Exercise-induced hypercalcemia and vasopressin-mediated bone resorption.

Our human observational study showed that elevated arginine vasopressin levels by heavy exercise, not catecholamines, were associated with elevated serum tartrate-resistant acid phosphatase 5b (TRACP-5b). The increase in serum calcium was positively associated with percent changes of TRACP-5b, implying the involvement of bone resorption in the pathogenesis of exercise-induced hypercalcemia. INTRODUCTION: It remains unclear whether enhanced bone resorption explains exercise-induced hypercalcemia. An experimental study demonstrated that arginine vasopressin (AVP) stimulated osteoclast activity. METHODS: We conducted a prospective observational study, enrolling 65 trained healthy male officers of the Japan Self-Defense Forces (34 and 31 in waves 1 and 2, respectively). Before and after a 5-h heavy exercise, we collected laboratory data including bone markers, symptoms, and ionized calcium (iCa; wave 2 only). As blood calcium levels change after exercise, we estimated calcium (corrected calcium) levels immediately after the exercise using the correlation between blood calcium and time from the end of exercise in another cohort. RESULTS: Body weight decreased by 6.9% after the exercise. Corrected post-exercise serum total calcium (tCa) and iCa levels were significantly higher than pre-exercise levels, and 18% of participants showed hypercalcemia defined as corrected tCa >10.4 mg/dL or iCa >1.30 mmol/L. Serum tartrate-resistant acid phosphatase 5b (TRACP-5b), plasma three fractions of catecholamines, and AVP elevated significantly (median 14.3 pg/mL), while procollagen type 1 N-terminal propeptide and whole parathyroid hormone showed significant decreases. Corrected tCa increase showed a non-linear positive association with percent changes of TRACP-5b (%ΔTRACP-5b) even after adjustment for confounders. In addition, %ΔTRACP-5b was not associated with catecholamines, but with post-exercise AVP levels after adjustment for pre-exercise TRACP-5b. Symptoms of nausea or vomiting (observed in 20%) were positively associated with corrected post-exercise iCa after adjustment for post-exercise blood pH. CONCLUSION: AVP elevation may explain bone resorption and the following hypercalcemia in the setting of heavy exercise.

Observation of a Goos-Hänchen-like Phase Shift for Magnetostatic Spin Waves.

In optics, a light beam experiences a spatial shift in the beam plane upon total internal reflection. This shift is usually referred to as the Goos-Hänchen shift. When dealing with plane waves, it manifests itself as a phase shift between an incoming and reflected wave that depends on the wave vector component along the interface. In the experiments presented here, plane spin waves are excited in a 60-nm-thick Permalloy film and propagate towards the edge of the film. By means of time-resolved scanning Kerr microscopy, we are able to directly detect a phase shift between the incoming and reflected wave. With the help of a numerical model, we show that this phase shift naturally occurs for spin waves in the dipolar regime.

Microscopic Investigation into the Electric Field Effect on Proximity-Induced Magnetism in Pt.

Electric field effects on magnetism in metals have attracted widespread attention, but the microscopic mechanism is still controversial. We experimentally show the relevancy between the electric field effect on magnetism and on the electronic structure in Pt in a ferromagnetic state using element-specific measurements: x-ray magnetic circular dichroism (XMCD) and x-ray absorption spectroscopy (XAS). Electric fields are applied to the surface of ultrathin metallic Pt, in which a magnetic moment is induced by the ferromagnetic proximity effect resulting from a Co underlayer. XMCD and XAS measurements performed under the application of electric fields reveal that both the spin and orbital magnetic moments of Pt atoms are electrically modulated, which can be explained not only by the electric-field-induced shift of the Fermi level but also by the change in the orbital hybridizations.

Snell's Law for Spin Waves.

We report the experimental observation of Snell's law for magnetostatic spin waves in thin ferromagnetic Permalloy films by imaging incident, refracted, and reflected waves. We use a thickness step as the interface between two media with different dispersion relations. Since the dispersion relation for magnetostatic waves in thin ferromagnetic films is anisotropic, deviations from the isotropic Snell's law known in optics are observed for incidence angles larger than 25° with respect to the interface normal between the two magnetic media. Furthermore, we can show that the thickness step modifies the wavelength and the amplitude of the incident waves. Our findings open up a new way of spin wave steering for magnonic applications.

Antitumor effects of baculovirus-infected dendritic cells against human pancreatic carcinoma.

Recently, we showed that baculovirus (BV)-infected dendritic cells (DCs) (BV-DCs) induced antitumor immunity against established tumors in mice. These antitumor effects were CD8(+) T-cell and natural killer (NK) cell dependent but CD4(+) T-cell independent. In the current study, we examined the antitumor effect of BV-DCs on human pancreatic cancer cells (AsPC-1). After treatment with BV-infected bone marrow-derived dendritic cells (BMDCs), human pancreatic tumors caused by AsPC-1 cells in a nude mouse model were significantly reduced in size, and the survival of the mice was improved compared with that of non-immature BMDC (iDC)- and BV-DC-immunized mice. We also found that wild-type BV could activate human DCs (HDCs) and that NK cells were activated by BV-infected HDCs (BHDCs). Our findings show that BV-DCs can induce antitumor immunity, which paves the way for the use of this technique as an effective tool for DC immunotherapy against malignancies.

Mechanisms underpinning inattention and hyperactivity: neurocognitive support for ADHD dimensionality.

BACKGROUND: Taxometric and behavioral genetic studies suggest that attention deficit hyperactivity disorder (ADHD) is best modeled as a dimension rather than a category. We extended these analyses by testing for the existence of putative ADHD-related deficits in basic information processing (BIP) and inhibitory-based executive function (IB-EF) in individuals in the subclinical and full clinical ranges. Consistent with the dimensional model, we predicted that ADHD-related deficits would be expressed across the full spectrum, with the degree of deficit linearly related to the severity of the clinical presentation. METHOD: A total of 1547 children (aged 6-12 years) participated in the study. The Development and Well-Being Assessment (DAWBA) was used to classify children into groups according to levels of inattention and hyperactivity independently: (1) asymptomatic, (2) subthreshold minimal, (3) subthreshold moderate and (4) clinical ADHD. Neurocognitive performance was evaluated using a two-choice reaction time task (2C-RT) and a conflict control task (CCT). BIP and IB-EF measures were derived using a diffusion model (DM) for decomposition of reaction time (RT) and error data. RESULTS: Deficient BIP was found in subjects with minimal, moderate and full ADHD defined in terms of inattention (in both tasks) and hyperactivity/impulsivity dimensions (in the 2C-RT). The size of the deficit increased in a linear manner across increasingly severe presentations of ADHD. IB-EF was unrelated to ADHD. CONCLUSIONS: Deficits in BIP operate at subclinical and clinical levels of ADHD. The linear nature of this relationship provides support for a dimensional model of ADHD in which diagnostic thresholds are defined in terms of clinical and societal burden rather than representing discrete pathophysiological states.

Specificity of basic information processing and inhibitory control in attention deficit hyperactivity disorder.

BACKGROUND: Both inhibitory-based executive functioning (IB-EF) and basic information processing (BIP) deficits are found in clinic-referred attention deficit hyperactivity disorder (ADHD) samples. However, it remains to be determined whether: (1) such deficits occur in non-referred samples of ADHD; (2) they are specific to ADHD; (3) the co-morbidity between ADHD and oppositional defiant disorder/conduct disorder (ODD/CD) has additive or interactive effects; and (4) IB-EF deficits are primary in ADHD or are due to BIP deficits. METHOD: We assessed 704 subjects (age 6-12 years) from a non-referred sample using the Development and Well-Being Assessment (DAWBA) and classified them into five groups: typical developing controls (TDC; n = 378), Fear disorders (n = 90), Distress disorders (n = 57), ADHD (n = 100), ODD/CD (n = 40) and ADHD+ODD/CD (n = 39). We evaluated neurocognitive performance with a Two-Choice Reaction Time Task (2C-RT), a Conflict Control Task (CCT) and a Go/No-Go (GNG) task. We used a diffusion model (DM) to decompose BIP into processing efficiency, speed-accuracy trade-off and encoding/motor function along with variability parameters. RESULTS: Poorer processing efficiency was found to be specific to ADHD. Faster encoding/motor function differentiated ADHD from TDC and from fear/distress whereas a more cautious (not impulsive) response style differentiated ADHD from both TDC and ODD/CD. The co-morbidity between ADHD and ODD/CD reflected only additive effects. All ADHD-related IB-EF classical effects were fully moderated by deficits in BIP. CONCLUSIONS: Our findings challenge the IB-EF hypothesis for ADHD and underscore the importance of processing efficiency as the key specific mechanism for ADHD pathophysiology.

Threat bias in attention orienting: evidence of specificity in a large community-based study.

BACKGROUND: Preliminary research implicates threat-related attention biases in paediatric anxiety disorders. However, major questions exist concerning diagnostic specificity, effects of symptom-severity levels, and threat-stimulus exposure durations in attention paradigms. This study examines these issues in a large, community school-based sample. Method A total of 2046 children (ages 6-12 years) were assessed using the Development and Well Being Assessment (DAWBA), Childhood Behavior Checklist (CBCL) and dot-probe tasks. Children were classified based on presence or absence of 'fear-related' disorders, 'distress-related' disorders, and behavioural disorders. Two dot-probe tasks, which differed in stimulus exposure, assessed attention biases for happy-face and threat-face cues. The main analysis included 1774 children. RESULTS: For attention bias scores, a three-way interaction emerged among face-cue emotional valence, diagnostic group, and internalizing symptom severity (F = 2.87, p < 0.05). This interaction reflected different associations between internalizing symptom severity and threat-related attention bias across diagnostic groups. In children with no diagnosis (n = 1411, mean difference = 11.03, s.e. = 3.47, df = 1, p < 0.001) and those with distress-related disorders (n = 66, mean difference = 10.63, s.e. = 5.24, df = 1, p < 0.05), high internalizing symptoms predicted vigilance towards threat. However, in children with fear-related disorders (n = 86, mean difference = -11.90, s.e. = 5.94, df = 1, p < 0.05), high internalizing symptoms predicted an opposite tendency, manifesting as greater bias away from threat. These associations did not emerge in the behaviour-disorder group (n = 211). CONCLUSIONS: The association between internalizing symptoms and biased orienting varies with the nature of developmental psychopathology. Both the form and severity of psychopathology moderates threat-related attention biases in children.

Behavioral evidence for internal factors affecting duration of conglobation in pill bugs (Armadillidium vulgare, Isopoda, Crustacea). Short communication.

Pill bugs individually walked an experimental pathway, then were induced to conglobate with a puff of air. After recovering, they were stimulated again. Sixty of 80 pill bugs conglobated both times, first moving either antennae (A) or legs (L) during recovery. Both AA and LL groups showed a significant positive correlation between first (t1) and second (t2) conglobation times. In the AL group, pathway locomotion time (t0) was significantly positively correlated to both t1 and t2. We conclude that pill bugs determine conglobation time based partly on their previous states.

The 2021 Magnonics Roadmap.

Magnonics is a budding research field in nanomagnetism and nanoscience that addresses the use of spin waves (magnons) to transmit, store, and process information. The rapid advancements of this field during last one decade in terms of upsurge in research papers, review articles, citations, proposals of devices as well as introduction of new sub-topics prompted us to present the first roadmap on magnonics. This is a collection of 22 sections written by leading experts in this field who review and discuss the current status besides presenting their vision of future perspectives. Today, the principal challenges in applied magnonics are the excitation of sub-100 nm wavelength magnons, their manipulation on the nanoscale and the creation of sub-micrometre devices using low-Gilbert damping magnetic materials and its interconnections to standard electronics. To this end, magnonics offers lower energy consumption, easier integrability and compatibility with CMOS structure, reprogrammability, shorter wavelength, smaller device features, anisotropic properties, negative group velocity, non-reciprocity and efficient tunability by various external stimuli to name a few. Hence, despite being a young research field, magnonics has come a long way since its early inception. This roadmap asserts a milestone for future emerging research directions in magnonics, and hopefully, it will inspire a series of exciting new articles on the same topic in the coming years.

A new allele of the lpr locus, lprcg, that complements the gld gene in induction of lymphadenopathy in the mouse.

Several mice with generalized lymphadenopathy were found in the CBA/KlJms (CBA) colony maintained at our institute. A new mutant strain of mice that develop massive lymphoid hyperplasia at 100% incidence within 5 mo after birth was established by crossing these diseased mice. Genetic studies on lymphadenopathy were conducted in F1, F2, and backcross populations from crosses between mutant CBA (CBA-m) and various inbred strains of mice. The results supported the control of lymphadenopathy by a single autosomal recessive gene. Since C3H/He-gld/gld (C3H-gld), MRL/MpJ-lpr/lpr (MRL-lpr), and C3H/HeJ-lpr/lpr (C3H-lpr) mice develop the same type of lymphoid hyperplasia, allelism of the mutant gene with gld or lpr was tested by investigating lymphadenopathy in F1 and backcross populations from crosses between CBA-m and C3H-gld, MRL-lpr, or C3H-lpr mice. The gene was confirmed to be allelic with lpr but not with gld. Interestingly, however, the mutant gene interacted with gld to induce less severe lymphadenopathy. Thus, the mutant gene was named lprcg, an lpr gene complementing gld in induction of lymphoproliferation. The genetic conclusion was supported by the same profile of surface markers of lymphoid cells with gld/gld, lpr/lpr, lprcg/lprcg, lprcg/lpr, and +/gld +/lprcg genotypes, as well as by massive lymph node hyperplasia and high titers of autoantibodies in the first four genotypes, but slight hyperplasia and insignificant autoantibody production in the last. The discovery of lprcg provided strong genetic evidence for the parallels between anomalous phenotypes of gld and lpr, and CBA/KlJms-lprcg/lprcg mice will contribute to elucidation of the mechanism of induction of the same abnormal differentiation and functions of lymphocytes by gld and lpr.

Mechanisms of class I restricted immunopathology. A transgenic mouse model of fulminant hepatitis.

The molecular and cellular mechanisms responsible for cytotoxic T lymphocyte (CTL)-induced immunopathology are not well defined. Using a model in which hepatitis B surface antigen (HBsAg)-specific CTL cause an acute necroinflammatory liver disease in HBsAg transgenic mice, we demonstrate that class I-restricted disease pathogenesis is an orderly, multistep process that involves direct as well as indirect consequences of CTL activation. It begins (step 1) almost immediately as a direct antigen-specific CTL-target cell interaction that triggers the HBsAg-positive hepatocyte to undergo programmed cell death (apoptosis). It progresses (step 2) within hours to a focal inflammatory response in which antigen-nonspecific lymphocytes and neutrophils amplify the local cytopathic effect of the CTL. The most destructive pathogenetic function of the CTL, however, is to secrete interferon gamma when they encounter antigen in vivo, thereby activating the intrahepatic macrophage and inducing a delayed-type hypersensitivity response (step 3) that destroys the liver and kills the mouse. We propose that the principles illustrated in this study are generally applicable to other models of class I-restricted, CTL-induced immunopathology, and we suggest that they contribute to the immunopathogenesis of viral hepatitis during hepatitis B virus infection in humans.

Autofluorescence imaging colonoscopy for the detection of dysplastic lesions in ulcerative colitis: a pilot study.

AIM: Autofluorescence imaging (AFI) is a novel technology for endoscopy, which enhances neoplastic lesions of the gastrointestinal tract. The aim of this investigation was to examine whether AFI colonoscopy can identify dysplasia in ulcerative colitis. METHOD: We examined 48 patients with ulcerative colitis by AFI colonoscopy. Apparently flat, coarse granular mucosa and visible protruding lesions under conventional colonoscopy were observed by AFI. Those target areas were classified into low AF and high AF according to the colour under AFI colonoscopy. The grade of dysplasia was determined in the specimens obtained from the target areas. RESULTS: About 126 sites (35 protruding lesions and 91 flat areas) were examined by AFI colonoscopy. AF was determined to be high in 42 areas and to be low in 84 areas. The positive rate of dysplasia was higher in protrusions (31%) than in flat mucosa (3.3%, P < 0.0001). The rate of positive dysplasia was not statistically different between lesions determined to be low AF (14%) and those to be high AF (5%, P = 0.09). The positive rate of dysplasia in protruding lesions was significantly higher in low AF than in high AF (45.0%vs 13.3%, P = 0.043), while the value in flat lesions was not different between low AF and high AF (8.2%vs 0%, P = 0.3). CONCLUSIONS: Autofluorescence imaging colonoscopy seems to have a role for the detection of dysplaia in ulcerative colitis.

Peripartum changes in serum activities of three major alkaline phosphatase isoenzymes in Holstein dairy cows.

This study investigated changes in serum levels of hepatic, bone, and intestinal alkaline phosphatase (ALP) isoenzymes (ALP2, ALP3, and ALP5, respectively) in Holstein cows around parturition. Tartrate-resistant acid phosphatase 5b (TRAP5b) activity and calcium (Ca) concen-trations were also measured. We analyzed blood samples from 11 late-pregnant heifers (primipa-rous group) and 13 multiparous (2-4 lactations; multiparous group) cows at 3 weeks (18-24 days prepartum; -3 weeks), 2 weeks (17-11 days prepartum; -2 weeks), and 1 week (10-4 days prepar-tum; -1 weeks) before parturition; the day of calving (within 12 h post-calving; day 0); and 5 days postpartum (5 days). ALP3 activity was significantly higher in the primiparous group than in the multiparous group, whereas the activities decreased significantly in both groups after 5 days. ALP2 and ALP5 activities did not change, whereas ALP2 activity was significantly higher in the primiparous group than in the multiparous group. TRAP5b activity was significantly higher in the primiparous group than in the multiparous group and showed a transient significant increase at day 0. Ca concentration significantly decreased at day 0 in both groups; the Ca level at day 0 was significantly higher in the primiparous group than in the multiparous group. These data show that ALP3 activity in serum may indicate a change in osteoblastic bone forma-tion after calving, but further study is needed to determine the clinical application for measuring ALP isoenzymes in bovine medicine.

Agarose gel electrophoresis pattern of serum alkaline phosphatase isoenzymes in Holstein cows during lactation.

A recent study found that an agarose gel electrophoresis (AGE) method yielded two distinct major bands corresponding to the hepatic and bone ALP isoenzymes (ALP2 and ALP3, respec-tively) in bovine serum treated with protease and neuraminidase (PN-treatment), although there were concerns that the intestinal ALP isoenzyme (ALP5) often overlapped with ALP3 in human serum treated with neuraminidase. Because ALP5 was separated from ALP3 in bovine serum treated with protease alone (P-treatment), we used a modified method employing both P- and PN-treated bovine sera to measure the activities of the three ALP isoenzymes in 53 lacta-ting Holstein cows: 24 primiparous and 29 multiparous. Upon electrophoresis, 51 of 53 samples (96.2%) subjected to P-treatment yielded a distinct fraction corresponding to ALP5, as did the control serum. All PN-treated sera yielded a definite ALP2 fraction. The ALP3 fraction was calculated as the remainder after excluding ALP2 and ALP5. The activities of total ALP (t-ALP) and ALP3 in primiparous cows were higher than those in multiparous cows (p ⟨ 0.001) at early-to-peak [10-110 days in milk (DIM)] and mid (111-220 DIM) lactation. In the multi-parous cows, the ALP3 activity at late lactation (221-477 DIM) was significantly higher than that at early-to-peak lactation. Thus, the modified AGE method described here is able to discrimi-nate three fractions of ALP isoenzymes in the sera of lactating cows. The AGE pattern of circu-lating ALP isoenzymes will contribute to the understanding of the physiological bone metabolism status in lactating cows.

Soybean beta-conglycinin as the main allergen in a patient with food-dependent exercise-induced anaphylaxis by tofu: food processing alters pepsin resistance.

BACKGROUND: Food-dependent exercise-induced anaphylaxis (FDEIA) due to soybeans is a rare disorder. The allergen responsible for FDEIA due to soybeans has not yet been determined. OBJECTIVE: We characterized the clinical features of a patient with FDEIA due to tofu, who was well tolerant to drinking soy milk. We then sought to identify the responsible soybean allergen(s) in that patient. We further studied whether different stabilities of the allergen(s) to pepsin digestion between two soybean products are related to their clinical allergenicity. METHODS: Skin prick tests and provocation tests using soybean products were performed to detect the responsible food and other factors that induced the allergic symptoms. Specific IgE to various soybean allergens were examined by ImmunoCAP, ELISA and protein microarray assays. Immunoblotting for soybeans and soybean products using the patient's serum was also performed. Soybean products were serially digested by pepsin to disclose the stability of the allergens. RESULTS: Provocation with ingestion of tofu and exercise induced the allergic symptoms, while ingestion of soy milk and exercise did not. Immunoblot analysis, ELISA and protein microarray assay revealed that beta-conglycinin mainly reacts with IgE antibodies in the patient's serum. By immunoblot analysis, beta-conglycinin in soy milk completely disappeared after pepsin digestion within 20 min, whereas beta-conglycinin in tofu was almost intact after more than 120 min of pepsin digestion. CONCLUSION: We identified beta-conglycinin as the causative allergen in a patient with FDEIA induced by tofu. The difference in resistance to pepsin digestion between tofu and soy milk suggests that the presence of undigested allergens in the digestive tract is a prerequisite for the development of FDEIA.

Immunobiology and pathogenesis of hepatocellular injury in hepatitis B virus transgenic mice.

The role of the immune response to hepatitis B virus (HBV)-encoded antigens in the pathogenesis of liver cell injury has not been defined because of the absence of appropriate experimental models. HBV envelope transgenic mice were used to show that HBV-encoded antigens are expressed at the hepatocyte surface in a form recognizable by major histocompatibility complex (MHC) class I-restricted, CD8+ cytotoxic T lymphocytes specific for a dominant T cell epitope within the major envelope polypeptide and by envelope-specific antibodies. Both interactions led to the death of the hepatocyte in vivo, providing direct evidence that hepatocellular injury in human HBV infection may also be immunologically mediated.

Successful therapeutic use of a single-dose of rituximab on relapse in adults with minimal change nephrotic syndrome.

Minimal change nephrotic syndrome (MCNS) usually is considered to have a good renal prognosis, but the frequency of relapses is a therapeutic challenge to physicians. The treatment of patients with multiple relapses remains a matter of controversy, because few controlled studies are available. We report the case of a 25-year-old man who experienced relapses of MCNS. Single-dose rituximab therapy (total dose 500 mg) was given during the fourth relapse. Complete remission occurred 10 days later, when no CD19/20-positive B cells were detected in the blood. This the first report of efficacy of single-dose rituximab therapy to treat multi-relapsing MCNS in an adult patient.