Bundling of collagen fibrils influences osteocyte network formation during bone modeling

Osteocytes form a cellular network by gap junctions between their cell processes. This network is important since intercellular communication via the network is essential for bone metabolism. However, the factors that influence the formation of this osteocyte network remain unknown. As the early stage of osteocyte network formation occurs on the bone surface, we observed a newly formed trabecular bone surface by orthogonal focused ion beam-scanning electron microscopy. The embedding late osteoblast processes tended to avoid bundled collagen fibrils and elongate into sparse collagen fibrils. Then, we examined whether the inhibition of bundling of collagen fibrils using a potent lysyl oxidase inhibitor, beta-aminopropionitrile (BAPN) changed the cellular network of the chick calvaria. The osteocyte shape of the control group was spindle-shape, while that of the BAPN group was sphere-shaped. In addition, the osteocyte processes of the control group were elongated vertically to the long axis of the cell body, whereas the osteocyte processes of the BAPN group were elongated radially. Therefore, it was suggested that the bundling of collagen fibrils influences normal osteocyte network formation during bone modeling

Atypical swelling gelation of chitin physical hydrogel and the tunable mechanical properties

Atypical swelling gelation of chitin physical hydrogels were investigated. Only by tuning the amount of N-acetylation reagent, the degree of acetylation varied and the moldable chitin hydrogels with a wide variety of gel concentration (0.21–6.4 wt%) were obtained. In response to the gel concentration, the mechanical properties ranged from swollen soft gels to shrunk rigid gels (compressive E = 4.22–310 kPa). Thus-prepared chitin hydrogels, which are made only of chitin and water, exhibited high transparency and integrity. The swelling gelation of chitin physical hydrogels was achieved owing both to the cationic charge of the amino groups inducing the osmotic pressure and the toughness of chitin hydrogels that endured the large volume change. These previously-unnoticed advantageous aspects of chitin have pioneered a novel region of swellable physical gels that has been exclusive to chemical gels

Identification of chitin allomorphs in poorly crystalline samples based on the complexation with ethylenediamine

Chitin is a key component of hard parts in many organisms, but the biosynthesis of the two distinctive chitin allomorphs, α- and β-chitin, is not well-understood. The accurate determination of chitin allomorphs in natural biomaterials is vital. Many chitin-secreting living organisms, however, produce poorly crystalline chitin which leads to spectrums with only broad lines and imprecise peak positions under conventional analytical methods such as X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), and solid state nuclear magnetic resonance spectroscopy (NMR), resulting in inconclusive identification of chitin allomorphs. Here, we developed a novel method for discerning chitin allomorphs based on their different complexation capacity and guest selectivity, using ethylenediamine (EDA) as a complexing agent. From the peak shift observed in XRD profiles of the chitin/EDA complex, the chitin allomorphs can be clearly discerned. By testing this method on a series of samples with different chitin allomorphs and crystallinity, we show that the sensitivity is sufficiently high to detect the chitin allomorphs even in near-amorphous, very poorly crystalline samples. This is a powerful tool for determining the chitin allomorphs in phylogenetically important chitin-producing organisms and will pave the way to clarify the evolution and mechanism of chitin biosynthesis

Predictive values of early head computed tomography for survival outcome after cardiac arrest in childhood: a pilot study

Abstract Predicting outcomes of children after cardiac arrest (CA) remains challenging. To identify useful prognostic markers for pediatric CA, we retrospectively analyzed the early findings of head computed tomography (CT) of patients. Subjects were non-traumatic, out-of-hospital CA patients < 16 years of age who underwent the first head CT within 24 h in our institute from 2006 to 2018 (n = 70, median age: 4 months, range 0–163). Of the 24 patients with return of spontaneous circulation, 14 survived up to 30 days after CA. The degree of brain damage was quantitatively measured with modified methods of the Alberta Stroke Program Early CT Score (mASPECTS) and simplified gray-matter-attenuation-to-white-matter-attenuation ratio (sGWR). The 14 survivors showed higher mASPECTS values than the 56 non-survivors (p = 0.035). All 3 patients with mASPECTS scores ≥ 20 survived, while an sGWR ≥ 1.14 indicated a higher chance of survival than an sGWR < 1.14 (54.5% vs. 13.6%). Follow-up magnetic resonance imaging for survivors validated the correlation of the mASPECTS < 15 with severe brain damage. Thus, low mASPECTS scores were associated with unfavorable neurological outcomes on the Pediatric Cerebral Performance Category scale. A quantitative analysis of early head CT findings might provide clues for predicting survival of pediatric CA

High-Titer Anti-ZSCAN1 Antibodies in a Toddler Clinically Diagnosed with Apparent Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation Syndrome

Severe obesity in young children prompts for a differential diagnosis that includes syndromic conditions. Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) syndrome is a potentially fatal disorder characterized by rapid-onset obesity associated with hypoventilation, neural crest tumors, and endocrine and behavioral abnormalities. The etiology of ROHHAD syndrome remains to be established, but recent research has been focusing on autoimmunity. We report on a 2-year-old girl with rapid-onset obesity during the first year of life who progressed to hypoventilation and encephalitis in less than four months since the start of accelerated weight gain. The patient had a high titer of anti-ZSCAN1 antibodies (348; reference range < 40), and the increased values did not decline after acute phase treatment. Other encephalitis-related antibodies, such as the anti-NDMA antibody, were not detected. The rapid progression from obesity onset to central hypoventilation with encephalitis warns about the severe consequences of early-onset ROHHAD syndrome. These data indicate that serial measurements of anti-ZSCAN1 antibodies might be useful for the diagnosis and estimation of disease severity. Further research is needed to determine whether it can predict the clinical course of ROHHAD syndrome and whether there is any difference in antibody production between patients with and without tumors

Yonemoto_SM_0214_2018 – Supplemental material for Early Intervention With Adrenocorticotropin for Acute Encephalopathy-Associated Epileptic Spasms: Report of Two Cases

<p>Supplemental material, Yonemoto_SM_0214_2018 for Early Intervention With Adrenocorticotropin for Acute Encephalopathy-Associated Epileptic Spasms: Report of Two Cases by Kousuke Yonemoto, Yuko Ichimiya, Masafumi Sanefuji, Noriyuki Kaku, Ayumi Sakata, Rieko Baba, Fumiya Yamashita, Satoshi Akamine, Michiko Torio, Yoshito Ishizaki, Yoshihiko Maehara, Yasunari Sakai and Shouichi Ohga in Clinical EEG and Neuroscience</p

Long-term safety and efficacy of alogliptin, a DPP-4 inhibitor, in patients with type 2 diabetes: a 3-year prospective, controlled, observational study (J-BRAND Registry)

Introduction Given an increasing use of dipeptidyl peptidase-4 (DPP-4) inhibitors to treat patients with type 2 diabetes mellitus in the real-world setting, we conducted a prospective observational study (Japan-based Clinical Research Network for Diabetes Registry: J-BRAND Registry) to elucidate the safety and efficacy profile of long-term usage of alogliptin.Research design and methods We registered 5969 patients from April 2012 through September 2014, who started receiving alogliptin (group A) or other classes of oral hypoglycemic agents (OHAs; group B), and were followed for 3 years at 239 sites nationwide. Safety was the primary outcome. Symptomatic hypoglycemia, pancreatitis, skin disorders of non-extrinsic origin, severe infections, and cancer were collected as major adverse events (AEs). Efficacy assessment was the secondary outcome and included changes in hemoglobin A1c (HbA1c), fasting blood glucose, fasting insulin and urinary albumin.Results Of the registered, 5150 (group A: 3395 and group B: 1755) and 5096 (3358 and 1738) were included for safety and efficacy analysis, respectively. Group A patients mostly (&gt;90%) continued to use alogliptin. In group B, biguanides were the primary agents, while DPP-4 inhibitors were added in up to ~36% of patients. The overall incidence of AEs was similar between the two groups (42.7% vs 42.2%). Kaplan-Meier analysis revealed the incidence of cancer was significantly higher in group A than in group B (7.4% vs 4.8%, p=0.040), while no significant incidence difference was observed in the individual cancer. Multivariate Cox regression analysis revealed that the imbalanced patient distribution (more elderly patients in group A than in group B), but not alogliptin usage per se, contributed to cancer development. The incidence of other major AE categories was with no between-group difference. Between-group difference was not detected, either, in the incidence of microvascular and macrovascular complications. HbA1c and fasting glucose decreased significantly at the 0.5-year visit and nearly plateaued thereafter in both groups.Conclusions Alogliptin as a representative of DPP-4 inhibitors was safe and durably efficacious when used alone or with other OHAs for patients with type 2 diabetes in the real world setting