Blood biomarker profiles in young-onset neurocognitive disorders: A cohort study.

Introduction: Young-onset neurocognitive symptoms result from a heterogeneous group of neurological and psychiatric disorders which present a diagnostic challenge. To identify such factors, we analysed the Biomarkers in Younger-Onset Neurocognitive Disorders cohort, a study of individuals <65 years old presenting with neurocognitive symptoms for a diagnosis and who have undergone cognitive and biomarker analyses.

Methods: Sixty-five participants (median age at assessment of 56 years, 45% female) were recruited during their index presentation to the Royal Melbourne Hospital Neuropsychiatry Centre, a tertiary specialist service in Melbourne, Australia, and categorized as either early-onset Alzheimer's disease ( = 18), non-Alzheimer's disease neurodegeneration ( = 23) or primary psychiatric disorders ( = 24).

Pax proteins mediate segment-specific functions in proximal tubule survival and response to ischemic injury.

Acute kidney injury (AKI) is a common clinical syndrome with few effective treatments. Though the kidney can regenerate after injury, the molecular mechanisms regulating this process remain poorly understood. Pax2 and Pax8 are DNA-binding transcription factors that are upregulated after kidney injury.

Sustained alterations in proximal tubule gene expression in primary culture associate with HNF4A loss.

Primary cultures of proximal tubule cells are widely used to model the behavior of kidney epithelial cells in vitro. However, de-differentiation of primary cells upon culture has been observed and appreciated for decades, yet the mechanisms driving this phenomenon remain poorly understood. This confounds the interpretation of experiments using primary kidney epithelial cells and prevents their use to engineer functional kidney tissue ex vivo.

Gene regulation in regeneration after acute kidney injury.

Acute kidney injury (AKI) is a common condition associated with significant morbidity, mortality, and cost. Injured kidney tissue can regenerate after many forms of AKI. However, there are no treatments in routine clinical practice to encourage recovery.

Renal-specific loss of ferroportin disrupts iron homeostasis and attenuates recovery from acute kidney injury.

Chronic kidney disease is increasing at an alarming rate and correlates with the increase in diabetes, obesity, and hypertension that disproportionately impact socioeconomically disadvantaged communities. Iron plays essential roles in many biological processes including oxygen transport, mitochondrial function, cell proliferation, and regeneration. However, excess iron induces the generation and propagation of reactive oxygen species, which lead to oxidative stress, cellular damage, and ferroptosis.

Pax protein depletion in proximal tubules triggers conserved mechanisms of resistance to acute ischemic kidney injury preventing transition to chronic kidney disease.

Acute kidney injury (AKI) is a common condition that lacks effective treatments. In part, this shortcoming is due to an incomplete understanding of the genetic mechanisms that control pathogenesis and recovery. Identifying the molecular and genetic regulators unique to nephron segments that dictate vulnerability to injury and regenerative potential could lead to new therapeutic targets to treat ischemic kidney injury.

Pax Protein Depletion in Proximal Tubules Triggers Conserved Mechanisms of Resistance to Acute Ischemic Kidney Injury and Prevents Transition to Chronic Kidney Disease.

Unlabelled: Acute kidney injury (AKI) is a common condition that lacks effective treatments. In part this shortcoming is due to an incomplete understanding of the genetic mechanisms that control pathogenesis and recovery. Pax2 and Pax8 are homologous transcription factors with overlapping functions that are critical for kidney development and are re-activated in AKI.

Pre-cultured, cell-encapsulating fibrin microbeads for the vascularization of ischemic tissues.

There is a significant clinical need to develop effective vascularization strategies for tissue engineering and the treatment of ischemic pathologies. In patients afflicted with critical limb ischemia, comorbidities may limit common revascularization strategies. Cell-encapsulating modular microbeads possess a variety of advantageous properties, including the ability to support prevascularization in vitro while retaining the ability to be injected in a minimally invasive manner in vivo.

High-throughput image analysis with deep learning captures heterogeneity and spatial relationships after kidney injury.

Recovery from acute kidney injury can vary widely in patients and in animal models. Immunofluorescence staining can provide spatial information about heterogeneous injury responses, but often only a fraction of stained tissue is analyzed. Deep learning can expand analysis to larger areas and sample numbers by substituting for time-intensive manual or semi-automated quantification techniques.

Parent perceptions of pediatric oncology care during the COVID-19 pandemic: An Australian study.

Background: We examined parents' perceptions of their child's oncology care during a period of significant COVID-19 restrictions in Australia.

Methods: Parents of children, 0-18 years, receiving hospital-based cancer treatment, completed a survey examining their COVID-19 exposure and impact, information and knowledge, and perception of their child's medical care. Recruitment occurred between October and November 2020.

Vaccine hesitancy and reported non-vaccination in an Irish pediatric outpatient population.

Vaccine hesitancy is defined as a delay in acceptance, or refusal, of vaccines, despite availability. It is a complex and context specific phenomenon and identified as a global health priority. The "Parent Attitudes about Childhood Vaccines" (PACV) questionnaire is a validated tool for identifying vaccine hesitancy.

Stromal cell identity modulates vascular morphogenesis in a microvasculature-on-a-chip platform.

Supportive stromal cells of mesenchymal origins regulate vascular morphogenesis in developmental, pathological, and regenerative contexts, contributing to vessel formation, maturation, and long-term stability, in part via the secretion of bioactive molecules. In this work, we adapted a microfluidic lab-on-a-chip system that enables the formation and perfusion of microvascular capillary beds with connections to arteriole-scale endothelialized channels to explore how stromal cell (SC) identity influences endothelial cell (EC) morphogenesis. We compared and contrasted lung fibroblasts (LFs), dermal fibroblasts (DFs), and bone marrow-derived mesenchymal stem cells (MSCs) for their abilities to support endothelial morphogenesis and subsequent perfusion of microvascular networks formed in fibrin hydrogels within the microfluidic device.

Injectable pre-cultured tissue modules catalyze the formation of extensive functional microvasculature in vivo.

Revascularization of ischemic tissues is a major barrier to restoring tissue function in many pathologies. Delivery of pro-angiogenic factors has shown some benefit, but it is difficult to recapitulate the complex set of factors required to form stable vasculature. Cell-based therapies and pre-vascularized tissues have shown promise, but the former require time for vascular assembly in situ while the latter require invasive surgery to implant vascularized scaffolds.

Cell-mediated matrix stiffening accompanies capillary morphogenesis in ultra-soft amorphous hydrogels.

There is a critical need for biomaterials that support robust neovascularization for a wide-range of clinical applications. Here we report how cells alter tissue-level mechanical properties during capillary morphogenesis using a model of endothelial-stromal cell co-culture within poly(ethylene glycol) (PEG) based hydrogels. After a week of culture, we observed substantial stiffening in hydrogels with very soft initial properties.

Deciphering the relative roles of matrix metalloproteinase- and plasmin-mediated matrix degradation during capillary morphogenesis using engineered hydrogels.

Extracellular matrix (ECM) remodeling is essential for the process of capillary morphogenesis. Here we employed synthetic poly(ethylene glycol) (PEG) hydrogels engineered with proteolytic specificity to either matrix metalloproteinases (MMPs), plasmin, or both to investigate the relative contributions of MMP- and plasmin-mediated ECM remodeling to vessel formation in a 3D-model of capillary self-assembly analogous to vasculogenesis. We first demonstrated a role for both MMP- and plasmin-mediated mechanisms of ECM remodeling in an endothelial-fibroblast co-culture model of vasculogenesis in fibrin hydrogels using inhibitors of MMPs and plasmin.

Mass Flow through Solid ^{3}He in the bcc Phase.

A number of experiments have shown that mass can be transported through solid ^{4}He at temperatures as low as 16 mK, with features that suggest superflow. But the nature of this flow remains unclear. The Fermi isotope ^{3}He provides the possibility of a direct comparison to a solid in which quantum effects are even more important but superfluidity is not expected.

Plastic Deformation in a Quantum Solid: Dislocation Avalanches and Creep in Helium.

Conventional solids deform elastically for small stresses-reversibly with a linear, rate-independent relationship between stress and strain. Beyond the yield point, plastic deformation begins-irreversible, nonlinear, and time dependent. Plasticity involves the motion and multiplication of dislocations, and here we report observations of such "metallurgical" phenomena in hcp ^{4}He, a solid whose defect behavior is dominated by quantum effects.

Engineered extracellular matrices with controlled mechanics modulate renal proximal tubular cell epithelialization.

Acute kidney injury (AKI) is common and associated with significant morbidity and mortality. Recovery from many forms of AKI involves the proliferation of renal proximal tubular epithelial cells (RPTECs), but the influence of the microenvironment in which this recovery occurs remains poorly understood. Here we report the development of a poly(ethylene glycol) (PEG) hydrogel platform to study the influence of substrate mechanical properties on the proliferation of human RPTECs as a model for recovery from AKI.

Erratum: Compression-Driven Mass Flow in Bulk Solid ^{4}He [Phys. Rev. Lett. 117, 025301 (2016)].

This corrects the article DOI: 10.1103/PhysRevLett.117.

Compression-Driven Mass Flow in Bulk Solid ^{4}He.

Mass flow has been observed in solid ^{4}He coexisting with superfluid confined in Vycor, but its physical mechanism remains an open question. Here we report observations of flow in experiments in which Vycor has been eliminated, allowing us to study the intrinsic flow in solid ^{4}He without the complications introduced by the presence of superfluid and the associated solid-liquid interfaces. By growing crystals with ^{3}He concentration as low as x_{3}=5×10^{-12}, we also avoided the low temperature flow suppression observed in previous experiments and found that the flow rate continued to increase down to at least 28 mK without saturation.

Assessing the effectiveness of a three-stage on-farm biobed in treating pesticide contaminated wastewater.

Agricultural point source pesticide pollution arising from contaminated machinery washings and accidental spillages pose a significant threat to river water and groundwater quality. In this study, we assess the effectiveness of a three-stage on-farm biobed for treating pesticide contaminated wastewater from a large (20 km(2)) commercial arable estate. The facility consisted of an enclosed machinery wash-down unit (stage 1), a 49 m(2) lined compost-straw-topsoil biobed (stage 2), and a 200 m(2) drainage field with a trickle irrigation system (stage 3).

Search for Dislocation Free Helium 4 Crystals.

The giant plasticity of [Formula: see text]He crystals has been explained as a consequence of the large mobility of their dislocations. Thus, the mechanical properties of dislocation free crystals should be quite different from those of usual ones. In 1996-1998, Ruutu et al.

Helium mass flow through a solid-superfluid-solid junction.

We report the results of flow experiments in which two chambers containing solid ^{4}He are connected by a superfluid Vycor channel. At low temperatures and pressures, mechanically squeezing the solid in one chamber produced a pressure increase in the second chamber, a measure of mass transport through our solid-superfluid-solid junction. This pressure response is very similar to the flow seen in recent experiments at the University of Massachusetts: it began around 600 mK, increased as the temperature was reduced, then decreased dramatically at a temperature, T_{d}, which depended on the ^{3}He impurity concentration.