High-Fat Diet-Induced Diabetic Conditions Exacerbate Cognitive Impairment in a Mouse Model of Alzheimer's Disease Via a Specific Tau Phosphorylation Pattern.

BACKGROUND: Epidemiological evidence has demonstrated a clear association between diabetes mellitus and increased risk of Alzheimer's disease (AD). Cerebral accumulation of phosphorylated tau aggregates, a cardinal neuropathological feature of AD, is associated with neurodegeneration and cognitive decline. Clinical and experimental studies indicate that diabetes mellitus affects the development of tau pathology; however, the underlying molecular mechanisms remain unknown. OBJECTIVE: In the present study, we used a unique diabetic AD mouse model to investigate the changes in tau phosphorylation patterns occurring in the diabetic brain. DESIGN: Tau-transgenic mice were fed a high-fat diet (n = 24) to model diabetes mellitus. These mice developed prominent obesity, severe insulin resistance, and mild hyperglycemia, which led to early-onset neurodegeneration and behavioral impairment associated with the accumulation of hyperphosphorylated tau aggregates. RESULTS: Comprehensive phosphoproteomic analysis revealed a unique tau phosphorylation signature in the brains of mice with diabetic AD. Bioinformatic analysis of the phosphoproteomics data revealed putative tau-related kinases and cell signaling pathways involved in the interaction between diabetes mellitus and AD. CONCLUSION: These findings offer potential novel targets that can be used to develop tau-based therapies and biomarkers for use in AD.

First observation of 28O.

Subjecting a physical system to extreme conditions is one of the means often used to obtain a better understanding and deeper insight into its organization and structure. In the case of the atomic nucleus, one such approach is to investigate isotopes that have very different neutron-to-proton (N/Z) ratios than in stable nuclei. Light, neutron-rich isotopes exhibit the most asymmetric N/Z ratios and those lying beyond the limits of binding, which undergo spontaneous neutron emission and exist only as very short-lived resonances (about 10-21 s), provide the most stringent tests of modern nuclear-structure theories. Here we report on the first observation of 28O and 27O through their decay into 24O and four and three neutrons, respectively. The 28O nucleus is of particular interest as, with the Z = 8 and N = 20 magic numbers1,2, it is expected in the standard shell-model picture of nuclear structure to be one of a relatively small number of so-called 'doubly magic' nuclei. Both 27O and 28O were found to exist as narrow, low-lying resonances and their decay energies are compared here to the results of sophisticated theoretical modelling, including a large-scale shell-model calculation and a newly developed statistical approach. In both cases, the underlying nuclear interactions were derived from effective field theories of quantum chromodynamics. Finally, it is shown that the cross-section for the production of 28O from a 29F beam is consistent with it not exhibiting a closed N = 20 shell structure.

Short communication: Effects of feeding purple corn (Zea mays L.) silage on productivity and blood superoxide dismutase concentration in lactating cows.

The objective of this study was to evaluate the effects of feeding purple corn (Zea mays L.) silage on productivity and blood superoxide dismutase concentration in lactating cows. We hypothesized that feeding purple corn silage (AX-152; Nagano Animal Industry Experiment Station, Nagano, Japan, and Takii and Co. Ltd., Tokyo, Japan), which is high in anthocyanin content, would increase milk production and blood concentration of superoxide dismutase. We assigned 16 Holstein cows (8 primiparous and 8 multiparous) in mid lactation to 1 of 2 treatments in a randomized block design, with efforts to balance parity, body weight, and days in milk between treatments. Experimental diets contained either purple corn silage [PCS; 31.2% dry matter (DM), 8.4% crude protein, 40.2% neutral detergent fiber, and 26.6% starch] or conventional corn silage (CONT; 30.5% dry matter, 8.7% crude protein, 42.1% neutral detergent fiber, and 26.5% starch) at approximately 32% of diet DM. Both PCS and CONT were ensiled for 5 mo before the study. Treatment diets were fed as total mixed rations ad libitum for 12 wk from February 1 to April 25, 2016. Cows fed the PCS had increased milk yield (31.7 vs. 29.2 kg/d) and blood superoxide dismutase concentrations (9,333 vs. 8,467 U/mL) compared with those fed CONT. However, anthocyanin concentration in the PCS decreased over the 12-wk experiment: 70 mg/kg of DM for the first 4 wk, 20 mg/kg of DM for the second 4 wk, and undetectable for the last 4 wk. We did not detect anthocyanins in the CONT group at any time point. Feeding PCS may increase antioxidant capacity and milk production in dairy cows, but anthocyanin in PCS may be degraded during storage.

Potential survival of the lichen Caloplaca flavovirescens under high helium-beam doses.

Testing the limits of survivability in space is the primary focus in astrobiological research. Although a number of previous studies have examined terrestrial life survival in an extraterrestrial environment, only a few have investigated how life systems respond to high doses of alpha cosmic ray, the main component of cosmic rays. We used respiration and photosynthetic rates as indicators of the vital signs of the lichen Caloplaca flavovirescens, which is a symbiotic life form including fungi and algae. Our experiment demonstrated that the photosynthetic rate decreased with increased helium-beam doses, whereas the respiration rate was relatively unaffected. Specifically, under a helium-beam dose greater than 10 Gy, the respiration rate remained nearly constant regardless of further increases in the radiation rate. Our results indicate that the different metabolic systems of terrestrial life forms might exhibit different survival characteristics when they are in space.

Telephone-based motivational interviewing versus usual care in primary care to increase physical activity: a randomized pilot study.

BACKGROUND: Diabetes and prediabetes are chronic conditions that affect over 40% of the US adult population combined. Regular physical activity can benefit people with diabetes through improved glucose control and can reduce the conversion of prediabetes to diabetes. Studies are needed in settings where people with these conditions can be identified and provided the skills and support to increase physical activity. The primary care setting meets this need, but there are insufficient high-quality trials to recommend this approach be broadly implemented. METHODS: We conducted a randomized, 24-week pilot study in Southern California to assess the feasibility of using information technology systems available in primary care for identifying potential participants, test methods for obtaining physical activity clearance, conducting mail-based assessments, and delivering telephone-based motivational interviewing to increase physical activity. Eligibility criteria included age between 18 and 74 years, diabetes or prediabetes, and physically inactive based on a clinical assessment tool. At baseline and follow-up, physical activity was assessed by a 7-day accelerometry, cardiometabolic risk factors were collected from electronic medical records, and psychosocial factors were assessed from validated questionnaires administered through a mail survey. Participants were block randomized into intervention or usual care. Staff collecting outcome data were blinded to group assignment. Analysis of covariance was used to assess the difference at follow-up between the intervention and usual care, adjusting for baseline. RESULTS: A total of 67 participants were randomized. Follow-up mail assessments were completed by 53 participants. Of 224 potential intervention calls, 194 were completed (87%). Psychosocial measures significantly improved in four of the five factors for physical activity motivation relative to participants in the usual care arm. The more internally focused factors for exercise self-regulation and outcome expectancies scores were significantly greater for participants in intervention compared with usual care. Moderate to vigorous physical activity improved in intervention participants relative to usual care, but the difference was not statistically significant. No adverse events were noted. CONCLUSIONS: The objectives of this pilot study were met. If a fully powered trial is successful, primary care settings with "behind-the-scenes" information technology support may be appropriate to increase physical activity among patients with prediabetes and diabetes. TRIAL REGISTRATION: Exercise Promotion in Primary Care (EPPC), NCT03429088, registered on February 5, 2018.

Excitation of the Isovector Spin Monopole Resonance via the Exothermic

The (^{12}N, ^{12}C) charge-exchange reaction at 175 MeV/u was developed as a novel probe for studying the isovector spin giant monopole resonance (IVSMR), whose properties are important for better understanding the bulk properties of nuclei and asymmetric nuclear matter. This probe, now available through the production of ^{12}N as a secondary rare-isotope beam, is exothermic, is strongly absorbed at the surface of the target nucleus, and provides selectivity for spin-transfer excitations. All three properties enhance the excitation of the IVSMR compared to other, primarily light-ion, probes, which have been used to study the IVSMR thus far. The ^{90}Zr(^{12}N,^{12}C) reaction was measured and the excitation energy spectra up to about 70 MeV for both the spin-transfer and non-spin-transfer channels were deduced separately by tagging the decay by γ emission from the ^{12}C ejectile. Besides the well-known Gamow-Teller and isobaric analog transitions, a clear signature of the IVSMR was identified. By comparing with the results from light-ion reactions on the same target nucleus and theoretical predictions, the suitability of this new probe for studying the IVSMR was confirmed.

Spectroscopy of Pionic Atoms in

We observed the atomic 1s and 2p states of π^{-} bound to ^{121}Sn nuclei as distinct peak structures in the missing mass spectra of the ^{122}Sn(d,^{3}He) nuclear reaction. A very intense deuteron beam and a spectrometer with a large angular acceptance let us achieve a potential of discovery, which includes the capability of determining the angle-dependent cross sections with high statistics. The 2p state in a Sn nucleus was observed for the first time. The binding energies and widths of the pionic states are determined and found to be consistent with previous experimental results of other Sn isotopes. The spectrum is measured at finite reaction angles for the first time. The formation cross sections at the reaction angles between 0° and 2° are determined. The observed reaction-angle dependence of each state is reproduced by theoretical calculations. However, the quantitative comparison with our high-precision data reveals a significant discrepancy between the measured and calculated formation cross sections of the pionic 1s state.

Test of the Brink-Axel Hypothesis for the Pygmy Dipole Resonance.

The gamma strength function and level density of 1^{-} states in ^{96}Mo have been extracted from a high-resolution study of the (p[over →], p[over →]^{'}) reaction at 295 MeV and extreme forward angles. By comparison with compound nucleus γ decay experiments, this allows a test of the generalized Brink-Axel hypothesis in the energy region of the pygmy dipole resonance. The Brink-Axel hypothesis is commonly assumed in astrophysical reaction network calculations and states that the gamma strength function in nuclei is independent of the structure of the initial and final state. The present results validate the Brink-Axel hypothesis for ^{96}Mo and provide independent confirmation of the methods used to separate gamma strength function and level density in γ decay experiments.

Candidate Resonant Tetraneutron State Populated by the

A candidate resonant tetraneutron state is found in the missing-mass spectrum obtained in the double-charge-exchange reaction ^{4}He(^{8}He,^{8}Be) at 186 MeV/u. The energy of the state is 0.83±0.65(stat)±1.25(syst) MeV above the threshold of four-neutron decay with a significance level of 4.9σ. Utilizing the large positive Q value of the (^{8}He,^{8}Be) reaction, an almost recoilless condition of the four-neutron system was achieved so as to obtain a weakly interacting four-neutron system efficiently.

Significance of Development and Reversion of Collaterals on MRI in Early Neurologic Improvement and Long-Term Functional Outcome after Intravenous Thrombolysis for Ischemic Stroke.

BACKGROUND AND PURPOSE: Predicting response to rtPA is essential in the era of endovascular therapy for stroke. The purpose of this study was to elucidate prognostic factors of early neurologic improvement and long-term outcome with respect to the development and reversion of leptomeningeal collaterals in recanalization therapy after acute ischemic stroke. MATERIALS AND METHODS: We analyzed consecutive patients with proximal MCA occlusion treated with rtPA from 2007 to 2012 at 2 hospital stroke centers. All patients routinely underwent brain MR imaging before rtPA. To assess the reversion of collateral signs, we included patients who underwent follow-up MR imaging. We assessed the development and reversion of collaterals by using a combination of 2 MR imaging collateral markers, the hyperintense vessel sign and the posterior cerebral artery laterality sign. Early neurologic improvement was defined as a decrease in the NIHSS score of ≥10 or a score of ≤2 at 24 hours of treatment. RESULTS: Early neurologic improvement was observed in 22 of 48 eligible patients. The development of collaterals at arrival (15/22 versus 9/26, P = .042) was significantly associated with early neurologic improvement. Multivariate analysis adjusting for other variables showed that the development of collaterals at arrival (OR, 4.82; 95% CI, 1.34-19.98; P = .015) was independently associated with early neurologic improvement. Reversion of collaterals was significantly associated with successful recanalization (P < .001), and multivariate analysis showed that the reversion of collaterals was an independent prognostic factor of long-term functional outcome (OR, 5.07; 95% CI, 1.38-22.09; P = .013). CONCLUSIONS: Our results indicate that the development of leptomeningeal collaterals plays a crucial role in achieving early neurologic improvement, and reversion of collaterals predicts a favorable outcome via arterial recanalization after rtPA treatment for acute stroke.

Variation in patient position and impact on carbon-ion scanning beam distribution during prostate treatment.

OBJECTIVE: We assessed the impact of changes in patient position on carbon-ion scanning beam distribution during treatment for prostate cancer. METHODS: 68 patients were selected. Carbon-ion scanning dose was calculated. Two different planning target volumes (PTVs) were defined: PTV1 was the clinical target volume plus a set-up margin for the anterior/lateral sides and posterior side, while PTV2 was the same as PTV1 minus the posterior side. Total prescribed doses of 34.4 Gy [relative biological effectiveness (RBE)] and 17.2 Gy (RBE) were given to PTV1 and PTV2, respectively. To estimate the influence of geometric variations on dose distribution, the dose was recalculated on the rigidly shifted single planning CT based on two dimensional-three dimensional rigid registration of the orthogonal radiographs before and after treatment for the fraction of maximum positional changes. RESULTS: Intrafractional patient positional change values averaged over all patients throughout the treatment course were less than the target registration error = 2.00 mm and angular error = 1.27°. However, these maximum positional errors did not occur in all 12 treatment fractions. Even though large positional changes occurred during irradiation in all treatment fractions, lowest dose encompassing 95% of the target (D95)-PTV1 was >98% of the prescribed dose. CONCLUSION: Intrafractional patient positional changes occurred during treatment beam irradiation and degraded carbon-ion beam dose distribution. Our evaluation did not consider non-rigid deformations, however, dose distribution was still within clinically acceptable levels. ADVANCES IN KNOWLEDGE: Inter- and intrafractional changes did not affect carbon-ion beam prostate treatment accuracy.

Validation of a commercial serodiagnostic kit for diagnosing pulmonary Mycobacterium avium complex disease.

SETTING: A commercial serodiagnostic kit for diagnosing pulmonary disease due to Mycobacterium avium complex (MAC-PD) was developed and launched in Japan in 2011. OBJECTIVE: To evaluate the performance of this kit in routine clinical settings. METHODS: In this retrospective single-centre study, data on serum levels of anti-glycopeptidolipid (GPL) core IgA antibody (U/ml) measured using the kit were analysed in patients diagnosed with MAC-PD according to American Thoracic Society criteria, in those with pulmonary tuberculosis (PTB) or pulmonary M. kansasii disease and in healthy volunteers. RESULTS: The anti-GPL-core IgA antibody levels of serum were significantly higher (P < 0.0001) in patients with MAC-PD (n = 485) than in those with PTB (n = 133) or pulmonary M. kansasii disease (n = 23) or in healthy subjects (n = 265). When the cut-off level was set at 0.7 U/ml, the sensitivity and specificity were respectively 78.6% and 96.9%. Higher antibody levels were observed in patients with greater extent of disease on chest computed tomography (P < 0.0001). CONCLUSIONS: The serodiagnostic kit revealed good sensitivity and specificity. The antibody levels may reflect disease activity. Additional work is needed to determine whether the diagnostic assay could be used in conjunction with current diagnostic criteria to improve the diagnosis of MAC-PD.

Implementation of a target volume design function for intrafractional range variation in a particle beam treatment planning system.

OBJECTIVE: Treatment planning for charged particle therapy in the thoracic and abdominal regions should take account of range uncertainty due to intrafractional motion. Here, we developed a design tool (4Dtool) for the target volume [field-specific target volume (FTV)], which accounts for this uncertainty using four-dimensional CT (4DCT). METHODS: Target and normal tissue contours were input manually into a treatment planning system (TPS). These data were transferred to the 4Dtool via the picture archiving and communication system (PACS). Contours at the reference phase were propagated to other phases by deformable image registration. FTV was calculated using 4DCT on the 4Dtool. The TPS displays FTV contours using digital imaging and communications in medicine files imported from the PACS. These treatment parameters on the CT image at the reference phase were then used for dose calculation on the TPS. The tool was tested in single clinical case randomly selected from patients treated at our centre for lung cancer. RESULTS: In this clinical case, calculation of dose distribution with the 4Dtool resulted in the successful delivery of carbon-ion beam at the reference phase of 95% of the prescribed dose to the clinical target volume (CTV). Application to the other phases also provided sufficient dose to the CTV. CONCLUSION: The 4Dtool software allows the design of the target volume with consideration to intrafractional range variation and is now in routine clinical use at our institution. ADVANCES IN KNOWLEDGE: Our alternative technique represents a practical approach to four-dimensional treatment planning within the current state of charged particle therapy.

Physics of stimulated L→H transitions.

We report on model studies of stimulated L→H transitions. These studies use a novel reduced mesoscale model. Studies reveal that L→H transitions can be triggered by particle injection into a subcritical state (i.e., P

Identification of the ß+ isovector spin monopole resonance via the 208Pb and 90Zr(t,3He) reactions at 300 MeV/u.

The double-differential cross sections for the (208)Pb and (90)Zr(t,(3)He) reactions at 300 MeV/u have been measured at the RI Beam Factory at RIKEN. This was the first physics experiment with the SHARAQ magnetic spectrometer. The combined analysis of the present (t,(3)He) data and previous (n,p) data provides the clearest identification for the ß(+) isovector spin monopole resonance both in the (208)Tl and (90)Y nuclei, and puts the observations of this giant resonance on a firm foundation. The measured distributions of the (t,(3)He) monopole cross sections were well reproduced by the distorted-wave Born approximation calculation, where the target transition density was calculated with the self-consistent Hartree-Fock plus random-phase approximation using the T43 Skyrme interaction. A major part of the expected ß(+) isovector spin monopole strength was found in the measured cross section spectra.

Long-term radiographic outcome of nodular bronchiectatic Mycobacterium avium complex pulmonary disease.

BACKGROUND: Although Mycobacterium avium complex pulmonary disease (MAC-PD) is a growing health problem, little is known about long-term radiographic outcome and factors for deterioration in patients with MAC-PD. METHODS: Data on patients with nodular bronchiectatic (NBE) MAC-PD who underwent regular follow-up for >5 years were retrospectively reviewed. Changes in plain chest radiograph (CXR) and baseline characteristics were compared between the stable and deteriorated groups. RESULTS: Seventy-two patients were investigated, including 30 patients who were examined 10 years after the initial visit. One patient (1.4%) showed progressive or remarkably progressive disease on CXR at 1 year; this rate increased to 22.2% at 5 years and to 53.3% at 10 years. Body mass index (BMI) at the initial visit was lower in the deteriorated group than in the stable group. Cavitary disease and resistance to a macrolide were seen more frequently at the initial visit in the deteriorated group than in the stable group. CONCLUSIONS: NBE MAC-PD is a slowly but substantially progressive long-term infection (5-10 years). Our data suggest that patients with lower BMI, cavitary disease and resistance to a macrolide at initial visit are more likely to progress to deteriorating disease.