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Psychosocial stressors - life events that challenge social support and relationships - represent powerful risk factors for human disease; included amongst these events are relocation, isolation and displacement. To evaluate the impact of a controlled psychosocial stressor on physiology and underlying molecular pathways, we longitudinally studied the influence of a 28-day period of quarantine on biomarkers of immune signalling, microbial translocation, glycaemic health and blood transcriptome in the wild-born vervet monkey. This event caused a coordinated, mostly transient, reduction of circulating levels of nine immune signalling molecules. These were paralleled by a massive dysregulation of blood transcriptome, including genes implicated in chronic pathologies and immune functions. Immune and inflammatory functions were enriched among the genes downregulated in response to stress. An upregulation of genes involved in blood coagulation, platelet activation was characteristic of the rapid response to stress induction. Stress also decreased neutrophils and increased CD4 + T cell proportions in blood. This model of psychosocial stress, characterised by an immune dysregulation at the transcriptomic, molecular and cellular levels, creates opportunities to uncover the underlying mechanisms of stress-related diseases with an immune component, including cardiovascular diseases and susceptibility to infections.Little is known about the effects of posterior tethers on the development of proximal junctional kyphosis (PJK). We evaluated the ability of posterior tethers to the proximal motion segment stiffness in long instrumented spinal instrumentation and fusion using a whole body human FE model. A series of finite element (FE) analysis of long segmental spinal fusion (SF) from the upper thoracic vertebra (T1) or lower thoracic vertebra (T9) to the sacrum with pedicle screws and rods were performed using an entire human body FE model (includes 234,910 elements), and compressive stresses (CS) on the anterior column, and tensile stresses (TS) on the posterior ligamentous complex (PLC) in the upper-instrumented vertebra (UIV) and the vertebra adjacent to the UIV (UIV + 1) were evaluated with posterior tethers or without posterior tethers. The models were tested at three T1 tilts (0, 20, 40 deg.), with 20% muscle contraction. Deformable material models were assigned to all body parts. Muscle-tendon complexes were modeled by truss elements with a Hill-type muscle material model. The CS of anterior column decreased with increasing T1 slope with tethers in both models, while the CS remained relatively large in T9 model compared with T1 model (T1 UIV; 0.96 to 1.56 MPa, T9 UIV; 4.79 to 5.61 MPa). The TS of the supraspinous ligament was markedly reduced in both T1 and T9 models with posterior tethers (11-35%). High vertebral CS on UIV and UIV + 1 were seen in the T9 UIV model, and the TS on the PLC were increased in both UIV models. Posterior tethers may decrease PJK development after SF with a proximal thoracic UIV, while both posterior tethers and vertebral augmentation may be necessary to reduce PJK development with a lower thoracic UIV.Pathogenic variants in the PSEN1 gene are known to be the most common cause of early-onset Alzheimer's disease but there are few data on the frequency and spectrum of PSEN1 variants in Korea. In this study, we investigated PSEN1 variants in a consecutive series of clinically suspicious early-onset familial AD (EOFAD) Korean patients and their clinical characteristics and imaging findings. From January 2007 to December 2013, EOFAD patients with very early onset AD ( less then 50 yr), early onset AD ( less then 60 yr) with two or more relatives with AD, and early onset AD ( less then 60 yr) with one or more first-degree relatives with very early onset AD ( less then 50 yr) were enrolled in this study. Sequence analysis of the PSEN1 gene was performed by Sanger sequencing. Neuroimaging data and conventional brain MRIs and FDG-PET and/or [11C] PiB-PET scans were analyzed in patients with PSEN1 variants. Among the 28 patients with EOFAD, six (21.4%, 6/28) patients had pathogenic or likely pathogenic variants in the PSEN1 gene. selleck products Two pathogenic variants were p.Glu120Lys and p.Ser170Phe and four likely pathogenic variants were p.Thr119Ile, p.Tyr159Cys, p.Leu282Pro, and p.Ala285Ser. Two patients had variants of unknown significance, p.Tyr389His and p.Tyr389Ser. EOFAD patients with PSEN1 variants showed early AD onset, frequent visuospatial dysfunction, movement disorders, and rapid disease progression. Brain MRIs revealed diffuse cortical atrophy, including parietal lobe atrophy, and/or hippocampal atrophy. FDG-PET scans also revealed significant hypometabolism in the bilateral temporo-parietal regions. Our findings provide insight to better understand the genetic background of Korean EOFAD patients.In this study, the Ho-substituted BaZrO3 electrolyte ceramics (BaZr1-xHoxO3-δ, 0.05 ≤ x ≤ 0.20) were synthesized through a low-cost flash pyrolysis process followed by conventional sintering. The effects of Ho-substitution in BaZrO3 studied in terms of the structural phase relationship, microstructure and electrical conductivity to substantiate augmented total electrical conductivity for intermediate temperature solid oxide fuel cells (IT-SOFCs). The Rietveld refined X-ray diffraction (XRD) patterns revealed that pure phase with [Formula see text] space group symmetry of cubic crystal system as originated in all samples sintered at 1600 °C for 8 h. The Raman spectroscopic investigations also approved that Ho incorporation in BaZrO3 ceramics. Field Emission Scanning Microscopic (FESEM) study informed a mixture of fine and coarse grains in the fracture surface of Ho-substituted BaZrO3 sintered samples. The relative density and average grain size of samples were observed to decrease as per the addition of Ho-substitution in BaZrO3 ceramics. The electrical conductivity study was accomplished by Electrical Impedance Spectroscopy (EIS) under 3% humidified O2 atmosphere from 300 to 800 °C. Furthermore, the total electrical conductivity of BaZr0.8Ho0.2O3-δ ceramic was found to be 5.8 × 10-3 S-cm-1 at 600 °C under 3% humidified atmosphere, which may be a promising electrolyte for IT-SOFCs.

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