A Novel Alaska Pollock Gelatin Sealant Shows Higher Bonding Strength and Nerve Regeneration Comparable to That of Fibrin Sealant in a Cadaveric Model and a Rat Model.

BACKGROUND: A novel biocompatible sealant composed of Alaska pollock-derived gelatin (ApGltn) has recently shown good burst strength and biocompatibility in a porcine aorta. The purpose of this study was to investigate the bonding strength and biocompatibility of the ApGltn sealant in transected digital nerves of fresh frozen cadavers and in the sciatic nerves of a rat model. METHODS: Eighty human digital nerves of fresh frozen cadavers were transected for biomechanical traction testing. They were treated with four surgical interventions: (1) suture plus ApGltn sealant; (2) suture; (3) ApGltn sealant; and (4) fibrin sealant. Forty-three sciatic nerves of male Wistar rats were used for functional and histopathologic evaluation. They were treated with six surgical interventions: (1) suture plus ApGltn sealant; (2) suture; (3) ApGltn sealant; (4) fibrin sealant; (5) resection with a 5-mm gap (10 rats per group); and (6) sham operation (three rats). Macroscopic confirmation, muscle weight measurement, and histopathologic findings including G-ratio were examined 8 weeks after the procedure. RESULTS: The maximum failure load of the ApGltn sealant was significantly higher than that of a fibrin sealant (0.22 ± 0.05 N versus 0.06 ± 0.04 N). The maximum failure load of the ApGltn sealant was significantly lower that of suture plus ApGltn sealant (1.37 N) and suture (1.27 N). Functional evaluation and histologic examination showed that sciatic nerves repaired with ApGltn sealant showed similar nerve recovery compared to repair with the suture and fibrin sealant. CONCLUSION: The ApGltn sealant showed higher bonding strength and equal effect of nerve regeneration when compared with the fibrin sealant.

Optical manipulation of local cerebral blood flow in the deep brain of freely moving mice.

An artificial tool for manipulating local cerebral blood flow (CBF) is necessary for understanding how CBF controls brain function. Here, we generate vascular optogenetic tools whereby smooth muscle cells and endothelial cells express optical actuators in the brain. The illumination of channelrhodopsin-2 (ChR2)-expressing mice induces a local reduction in CBF. Photoactivated adenylyl cyclase (PAC) is an optical protein that increases intracellular cyclic adenosine monophosphate (cAMP), and the illumination of PAC-expressing mice induces a local increase in CBF. We target the ventral striatum, determine the temporal kinetics of CBF change, and optimize the illumination intensity to confine the effects to the ventral striatum. We demonstrate the utility of this vascular optogenetic manipulation in freely and adaptively behaving mice and validate the task- and actuator-dependent behavioral readouts. The development of vascular optogenetic animal models will help accelerate research linking vasculature, circuits, and behavior to health and disease.

Effect of Layer Directions on Internal Structures and Tensile Properties of 17-4PH Stainless Steel Parts Fabricated by Fused Deposition of Metals.

17-4PH stainless steel specimens were fabricated by fused deposition of metals (FDMet) technology, which combines 17-4PH particles with an organic binder. FDMet promises a low-cost additive manufacturing process. The present research aims to clarify the influence of layer directions in the 3D printing process on the mechanical and shrinkage properties of as-sintered and as-aged specimens. All specimens (the as-sintered and as-aged specimens printed in three layer directions) exhibited high relative density (97.5-98%). The highest ultimate strengths (880 and 1140 MPa in the as-sintered and as-aged specimens, respectively) were obtained when the layer direction was perpendicular to the tensile direction. Conversely, the specimens printed with their layer direction parallel to the tensile direction presented a low ultimate strength and low strain at breakage. The fact that the specimens with their layer direction parallel to the tensile direction presented a low ultimate strength and low strain at breakage is a usual behavior of parts obtained by means of FDM. The SEM images revealed oriented binder domains in the printed parts and oriented voids in the sintered parts. It was assumed that large binder domains in the filament were oriented perpendicular to the layer directions during the fused deposition modeling printing, and remained as oriented voids after sintering. Stress concentration in the oriented void defects was likely responsible for the poor tensile properties of these specimens.

Influence of the Layer Directions on the Properties of 316L Stainless Steel Parts Fabricated through Fused Deposition of Metals.

Metal specimens were fabricated via the fused deposition of metals (FDMet) technique with a filament composed of the 316L stainless steel particles and an organic binder. This process was adopted due to its potential as a low-cost additive manufacturing process. The objective of this study is to investigate the influence of the processing conditions-layer directions and layer thicknesses-on the mechanical and shrinkage properties of the metal components. The specimens were printed in three different layer directions. The highest ultimate strength of 453 MPa and strain at break of 48% were obtained in the specimen printed with the layer direction perpendicular to the tensile direction. On the other hand, the specimen printed in the layer direction parallel to the tensile direction exhibited poor mechanical properties. The reason for the anisotropy of the properties was investigated through systematic SEM observations. The observations revealed the presence of segregated binder domains in the filaments. It was deduced that the binder domain was oriented in the direction perpendicular to that of the layer and remained as oriented voids even after sintering. The voids oriented perpendicular to the tensile direction act as defects that could cause stress concentration, thus resulting in poor mechanical properties.

Prognosis of Hippocampal Function after Sub-lethal Irradiation Brain Injury in Patients with Nasopharyngeal Carcinoma.

This work emphasizes the value of assessing hippocampal function by making a timely MRI-based prognosis following a minor dose of hippocampal irradiation after nasopharyngeal carcinomas (NPC) radiotherapy. A quasi-experiment with case-control design and functional assessments (e.g., neuroimaging analysis with fMRI) was conducted to assess hippocampal function after radiotherapy. We delivered 70 Gy of irradiation to nasopharyngeal carcinomas by 6MV helical radiotherapy and collected data from twenty NPC patients and 24 healthy age-matched subjects. Inevitably, hippocampi also received an average dose of 6.89 Gy (range, 2.0-14 Gy). Seed-based functional connectivity of the hippocampus was applied to estimate the cognitive alteration by time before, one month, and four months after irradiation. Afterward, longitudinal-and-cross-sessional statistical inference was determined with time-dependent measurement analysis of variance (ANOVA) with controlled covariance. Over time, there were longitudinal changes in the functional connectivity of hippocampal-related cortices, including the right middle frontal lobe, left superior temporal lobe, and left postcentral gyrus. The findings indicate the presence of functional plasticity, demonstrating how minor irradiation affects functional performance during the early delayed phase of irradiation-induced brain injury.

Association of habitual physical activity measured by an accelerometer with high-density lipoprotein cholesterol levels in maintenance hemodialysis patients.

After confirming the relationship between high-density lipoprotein cholesterol (HDL-C) levels and mortality in hemodialysis patients for study 1, we investigated the effect of physical activity on their HDL-C levels for study 2. In study 1, 266 hemodialysis patients were monitored prospectively for five years, and Cox proportional hazard regression confirmed the contribution of HDL-C to mortality. In study 2, 116 patients were recruited after excluding those with severe comorbidities or requiring assistance from another person to walk. Baseline characteristics, such as demographic factors, physical constitution, primary kidney disease, comorbid conditions, smoking habits, drug use, and laboratory parameters, were collected from patient hospital records. An accelerometer measured physical activity as the number of steps per day over five consecutive days, and multiple regression evaluated the association between physical activity and HDL-C levels. Seventy-seven patients died during the follow-up period. In study 1, we confirmed that HDL-C level was a significant predictor of mortality (P = 0.03). After adjusting for patient characteristics in study 2, physical activity was independently associated with HDL-C levels (adjusted R (2) = 0.255; P = 0.005). In conclusion, physical inactivity was strongly associated with decreased HDL-C levels in hemodialysis patients.

Dysadherin: expression and clinical significance in thyroid carcinoma.

Dysadherin is a cancer-associated cell membrane glycoprotein. Its cDNA encodes 178 amino acids, including a putative signal sequence, a potential O-glycosylated extracellular domain, a single transmembrane domain, and a short cytoplasmic tail. Dysadherin is believed to down-regulate the expression of E-cadherin, the prime mediator of cell-cell adhesion in epithelial cells, by a posttranscriptional mechanism and promote the metastasis of carcinoma cells. To evaluate the association between dysadherin expression and E-cadherin expression in thyroid carcinoma, immunostaining for dysadherin and E-cadherin was performed in 51 papillary, 10 follicular, and 31 undifferentiated carcinomas. Immunoreactivity for dysadherin, localized at cell-cell boundaries, was detected in 39 of the 51 papillary carcinomas and all 31 undifferentiated carcinomas but not in the follicular carcinomas or normal thyroid tissue controls. Dysadherin expression was significantly higher in undifferentiated carcinoma than in papillary carcinoma and follicular carcinoma and showed significant negative correlation with E-cadherin expression. The degree of dysadherin expression was significantly associated with the prognosis, occurrence of secondary undifferentiated carcinomas, size of the primary tumor, and metastasis to the regional lymph nodes and lungs. In conclusion, a process involving increased dysadherin expression may lead to an adverse clinical outcome.

Expression of RET in follicular cell-derived tumors of the thyroid gland: prevalence and implication of morphological type.

Expression of the wild-type RET proto-oncogene has been observed in non-medullary, follicular cell-derived tumors (FCDT), but the relation with the histopathological features has not been fully demonstrated. To assess the expression of RET and protein products in relation to morphological types of FCDT, including follicular adenoma (FA), papillary carcinoma (PTC), follicular carcinoma (FTC) and anaplastic carcinoma (AnC), 58 non-neoplastic and neoplastic samples using pathological paraffin sections by immunohistochemistry (IHC), reverse transcriptase-polymerase chain reaction (RT-PCR) and laser capture microdissection (LCM) methods were analyzed. Expression of RET proto-oncogene was detected in 27.3% of FCDT by IHC and 25.5% by RT-PCR using a primer set at a regular break point. The present study also found higher expression ratios of RET in FA (50.0%) and the follicular variant of PTC (50.0%), in contrast to FTC (20.0%), ordinary PTC (20.0%) and poorly differentiated or AnC (14.3%) by RT-PCR. One patient with PTC showed a discrepancy in the results by RT-PCR using a different primer set at the C-terminus of RET. The study found that the RET proto-oncogene is often stimulated in FCDT, not only in PTC but also in follicular tumors (FA and FTC), and may contribute to tumorigenesis of these tumors.

Expression and significance of c-met protein in papillary thyroid carcinoma.

The c-met protein, encoded by the c-met oncogene and its ligand, the hepatocellular growth factor/scatter factor, are known to be responsible for the motility and mitogenesis of epithelial cells including cancer cells. Recent studies have reported the prognostic significance of the c-met protein in malignant tumors. Papillary thyroid carcinoma, the most common histological type of thyroid carcinoma, can easily metastasize to regional lymph nodes, reflecting the activated motility and invasiveness of the carcinoma cells. We examined the expression of c-met protein in papillary thyroid carcinomas to assess its significance. Immunohistochemical staining of the c-met protein was performed on archival materials. The c-met protein was expressed in 10 cases of papillary thyroid carcinoma with recurrence, and in 5 of 10 cases without recurrence. Normal thyroids were negative for c-met protein. Expression of the c-met protein was statistically associated with recurrence of the thyroid carcinoma (p = 0.016). It is suggested that expression of the c-met protein plays a role in the recurrence of papillary thyroid carcinoma.

Discordant secretion of calcitonin and chromogranin in the human medullary thyroid carcinoma cell line.

A cell fine of human medullary carcinoma of the thyroid, abundantly producing calcitonin (Ct) and related hormones, has proved remarkably useful as an endocrine tumor model for the study of the secretion mechanism. This cell line (TT cell) was used in studies to elucidate the dynamics of the release of Ct and chromogranin (Cg) to culture medium. The studies evaluated the intracellular concentration of Ct and Cg and the concentration changes elicited by the protein kinase C activator, phorbol ester (TPA); the adenylate cyclase-associated protein kinase A activator, forskolin; and the calcium ionophore, A23187. In addition, immunogold labeling of Ct and Cg was carried out to investigate the ultrastructural changes resulting from the stimulations. All these secretagogues effected the release of Ct and Cg into the medium in a dose-dependent manner, and the rate of the increase in the Ct secretion was consistently and markedly higher than that of Cg in more than certain dosages of the secretagogues. Most cells contained secretory granules immunolabeled for both Ct and Cg, and a considerable decrease was noted in the poststimulation count of the granules containing both substances, with the cells retaining more Cg than Ct. The discordance may be explained by different secretory pathways of the two proteins or different rates of synthesis.