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.

Effects of pruritogens and algogens on rostral ventromedial medullary ON and OFF cells.

Rostroventromedial medulla (RVM) ON and OFF cells are thought to facilitate and inhibit spinal nociceptive transmission, respectively. However, it is unknown how ON and OFF cells respond to pruritic stimuli or how they contribute to descending modulation of spinal itch signaling. In pentobarbital sodium-anesthetized mice, single-unit recordings were made in RVM from ON and OFF cells identified by their respective increase or decrease in firing that occurred just before nocifensive hindlimb withdrawal elicited by paw pinch. Of RVM ON cells, 75% (21/28) were excited by intradermal histamine, 50% (10/20) by intradermal chloroquine, and 75% (27/36) by intradermal capsaicin. Most chemically responsive units also responded to a scratch stimulus applied to the injected hindpaw. Few ON cells responded to intradermal injection of vehicle (saline: 5/32; Tween 2/17) but still responded to scratching. For OFF cells, intradermal histamine and scratching inhibited 32% (6/19) with no effect of histamine in the remainder. Intradermal chloroquine inhibited 44% (4/9) and intradermal capsaicin inhibited 61% (11/18) of OFF cells. Few OFF cells were affected by vehicles (Tween: 1 inhibited, 7 unaffected; saline: 3 excited, 1 inhibited, 8 unaffected). Both ON and OFF cells that responded to one chemical usually also responded to others, whereas units unresponsive to the first-tested chemical tended not to respond to others. These results indicate that ascending pruriceptive signals activate RVM ON cells and inhibit RVM OFF cells. These effects are considered to facilitate and disinhibit spinal pain transmission, respectively. It is currently not clear if spinal itch transmission is similarly modulated. NEW & NOTEWORTHY The rostroventromedial medulla (RVM) contains ON and OFF cells that are, respectively, excited and inhibited by noxious stimuli and have descending projections that facilitate and inhibit spinal nociceptive transmission. Most RVM ON cells were excited, and OFF cells inhibited, by intradermal injection of the pruritogens histamine and chloroquine, as well as the algogen capsaicin. These results indicate that itchy stimuli activate RVM neurons that presumably give rise to descending modulation of spinal itch transmission.

Key factors for school health policy implementation in Thailand.

Thailand formulated a National School Health Policy (NSHP) in 1998, and it has been widely implemented but has not been evaluated. This case study aimed to identify factors that have influenced the implementation of NSHP in Thailand. For this purpose, we conducted a document review and key informant interviews. We selected key interviewees, from NSHP implementers at national, provincial and school levels in four geographical areas. We adopted a content analysis method, using a framework of 12 influential components of successful policy implementation and triangular policy framework. This study showed that NSHP was well-disseminated and implemented at whole country. We identified seven positive factors influencing NSHP implementation, namely matching with ongoing educational strategy, competition and encouragement by an awarding system, sustainable human capacity building at school level, participation of multiple stakeholders, sufficient understanding and acceptance of school health concepts, sharing information and collaboration among schools in the same clusters and functional fund raising activities. In addition, we identified three negative factors, namely lack of institutional sustainability, vague role of provincial officers and diverse health problems among Thai children. The government should clarify the role of provincial level and set up institutionalized capacity-building system as measures to strengthen monitoring and evaluation activities.

Innocuous warming enhances peripheral serotonergic itch signaling and evokes enhanced responses in serotonin-responsive dorsal horn neurons in the mouse.

Itch is often triggered by warming the skin in patients with itchy dermatitis, but the underlying mechanism is largely unknown. We presently investigated if warming the skin enhances histamine- or serotonin (5-HT)-evoked itch behavior or responses of sensory dorsal root ganglion (DRG) cells, and if responses of superficial dorsal horn neurons to innocuous warming are enhanced by these pruritogens. In a temperature-controlled environmental chamber, mice exhibited greater scratching following intradermal injection of 5-HT, but not histamine, SLIGRL, or BAM8-22, when the skin surface temperature was above 36°C. Calcium imaging of DRG cells in a temperature-controlled bath revealed that responses to 5-HT, but not histamine, were significantly greater at a bath temperature of 35°C vs. lower temperatures. Single-unit recordings revealed a subpopulation of superficial dorsal horn neurons responsive to intradermal injection of 5-HT. Of these, 58% responded to innocuous skin warming (37°C) prior to intradermal injection of 5-HT, while 100% responded to warming following intradermal injection of 5-HT. Warming-evoked responses were superimposed on the 5-HT-evoked elevation in firing and were significantly larger compared with responses pre-5-HT, as long as 30 min after the intradermal injection of 5-HT. Five-HT-insensitive units, and units that either did or did not respond to intradermal histamine, did not exhibit any increase in the incidence of warmth sensitivity or in the mean response to warming following intradermal injection of the pruritogen. The results suggest that 5-HT-evoked responses of pruriceptors are enhanced during skin warming, leading to increased firing of 5-HT-sensitive dorsal horn neurons that signal nonhistaminergic itch. NEW & NOTEWORTHY: Skin warming often exacerbates itch in patients with itchy dermatitis. We demonstrate that warming the skin enhanced serotonin-evoked, but not histamine-evoked, itch behavior and responses of sensory dorsal root ganglion cells. Moreover, serotonin, but not histamine, enhanced responses of superficial dorsal horn neurons to innocuous warming. The results suggest that skin warming selectively enhances the responses of serotonin-sensitive pruriceptors, leading to increased firing of serotonin-sensitive dorsal horn neurons that signal nonhistaminergic itch.

Best practices for the management of local-regional recurrent chordoma: a position paper by the Chordoma Global Consensus Group.

Chordomas are rare, malignant bone tumors of the skull-base and axial skeleton. Until recently, there was no consensus among experts regarding appropriate clinical management of chordoma, resulting in inconsistent care and suboptimal outcomes for many patients. To address this shortcoming, the European Society of Medical Oncology (ESMO) and the Chordoma Foundation, the global chordoma patient advocacy group, convened a multi-disciplinary group of chordoma specialists to define by consensus evidence-based best practices for the optimal approach to chordoma. In January 2015, the first recommendations of this group were published, covering the management of primary and metastatic chordomas. Additional evidence and further discussion were needed to develop recommendations about the management of local-regional failures. Thus, ESMO and CF convened a second consensus group meeting in November 2015 to address the treatment of locally relapsed chordoma. This meeting involved over 60 specialists from Europe, the United States and Japan with expertise in treatment of patients with chordoma. The consensus achieved during that meeting is the subject of the present publication and complements the recommendations of the first position paper.

Intradermal endothelin-1 excites bombesin-responsive superficial dorsal horn neurons in the mouse.

Endothelin-1 (ET-1) has been implicated in nonhistaminergic itch. Here we used electrophysiological methods to investigate whether mouse superficial dorsal horn neurons respond to intradermal (id) injection of ET-1 and whether ET-1-sensitive neurons additionally respond to other pruritic and algesic stimuli or spinal superfusion of bombesin, a homolog of gastrin-releasing peptide (GRP) that excites spinal itch-signaling neurons. Single-unit recordings were made from lumbar dorsal horn neurons in pentobarbital-anesthetized C57BL/6 mice. We searched for units that exhibited elevated firing after id injection of ET-1 (1 µg/µl). Responsive units were further tested with mechanical stimuli, bombesin (spinal superfusion, 200 µg·ml(-1)·min(-1)), heating, cooling, and additional chemicals [histamine, chloroquine, allyl isothiocyanate (AITC), capsaicin]. Of 40 ET-1-responsive units, 48% responded to brush and pinch [wide dynamic range (WDR)] and 52% to pinch only [high threshold (HT)]. Ninety-three percent responded to noxious heat, 50% to cooling, and >70% to histamine, chloroquine, AITC, and capsaicin. Fifty-seven percent responded to bombesin, suggesting that they participate in spinal itch transmission. That most ET-1-sensitive spinal neurons also responded to pruritic and algesic stimuli is consistent with previous studies of pruritogen-responsive dorsal horn neurons. We previously hypothesized that pruritogen-sensitive neurons signal itch. The observation that ET-1 activates nociceptive neurons suggests that both itch and pain signals may be generated by ET-1 to result in simultaneous sensations of itch and pain, consistent with observations that ET-1 elicits both itch- and pain-related behaviors in animals and burning itch sensations in humans.

Electric-field-induced modification of the magnon energy, exchange interaction, and curie temperature of transition-metal thin films.

The electric-field-induced modification in the Curie temperature of prototypical transition-metal thin films with the perpendicular magnetic easy axis, a freestanding Fe(001) monolayer and a Co monolayer on Pt(111), is investigated by first-principles calculations of spin-spiral structures in an external electric field (E field). An applied E field is found to modify the magnon (spin-spiral formation) energy; the change arises from the E-field-induced screening charge density in the spin-spiral states due to p-d hybridizations. The Heisenberg exchange parameters obtained from the magnon energy suggest an E-field-induced modification of the Curie temperature, which is demonstrated via Monte Carlo simulations that take the magnetocrystalline anisotropy into account.

LET Dependence of 8-Hydroxy-2'-deoxyguanosine (8-OHdG) Generation in Mammalian Cells under Air-Saturated and Hypoxic Conditions: A Possible Experimental Approach to the Mechanism of the Decreasing Oxygen Effect in the High-LET Region.

One of the most distinguished features in biological effects of heavy ions would be the decrease of oxygen effect in the high-LET region. This feature has been referred to as the radiobiological basis for the control of hypoxic fraction in cancer radiotherapy. However, mechanisms to explain this phenomenon have not been fully understood. One of the explanations was given by the oxygen in the track hypothesis, which proposes that oxygen is produced along ion tracks even in the hypoxic irradiation condition. In the present study, we designed an experimental approach to support this hypothesis by using 8-hydroxy-2'-deoxyguanosine (8-OHdG) as DNA damage requiring oxygen to produce. The LET dependence of 8-OHdG under hypoxic condition revealed that with increasing LET 8-OHdG yield seems to increase, despite that the yield of OH radical, which is also required for the production of 8-OHdG, decreases in the high-LET region. This result is consistent with the explanation that the local generation of oxygen along ion tracks contributes to the increase of 8-OHdG yield.

Atomic-layer alignment tuning for giant perpendicular magnetocrystalline anisotropy of 3d transition-metal thin films.

The magnetocrystalline anisotropy (MA) of Fe-based transition-metal thin films, consisting of only magnetic 3d elements, was systematically investigated from full-potential linearized augmented plane-wave calculations. The results predict that giant MA with a perpendicular magnetic easy axis (PMA) can be achieved by tuning the atomic-layer alignments in an Fe-Ni thin film. This giant PMA arises from the spin-orbit coupling interaction between occupied and unoccupied Ni dx2-y2,xy bands crossing the Fermi level. A promising 3d transition-metal thin film for the MgO-based magnetic tunnel junctions with the giant PMA was, thus, demonstrated.

Self-assessed approach to improving school health in Niger.

INTRODUCTION: Award schemes and self-evaluation systems have been developed to implement the 'Health-Promoting School (HPS)' concept in European and Asian countries. While there have been many successes in these regions, the implementation of HPS in African countries has been minimal. This study evaluated the impact of a self-evaluation system on school health in Niger. METHODS: A school health activity guide was developed and distributed to 1999 primary schools in the Niger Tahoua region to raise awareness and solve problems related to school health and hygiene. The number of schools that planned or implemented health-related activities, and the budget and implementation status of their activities was compared over 3 years (before, soon after, and 1 year after distribution). Focus group discussions (FGDs) were also conducted targeting Conseillers Pédagogiques (CPs), who supervise primary schools and teachers, primary school principals and members of Comité de Gestion des Etablissement Scolaire (COGES), which is a type of school steering committee. RESULTS: The number of schools planning at least one health-related activity increased from 47% to 79% soon after distribution of the guide (p <0.001).The number of schools implementing activities increased from 44% to 65% one year after distribution (p <0.001). Health-related budget per school also increased after distribution (p <0.0001) and increases were maintained 1 year after the intervention (p=0.8414). Fulfilment or partial fulfilment rates for health-related activities were lower compared with other (non-health) activities in all three years (80%, 77% & 84% in health-related activities vs 88%, 90% & 91% in others; p <0.001, p <0.001, & p=0.004, respectively). Most FGD participants expressed a positive impression of the program and noted the usefulness of the guide. However, some respondents reported difficulties, especially in relation to budget. CONCLUSION: The introduction of a health activity guide for self-assessment was effective in increasing health-related activities in primary schools in Niger, where a simple monitoring system should be introduced to establish the HPS concept.

Laboratory tests of CO2 laser collective Thomson scattering for measurements of ion temperature in the divertor.

Collective Thomson scattering (CTS) is a diagnostic method that measures the ion velocity distribution of a plasma. CO2 laser CTS measurements are challenging because of the inherently small Doppler broadening and scattering signals that are difficult to detect. We implemented a heterodyne detection scheme to measure spectrum changes of less than a GHz. To maximize the collected light at small scattering angles, we designed a unique light collection approach consisting of a customized conical-shaped (axicon) lens with a hole in the center. The axicon lens is used to collect the scattered light emitted within an annular cross-section from the scattering volume while the probe beam is passed through the hole at the center of the lens. The performance of the heterodyne detection scheme and annular collection approach was demonstrated using a Transverse Excited Atmospheric pressure CO2 laser with a pulse energy of 160 mJ at λ = 10.59 µm.

Neck Location on the Outer Convexity is a Predictor of Incomplete Occlusion in Treatment with the Pipeline Embolization Device: Clinical and Angiographic Outcomes.

BACKGROUND AND PURPOSE: With the increasing use of the Pipeline Embolization Device for the treatment of aneurysms, predictors of clinical and angiographic outcomes are needed. This study aimed to identify predictors of incomplete occlusion at last angiographic follow-up. MATERIALS AND METHODS: In our retrospective, single-center cohort study, 105 ICA aneurysms in 89 subjects were treated with Pipeline Embolization Devices. Patients were followed per standardized protocol. Clinical and angiographic outcomes were analyzed. We introduced a new morphologic classification based on the included angle of the parent artery against the neck location: outer convexity type (included angle, <160°), inner convexity type (included angle, >200°), and lateral wall type (160° ≤ included angle ≤200°). This classification reflects the metal coverage rate and flow dynamics. RESULTS: Imaging data were acquired in 95.3% of aneurysms persistent at 6 months. Complete occlusion was achieved in 70.5%, and incomplete occlusion, in 29.5% at last follow-up. Multivariable regression analysis revealed that 60 years of age or older (OR, 5.70; P = .001), aneurysms with the branching artery from the dome (OR, 10.56; P = .002), fusiform aneurysms (OR, 10.2; P = .009), and outer convexity-type saccular aneurysms (versus inner convexity type: OR, 30.3; P < .001; versus lateral wall type: OR, 9.71; P = .001) were independently associated with a higher rate of incomplete occlusion at the last follow-up. No permanent neurologic deficits or rupture were observed in the follow-up period. CONCLUSIONS: The aneurysm neck located on the outer convexity is a new, incomplete occlusion predictor, joining older age, fusiform aneurysms, and aneurysms with the branching artery from the dome. No permanent neurologic deficits or rupture was observed in the follow-up, even with incomplete occlusion.

Facial injections of pruritogens and algogens excite partly overlapping populations of primary and second-order trigeminal neurons in mice.

Intradermal cheek injection of pruitogens or algogens differentially elicits hindlimb scratching or forelimb wiping, suggesting that these behaviors distinguish between itch and pain. We studied whether pruritogens and algogens excite separate or overlapping populations of primary afferent and second-order trigeminal neurons in mice. Calcium imaging of primary sensory trigeminal ganglion (TG) cells showed that 15.4% responded to histamine, 5.8% to the protease-activated receptor (PAR)-2 agonist, 13.4% to allyl isothiocyanate (AITC), and 36.7% to capsaicin. AITC and/or capsaicin activated the vast majority of histamine- and PAR-2 agonist-sensitive TG cells. A chemical search strategy identified second-order neurons in trigeminal subnucleus caudalis (Vc) responsive to histamine, the PAR-2 agonist, or AITC. A minority of histamine or PAR-2 agonist-responsive Vc neurons responded to the other pruritogen, whereas a large majority of puritogen-responsive Vc neurons responded to capsaicin and/or AITC. A minority of AITC-responsive Vc neurons responded to pruritogens, whereas most responded to capsaicin. These data indicate that most primary and higher-order trigeminal sensory neurons are activated by both pruritic and algesic stimuli, although a minority exhibit selectivity. The results are discussed in terms of population codes for itch and pain that result in distinct behavioral responses of hindlimb scratching and forelimb wiping that are mediated at lumbar and cervical segmental levels, respectively.

Portal vein thrombosis treated using danaparoid sodium and antithrombin III.

A 45-year-old man under treatment for liver cirrhosis (LC) due to chronic hepatitis C and hemophilia A was seen in our emergency room because of a 10-kg weight gain in the previous week due to ascites. Portal vein thrombosis (PVT) was detected with computer tomography (CT) and ultrasonographic (US). Danaparoid sodium (DS) and antithrombin III (AT III) were administrated and doppler US images showed improvement of portal venous blood flow. DS or AT III may be safe and alternative therapies for PVT.

The sacral chordoma margin.

OBJECTIVE: Aim of the manuscript is to discuss how to improve margins in sacral chordoma. BACKGROUND: Chordoma is a rare neoplasm, arising in half cases from the sacrum, with reported local failure in >50% after surgery. METHODS: A multidisciplinary meeting of the "Chordoma Global Consensus Group" was held in Milan in 2017, focusing on challenges in defining and achieving optimal margins in chordoma with respect to surgery, definitive particle radiation therapy (RT) and medical therapies. This review aims to report on the outcome of the consensus meeting and to provide a summary of the most recent evidence in this field. Possible new ways forward, including on-going international clinical studies, are discussed. RESULTS: En-bloc tumor-sacrum resection is the cornerstone of treatment of primary sacral chordoma, aiming to achieve negative microscopic margins. Radical definitive particle therapy seems to offer a similar outcome compared to surgery, although confirmation in comparative trials is lacking; besides there is still a certain degree of technical variability across institutions, corresponding to different fields of treatment and different tumor coverage. To address some of these questions, a prospective, randomized international study comparing surgery versus definitive high-dose RT is ongoing. Available data do not support the routine use of any medical therapy as (neo)adjuvant/cytoreductive treatment. CONCLUSION: Given the significant influence of margins status on local control in patients with primary localized sacral chordoma, the clear definition of adequate margins and a standard local approach across institutions for both surgery and particle RT is vital for improving the management of these patients.

Specific proto-oncogenic tyrosine kinases of src family are enriched in cell-to-cell adherens junctions where the level of tyrosine phosphorylation is elevated.

To approach the transmembrane signaling pathway in the cell-to-cell adherens junctions (AJ), AJ-specific tyrosine phosphorylation was analyzed. When various types of rat adult tissues were pretreated with sodium orthovanadate, a potent inhibitor of tyrosine phosphatase, immunofluorescence microscopy showed that anti-phosphotyrosine polyclonal antibody specifically stained the undercoat of the cell-to-cell AJ. This indicates that the tyrosine kinase activity is elevated at the undercoat of the cell-to-cell AJ of adult tissues. To identify tyrosine kinases responsible for the high level of tyrosine phosphorylation at AJ, we have performed in vitro phosphorylation experiments with cell-to-cell AJ isolated from rat liver (Tsukita, Sh. and Sa. Tsukita. 1989. J. Cell Biol. 108:31-41) and immunoblotting analyses with specific antibodies for tyrosine kinases. As a result, three proto-oncogenic tyrosine kinases of src family, c-yes, c-src, and lyn kinases, were identified as major tyrosine kinases in the cell-to-cell AJ of hepatocytes. Furthermore, it was immunofluorescently shown that at least two of these kinases, c-yes and c-src kinases, were enriched at the cell-to-cell AJ of various types of cells including hepatocytes. Based on these findings, it is concluded that, in various types of cells, specific proto-oncogenic tyrosine kinases of src-family (c-yes and c-src) are enriched to work as signal mediators in the cell-to-cell AJ where the level of tyrosine phosphorylation is elevated.

The product of the human c-erbB-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity.

Antibodies were raised against a synthetic peptide corresponding to 14 amino acid residues at the COOH-terminus of a protein deduced from the human c-erbB-2 nucleotide sequence. These antibodies immunoprecipitated a 185-kilodalton glycoprotein from MKN-7 adenocarcinoma cells. Incubation of the immunoprecipitates with (gamma-32P)ATP resulted in the phosphorylation of this protein on tyrosine residues. These results indicate that the human c-erbB-2 gene product is the 185-kilodalton glycoprotein that is associated with tyrosine kinase activity. Although the c-erbB-2 protein was predicted to encode a protein very similar to epidermal growth factor (EGF) receptor, EGF did not stimulate this kinase activity either in vivo or in vitro.

Asef, a link between the tumor suppressor APC and G-protein signaling.

The adenomatous polyposis coli gene (APC) is mutated in familial adenomatous polyposis and in sporadic colorectal tumors. Here the APC gene product is shown to bind through its armadillo repeat domain to a Rac-specific guanine nucleotide exchange factor (GEF), termed Asef. Endogenous APC colocalized with Asef in mouse colon epithelial cells and neuronal cells. Furthermore, APC enhanced the GEF activity of Asef and stimulated Asef-mediated cell flattening, membrane ruffling, and lamellipodia formation in MDCK cells. These results suggest that the APC-Asef complex may regulate the actin cytoskeletal network, cell morphology and migration, and neuronal function.

Rapid colorectal adenoma formation initiated by conditional targeting of the Apc gene.

Familial adenomatous polyposis coli (FAP) is a disease characterized by the development of multiple colorectal adenomas, and affected individuals carry germline mutations in the APC gene. With the use of a conditional gene targeting system, a mouse model of FAP was created that circumvents the embryonic lethality of Apc deficiency and directs Apc inactivation specifically to the colorectal epithelium. loxP sites were inserted into the introns around Apc exon 14, and the resultant mutant allele (Apc580S) was introduced into the mouse germline. Mice homozygous for Apc580S were normal; however, upon infection of the colorectal region with an adenovirus encoding the Cre recombinase, the mice developed adenomas within 4 weeks. The adenomas showed deletion of Apc exon 14, indicating that the loss of Apc function was caused by Cre-loxP-mediated recombination.

Negative regulation of Wingless signaling by D-axin, a Drosophila homolog of axin.

Wnt/Wingless directs many cell fates during development. Wnt/Wingless signaling increases the amount of beta-catenin/Armadillo, which in turn activates gene transcription. Here the Drosophila protein D-Axin was shown to interact with Armadillo and D-APC. Mutation of d-axin resulted in the accumulation of cytoplasmic Armadillo and one of the Wingless target gene products, Distal-less. Ectopic expression of d-axin inhibited Wingless signaling. Hence, D-Axin negatively regulates Wingless signaling by down-regulating the level of Armadillo. These results establish the importance of the Axin family of proteins in Wnt/Wingless signaling in Drosophila.