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Abstract Mucopolysaccharidosis type IIIA (MPS IIIA) is a rare paediatric lysosomal storage disorder, caused by the progressive accumulation of heparan sulphate, resulting in neurocognitive decline and behavioural abnormalities. Anecdotal reports from paediatricians indicate a more severe neurodegeneration in MPS IIIA patients, following infection, suggesting inflammation as a potential driver of neuropathology. To test this hypothesis, we performed acute studies in which WT and MPS IIIA mice were challenged with the TLR3-dependent viral mimetic poly(I:C). The challenge with an acute high poly(I:C) dose exacerbated systemic and brain cytokine expression, especially IL-1β in the hippocampus. This was accompanied by an increase in caspase-1 activity within the brain of MPS IIIA mice with concomitant loss of hippocampal GFAP and NeuN expression. Similar levels of cell damage, together with exacerbation of gliosis, were also observed in MPS IIIA mice following low chronic poly(I:C) dosing. While further investigation is warranted to fully understand the extent of IL-1β involvement in MPS IIIA exacerbated neurodegeneration, our data robustly reinforces our previous findings, indicating IL-1β as a pivotal catalyst for neuropathological processes in MPS IIIA.

Abstract Background Clinical evidence is required about the long-term efficacy and safety of melatonin treatment for sleep problems in children with neurodevelopmental disorders (NDDs) who underwent adequate sleep hygiene interventions. Methods We conducted a 26-week, multicenter, collaborative, uncontrolled, open-label, phase III clinical trial of melatonin granules in children 6 to 15 years of age who had NDDs and sleep problems. The study consisted of the 2-week screening phase, the 26-week medication phases I and II, and the 2-week follow-up phase. Children received 1, 2, or 4 mg melatonin granules orally in the medication phases. Variables of sleep status including sleep onset latency (SOL), aberrant behaviors listed on the Aberrant Behavior Check List-Japanese version (ABC-J), and safety were examined. The primary endpoint was SOL in the medication phase I. Results Between June 2016 and July 2018, 99 children (80 males and 19 females, 10.4 years in mean age) were enrolled at 17 medical institutions in Japan—74, 60, 22, 9, 6, and 1 of whom had autism spectrum disorder, attention-deficit/hyperactivity disorder, intellectual disabilities, motor disorders, specific learning disorder, and communication disorders, respectively, at baseline. Fifteen children received the maximal dose of 4 mg among the prespecified dose levels. SOL recorded with the electronic sleep diary shortened significantly (mean ± standard deviation [SD], − 36.7 ± 46.1 min; 95% confidence interval [CI], − 45.9 to − 27.5; P

Abstract Purpose To determine whether the presence of intact cumulus cells during the preincubation period for ICSI should be considered as a critical factor in fertilization and embryonic development. Methods The cohort of this prospective randomized study was limited to infertile women younger than 39 years of age who underwent controlled ovarian stimulation for ICSI between October 2013 and May 2015 and whose embryos were to be incubated until day 5. Women with estradiol levels of

This study aimed to elucidate the role of the Sonic hedgehog (Shh)–Patched (Ptch)–Gli signaling pathway in maintaining dental epithelial and pulp stem/progenitor cells and regulating the function of odontoblasts. Doxycycline (dox)-inducible histone 2B (H2B)–green fluorescent protein (GFP) transgenic mice ingested dox at prenatal embryonic days 14.5 or 15.5 and their offspring were collected from postnatal day 1 (P1) to week 3 (P3W). Immunohistochemistry for Gli1, Ptch1, and Ptch2 and in situ hybridization for Shh and Ptch1 were conducted. Mandibular incisors of postnatal day 2 H2B-GFP transgenic and wild-type mice were cultivated in a nutrient medium with Shh antibody for 4 days and subsequently processed for immunohistochemistry for Sox2. In molars, dense H2B-GFP-label-retaining cells (H2B-GFP-LRCs) were densely distributed throughout the dental pulp during P1 to postnatal week 2 (P2W) and decreased in number by postnatal P3W, whereas the number of dense H2B-GFP-LRCs in the subodontoblastic layer increased in number at P2W. Gli1+ and Pthc1+ cells were distributed throughout the enamel organ and dental pulp, including the odontoblast and subodontoblastic layers. Shh mRNA was expressed in the inner enamel epithelium and shifted into odontoblasts after dentin deposition. Ptch1 mRNA was expressed in the inner enamel epithelium and cuspal pulpal tissue on P1 and decreased in intensity from postnatal week 1 to P3W. In incisors, the apical bud contained H2B-GFP-LRCs, Gli1+ cells, and Ptch1+ cells. The addition of Shh antibody to explants induced a decrease in the number of Sox2+ cells due to the increase in apoptotic cells in the apical bud. Thus, the Shh–Ptch–Gli signaling pathway plays a role in maintaining quiescent adult stem cells and regulating the function of odontoblasts.

Large format sections (LS) first have been introduced in breast pathology more than a century ago. Since then, they constituted for longtime a research tool to better understand breast microanatomy and the relationship between radiological images and pathological features. Similarly LS have been used to study neoplastic, inflammatory, and degenerative diseases affecting various organs, as brain, lung, gastrointentinal tract, bone, urinary tract, prostate, and placenta. Currently LS are mostly applied to diagnostic routine to better stage tumours such as prostate and breast carcinomas or to correlate radiologic imaging to gross specimens. The purpose of the present paper is to review the historical background and the basis of the applications of LS in surgical pathology, with special emphasis on breast tumours.

Tomato (Solanum lycopersicum) is a rich source of lycopene, a carotenoid that confers various positive biological effects such as improved lipid metabolism. Here, we conducted a randomized, double-blind, placebo-controlled, parallel-group comparative study to investigate the effects of regular and continuous intake of a new high-lycopene tomato, a variety named PR-7, for 12 weeks, based on 74 healthy Japanese subjects with low-density lipoprotein cholesterol (LDL-C) levels ≥120 to <160 mg/dL. The subjects were randomly assigned to either the high-lycopene tomato or placebo (lycopene-free tomato) group. Each subject in the high-lycopene group ingested 50 g of semidried PR-7 (lycopene, 22.0–27.8 mg/day) each day for 12 weeks, while subjects in the placebo group ingested placebo semidried tomato. Medical interviews were conducted, vital signs were monitored, body composition was determined, and blood and saliva samples were taken at weeks 0 (baseline), 4, 8, and 12. The primary outcome assessed was LDL-C. The intake of high-lycopene tomato increased lycopene levels in this group compared to levels in the placebo group (p < 0.001). In addition, high-lycopene tomato intake improved LDL-C (p = 0.027). The intake of high-lycopene tomato, PR-7, reduced LDL-C and was confirmed to be safe. [ABSTRACT FROM AUTHOR]

We investigated how different processing of soy foods impacts their hypolipidemic properties. Male rats were fed a diet containing 300g/kg of roasted soybean, powdered soy milk, dried fresh tofu, or kori tofu for 21 days. Roasted soybean, a fiber-rich food, significantly increased the fecal total lipid content. The fecal excretion of bile acids was significantly stimulated by fresh tofu and kori tofu, both of which contain coagulated protein. Soy milk and tofu products, which are relatively rich in protein, partly suppressed hepatic lipogenesis compared to roasted soybean. Unfortunately, the impact of these differences was not apparent in reducing lipid levels in serum and liver. Given these observations, constant consumption of each soy food may modulate intestinal lipid absorption and hepatic lipogenesis differently. [ABSTRACT FROM AUTHOR]

Objective: With child rearing starting immediately after childbirth, there is a strong possibility of postnatal depression due to inexperience of the mother combined with irregular rhythms of the newborn to create perception of a large burden for the mother. This study used the Nursing Child Assessment of Feeding Scale (NCAFS) to observe the infant's behavioral state, cues during breastfeeding, and mother's responses on the fourth day after birth, and recorded the interactions of the mother and infant. This study also evaluated use of the NCAFS as an early postnatal measurement tool. Methods: A descriptive study was conducted to elucidate early postnatal mother-infant interactions and cues for these interactions in accordance with the component observation items (NCAFS). Subjects were primiparous mothers and infants hospitalized in a medical institution on the fourth day after birth. Observation was conducted using a network camera and microphone fixed inside the mother's room, with a digital video camera used for recording after breastfeeding started. Analysis was applied by evaluating the scenes from the start until the end of breastfeeding in accordance with the 76 NCAFS items (score range 0-76). Also, the actions of the mother and infant were written down. This study was approved by the Ethical Review Committee of the authors' institution and the institution where the study was conducted. Results: Breastfeeding scenes of 10 mother-infant dyads were recorded and observed. Breastfeeding frequency during the recorded period was a mean of 2.1 times (SD=0.7), with a mean duration of breastfeeding of 11.3minutes (SD=4.2). The NCAFS mean score was 54.1 points (SD=6.1). mother-infant dyads were chosen who scored lower compared to other subjects (