Patrickgolden6933

Data on the prevalence of mental distress among adult eosinophilic esophagitis (EoE) patients are scarce. Also, a significant gap remains in the understanding of which determinants are related to significant psychological symptoms and whether distressed patients require and receive mental care.

Adult EoE patients were invited to complete standardized measures on anxiety/depressive symptoms (HADS) and general psychopathology (SCL-90-R). All scores were compared to general population norms. Socio-demographic and clinical factors were assessed.

In total, 147 adult EoE patients (61% males, age 43 (IQR 29-52) years were included (response rate 71%). No difference with general population values was found for total anxiety and depressive symptoms (7.8±6.6 vs. 8.4±6.3; p=0.31). A total of 38/147(26%) patients reported high levels of anxiety and/or depressive symptoms (HADS-A≥8 35/147(24%) and HADS-D≥8 14/147(10%)), indicative of a possible psychiatric disorder. In a multivariate analysis, age between 18-35yearsnd treatment of these psychological symptoms in EoE practice seems essential.

In mice, Schwann cell (SC) progenitors give rise to autonomic ganglion cells and migrate into the gut to become enteric neurons. It is unknown whether SC progenitors have a similar fate in humans. In search of evidence for human SC-derived neurogenesis in the gastrointestinal (GI) tract, we studied the rectums from cadaveric controls and children with anorectal malformations (ARM).

We analyzed distal rectal tissue taken at autopsy from 10 children with normal GI tracts and resected rectal specimens in 48 cases of ARM. Of these specimens, 6 had neurons within the extrinsic rectal innervation. These were further investigated with immunohistochemistry for neuronal and SC/glial markers.

Perirectal tissue from control and ARM contained GLUT1-positive extrinsic nerves, many containing neurons. SC/glial markers (SOX10, CDH19, and PLP1) were expressed by glia in the enteric nervous system and perirectal nerves, while MPZ predominated only in glia of perirectal nerves, in both control and ARM. Neurons in perirectal nerves were 61% larger in ARM samples and co-expressed SOX10 (81%), PLP1 (73%), and CDH19 (56%). In ARM, cytoplasmic SOX10 was co-expressed with neuronal antigens in ~57% of submucosal and myenteric neurons, vs. ~3% in control. Furthermore, intrinsic gut neurons in ARM specimens co-expressed PLP1 (18%) and CDH19 (18%); however, neuronal co-expression of PLP1 and CDH19 was rarely (<2%) observed in controls.

Dual expression of glial and neuronal markers in rectal and perirectal neurons support a model of Schwann cell-derived neurogenesis in the innervation of the human GI tract.

Dual expression of glial and neuronal markers in rectal and perirectal neurons support a model of Schwann cell-derived neurogenesis in the innervation of the human GI tract.Living beings are autopoietic systems with highly context-dependent structural dynamics and interactions, that determine whether a disturbance in the genotype or environment will lead or not to phenotypic change. The concept of epigenesis entails how a change in the phenotype may not correspond to a change in the structure of an earlier developmental stage, including the genome. Disturbances of embryonic structure may fail to change the phenotype, as in regulated development, or when different genotypes are associated to a single phenotype. Likewise, the same genotype or early embryonic structure may develop different phenotypes, as in phenotypic plasticity. Disturbances that fail to trigger phenotypic change are considered neutral, but even so, they can alter unexpressed developmental potential. Here, we present conceptual diagrams of the "epigenic field" similar to Waddington's epigenetic landscapes, but including the ontogenic niche (organism/environment interactional dynamics during ontogeny) as a factor in defining epigenic fields, rather than just selecting among possible pathways. Our diagrams illustrate transgenerational changes of genotype, ontogenic niche, and their correspondence (or lack thereof) with changes of phenotype. Epigenic fields provide a simple way to understand developmental constraints on evolution, for instance how constraints evolve as a result of developmental system drift; how neutral changes can be involved in genetic assimilation and de-assimilation; and how constraints can evolve as a result of neutral changes in the ontogenic niche (not only the genotype). We argue that evolutionary thinking can benefit from a framework for evolution with conceptual foundations at the organismal level.Early-life immune challenges and inflammation are risk factors for a range of developmental disorders. During the course of a study examining interactions between the common antipyretic acetaminophen (APAP; paracetamol) and interleukin-1β (IL-1β)-induced inflammation in neonatal mice we observed that subcutaneous (s.c.) injection of IL-1β often leads to significantly shorter, blunt-tipped tails. Three times during early development, on postnatal day 5 (P5), P8, and P11, C57BL/6J pups were given s.c. injection of either .2 μg/kg IL-1β or 5 cc/kg injection of saline vehicle followed, after a 45 min delay, by a second injection, of either 103.9 mg/kg APAP or saline. IL-1β was observed to reduce tail length-via a blunting of the tail tip-in treated vs. untreated mice, an effect that was significant as early as P11 and persisted through the end of the study (~P74). Interestingly, IL-1β-induced tail blunting was significantly lessened by APAP, an interaction that may have occurred as a result of the opposing actions of APAP and IL-1β on cyclooxygenase-2. Although this specific hypothesis and the mechanisms underlying the effects of IL-1β on tail length require further study, they add to the literature suggesting that IL-1β may be a critical mediator of specific adverse effects of early-life inflammation.The ability of the extracellular matrix (ECM) to instruct progenitor cell differentiation has generated excitement for the development of materials-based regenerative solutions. Described a nanoparticulate mineralized collagen glycosaminoglycan (MC-GAG) material capable of inducing in vivo skull regeneration without exogenous growth factors or ex vivo progenitor cell-priming is described previously. Here, the contribution of titrating stiffness to osteogenicity is evaluated by comparing noncrosslinked (NX-MC) and crosslinked (MC) forms of MC-GAG. MMP-9-IN-1 manufacturer While both materials are osteogenic, MC demonstrates an increased expression of osteogenic markers and mineralization compared to NX-MC. Both materials are capable of autogenously activating the canonical BMPR signaling pathway with phosphorylation of Smad1/5. However, unlike NX-MC, human mesenchymal stem cells cultured on MC demonstrate significant elevations in the major mechanotransduction mediators YAP and TAZ expression, coincident with β-catenin activation in the canonical Wnt signaling pathway. Inhibition of YAP/TAZ activation reduces osteogenic expression, mineralization, and β-catenin activation in MC, with less of an effect on NX-MC. YAP/TAZ inhibition also results in a reciprocal increase in Smad1/5 phosphorylation and BMP2 expression. The results indicate that increasing MC-GAG stiffness induces osteogenic differentiation via the mechanotransduction mediators YAP/TAZ and the canonical Wnt signaling pathway, whereas the canonical BMPR signaling pathway is activated independent of stiffness.Dietary restriction extends lifespan in various organisms by reducing the levels of both nutrients and non-nutritional food-derived cues. However, the identity of specific food-derived chemical cues that alter lifespan remains unclear. Here, we identified several volatile attractants that decreased the longevity on food deprivation, a dietary restriction regimen in Caenorhabditis elegans. In particular, we found that the odor of diacetyl decreased the activity of DAF-16/FOXO, a life-extending transcription factor acting downstream of insulin/IGF-1 signaling. We then demonstrated that the odor of lactic acid bacteria, which produce diacetyl, reduced the nuclear accumulation of DAF-16/FOXO. Unexpectedly, we showed that the odor of diacetyl decreased longevity independently of two established diacetyl receptors, ODR-10 and SRI-14, in sensory neurons. Thus, diacetyl, a food-derived odorant, may shorten food deprivation-induced longevity via decreasing the activity of DAF-16/FOXO through binding to unidentified receptors.Normothermic machine perfusion (NMP) of injured kidneys offers the opportunity for interventions to metabolically active organs prior to transplantation. Mesenchymal stromal cells (MSCs) can exert regenerative and anti-inflammatory effects in ischemia-reperfusion injury. The aims of this study were to evaluate the safety and feasibility of MSC treatment of kidneys during NMP using a porcine autotransplantation model, and examine potential MSC treatment-associated kidney improvements up to 14 days posttransplant. After 75 min of kidney warm ischemia, four experimental groups of n = 7 underwent 14 h of oxygenated hypothermic machine perfusion. In three groups this was followed by 240 min of NMP with infusion of vehicle, 10 million porcine, or 10 million human adipose-derived MSCs. All kidneys were autotransplanted after contralateral nephrectomy. MSC treatment did not affect perfusion hemodynamics during NMP or cause adverse effects at reperfusion, with 100% animal survival. MSCs did not affect plasma creatinine, glomerular filtration rate, neutrophil gelatinase-associated lipocalin concentrations or kidney damage assessed by histology during the 14 days, and MSCs retention was demonstrated in renal cortex. Infusing MSCs during ex vivo NMP of porcine kidneys was safe and feasible. Within the short posttransplant follow-up period, no beneficial effects of ex vivo MSC therapy could be demonstrated.

Hepatitis B virus (HBV) was found to exist in semen and male germ cells of patients with chronic HBV infection. Our previous studies demonstrated that HBV surface protein (HBs) could induce sperm dysfunction by activating a calcium signaling cascade and triggering caspase-dependent apoptosis. However, the relationship between sperm dysfunction caused by HBs and caspase-independent apoptosis has not been investigated.

To evaluate the effects of HBs exposure on sperm dysfunction by activating caspase-independent apoptosis.

Spermatozoa were exposed to HBs at concentrations of 0, 25, 50, and 100μg/mL for 3h. Flow cytometry, qRT-PCR, immunofluorescence assay, ELISA, and zona-free hamster oocyte penetration assays were performed.

With increasing concentrations of HBs, various parameters of the spermatozoa changed. The number of Bcl2-positive cells declined and that of both Bax-positive cells and Apaf-1-positive cells increased. The transcription level of Bcl2 increased and that of both Bax and Apaf-1 declinimpact of HBV on male fertility in HBV-infected patients.We report on electrical double-layer capacitors (EDLCs) performing effectively at low temperature (down to -40 °C), owing to the tuned characteristics of both the ionic liquid (IL) electrolyte and carbonaceous electrodes. The transport properties of the electrolyte have been enhanced by adding a low-viscosity IL with the tetracyanoborate anion, [EMIm][TCB], to a mixture of [EMIm][FSI] with [EMIm][BF4 ], which was already successfully applied for this application. The formulated ternary electrolyte, [EMIm][FSI]0.6 [BF4 ]0.1 [TCB]0.3 , remained in the liquid state until it reached the glass transition at -99 °C and displayed a relatively low viscosity and high conductivity (η=23.6 mP s and σ=14.2 mS cm-1 at 20 °C, respectively). The electrodes were made of a hierarchical SiO2 -templated carbon with well-defined and uniform mesopores of ∼9 nm facilitating ion transport to the interconnected micropores accounted for the charge storage, whereas the high density of the electrodes promoted high volumetric energy outputs of the cells.