Search for Periodic Time Variations of the Solar

We report a search for time variations of the solar ^{8}B neutrino flux using 5804 live days of Super-Kamiokande data collected between May 31, 1996, and May 30, 2018. Super-Kamiokande measured the precise time of each solar neutrino interaction over 22 calendar years to search for solar neutrino flux modulations with unprecedented precision. Periodic modulations are searched for in a dataset comprising five-day interval solar neutrino flux measurements with a maximum likelihood method. We also applied the Lomb-Scargle method to this dataset to compare it with previous reports. The only significant modulation found is due to the elliptic orbit of the Earth around the Sun. The observed modulation is consistent with astronomical data: we measured an eccentricity of (1.53±0.35)%, and a perihelion shift of (-1.5±13.5) days.

Search for Cosmic-Ray Boosted Sub-GeV Dark Matter Using Recoil Protons at Super-Kamiokande.

We report a search for cosmic-ray boosted dark matter with protons using the 0.37 megaton×years data collected at Super-Kamiokande experiment during the 1996-2018 period (SKI-IV phase). We searched for an excess of proton recoils above the atmospheric neutrino background from the vicinity of the Galactic Center. No such excess is observed, and limits are calculated for two reference models of dark matter with either a constant interaction cross section or through a scalar mediator. This is the first experimental search for boosted dark matter with hadrons using directional information. The results present the most stringent limits on cosmic-ray boosted dark matter and exclude the dark matter-nucleon elastic scattering cross section between 10^{-33}cm^{2} and 10^{-27}cm^{2} for dark matter mass from 1 MeV/c^{2} to 300 MeV/c^{2}.

Erratum: Search for Cosmic-Ray Boosted Sub-GeV Dark Matter Using Recoil Protons at Super-Kamiokande [Phys. Rev. Lett. 130, 031802 (2023)].

This corrects the article DOI: 10.1103/PhysRevLett.130.031802.

Genome-wide DNA methylation profile implicates potential cartilage regeneration at the late stage of knee osteoarthritis.

OBJECTIVE: The aim of this work was to characterize the genome-wide DNA methylation profile of cartilage from three regions of tibial plateau isolated from patients with primary knee osteoarthritis (OA), providing the first DNA methylation study that reflects OA progression. METHODS: The unique model system was used to section three regions of tibial plateau: the outer lateral tibial plateau (oLT), the inner lateral tibial plateau (iLT) and the inner medial tibial plateau (iMT) regions which represented the early, intermediate and late stages of OA, respectively. Genome-wide DNA methylation profile was examined using Illumina Infinium HumanMethylation450 BeadChip array. Comparisons of the iLT/oLT and iMT/oLT groups were carried out to identify differentially methylated (DM) probes (DMPs) associated with OA progression. DM genes were analyzed to identify the gene ontologies (GO), pathways, upstream regulators and networks. RESULTS: No significant DMPs were identified in iLT/oLT group, while 519 DMPs were identified in iMT/oLT group. Over half of them (68.2%) were hypo-methylated and enriched in enhancers and OpenSea. Upstream regulator analysis identified many microRNAs. DM genes were enriched in transcription factors, especially homeobox genes and in Wnt/ß-catenin signaling pathway. These genes also showed changes in expression when analyzed with expression profiles generated from previous studies. CONCLUSION: Our data suggested the changes in DNA methylation occurred at the late stage of OA. Pathways and networks enriched in identified DM genes highlighted potential etiologic mechanism and implicated the potential cartilage regeneration in the late stage of knee OA.

Receptor Antagonist of IL-13 Exerts a Potential Negative Regulation During Early Infection of Human Schistosomiasis.

The pathology of schistosomiasis is associated with the formation of granulomas, and this process is associated with liver fibrosis. Studies indicate that Th1 cytokines reduce fibrosis in schistosomiasis, while Th2 cytokines play a part in the progression of fibrosis, and IL-13 has a critical role in this process. The IL-13Rα2 receptor, known as a 'receptor antagonist' binds with high affinity to IL-13, and studies have identified that this plays a part in reducing fibrosis and the size of granulomas. The objective of this study was to evaluate the function of IL-13Rα2 and cellular immune response in hepatic fibrosis. A negative correlation between IL-13Rα2 and IL-13 was found, suggesting an increase in cytokine in early fibrosis. Initially, a negative correlation between IFN-γ and IL-13 was found in patients without fibrosis, and subsequently, this correlation was found to be positive in patients with severe fibrosis, thereby highlighting a new mechanism for regulating the progress of periportal fibrosis. There was a positive correlation between the profiles of Th1 and Th2 cytokines, suggesting the presence of both responses, thus regulating the disease. The results contribute to a better understanding of the immune mechanisms that control the process of hepatic fibrogenesis in schistosomiasis in humans.

Histological evaluation of skeletonized internal thoracic artery using ForceTriad™.

BACKGROUND: The internal thoracic artery (ITA) is a useful graft for coronary artery bypass grafting. Skeletonization, a technique that uses an ultrasonic scalpel, is increasingly used. However, the cost of an ultrasonic scalpel is extremely high. The purpose of this study was to determine whether a new electrosurgical cautery device (ForceTriad™) is as effective as an ultrasonic scalpel. METHODS: Bilateral ITAs were harvested from eight pigs using the skeletonizing technique. The ITA on one side was harvested with an ultrasonic scalpel and on the other side using the ForceTriad™. Macroscopic and histological examinations were performed in sixteen ITAs. RESULTS: No significant differences in the time required for harvesting were observed. The macroscopic findings revealed no significant change in any of the samples. The histological findings showed that the degree of thermal injury was similar. The normal structure was maintained in all samples. The ForceTriad™ costs US$ 226.82 less per patient than the ultrasonic scalpel. CONCLUSION: The new electrosurgical cautery device ForceTriad™ was less expensive, but it was equally effective. It appears that skeletonization performed with the new device is equivalent to that performed with an ultrasonic scalpel.

Lactobacillus pentosus strain b240 suppresses pneumonia induced by Streptococcus pneumoniae in mice.

AIMS: Oral administration of probiotics has been known to improve inflammatory responses against infectious diseases. Here, we describe the inhibitory effect of oral intake of heat-killed Lactobacillus pentosus strain b240 (b240) on pneumococcal pneumonia in a murine experimental model. METHOD AND RESULTS: The mice treated with oral b240 for 21 days before Streptococcus pneumoniae infection exhibited prolonged survival time and less body weight loss, compared with saline-treated control mice. Mild pneumonia with significantly reduced secretion of inflammatory cytokines/chemokines according to related mitogen-activated protein kinase signalling molecules (phosphorylated c-Jun N-terminal kinase) was found in b240-treated mice, whereas severe pneumonia with hypercytokinemia was evident in control mice. Prominent reduction in the number of pneumococci and elevated expression of Toll-like receptor 2 and 4 in the lung tissues was concomitantly noted in b240-treated mice. CONCLUSIONS: These findings indicate that b240 has inhibitory effects on pneumococcal pneumonia induced by Strep. pneumoniae infection and improves inflammatory tissue responses, resulting in reduced damages to the respiratory tissues. SIGNIFICANCE AND IMPACT OF THE STUDY: These results demonstrate that oral administration of b240 might protect host animals from Strep. pneumoniae infection by augmentation of innate immune response.

Enhanced inhibitory effects of TBT chloride on the development of F1 rats.

Neurotoxicity is one of the major effects of tributyltin (TBT). The effects on the next generation of F(1) rats exposed to TBT via the placenta and their dams' milk may be stronger than those on adults. Pregnant Wister rats were exposed to TBT at 0 and 125 ppm in their food. Half of the female F(1) rats in both groups were exposed to TBT at 125 ppm in their food from 9 to 15 weeks of age. Female F(1) rats were divided into the following groups: the control-control (CC) group, with no exposure; the TBT-control (TC) group, exposed to TBT via the placenta and their dams' milk; the control-TBT (CT) group, exposed to TBT via their food from 9 to 15 weeks of age; and the TBT-TBT (TT) group, exposed to TBT via the placenta, their dams' milk, and their food (n = 10/group). After administration, an open-field test and prepulse inhibition (PPI) test were performed at 15 weeks of age. The mean body weights of the TC and TT groups were significantly lower than that of the CC group from 9 to 15 weeks of age. The mean relative thymus weight of the TC and TT groups was significantly lower than that of the CC group. In the open-field test, a marked decrease in the total locomotion distance was observed in the TT group. The mean values in the TT and TC groups were significantly lower than that in the CC group. For the locomotion distance between 15 and 20 min, the mean values in the CT, TC, and TT groups were significantly lower than that in the CC group. The mean locomotor distance between 25 and 30 min in the TT group was significantly lower than that in the CC and TC groups. The mean values of instances of wall rearing in the TC, CT, and TT groups were significantly lower than that in the CC group. The mean value of face washing or body washing in the TT group was significantly lower than that in the CT group. There were no significant differences in indexes of the PPI test. Exposure to TBT via the placenta and their dams' milk inhibited the development of F(1) rats, which continued after weaning. Inhibition of the rats' activity induced by exposure to TBT via the placenta and their dams' milk and/or via their food was suggested. The effects were most evident in the TT group.

MAP2-mediated in vitro interactions of brain microtubules and their modulation by cAMP.

Microtubule-associated proteins (MAPs) are involved in microtubule (MT) bundling and in crossbridges between MTs and other organelles. Previous studies have assigned the MT bundling function of MAPs to their MT-binding domain and its modulation by the projection domain. In the present work, we analyse the viscoelastic properties of MT suspensions in the presence or the absence of cAMP. The experimental data reveal the occurrence of interactions between MT polymers involving MAP2 and modulated by cAMP. Two distinct mechanisms of action of cAMP are identified, which involve on one hand the phosphorylation of MT proteins by the cAMP-dependent protein kinase A (PKA) bound to the end of the N-terminal projection of MAP2, and on the other hand the binding of cAMP to the RII subunit of the PKA affecting interactions between MTs in a phosphorylation-independent manner. These findings imply a role for the complex of PKA with the projection domain of MAP2 in MT-MT interactions and suggest that cAMP may influence directly the density and bundling of MT arrays in dendrites of neurons.

Two-dimensional gel electrophoresis analysis in simultaneous influenza pneumonia and bacterial infection in mice.

Severe pneumonia is found in simultaneous influenza pneumonia and bacterial infection, and suggests a relationship with immunological mechanisms. Here, we performed two-dimensional gel electrophoresis to detect immunological molecules related to the fulminant pneumonia caused by influenza virus and Streptococcus pneumoniae co-infection in mice. We found two spots that were expressed strongly in co-infected mouse lungs, compared with S. pneumoniae or influenza virus singly infected mouse lungs. The spots were analysed by mass spectrometry, and identified as alpha-1 anti-trypsin (A1AT), known as an anti-protease for neutrophil-derived proteolytic enzymes, and creatine kinase, which reflects a greater degree of lung damage and cell death. A1AT expression was increased significantly, and proteolytic enzymes from neutrophils, such as neutrophil elastase, myeloperoxidase and lysozyme, were also secreted abundantly in influenza virus and S. pneumoniae co-infected lungs compared with S. pneumoniae or influenza virus singly infected lungs. These data suggest that A1AT may play a central role as a molecule with broad anti-inflammatory properties, and regulation of the neutrophil-mediated severe lung inflammation is important in the pathogenesis of co-infection with influenza virus and bacteria.

Mirror visual feedback alleviates deafferentation pain, depending on qualitative aspects of the pain: a preliminary report.

OBJECTIVES: Following lesions in somatosensory pathways, deafferentation pain often occurs. Patients report that the pain is qualitatively complex, and its treatment can be difficult. Mirror visual feedback (MVF) treatment can improve deafferentation pain. We sought to classify the qualities of the pain in order to examine whether the potential analgesic effect of MVF depends on these qualities. METHODS: Twenty-two patients with phantom limb pain, or pain related to spinal cord or nerve injury, performed a single MVF procedure. Before and after the MVF procedure, we evaluated phantom limb awareness, movement representation of the phantom or affected/paralysed limb, pain intensity on an 11-point numerical rating scale (0-10) and the qualities of the pain [skin surface-mediated (superficial pain) vs deep tissue-mediated (deep pain)] using lists of pain descriptors for each of the two categories. RESULTS: Fifteen of the patients perceived the willed visuomotor imagery of the phantom or affected/paralysed limb after the MVF procedure. In most of the patients, a reduction in pain intensity and a decrease in the reporting of deep-pain descriptors were linked to the emergence of willed visuomotor imagery. CONCLUSIONS: In this pilot study, we roughly classified the pain descriptor items into two types for evaluating the qualities of deafferentation pain. We found that visually induced motor imagery by MVF was more effective for reducing deep pain than superficial pain. This suggests that the analgesic effect of MVF treatment does depend on the qualities of the pain. Further research will be required to confirm that this effect is a specific consequence of MVF.

Non-oxidative glucose disposal is reduced in type 2 diabetes, but can be restored by aerobic exercise.

Whole-body glucose utilization consists of mitochondrial glucose oxidation and non-oxidative glycogen synthesis. We examined whether reduction of both non-oxidative glucose disposal and glucose oxidation contributes to insulin resistance in type 2 diabetes. We also examined the effects of exercise on these two components. Whole-body glucose disposal rate (GDR, mg/kg/min) was evaluated in 37 type 2 diabetic (T2DM) and 17 non-diabetic (non-DM) subjects as the mean of glucose infusion rate during steady state in the euglycaemic-hyperinsulinaemic clamp study. Glucose oxidation rates were assessed by indirect calorimetry, and non-oxidative GDR was calculated by subtracting glucose oxidation rate from GDR. Intramyocellular lipid (IMCL) content of the soleus muscle was measured using (1)H-magnetic resonance spectroscopy. In 10 T2DM subjects, the changes in oxidative and non-oxidative glucose disposal during clamp were examined after 3-month exercise intervention. GDR (2.93 +/- 1.55 vs. 4.55 +/- 1.83, p = 0.001) and non-oxidative GDR (1.45 +/- 1.52 vs. 3.01 +/- 1.87, p = 0.002) were significantly lower in T2DM than in non-DM subjects. Glucose oxidation rate was comparable in the two groups, and inversely correlated with IMCL (n = 15, r =-0.565, p = 0.028). GDR (2.28 +/- 1.67 to 4.63 +/- 2.42, p = 0.021) and non-oxidative GDR (0.72 +/- 1.27 to 2.26 +/- 1.91, p = 0.047) were increased after exercise intervention, although the change in glucose oxidation rate was not significant. In summary, reduction of non-oxidative glucose disposal may contribute to decreased whole-body glucose utilization. In addition, exercise improves insulin resistance mainly by increasing non-oxidative glucose disposal in type 2 diabetes.

Gabexate mesilate suppresses influenza pneumonia in mice through inhibition of cytokines.

Gabexate mesilate is a synthetic protease inhibitor that is effective for acute pancreatitis. The effect of gabexate mesilate in influenza pneumonia in mice was investigated by examining the changes in pulmonary inflammatory cytokines and chemokines. Pathological changes in the lungs of treated mice were extremely mild, compared with changes in infected, untreated mice. Intrapulmonary levels of interleukin-6 and macrophage inflammatory protein-2 decreased in treated mice compared with untreated mice, despite similar viral titres in the lungs. Survival terms for treated and untreated groups were similar. These data indicate that gabexate mesilate has beneficial effects on influenza pneumonia, which may be due to the modulation of inflammatory cytokine/chemokine responses.

[Perioperative management following cardiovascular surgery in patients with renal insufficiency].

In recent years as the population becomes older, the number of patients undergoing cardiovascular surgery and thereafter suffering various complications has risen with increasing severity. Renal insufficiency is one of the characteristic complications. Most cardiovascular procedures require extracorporeal circulation. With extracorporeal circulation, kidney perfusion pressure and the perfusion volume decrease and this can result in potential renal tubule disorders following surgery. Therefore, it is important to prevent the postoperative aggravation of the renal function in patients with renal dysfunction before the induction of dialysis because they have a diminished renal reserve capacity and specific management is also required for patients on dialysis. The important points are as follows; (1) for the patient who is not on dialysis, it is important to maintain a sufficient blood pressure and prevent a shift to dialysis by avoiding exsiccation, (2) for the patient on dialysis, it is important to carefully evaluate the situation for each patient before resuming dialysis after surgery, (3) for both patient populations, it is important to always consider the dosage and dosage interval when any drugs are administered.

[Aprotinin reduces bleeding during off-pump coronary artery bypass grafting in a patient on ticlopidine; report of a case].

A 65-year-old man was admitted to a local hospital with symptoms of unstable angina pectoris. He was administered ticlopidine before drug eluting stent (DES) stenting for 2 weeks. Coronary angiography showed 3 vessel diseases. He was then admitted to our hospital due to a sudden onset of unstable angina following shock during the percutaneous coronary intervention (PCI) procedure, emergency off-pump coronary artery bypass grafting (OPCAB) was thus performed. He received aprotinin 5 hundred thousand KIU just at the start of surgery and 5 hundred thousand KIU after undergoing anastomosis of the coronary artery. Postoperatively, only some minor bleeding was observed. Aprotinin reduces bleeding, the transfusion requirements of packed red blood cells, platelets, and the total blood units in patients on ticlopidine who undergo emergency OPCAB.

[Posterior ventricular septal perforation successfully repaired through right ventricular approach].

A 65-year-old man underwent a successful repair of a posterior ventricular septal perforation (VSP) 9 days after suffering an acute inferior myocardial infarction. After hospitalization, his hemodynamic condition gradually worsened, in spite of administering intensive medical therapy. Emergent operation was performed on the 4th day after onset. An equine pericardial patch was sutured around the VSP through the right ventricular side of the septum using the double-patch repair method and the right ventricular wall was closed as using the standard extracorporeal perfusion technique. The dimensions of the VSP measured 5 mm in diameter. Transesophageal echocardiography was performed on the 14th postoperative day. Cardiac catheter examination was done on the 18th postoperative day. No residual shunt was recognized and cardiac function was good. He was discharged on the 20th postoperative day. The occurrence of a posterior VSP is comparatively rare, and repair of VSP is difficult to perform during an acute period. Therefore, the operative results of VSP cases remain poor.

Frequent overexpression of epidermal growth factor receptor (EGFR) in mammary high grade ductal carcinomas with myoepithelial differentiation.

AIMS: To evaluate the expression of common biological markers and the epidermal growth factor receptor (EGFR) in mammary high grade ductal carcinomas with myoepithelial differentiation (DCMDs). MATERIALS/METHODS: Thirty DCMDs were clinicopathologically and immunohistochemically analysed and compared with 36 control cases of high grade conventional invasive ductal carcinoma (IDC). RESULTS: EGFR, HER2/neu, oestrogen receptor, progesterone receptor, and p53 expression was seen in 21, one, three, four, and 20 of the 30 DCMDs, compared with eight, nine, 18, 17, and five of the 36 conventional IDCs (p<0.05), respectively. In 16 of the 30 DCMDs, metastases were found in the brain, lung, bone, and liver, within a maximum of 47 months (mean, 13.9) after initial surgery, whereas only four of the 36 conventional IDCs metastasised to the lung and bone within a maximum of 27 months (mean, 18.0) after initial surgery (p=0.0001). There was a significant difference in disease free survival between DCMD and conventional IDC (p=0.001). EGFR was frequently overexpressed in DCMD compared with conventional IDC, whereas the expression of HER2/neu and hormone receptors was lower in DCMD. Fluorescent in situ hybridisation revealed that the mean EGFR to chromosome 7 centromere (CEP7) ratio of the 24 DCMD cases available for evaluation was 1.03, and EGFR gene amplification was not detected in the 21 DCMD cases with EGFR overexpression. CONCLUSION: Immunohistochemistry for myoepithelial markers and EGFR is useful for the accurate diagnosis and molecular target treatment of high grade DCMD.

Penetration to the aortic wall by a metallic airway stent. A successfully treated case with left pneumonectomy and aortic repair.

Metallic airway stents were used widely at the beginning of airway stent use, but an accumulation of cases has revealed complications due to their use. A patient who received a Gianturco Z stent for bronchial tuberculosis suffered massive haemoptysis due to stent migration into the aortic wall. Left pneumonectomy with aortic repair was successfully performed. We suggest that metallic stents should not be used for benign airway palliation, as they may later cause life-threatening complications.

Adenovirus-mediated transfer of human acid maltase gene reduces glycogen accumulation in skeletal muscle of Japanese quail with acid maltase deficiency.

Acid maltase deficiency (AMD) causes a lysosomal glycogenosis inherited as an autosomal recessive trait. The infantile type of AMD (Pompe disease) leads to early death due to severe dysfunction of cardiac and respiratory muscles and no effective therapy is available. Replication-defective adenovirus vectors offer a promising tool for in vivo gene delivery and gene therapy. We constructed a recombinant adenovirus containing the human acid maltase (AM) cDNA downstream of the CAG promoter, composed of modified chicken beta-actin promoter and CMV IE enhancer (AxCANAM). Japanese quail with AMD was used for this study as an animal model for human AMD. When cultured fibroblasts from AMD quail were infected with AxCANAM, AM activity in the cells increased in proportion to the multiplicity of infection (MOI). When AxCANAM (4.5 x 10(8) PFU) was injected into unilateral superficial pectoral muscle of AMD quail, PAS staining showed that glycogenosomes disappeared and stainability of acid phosphatase was reduced in the injected area as compared with the contralateral muscle of the same birds. Biochemically, AM activity increased and glycogen content decreased in the injected muscle. Western blot analysis showed that AMD quail muscle injected with AxCANAM expressed human AM protein processed to active forms. These results suggest that the human AM cDNA transferred by an adenovirus vector was sufficiently expressed, leading to a marked reduction of the glycogen accumulation in the skeletal muscle of AMD quail.

Increased chymase activity in internal thoracic artery of patients with hypercholesterolemia.

Apart from ACE, various angiotensin II (Ang II)-forming serine proteinases (eg, chymase, kallikrein, and cathepsin G) are known to exist in human tissues, but their clinical significance or the regulatory mechanisms that control their activities are not well established. A recent clinical study has shown that chymase activity was significantly increased in human atherosclerotic or aneurysmal aorta. The association between vascular Ang II-forming activities (AIIFAs) in the human internal thoracic artery (ITA) and various clinical parameters was studied with the use of ITAs obtained from 32 patients who underwent coronary artery bypass graft surgery. Total and ACE- and chymase-dependent AIIFAs in homogenates of ITAs were determined. Total AIIFA was 8.67+/-0.86 (nmol Ang II formed. min(-1). mg protein(-1) [U]), and approximately 95% of the activities were due to chymase. Serum total cholesterol level, but no other risk factors, significantly correlated with chymase- (r=0. 60, P<0.001) and ACE- (r=0.35, P<0.05) dependent AIIFAs, respectively. LDL cholesterol level was also correlated with chymase-dependent AIIFAs (r=0.47, P<0.05). Mast cells identified through the use of toluidine blue or immunohistochemical staining appeared in the adventitia but not in the intima or media of ITAs. Our results suggest that an increased plasma LDL cholesterol level may induce increased arterial chymase and ACE activity.