Inclusion of Amine Isomers with Open-Chain Hosts Having a Partial Structure of p-tert-Butylthiacalixarene.

Porous materials, which can capture a specific compound from a hard-to-separate molecular mixture, are strongly desired for practical separation and purification processes. Aiming to develop such materials, we have investigated the performance of our original host compounds, [3,3'-thiobis(5-tert-butyl-2-hydroxybenzene)-1,1'-diyl]diacetic acid (2) and its monopropyl ester (3), in discriminating among regio- or stereoisomers of three groups of amines, 2-, 3-, and 4-methylpyridine, 2-, 6-, and 8-methylquinoline, and cis- and trans-4-cyclohexanamine. Diacid 2 selectively included 4-methylpyridine in hexane and 3-methylpyridine in toluene in competitive inclusion among the three regioisomers. Mechanistic studies revealed that the inclusions of 3- and 4-methylpyridine are favored under kinetic and thermodynamic control, respectively. Solvent-dependent switching in guest selectivity was also observed in competitive inclusion among the methylquinoline isomers with diacid 2, whereas trans-4-methylcyclohexanamine was selectively included over the cis-isomer by monoester 3, as well as diacid 2, regardless of the solvent employed. X-ray crystallographic analysis of the resulting inclusion crystals suggests that the wide guest scope of the host compounds originates from their flexible ability to form complexes with amines.

The Oral Provocation Test for Raw Egg in Patients with Hen Egg Allergy.

BACKGROUND: Many researchers have made efforts to develop diagnostic tools for predicting the outcome of oral food challenges (OFCs). The aim of this study was to assess the diagnostic value of the skin prick test (SPT) and blood-specific IgE concentrations based on the outcome of the OFCs for heated and raw hen egg. METHODS: This study included 103 children with suspected hen egg allergy (HEA; median age 23 months, range 10-155; 72 boys, 31 girls). Forty-three patients were diagnosed with HEA by OFC. Of 60 patients who tolerated heated egg white (HEW), 22 underwent the OFC for raw hen egg and 7 developed adverse reactions after ingesting raw egg. Their wheal diameters and specific IgE levels for egg white and ovomucoid were determined. RESULTS: Wheal diameters as well as blood-specific IgE levels for egg white and ovomucoid were significantly larger in children with positive OFC results for HEW than in those with negative results. However, there were no significant differences between the positive and negative test results for raw hen egg white (REW) in wheal diameter or blood-specific IgE levels. CONCLUSIONS: The SPT and blood-specific IgE can be used to diagnose HEA. However, the provocation test for REW in children without HEW allergy is important because the values of SPT and specific IgE were not significantly different between children with and without raw egg allergy.

[Successful treatment with dose-adjusted EPOCH-R for triple-hit lymphoma having BCL2, BCL6 and MYC translocations].

Double- and triple-hit lymphomas (DHL/THL), high-grade B-cell lymphomas with an extremely poor prognosis, are defined by a chromosomal breakpoint affecting the MYC/8q24 locus in combination with another recurrent breakpoint. The successful use of dose-adjusted (DA) EPOCH-R in patients with MYC-positive lymphoma and Burkitt lymphoma (BL) was recently reported. A 74-year-old man with acute renal dysfunction and hyperkalemia was transferred to our emergency center by ambulance. PET-CT revealed a left renal hilar mass enveloping the abdominal para-aortic domain and bladder and hydronephrosis. High (18)F-FDG uptake revealed lymph node, peritoneum, and multiple bone metastases. Analysis of the bone marrow aspirate revealed abnormal lymphoid cells with deeply basophilic cytoplasm and numerous vacuoles resembling Burkitt cells. Chromosomal analysis revealed a complex chromosomal karyotype, including t(14;18)(q32;q21), and FISH analysis confirmed split BCL2, BCL6, and MYC signals. Bone marrow biopsy revealed diffusely infiltrating large abnormal lymphoid cells with a CD10⁺, CD20⁺, BCL2⁺, BCL6⁺, c-MYC⁺ and MUM1(-) immunophenotype. B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma and BL, was diagnosed. The patient achieved a partial response after eight courses of DA-EPOCH-R chemotherapy. Our experience suggests that DA-EPOCH-R may be an effective treatment for DHL/THL.

Effects of Sacubitril/Valsartan on Glycemic Control in Japanese Patients With Heart Failure and/or Hypertension.

Background: Post hoc analysis of the PARADIGM-HF trial showed that sacubitril/valsartan (S/V) was more effective than enalapril in lowering HbA1c in patients with heart failure and diabetes. Methods and Results: In the present study, the effect of S/V on glycemic control was retrospectively analyzed in 150 patients (median age 74 years) who were prescribed S/V for the treatment of heart failure and/or hypertension. After a median period of 13 weeks treatment, mean (±SD) HbA1c levels decreased significantly from 6.56±0.68% to 6.49±0.63%. The decrease in HbA1c was evident in patients with (n=111), but not in those without, diabetes. There were no significant changes in renal function after S/V treatment, but systolic blood pressure was significantly reduced from 141±21 to 134±19 mmHg. Ninety patients had N-terminal pro B-type natriuretic peptide (NT-proBNP) tested, and S/V significantly decreased median NT-proBNP concentrations from 1,026 to 618 pg/mL; however, there was no correlation between the degree of decrease in HbA1c and that in NT-proBNP. Multiple regression analysis revealed that being diabetic, rather than having heart failure, was a significant independent variable for a reduction in HbA1c. Conclusions: Treatment with S/V improved glycemic control in patients with heart failure and/or hypertension, especially in those with concomitant diabetes. This favorable effect on glucose metabolism may be mediated by neprilysin inhibition and is desirable in the treatment of heart failure and hypertension in diabetic patients.

Impact of the COVID-19 Pandemic on Glycemic Control and Blood Pressure Control in Patients with Diabetes in Japan.

Objective In this study, we investigated whether and how the COVID-19 pandemic affected glycemic control and blood pressure (BP) control in patients with diabetes mellitus (DM). Methods DM patients whose HbA1c level was measured regularly before and after the declaration of a state of emergency were included in this study. Some patients were given questionnaires about changes in their lifestyle to determine the factors affecting glycemic control and BP control. Results The median HbA1c level of the 804 patients increased significantly from 6.8% before the state of emergency to 7.1% and 7.0% during and after the state of emergency, respectively. This was in contrast to the decrease one year earlier due to seasonal variations. In the 176 patients who responded to the questionnaire, the HbA1c level also increased significantly during and after the state of emergency. The worsening of glycemic control was more pronounced in the group that had achieved HbA1c of <7% before the state of emergency than in those with higher values. Unlike the rise in HbA1c, the BP did not rise during the state of emergency but did rise significantly afterwards. There was no marked decrease in HbA1c or BP after the state of emergency, even in patients who responded that they were much more careful with their diet, ate less, or exercised more. Conclusions The COVID-19 pandemic worsened glycemic control and BP control, even in patients who perceived no marked change in their diet or exercise, suggesting that more active lifestyle guidance is necessary for good treatment of DM patients.

Catheter-based ultrasound renal denervation in patients with resistant hypertension: the randomized, controlled REQUIRE trial.

Renal denervation is a promising new non-pharmacological treatment for resistant hypertension. However, there is a lack of data from Asian patients. The REQUIRE trial investigated the blood pressure-lowering efficacy of renal denervation in treated patients with resistant hypertension from Japan and South Korea. Adults with resistant hypertension (seated office blood pressure ≥150/90 mmHg and 24-hour ambulatory systolic blood pressure ≥140 mmHg) with suitable renal artery anatomy were randomized to ultrasound renal denervation or a sham procedure. The primary endpoint was change from baseline in 24-hour ambulatory systolic blood pressure at 3 months. A total of 143 patients were included (72 renal denervation, 71 sham control). Reduction from baseline in 24-hour ambulatory systolic blood pressure at 3 months was not significantly different between the renal denervation (-6.6 mmHg) and sham control (-6.5 mmHg) groups (difference: -0.1, 95% confidence interval -5.5, 5.3; p = 0.971). Reductions from baseline in home and office systolic blood pressure (differences: -1.8 mmHg [p = 0.488] and -2.0 mmHg [p = 0.511], respectively), and medication load, did not differ significantly between the two groups. The procedure-/device-related major adverse events was not seen. This study did not show a significant difference in ambulatory blood pressure reductions between renal denervation and a sham procedure in treated patients with resistant hypertension. Although blood pressure reduction after renal denervation was similar to other sham-controlled studies, the sham group in this study showed much greater reduction. This unexpected blood pressure reduction in the sham control group highlights study design issues that will be addressed in a new trial. CLINICAL TRIAL REGISTRATION: NCT02918305 ( http://www.clinicaltrials.gov ).

Mitigation of the allergenic activity of beta-lactoglobulin by electrolysis.

Beta-lactoglobulin (BLG) is the most prominent allergen causing milk allergy and contains disulfide (S-S) bonds that may be responsible for its allergic action. As S-S bonds may be reduced during electrolysis, this study was undertaken to evaluate modulation of the allergic action of BLG after electrolysis. A current of 85 mA/cm(2) was applied, and the allergic action was evaluated by means of competitive CAP-FEIA inhibition tests and skin prick tests (SPT). Modification of BLG was examined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF-MS). Although the number of total free sulfhydryl (SH) groups of BLG did not differ between the cathode and anode sides, BLG on the cathode side showed 54% lower inhibition than untreated BLG in the competitive CAP-FEIA inhibition tests, and reduced wheal reactions, by 71%, in the SPT compared with those with untreated BLG. The SPT results with BLG on the anode side did not differ significantly from those with untreated BLG. The MALDI-ToF-MS results for the dimer of untreated BLG or BLG on the anode side showed two distinct peptide fragments (residues (41)V-(60)K and (149)L-(162)I) but, on the contrary, the dimer of BLG on the cathode side did not give these fragments, this being similar to in the case of the monomer of BLG. The allergic action of BLG was markedly mitigated during electrolysis on the cathode side, a dimer of BLG with a different mass spectrometric pattern from that of the dimer of untreated BLG being simultaneously formed.

Characteristics of patients with emergency attendance for severe hypoglycemia and hyperglycemia in a general hospital in Japan.

ABSTRACT: Despite advances in treatments for diabetes mellitus (DM), severe acute glycemic crises still occur. In this study, the characteristics of patients who were transported to an emergency department due to acute glycemic crises were investigated.We enrolled patients who were transported to our hospital by ambulance due to hypoglycemia or hyperglycemia during the period from January 2015 to December 2019. Initial glucose levels below 70 mg/dL and above 250 mg/dL were defined as hypoglycemia and hyperglycemia, respectively.In the 5-year period, 16,910 patients were transported to our hospital by ambulance. Of those patients, 87 patients (0.51%) were diagnosed with hypoglycemia, 26 patients (0.15%) were diagnosed with hyperglycemia and 1 patient was diagnosed with lactic acidosis. Compared to patients with hypoglycemia, blood urea nitrogen, serum potassium and hemoglobin levels were higher in patients with hyperglycemia. Systolic blood pressure was lower and pulse rate was higher in patients with hyperglycemia, possibly reflecting dehydration in hyperglycemia. Patients with hyperglycemia were younger (63 vs 70 years old, median), more likely to be hospitalized (92.3% vs 23.0%) with poorer prognosis (23.1% vs 4.6%) than those with hypoglycemia. In 64 DM patients with hypoglycemia, 34 patients were treated with insulin and 24 patients were treated with sulfonylurea or glinide, and their medication was often inappropriate. Excessive alcohol intake and malnutrition were the main causes of hypoglycemia in 23 non-DM patients. The main reasons for hyperglycemia were interrupted treatment, forgetting insulin injection and infection.To avoid acute glycemic crises, optimization of anti-DM therapy and education of patients are needed.

Molecular cloning and allergenicity of Pen j 1, a major allergen of kuruma prawn, Penaeus japonicus.

Tropomyosins have been identified as a common allergen in crustaceans, but their allergenicity is not well understood. In the present study, we isolated an allergen, Pen j 1, a tropomyosin from kuruma prawn Penaeus japonicus, and determined its N-terminal amino acid sequence. The cDNA encoding the allergen was cloned by 5'- and 3'-rapid amplification of cDNA ends (RACE), and was found to code for a protein which consists of 284 amino acid residues. Sequencing analyses indicated for the first time that mature tropomyosin is formed by the elimination of a leader peptide of nine amino acid residues. To elucidate the binding sites of IgE antibodies in the sera of shrimp-sensitive patients, various recombinant peptides were expressed in Escherichia coli as fusion proteins with glutathione S-transferase (GST), and the examined with regard to reactivity with IgE antibodies. The IgE-binding epitopes were found to locate over the whole sequence of the allergen, and the IgE antibodies in the sera were found to recognize strongly its C-terminal region.

Hydrogel electrodeposition based on bipolar electrochemistry.

Bipolar electrochemistry has attracted great interest for applications based on sensing, electrografting, and electrodeposition, because the technique enables electrochemical reactions to be induced at multiple bipolar electrodes (BPEs) with only a single power supply. However, there are only a few reports on the biofabrication of hydrogels using BPEs. In this study, we applied bipolar electrochemistry to achieve the electrodeposition of calcium-alginate hydrogels at specified target areas, which is possible because of the use of water electrolysis to obtain acidification at the anodic pole. This scheme was used to successfully fabricate an array of hydrogel deposits at a BPE array. In addition, hydrogels were successfully fabricated either at only the target BPEs or only the target areas of BPEs by repositioning the driving electrodes. Furthermore, a hydrogel was drawn on a large BPE as a canvas by using small driving electrodes. As a demonstration of the electrodeposited hydrogels for bioapplications, mammal cells were cultured in the hydrogels. Because the amount and shape of the hydrogel deposits can be controlled by using the bipolar system, the system we developed can be used for biosensors and cell culture platforms.

Skin capacitance in normal and atopic infants, and effects of moisturizers on atopic skin.

Skin capacitance depends on the water content of the stratum corneum, and moisturizers have beneficial effects in atopic dermatitis. This study was performed to determine the skin capacitance in normal and atopic infants, and to evaluate the effects of different moisturizers on infantile atopic skin. The skin capacitance in 186 normal infants and 37 atopic infants was measured with a Moisture Checker. Measurements were also made for atopic infants after an application of pure petrolatum or an oil-in-water cream containing a humectant. Age-related decreases in skin capacitance were observed at the majority of dermal sites in normal infants. The skin capacitance was significantly lower in atopic infants compared with normal infants at all body sites. Pure petrolatum and oil-in-water creams containing humectants significantly augmented the capacitance from 2% to 7%. The reference values for skin capacitance may be helpful for delineating normal from atopic skin. Certain moisturizers can increase skin hydration.

Evaluation of the skin-prick test for predicting the outgrowth of cow's milk allergy.

BACKGROUND: Although considerable efforts have been made to develop diagnostic tools for predicting the outcome of oral food challenges, tests for predicting the outgrowth of food allergies are lacking. OBJECTIVE: The aim of this study was to assess the diagnostic value of the wheal size and skin index (SI) (the ratio of an allergen-induced wheal to a histamine-induced wheal diameter) of the skin-prick test based on the outcome of a controlled oral provocation test for cow's milk. Moreover, we assessed whether wheal size and/or SI were useful for predicting the outgrowth of cow's milk allergy (CMA). METHODS: This study included 135 children with suspected CMA. Eighty-one patients were definitely diagnosed by oral provocation tests for cow's milk, and their wheal diameters, SIs, and cow milk's-specific serum immunoglobulin E concentrations were determined. RESULTS: The wheal diameters were significantly larger and the SIs significantly higher in children with positive oral provocation test results than in those with negative test results. We found that 50% of the patients were expected to be able to drink cow's milk by age 5 years. In these patients, the wheal diameters were significantly smaller and the SIs significantly lower at the time of CMA outgrowth than at the time of diagnosis, whereas these values were apt to increase in patients who did not outgrow CMA, with no significant difference. CONCLUSIONS: The skin-prick test can be used to diagnose CMA and predict CMA outgrowth. A wheal diameter of 8 mm or/and an SI of 1.0 is informative, not only in diagnosing CMA but also in predicting a natural CMA outgrowth.

Infarct size limitation by nicorandil: roles of mitochondrial K(ATP) channels, sarcolemmal K(ATP) channels, and protein kinase C.

OBJECTIVES: This study aimed to examine:1) whether nicorandil protects the ischemic myocardium by activating sarcolemmal adenosine triphosphate (ATP)-sensitive K(+) (sarcK(ATP)) channels or the mitochondrial K(ATP) (mitoK(ATP)) channels, and 2) whether protein kinase C (PKC) activity is necessary for cardioprotection afforded by nicorandil. BACKGROUND: Nicorandil is a hybrid of nitrate and a K(ATP) channel opener that activates the sarcK(ATP) and mitoK(ATP) channels. Both of these K(ATP) channels are regulated by PKC, and this kinase may be activated by nitric oxide and also by oxygen free radicals (OFR) generated after mitoK(ATP) channel opening. METHODS: In isolated rabbit hearts, infarction was induced by 30-min global ischemia/2-h reperfusion with monitoring of the activation recovery interval (ARI), an index of action potential duration. Protein kinase C translocation was assessed by Western blotting. RESULTS: Nicorandil did not change ARI before ischemia, but it accelerated ARI shortening after the onset of ischemia and reduced infarct size by 90%. A sarcK(ATP) channel selective blocker, HMR1098, abolished acceleration of ischemia-induced ARI-shortening by nicorandil and eliminated 40% of nicorandil-induced infarct size limitation. A mitoK(ATP) channel selective blocker, 5-hydroxydecanoate, abolished the protection afforded by nicorandil without affecting ARI. Cardioprotection by nicorandil was inhibited neither by an OFR scavenger, N-2-mercaptopropionylglycine nor by a PKC inhibitor, calphostin C, at a dose that was capable of inhibiting PKC- epsilon translocation after preconditioning. CONCLUSIONS: Both the sarcK(ATP) and mitoK(ATP) channels are involved in anti-infarct tolerance afforded by nicorandil, but PKC activation induced by nitric oxide or OFR generation, if any, does not play a crucial role.

Cytokine production and modulation: comparison of patients with chronic fatigue syndrome and normal controls.

We studied cytokine production in 15 patients with chronic fatigue syndrome (CFS) and 23 controls. CFS patients' peripheral blood mononuclear cells were cultured with lipopolysaccharide or phytohemagglutinin. Enzymatic immunoassay indicated cytokine concentration in culture supernatants. CFS patients showed significantly lower mRNA levels and transforming growth factor-beta1 (TGF-beta1) production. Cytokine dysregulation affects CFS pathogenesis. TGF-beta1 may aid treatment because it affects CFS inflammatory characteristics.

Attenuated Allergenic Activity of Ovomucoid After Electrolysis.

Ovomucoid (OMC) is the most prominent allergen causing hen's egg allergy, containing disulfide (S-S) bonds that may be responsible for its allergic action. As S-S bonds may be reduced during electrolysis, this study was undertaken to evaluate modulation of the allergic action of OMC after electrolysis. Electrolysis was carried out for 1% OMC containing 1% sodium chloride for 30 minutes with a voltage difference of 90 V, 0.23 A (30 mA/cm²). Protein assays, amino acid measurement, and mass spectrometry in untreated OMC and OMC on both the anode and cathode sides after electrolysis were performed. Moreover, 21 patients with IgE-mediated hen's egg allergy were evaluated by using the skin prick test (SPT) for untreated OMC and OMC after electrolysis. The allergic action of OMC was reduced after electrolysis on both the anode and cathode sides when evaluated by the SPT. The modifications of OMC on electrolysis caused the loss of 2 distinct peptide fragments (57E-63K and 123H-128R) as seen on matrix-associated laser desorption/ionization time-of-flight mass spectrometry. The total free SH groups in OMC were increased on the cathode side. Although the regions of S-S broken bonds were not determined in this study, the change in S-S bonds in OMC on both the anode and cathode sides may reduce the allergenic activity.

Aortic valve aneurysm responsible for acute congestive heart failure and histological findings: A case report.

We experienced a case of acute congestive heart failure in a 73-year-old man who had been followed up due to mild-to-moderate aortic stenosis and moderate-to-severe aortic regurgitation. A huge aortic valve aneurysm was found to extend from his right coronary cusp to a left ventricular outflow tract, resulting in moderate subaortic obstruction and severe aortic regurgitation. Surgical repair was performed and a perforated aneurysm of right aortic cusp was identified. Histological examinations suggested that healed infective endocarditis was responsible for the formation of an aneurysm in the aortic valve. .

Direct imaging of bridged twin protoplanetary disks in a young multiple star.

Studies of the structure and evolution of protoplanetary disks are important for understanding star and planet formation. Here we present the direct image of an interacting binary protoplanetary system. Both circumprimary and circumsecondary disks are resolved in the near-infrared. There is a bridge of infrared emission connecting the two disks and a long spiral arm extending from the circumprimary disk. Numerical simulations show that the bridge corresponds to gas flow and a shock wave caused by the collision of gas rotating around the primary and secondary stars. Fresh material streams along the spiral arm, consistent with the theoretical scenarios in which gas is replenished from a circummultiple reservoir.

Mite penetration of different types of material claimed as mite proof by the Siriraj chamber method.

BACKGROUND: There are different materials and principles used in the construction of bed encasings. Although these covers claim to have antimite properties, they might not be mite proof. OBJECTIVE: This study evaluated the effectiveness of mite penetration of these covers by using the Siriraj chamber method. METHODS: Thirty-two covers collected from 9 different countries were categorized according to the materials used to manufacture them. They were (1) tightly woven, (2) film or membrane coated and loosely woven, (3) acaricidal coated and loosely woven, (4) nonwoven, (5) film coated and nonwoven, (6) acaricidal coated and nonwoven, and (7) plastic. Adult mites, Dermatophagoides pteronyssinus, were placed on either the outer or inner surfaces of each of the test fabrics for 3 replications, resulting in a total of 6 samples per fabric. All samples were observed for penetration every day for 1 week under a stereomicroscope. If a single mite penetrated any fabric, it was scored as a penetration. RESULTS: Mites penetrated (1) into all samples of film-coated woven and nonwoven covers, an acaricide-coated nonwoven cover, and nonwoven types; (2) from both sides and colonized within the matrix of some samples; and (3) completely in other cases. All of the woven covers and the plastic cover prevented mite penetration. Photomicrographs documented all penetrations. CONCLUSIONS: Tightly woven covers and plastic prevent mite penetration, whereas nonwoven, loosely woven, acaricide-coated, and laminated materials do not. The Siriraj chamber method adequately evaluates the effectiveness of antimite barriers. CLINICAL IMPLICATIONS: For mite avoidance, allergists should recommend the use of tightly woven covers on suspected bedding containing dust mites.

The occurrence of mite-containing wheat flour.

Anaphylaxis after eating mite-infested wheat flour has been recently reported. This paper is to describe two cases and examine the occurrence of mite contamination in wheat flour in Japan. Packages of wheat flour from retail outlets and homes were examined microscopically for the presence of mites. Three of 176 packages from retail outlets and seven of 127 from homes were infested with mites, and it seems likely that the mite contamination takes place in most cases at homes after the packages have been opened. No mites were found in packages stored in a refrigerator, therefore, mite-sensitive patients must be advised to store wheat flour products in a refrigerator.