ ALL‐like gene expression profile. The patient poorly responded to dasatinib but partially responded to imatinib. Treatment using tyrosine kinase inhibitors requires further investigation to optimize the genotype‐based treatment stratification for patients with SNX2‐ABL1 fusion.     

Comprehensive Tool to Assess Oral Feeding Support for Functional Recovery in Post-acute Rehabilitation

Objective

To determine the influence of the Kuchi-kara Taberu (KT) index on rehabilitation outcomes during hospitalized convalescent rehabilitation.

Sinomenine and magnoflorine,major constituents of Sinomeni Caulis et Rhizoma,show potent protective effects against membrane damage induced by lysophosphatidylcholine in rat erythrocytes

The effects of the water extract of Sinomeni Caulis et Rhizoma (SCR-WE) and its major constituents, sinomenine (SIN) and magnoflorine (MAG), on moderate hemolysis induced by lysophosphatidylcholine (LPC) were investigated in rat erythrocytes and compared with the anti-hemolytic effects of lidocaine (LID) and propranolol (PRO) as reference drugs. LPC caused hemolysis at concentrations above the critical micelle concentration (CMC), and the concentration of LPC producing moderate hemolysis (60 %) was approximately 10 μM. SCR-WE at 1 ng/mL–100 μg/mL significantly inhibited the hemolysis induced by LPC. SIN and MAG attenuated LPC-induced hemolysis in a concentration-dependent manner from very low to high concentrations (1 nM–100 μM and 10 nM–100 μM, respectively). In contrast, the inhibiting effects of LID and PRO on LPC-induced hemolysis were observed at higher concentrations (1–100 μM) but not at lower concentrations (1–100 nM). Neither SIN nor MAG affected micelle formation of LPC, nor, at concentrations of 1 nM–1 μM, did they attenuate the hemolysis induced by osmotic imbalance (hypotonic hemolysis). Similarly, SCR-WE also did not modify micelle formation or hypotonic hemolysis, except at the highest concentration. These results suggest that SIN and MAG potently protect the erythrocyte membrane from LPC-induced damage and contribute to the beneficial action of SCR-WE. The protective effects of SIN and MAG are mediated by some mechanism other than prevention of micelle formation or protection of the erythrocyte membrane against osmotic imbalance.