Imaging and mapping of mouse bone using MALDI-imaging mass spectrometry

Matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS) is an advanced method used globally to analyze the distribution of biomolecules on tissue cryosections without any probes. In bones, however, hydroxyapatite crystals make it difficult to determine the distribution of biomolecules using MALDI-IMS. Additionally, there is limited information regarding the use of this method to analyze bone tissues. To determine whether MALDI-IMS analysis of bone tissues can facilitate comprehensive mapping of biomolecules in mouse bone, we first dissected femurs and tibiae from 8-week-old male mice and characterized the quality of multiple fixation and decalcification methods for preparation of the samples. Cryosections were mounted on indium tin oxide-coated glass slides, dried, and then a matrix solution was sprayed on the tissue surface. Images were acquired using an iMScope at a mass-to-charge range of 100–1000. Hematoxylin-eosin, Alcian blue, Azan, and periodic acid-Schiff staining of adjacent sections was used to evaluate histological and histochemical features. Among the various fixation and decalcification conditions, sections from trichloroacetic acid-treated samples were most suitable to examine both histology and comprehensive MS images. However, histotypic MS signals were detected in all sections. In addition to the MS images, phosphocholine was identified as a candidate metabolite. These results indicate successful detection of biomolecules in bone using MALDI-IMS. Although analytical procedures and compositional adjustment regarding the performance of the device still require further development, IMS appears to be a powerful tool to determine the distribution of biomolecules in bone tissues

Hyperbaric Oxygen Exposure Reduces Age-Related Decrease in Oxidative Capacity of the Tibialis Anterior Muscle in Mice

The effects of exposure to hyperbaric oxygen on the oxidative capacity of the skeletal muscles in mice at different ages were investigated. We exposed 5-, 34-, 55-, and 88-week-old mice to 36% oxygen at 950 mmHg for 6 hours per day for 2 weeks. The activities of succinate dehydrogenase (SDH), which is a mitochondrial marker enzyme, of the tibialis anterior muscle in hyperbaric mice were compared with those in age-matched mice under normobaric conditions (21% oxygen at 760 mmHg). Furthermore, the SDH activities of type IIA and type IIB fibers in the muscle were determined using quantitative histochemical analysis. The SDH activity of the muscle in normobaric mice decreased with age. Similar results were observed in both type IIA and type IIB fibers in the muscle. The decrease in the SDH activity of the muscle was reduced in hyperbaric mice at 57 and 90 weeks. The decreased SDH activities of type IIA and type IIB fibers were reduced in hyperbaric mice at 90 weeks and at 57 and 90 weeks, respectively. We conclude that exposure to hyperbaric oxygen used in this study reduces the age-related decrease in the oxidative capacity of skeletal muscles

Cryptosporidiosis in a transplant recipient with severe intractable diarrhea : Detection of Cryptosporidium oocysts by intestinal biopsies

Disseminated Cryptosporidium infection results in manifestations similar to those of graft‐versus‐host disease (GVHD), which hampers the detection of Cryptosporidium infection after allogeneic hematopoietic stem cell transplantation. Surveillance of oocysts on the surface of intestinal epithelial cells is needed for early and appropriate detection of Cryptosporidium infection in transplant recipients on immunosuppressants with severe intractable diarrhea. We present the first case of Cryptosporidium meleagridis infection in Japan after allogeneic cord blood transplantation

Lenvatinib for Anaplastic Thyroid Cancer

Background: Lenvatinib has been approved by regulatory agencies in Japan, the United States, and the European Union for treatment of radioiodine-refractory differentiated thyroid cancer (RR-DTC). Thyroid cancer, however, is a clinically diverse disease that includes anaplastic thyroid cancer (ATC), the subtype associated with the highest lethality. Effective therapy for ATC is an unmet need. Patients and methods: This phase 2, single-arm, open-label study in patients with thyroid cancer, including ATC, RR-DTC, and medullary thyroid cancer was conducted from 3 September 2012 to 9 July 2015. Patients received lenvatinib 24 mg daily until disease progression or development of unacceptable toxicity. The primary endpoint was safety, and the secondary endpoint was efficacy, as assessed by progression-free survival (PFS), overall survival (OS), and objective response rate. Results: At data cutoff, 17 patients with ATC were enrolled. All experienced >= 1 treatment-emergent adverse event (TEAE). The most frequent TEAEs were decreased appetite (82%), hypertension (82%), fatigue (59%), nausea (59%), and proteinuria (59%). Of note, only one patient required lenvatinib withdrawal because of a TEAE, and this TEAE was considered unrelated to lenvatinib. The median PFS was 7.4 months [95% confidence interval (CI): 1.7-12.9], the median OS was 10.6 months (95% CI: 3.8-19.8), and the objective response rate was 24%. Conclusion: In this study, lenvatinib demonstrated manageable toxicities with dose adjustments and clinical activity in patients with ATC. This clinical activity of lenvatinib warrants further investigation in ATC

Quantitative Aspects of Communicative Impairment Ascertained in a Large National Survey of Japanese Children

The Japanese version of the Children’s Communication Checklist-2 (CCC-2) was rated by caregivers in a large national population sample of 22,871 children aged 3–15 years. The General Communication Composite (GCC) of the CCC-2 exhibited a distribution with a single-factor structure. The GCC distribution between autism spectrum disorders (ASD) and language impairment (LI) groups in the general population fit inside a bell curve with significant overlap with the general population, and a continuum was evident between groups. No evidence of a natural cutoff that would differentiate categorically affected from unaffected children was seen. The Social Interaction Deviance Composite (SIDC) supported the notion that ASD and LI are on the opposite endpoints of a SIDC continuum of communication impairment. © 2017 Springer Science+Business Media, LLCEmbargo Period 12 month

Linked color imagingはsessile serrated adenoma/polypsの検出率を向上させる

Background and study aims Although new image-enhanced endoscopy (IEE) technologies such as blue laser imaging (BLI), BLI-bright, and linked color imaging (LCI) have been developed, their utility for the detection of sessile serrated adenoma/polyps (SSA/Ps) is still unclear. This study aimed to evaluate the utility of BLI, BLI-bright, and LCI for SSA/P detection in still image examinations and in a prospective randomized controlled trial (RCT). Patients and methods A group of 6 expert and non-expert endoscopists read 200 endoscopic still images containing SSA/P lesions using white light image (WLI), BLI, BLI-bright, and LCI. Color differences were calculated using the color space method. A prospective RCT of tandem colonoscopy with WLI and LCI was performed. Patients with SSA/P and those with a history of SSA/P that had been endoscopically removed were enrolled and randomly allocated to WLI-LCI or LCI-WLI groups. Additional endoscopic detection rates for SSA/P were compared between the 2 groups. Results LCI showed the highest SSA/P detection rate among the 4 modes for both expert and non-expert endoscopists. The detection rate with LCI for the 6 expert endoscopists (mean 98.3 ± standard deviation 2.0%) was significantly higher than that with WLI (86.7 ± 6.0 %, P < 0.01). Likewise, the detection rate with LCI for the 6 non-expert endoscopists (92.3 ± 2.9 %) was significantly higher than that with WLI (72.7±11.5%, P < 0.01). The color difference of SSA/P with LCI was the highest among the 4 modes, and was significantly higher than with WLI (median 15.9, (interquartile range 13.7 – 20.6) vs. 10.2, (7.6 – 14.2); P < 0.0001). In the RCT, a total of 44 patients (WLI-LCI 22 vs. LCI-WLI 22) underwent colonoscopy. The additional detection rate for SSA/P in the second inspection in the WLI-LCI group (21.6 %, 8/37) was significantly higher than in the LCI-WLI group (3.2 %, 1/31; P = 0.02). The small, flat, non-mucus and isochromatic SSA/Ps in the transverse colon were detected more frequently in the second inspection with LCI. Conclusions LCI was the most sensitive mode for SSA/P detection among WLI, BLI, BLI-bright, and LCI in the still image examinations. Our RCT strongly suggests that LCI is superior to conventional WLI for SSA/P detection during colonoscopy. UMIN000017599

Change in brain plasmalogen composition by exposure to prenatal undernutrition leads to behavioral impairment of rats.

Epidemiological studies suggest that poor nutrition during pregnancy influences offspring predisposition to experience developmental and psychiatric disorders. Animal studies have shown that maternal undernutrition leads to behavioral impairment, which is linked to alterations in monoaminergic systems and inflammation in the brain. In this study, we focused on the ethanolamine plasmalogen of the brain as a possible contributor to behavioral disturbances observed in offspring exposed to maternal undernutrition. Maternal food or protein restriction between gestational day (GD) 5.5 and GD 10.5 resulted in hyperactivity of rat male adult offspring. Genes related to the phospholipid biosynthesis were found to be activated in the prefrontal cortex (PFC), but not in the nucleus accumbens or striatum, in the offspring exposed to prenatal undernutrition. Corresponding to these gene activations, increased ethanolamine plasmalogen (18:0p-22:6) was observed in the PFC using mass spectrometry imaging. A high number of crossings and the long time spent in the center area was observed in the offspring exposed to prenatal undernutrition and was mimicked in adult rats via the intravenous injection of ethanolamine plasmalogen (18:0p-22:6) incorporated into the liposome. Additionally, plasmalogen (18:0p-22:6) increased only in the PFC, and not in the nucleus accumbens or striatum. These results suggest that brain plasmalogen is one of the key molecules to control behavior and its injection using liposome is a potential therapeutic approach for cognitive impairment.Significance Statement:Maternal undernutrition correlates to developmental and psychiatric disorders. Here, we found that maternal undernutrition in early pregnancy led to hyperactivity in rat male offspring and induced gene activation of phospholipid-synthesizing enzyme and elevation of ethanolamine plasmalogen (18:0p-22:6) level in the prefrontal cortex (PFC). Intravenous injection of ethanolamine plasmalogen (18:0p-22:6) incorporated into the liposome maintained crossing activity and was circumscribed to the center area for a long time period, in prenatally undernourished offspring with aberrant behavior. Furthermore, the amount of ethanolamine plasmalogen (18:0p-22:6) increased in the PFC of the rat after injection. Our result suggests that brain plasmalogen is one of the key molecules to control behavior and that its injection using liposome is a potential therapeutic approach for cognitive impairment

Seasonal effects on the continuous positive airway pressure adherence of patients with obstructive sleep apnea.

[Objective] This study examined seasonal differences in continuous positive airway pressure (CPAP) therapy adherence among patients with obstructive sleep apnea (OSA). [Methods] Patients aged ≥20 years with OSA who had used CPAP devices on the automatic setting for >12 consecutive months (n = 141) were included in this retrospective study from December 2015–2016. The information of CPAP use (pressure, hours of actual use) was extracted from database downloaded from patients’ CPAP devices. Patients were divided into adherent and non-adherent groups using the cutoff point of 70% CPAP use for ≥4 h daily over the 1-year study period. CPAP use data were averaged for each season. [Results] Patients in the adherent group were significantly older than those in the non-adherent group (p < 0.001). In the adherent group, the rate of ≥4 h daily CPAP use was significantly lower, the daily duration of CPAP use was significantly shorter, and the residual apnea–hypopnea index (AHI; events/hour) was significantly higher in summer than in other seasons (all p < 0.001). In the non-adherent group, the duration of daily CPAP use and the AHI differed significantly between winter and summer (p = 0.008 and p < 0.001, respectively). [Conclusions] Seasonal changes were associated with the CPAP adherence of patients with OSA. The study findings suggest that there is possibility of increasing the duration of CPAP use by adjusting the bedroom environment in hot and humid seasons

Temperature controls nuclear import of Tam3 transposase in Antirrhinum

It has been proposed that environmental stimuli can activate transposable elements (TEs), while few substantial mechanisms have been shown so far. The class II element Tam3 from Antirrhinum majus exhibits a unique property of low-temperature-dependent transposition (LTDT). LTDT has proved invaluable in developing the gene isolation technologies that have underpinned much of modern plant developmental biology. Here, we reveal that LTDT involves differential sub-cellular localization of the Tam3 transposase (TPase) in cells grown at low (15℃) and high (25℃) temperatures. The mechanism is associated with the nuclear import of Tam3 TPase in Antirrhinum cells. At high temperature, the nuclear import of Tam3 TPase is severely restricted in Antirrhinum cells, while at low temperature, the nuclear localization of Tam3 TPase is observed in about 20% of the cells. However, in tobacco BY-2 and onion cells, Tam3 TPase is transported into most nuclei. In addition to three nuclear localization signals (NLSs), the Tam3 TPase is equipped with a nuclear localization inhibitory domain (NLID), which functions to abolish nuclear import of the TPase at high temperature in Antirrhinum. NLID in Tam3 TPase is considered to interact with Antirrhinum specific factor(s). The host-specific regulation of the nuclear localization of transposase represents a new repertoire controlling class II TEs