Communication Among Emerging Adult Siblings

The study sought to explore the emerging adult sibling dyad through qualitativeinquiry. By doing so, the collected data bring new meaning to why and how emerging adult siblings communicate. Also, by including both siblings, this study sought to highlight a different perspective of sibling communication. Extant research on the emerging adulthood stage of life is limited. The current study explored the sibling dyad during this phase of life, and three themes emerged: siblings become friends, changes during emerging adulthood, conflict negotiation, and taking a parental role

Apathy and Striatal Gray Matter Patterns in Schizophrenia and Huntington’s Disease

Apathy is a symptom of many neurodegenerative and neuropsychiatric disorders, such as Huntington\u27s disease and schizophrenia. Apathy is often conceptualized as a combination of three domains, cognitive, behavioral, and emotional, characterized by impaired goal-directed behavior. The striatum has been shown to be significantly associated with executive functions and planned motor behavior via projection to the prefrontal cortex (PFC). Due to its connection to the PFC and its involvement in the basal ganglia motor circuit, the striatum is thought to be a significant part of the circuit that controls goal-directed behavior. The purpose of this study was to investigate the relationship between apathy severity and dorsal striatal grey matter concentration across several disorders, specifically Huntington\u27s disease and schizophrenia. With access to the PREDICT-HD and FBIRN datasets, structural MRI images and clinical assessments were collected from 823 and 178 participants, respectively. We employed the use of SBM to isolate relevant basal ganglia components and used the resulting loading coefficients for a multivariate analysis. In parallel, we also conducted a univariate analysis using segmented subcortical volumetric data. We then constructed a mixed linear model to examine the relationship between apathy and any gray matter patterns in the striatum. In Huntington’s disease, our results indicate that apathy is significantly related to the caudate and putamen atrophy with covarying in the medial PFC. In schizophrenia, our results indicate that apathy is significantly related to the putamen with covarying regions in the gyrus rectus and orbital medial PFC. We concluded that Huntington’s disease and schizophrenia manifest apathy in different ways in unique structures

Recombinant human gelsolin promotes the migration of human articular cartilage chondrocytes by regulating gene expression in vitro

Objective It is known that recombinant human gelsolin (rhuGSN) supports wound closure and migration processes in avascular tissue. Since articular cartilage degradation plays an important role in osteoarthritis (OA), we are investigating how rhuGSN affects regeneration processes in human articular cartilage and represents a promising new therapeutic approach for the treatment of OA. Methods Primary human chondrocytes (phCs) from articular knee cartilage were cultured with different concentrations of rhuGSN to analyse its direct effect in vitro. In addition, phCs were stimulated with 10 ng/mL IL-1β or TNF-α to simulate osteoarthritis in vitro and treated with different concentrations of rhuGSN to investigate the beneficial effect in disease treatment. Cytokine secretion and gene expression as well as wound assays were performed. Results GSN significantly promotes wound closure in phCs after 60 h compared to untreated cells. After 24 h treatment with 30 μg/mL rhuGSN, TGF-β secretion increases significantly in the in vitro osteoarthritis model. Gene expression of MMP1 as well as SPARC is reduced in chondrocytes due to treatment with GSN in the OA model. At the same time, CXCR4 expression increases significantly after 24 h treatment with 3 μg/mL GSN. Conclusion In the in vitro model of osteoarthritis, rhuGSN promotes wound closure of chondrocytes by a supported migration as well as expression of reconstructive and down regulated expression of deconstructive genes concentration dependently. Further experiments are needed to fully understand the beneficial effect of gelsolin on human chondrocytes and to verify this promising approach for a pharmacological treatment of osteoarthritis

Crumples as a generic stress-focusing instability in confined sheets

Thin elastic solids are easily deformed into a myriad of three-dimensional shapes, which may contain sharp localized structures as in a crumpled candy wrapper, or have smooth and diffuse features like the undulating edge of a flower. Anticipating and controlling these morphologies is crucial to a variety of applications involving textiles, synthetic skins, and inflatable structures. Here we show that a "wrinkle-to-crumple" transition, previously observed in specific settings, is a ubiquitous response for confined sheets. This unified picture is borne out of a suite of model experiments on polymer films confined to liquid interfaces with spherical, hyperbolic, and cylindrical geometries, which are complemented by experiments on macroscopic membranes inflated with gas. We use measurements across this wide range of geometries, boundary conditions, and lengthscales to quantify several robust morphological features of the crumpled phase, and we build an empirical phase diagram for crumple formation that disentangles the competing effects of curvature and compression. Our results suggest that crumples are a generic microstructure that emerge at large curvatures due to a competition of elastic and substrate energies.Comment: 12 pages, 7 figure

Anti-inflammatory effects of an autologous gold-based serum therapy in osteoarthritis patients

Osteoarthritis (OA) involves activation and recruitment of immune cells to affected joints, including the production of pro-inflammatory cytokines. Here, a gold-based autologous serum therapy is investigated for its effect on peripheral blood cell composition and cytokine levels in OA patients. From six OA patients serum and blood samples were collected before and after second therapy treatment for analysis of peripheral blood cell composition as well as cytokine levels compared to control samples. This therapy significantly downregulates CD4+ T cells and B cells in OA patients after second treatment compared to healthy controls. Monocytes are significantly upregulated in patients after second treatment Serum IL-9 and TNF-α levels are downregulated in patients after second treatment compared to healthy control serum. The activation status of immune cells was modulated after therapy in patients. Anti-inflammatory effects of the peripheral blood cell composition in OA patients can be seen after therapy treatment. After two treatments IL-9 and TNF-α are significantly downregulated in patient serum. Here, primary data of a new autologous therapy for OA treatment and its modulatory effects on cytokines are presented

High and low levels of an NTRK2-driven genetic profile affect motor- and cognition-associated frontal gray matter in prodromal Huntington's disease

This study assessed how BDNF (brain-derived neurotrophic factor) and other genes involved in its signaling influence brain structure and clinical functioning in pre-diagnosis Huntington’s disease (HD). Parallel independent component analysis (pICA), a multivariate method for identifying correlated patterns in multimodal datasets, was applied to gray matter concentration (GMC) and genomic data from a sizeable PREDICT-HD prodromal cohort (N = 715). pICA identified a genetic component highlighting NTRK2, which encodes BDNF’s TrkB receptor, that correlated with a GMC component including supplementary motor, precentral/premotor cortex, and other frontal areas (p < 0.001); this association appeared to be driven by participants with high or low levels of the genetic profile. The frontal GMC profile correlated with cognitive and motor variables (Trail Making Test A (p = 0.03); Stroop Color (p = 0.017); Stroop Interference (p = 0.04); Symbol Digit Modalities Test (p = 0.031); Total Motor Score (p = 0.01)). A top-weighted NTRK2 variant (rs2277193) was protectively associated with Trail Making Test B (p = 0.007); greater minor allele numbers were linked to a better performance. These results support the idea of a protective role of NTRK2 in prodromal HD, particularly in individuals with certain genotypes, and suggest that this gene may influence the preservation of frontal gray matter that is important for clinical functioning

Tff3 Deficiency Protects against Hepatic Fat Accumulation after Prolonged High-Fat Diet

Trefoil factor 3 (Tff3) protein is a small secretory protein expressed on various mucosal surfaces and is involved in proper mucosal function and recovery via various mechanisms, including immune response. However, Tff3 is also found in the bloodstream and in various other tissues, including the liver. Its complete attenuation was observed as the most prominent event in the early phase of diabetes in the polygenic Tally Ho mouse model of diabesity. Since then, its role in metabolic processes has emerged. To elucidate the complex role of Tff3, we used a new Tff3-deficient mouse model without additional metabolically relevant mutations (Tff3-/-/C57BL/6NCrl) and exposed it to a high-fat diet (HFD) for a prolonged period (8 months). The effect was observed in male and female mice compared to wild-type (WT) counter groups (n = 10 animals per group). We monitored the animals’ general metabolic parameters, liver morphology, ultrastructure and molecular genes in relevant lipid and inflammatory pathways. Tff3-deficient male mice had reduced body weight and better glucose utilization after 17 weeks of HFD, but longer HFD exposure (32 weeks) resulted in no such change. We found a strong reduction in lipid accumulation in male Tff3-/-/C57BL/6NCrl mice and a less prominent reduction in female mice. This was associated with downregulated peroxisome proliferator-activated receptor gamma (Pparγ) and upregulated interleukin-6 (Il-6) gene expression, although protein level difference did not reach statistical significance due to higher individual variations. Tff3-/-/C57Bl6N mice of both sex had reduced liver steatosis, without major fatty acid content perturbations. Our research shows that Tff3 protein is clearly involved in complex metabolic pathways. Tff3 deficiency in C57Bl6N genetic background caused reduced lipid accumulation in the liver ; further research is needed to elucidate its precise role in metabolism-related events

Effect of Tff3 Deficiency and ER Stress in the Liver

Endoplasmic reticulum (ER) stress, a cellular condition caused by the accumulation of unfolded proteins inside the ER, has been recognized as a major pathological mechanism in a variety of conditions, including cancer, metabolic and neurodegenerative diseases. Trefoil factor family (TFFs) peptides are present in different epithelial organs, blood supply, neural tissues, as well as in the liver, and their deficiency has been linked to the ER function. Complete ablation of Tff3 expression is observed in steatosis, and as the most prominent change in the early phase of diabetes in multigenic mouse models of diabesity. To elucidate the role of Tff3 deficiency on different pathologically relevant pathways, we have developed a new congenic mouse model Tff3-/-/C57BL6/N from a mixed background strain (C57BL6/N /SV129) by using a speed congenics approach. Acute ER stress was evoked by tunicamycin treatment, and mice were sacrificed after 24 h. Afterwards the effect of Tff3 deficiency was evaluated with regard to the expression of relevant oxidative and ER stress genes, relevant proinflammatory cytokines/chemokines, and the global protein content. The most dramatic change was noticed at the level of inflammation-related genes, while markers for unfolded protein response were not significantly affected. Ultrastructural analysis confirmed that the size of lipid vacuoles was affected as well. Since the liver acts as an important metabolic and immunological organ, the influence of Tff3 deficiency and physiological function possibly reflects on the whole organism

Effect of Tff3 Deficiency and ER Stress in the Liver

Endoplasmic reticulum (ER) stress, a cellular condition caused by the accumulation of unfolded proteins inside the ER, has been recognized as a major pathological mechanism in a variety of conditions, including cancer, metabolic and neurodegenerative diseases. Trefoil factor family (TFFs) peptides are present in different epithelial organs, blood supply, neural tissues, as well as in the liver, and their deficiency has been linked to the ER function. Complete ablation of Tff3 expression is observed in steatosis, and as the most prominent change in the early phase of diabetes in multigenic mouse models of diabesity. To elucidate the role of Tff3 deficiency on different pathologically relevant pathways, we have developed a new congenic mouse model Tff3−/−/C57BL6/N from a mixed background strain (C57BL6/N /SV129) by using a speed congenics approach. Acute ER stress was evoked by tunicamycin treatment, and mice were sacrificed after 24 h. Afterwards the effect of Tff3 deficiency was evaluated with regard to the expression of relevant oxidative and ER stress genes, relevant proinflammatory cytokines/chemokines, and the global protein content. The most dramatic change was noticed at the level of inflammation-related genes, while markers for unfolded protein response were not significantly affected. Ultrastructural analysis confirmed that the size of lipid vacuoles was affected as well. Since the liver acts as an important metabolic and immunological organ, the influence of Tff3 deficiency and physiological function possibly reflects on the whole organism