Heat curing of UTMA-based hybrid resin: effects on the degree of conversion and cytotoxicity

This study was designed to determine the effects of the heat curing time on a urethane tetramethacrylate (UTMA)-based hybrid resin and specifically on the degree of conversion (DC) and cytotoxicity. The materials used in this study were Estenia, a new-generation hybrid resin, and an experimental fiber reinforcement, Br-100. The DC values of the hybrid resin samples were measured using a Fourier transform infrared (FTIR) spectrophotometer after 180s of light curing followed by heat curing (0, 15, 30, and 60min). A method comparing intensities of C = C and N—H vibrations of the sample was used to calculate the final DC values. FTIR spectra were measured both inside and on the surface of the sample. The calculated DC values increased by increasing the heat curing times. After light curing only and after 15-min heat curing, the DC values inside the samples were smaller than the corresponding DC values at the surfaces of the samples. After 60min of heat curing, the samples achieved homogeneous polymerization (DC% = 65). The cytotoxicity of the material was studied from the glass fiber-reinforced hybrid resin samples, which were first light cured and then heat cured (15, 30, and 60min). Cytotoxicity was tested using both direct contact and extract methods. For the extract tests, the test specimens were incubated in a cell culture media at 37°, 54°, or 72°C for 24h. The heat curing times used had no effect on cytotoxicity. The incubation temperature, however, did have a significant effect. The extract obtained from 72°C incubation showed a cytotoxic effect whereas the others did not. The direct contact test did not show cytotoxicity.     

Traumatic unilateral temporomandibular joint dislocation overlooked for more than two decades

Forward dislocation of the temporomandibular joint commonly can be easily diagnosed and successfully reduced by manual repositioning. In this report, we discuss a rare case of prolonged temporomandibular dislocation that had persisted for more than 20 years because the otolaryngologist and dentist had missed the dislocation. This patient underwent open reduction and mandibular joint plasty with preoperative orthodontic therapy. It is possible that strong pain and mouth-closing disability may gradually remit and only deviated mandibular prognathism like malocclusion may persist. Therefore, abnormal occlusion warrants careful attention to temporomandibular joint dislocation.     

Disruption of actin‐binding domain‐containing Dystonin protein causes dystonia musculorum in mice

The Dystonin gene (Dst) is responsible for dystonia musculorum (dt), an inherited mouse model of hereditary neuropathy accompanied by progressive motor symptoms such as dystonia and cerebellar ataxia. Dst‐a isoforms, which contain actin‐binding domains, are predominantly expressed in the nervous system. Although sensory neuron degeneration in the peripheral nervous system during the early postnatal stage is a well‐recognised phenotype in dt, the histological characteristics and neuronal circuits in the central nervous system responsible for motor symptoms remain unclear. To analyse the causative neuronal networks and roles of Dst isoforms, we generated novel multipurpose Dst gene trap mice, in which actin‐binding domain‐containing isoforms are disrupted. Homozygous mice showed typical dt phenotypes with sensory degeneration and progressive motor symptoms. The gene trap allele (Dst^Gt) encodes a mutant Dystonin‐LacZ fusion protein, which is detectable by X‐gal (5‐bromo‐4‐chloro‐3‐indolyl‐β‐D‐galactoside) staining. We observed wide expression of the actin‐binding domain‐containing Dystonin isoforms in the central nervous system (CNS) and peripheral nervous system. This raised the possibility that not only secondary neuronal defects in the CNS subsequent to peripheral sensory degeneration but also cell‐autonomous defects in the CNS contribute to the motor symptoms. Expression analysis of immediate early genes revealed decreased neuronal activity in the cerebellar‐thalamo‐striatal pathway in the homozygous brain, implying the involvement of this pathway in the dt phenotype. These novel Dst^Gt mice showed that a loss‐of‐function mutation in the actin‐binding domain‐containing Dystonin isoforms led to typical dt phenotypes. Furthermore, this novel multipurpose Dst^Gt allele offers a unique tool for analysing the causative neuronal networks involved in the dt phenotype.     

“Gliomatosis encephali” as a novel category of brain tumors by the first autopsy case report of gliomatosis cerebelli

Gliomatosis cerebri is a rare diffuse glioma that is neither mass‐forming nor necrotic, and does not disrupt existing structures. Gliomatosis occurring in the cerebellum is known as gliomatosis cerebelli, and only three such cases examined by biopsy have been reported. Here we describe the first autopsy findings of a patient who was diagnosed as having gliomatosis in the cerebellum. Neuropathological examination identified the tumor cells as being positive for glial fibrillary acidic protein, vimentin and nestin, with atypical nuclei that were cashew‐nut‐ or dishcloth‐gourd‐shaped. These tumor cells were dense in the right cerebellum, but also spread broadly throughout the brain including the left cerebrum and optic nerve. Mitotic figures were frequently seen in the cerebellum, brain stem and cerebrum. Scherer's secondary structures were evident not only in the cerebellum but also the cerebrum. No necrosis, microvascular proliferation or destruction of anatomical structures was detected in the whole brain. Differences in the origin of the tumors of the gliomatoses cerbri and cerebelli suggests these tumors are different types of brain tumors. Thus the findings support that the gliomatosis cerebelli is a novel type of brain tumor classification. Furthermore, by the similarities of the histological features among the tumors, it appears appropriate to establish a novel category of “gliomatosis encephali” which includes both gliomatosis cerebri and gliomatosis cerebelli.     

Nuclear Notch3 Expression is Associated with Tumor Recurrence in Patients with Stage II and III Colorectal Cancer

Background

The importance of Notch signaling in colorectal cancer (CRC) tumorigenesis has been recently recognized. However, the significance of Notch3 expression and its association with Notch1 expression in CRC is unclear. In the present study, we investigated Notch1 and Notch3 expression in Stage II and III CRC to assess their association with clinicopathological characteristics.

Methods

The protein expression of Notch1 and Notch3 was examined using immunohistochemistry in 305 CRC specimens. Nuclear expression of Notch1 and Notch3 and their associations with clinicopathological characteristics and distant relapse-free survival (dRFS) were evaluated.

Results

Nuclear Notch1 was overexpressed in 37 % of specimen, and nuclear Notch3 in 38 %. Nuclear Notch3 expression correlated with tumor differentiation status (P = 0.0099). Nuclear expression of Notch1 and Notch3 was associated with tumor recurrence (P = 0.0311 and P = 0.0053, respectively). In multivariate analysis, nuclear Notch3 expression [hazard ratio (HR) = 1.71; 95 % confidence interval (CI), 1.06–2.78; P = 0.0271), lymph node metastasis, and venous involvement were independently correlated with dRFS. In subgroup analysis, nuclear Notch3 expression was strongly associated with dRFS in Stage II CRC (HR = 3.47; 95 % CI 1.44–9.22; P = 0.0055). Both nuclear Notch1 and Notch3 were positive in 67 specimens (22 %) and both were negative in 144 specimens (47 %). Coexpression of nuclear Notch1 and Notch3 had an additive effect toward poorer dRFS compared with a negative subtype (HR = 2.48; 95 % CI, 1.41–4.40; P = 0.0019).

Conclusions

Nuclear Notch3 expression might be a novel predictive marker for recurrence in Stage II and III CRC.     

Alteration of the Intestinal Environment by Lubiprostone Is Associated with Amelioration of Adenine-Induced CKD

The accumulation of uremic toxins is involved in the progression of CKD. Various uremic toxins are derived from gut microbiota, and an imbalance of gut microbiota or dysbiosis is related to renal failure. However, the pathophysiologic mechanisms underlying the relationship between the gut microbiota and renal failure are still obscure. Using an adenine-induced renal failure mouse model, we evaluated the effects of the ClC-2 chloride channel activator lubiprostone (commonly used for the treatment of constipation) on CKD. Oral administration of lubiprostone (500 µg/kg per day) changed the fecal and intestinal properties in mice with renal failure. Additionally, lubiprostone treatment reduced the elevated BUN and protected against tubulointerstitial damage, renal fibrosis, and inflammation. Gut microbiome analysis of 16S rRNA genes in the renal failure mice showed that lubiprostone treatment altered their microbial composition, especially the recovery of the levels of the Lactobacillaceae family and Prevotella genus, which were significantly reduced in the renal failure mice. Furthermore, capillary electrophoresis–mass spectrometry-based metabolome analysis showed that lubiprostone treatment decreased the plasma level of uremic toxins, such as indoxyl sulfate and hippurate, which are derived from gut microbiota, and a more recently discovered uremic toxin, trans-aconitate. These results suggest that lubiprostone ameliorates the progression of CKD and the accumulation of uremic toxins by improving the gut microbiota and intestinal environment.     

Predictive Validity of the Classification Schema for Functional Mobility Tests in Instrumental Activities of Daily Living Decline Among Older Adults

Shimada H, Sawyer P, Harada K, Kaneya S, Nihei K, Asakawa Y, Yoshii C, Hagiwara A, Furuna T, Ishizaki T. Predictive validity of the classification schema for functional mobility tests in instrumental activities of daily living decline among older adults.

Objective

To determine predictive validity for cut points of the Timed Up & Go (TUG) test and life-space assessment (LSA) on decline in instrumental activities of daily living (IADLs) among older adults.

Design

Cross-sectional and 1-year follow-up study.

Setting

Preventive health care services.

Participants

In a cross-sectional study, 2404 older adults (65-100y) were recruited to determine cut points for the TUG and LSA for IADLs limitation. For longitudinal analysis, 436 older adults (65-100y) were followed over 1 year to explore the validity of a classification model using the cut points to predict incident IADLs decline.

Interventions

Not applicable.

Main Outcome Measures

The TUG, LSA, and Tokyo Metropolitan Institute of Gerontology index of IADLs measurement.

Results

The cut points associated with IADLs limitations for the TUG and LSA were 12 seconds and 56 points, respectively. Participants were classified into fast/high (most able; TUG <12 and LSA >56), fast/low, slow/high, and slow/low (vulnerable; TUG ≥12 and LSA ≤56) groups; there were 813 (34%), 385 (16%), 246 (10%), and 960 (40%) participants in each group, respectively. The proportions of participants with IADLs limitation in the most able, fast/low, slow/high, and vulnerable groups were 19%, 64%, 61%, and 89%, respectively. The vulnerable group included significantly more participants with IADLs limitation than any other group (P<.001). Compared with a most able group, the odds ratios of IADLs decline for the fast/low and vulnerable groups were 2.52 (95% confidence interval 1.15-5.53, P<.05) and 2.87 (95% confidence interval 1.38-5.96, P<.01), respectively.

Conclusions

The combination of TUG and LSA identifies persons with future IADLs decline and has the potential to be used by community health care services to target individualized interventions.