Cold-Spray Deposition of Antibacterial Molybdenum Coatings on Poly(dimethylsiloxane).

Despite their widespread utilization in biomedical applications, these synthetic materials can be susceptible to microbial contamination, potentially compromising their functionality and increasing the risk of infection in patients. In this study, molybdenum (Mo), an essential metal in biological systems, was investigated as a Mo-based cold-sprayed coating on poly(dimethylsiloxane) (PDMS) for its potential use as biocompatible and antimicrobial surfaces for biomedical applications. Various cold-spray parameters were employed in the fabrication of Mo-embedded PDMS surfaces to alter the surface structure of the substrate, Mo loading density, and embedding layer thickness.

Pilot Screening of TREM1 Inhibitors in Cell-Based Reporter Assays Reflecting TREM1/DAP12 Receptor Assembly and Functionality.

Proinflammatory TREM1 receptors expressed on myeloid-derived cells have recently been recognized as a new oncogenic target in cancer, including gliomas. They are established chemotherapeutic targets in neurodegenerative Parkinson's and Alzheimer's diseases, and they also contribute to stroke and sepsis severities. TREM1 activation requires the TREM1/DAP12 interaction for receptor clustering and signal transduction coordinated by TREM1 ligands.

N-SREBP2 Provides a Mechanism for Dynamic Control of Cellular Cholesterol Homeostasis.

Cholesterol is required to maintain the functional integrity of cellular membrane systems and signalling pathways, but its supply must be closely and dynamically regulated because excess cholesterol is toxic. Sterol regulatory element-binding protein 2 (SREBP2) and the ER-resident protein HMG-CoA reductase (HMGCR) are key regulators of cholesterol biosynthesis. Here, we assessed the mechanistic aspects of their regulation in hepatic cells.

In a circuit necessary for cognition and emotional affect, Alzheimer's-like pathology associates with neuroinflammation, cognitive and motivational deficits in the young adult TgF344-AD rat.

In addition to extracellular amyloid plaques, intracellular neurofibrillary tau tangles, and inflammation, cognitive and emotional affect perturbations are characteristic of Alzheimer's disease (AD). The cognitive and emotional domains impaired by AD include several forms of decision making (such as intertemporal choice), blunted motivation (increased apathy), and impaired executive function (such as working memory and cognitive flexibility). However, the interaction between these domains of the mind and their supporting neurobiological substrates at prodromal stages of AD, or whether these interactions can be predictive of AD severity (individual variability), remain unclear.

Late-Stage Skeletal Muscle Transcriptome in Duchenne muscular dystrophy shows a BMP4-Induced Molecular Signature.

Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive disease due to loss-of-function mutations in the gene. DMD-related skeletal muscle wasting is typified by an aberrant immune response involving upregulation of TGFβ family of cytokines. We previously demonstrated that bone morphogenetic protein 4 (BMP4) is increased in DMD and BMP4 stimulation induces a 20-fold upregulation of transcription.

Poly(ADP-ribose) mediates bioenergetic defects and redox imbalance in neurons following oxygen and glucose deprivation.

PARP-1 over-activation results in cell death via excessive PAR generation in different cell types, including neurons following brain ischemia. Glycolysis, mitochondrial function, and redox balance are key cellular processes altered in brain ischemia. Studies show that PAR generated after PARP-1 over-activation can bind hexokinase-1 (HK-1) and result in glycolytic defects and subsequent mitochondrial dysfunction.

Association of Posttraumatic Stress Disorder and Race on Readmissions After Stroke.

Background: There is limited research on outcomes of patients with posttraumatic stress disorder (PTSD) who also develop stroke, particularly regarding racial disparities. Our goal was to determine whether PTSD is associated with the risk of hospital readmission after stroke and whether racial disparities existed.

Methods: The analytical sample consisted of all veterans receiving care in the Veterans Health Administration who were identified as having a new stroke requiring inpatient admission based on the codes.

Sensory Chronic Inflammatory Demyelinating Polyradiculoneuropathy: Neglected Immunotherapy-Responsive Sensory Neuropathy.

Background And Purpose: To report an improvement with immunotherapy in 34 (85%)/40 patients who required an immunotherapy among 56 patients with sensory chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

Methods: Sensory CIDP was diagnosed when two inclusion criteria are met: 1) acquired, chronic progressive or relapsing symmetrical or asymmetrical sensory polyneuropathy that had progressed for >2 months; and 2) definite electrophysiological and/or biopsy evidence of demyelinating neuropathy.

Results: Fifty-six patients with sensory CIDP were identified.

Skeletal muscle as a molecular and cellular biomarker of disease progression in amyotrophic lateral sclerosis: a narrative review.

Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target. Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis, there is considerable heterogeneity, including clinical presentation, progression, and the underlying triggers for disease initiation. Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations, it has become apparent that overt disease is preceded by a prodromal phase, possibly in years, where compensatory mechanisms delay symptom onset.

Somatic mutations of CADM1 in aldosterone-producing adenomas and gap junction-dependent regulation of aldosterone production.

Aldosterone-producing adenomas (APAs) are the commonest curable cause of hypertension. Most have gain-of-function somatic mutations of ion channels or transporters. Herein we report the discovery, replication and phenotype of mutations in the neuronal cell adhesion gene CADM1.

Surface Characteristics and Bone Biocompatibility of Cold-Sprayed Porous Titanium on Polydimethylsiloxane Substrates.

A variant of the cold spray (CS) technique was applied for the functionalization of polymer-based materials such as polydimethylsiloxane (PDMS) to improve the extent of mammalian cell interactions with these substrates. This was demonstrated by the embedment of porous titanium (pTi) into PDMS substrates using a single-step CS technique. CS processing parameters such as gas pressure and temperature were optimized to achieve the mechanical interlocking of pTi in the compressed PDMS to fabricate a unique hierarchical morphology possessing micro-roughness.

Evaluating childsmile, Scotland's National Oral Health Improvement Programme for children.

In the early 2000s, a Scottish Government Oral Health Action Plan identified the need for a national programme to improve child oral health and reduce inequalities. 'Childsmile' aimed to improve child oral health in Scotland, reduce inequalities in outcomes and access to dental services, and to shift the balance of care from treatment to prevention through targeted and universal components in dental practice, community and educational settings. This paper describes how an embedded, theory-based research and evaluation arm with multi-disciplinary input helps determine priorities and provides important strategic direction.

Transcriptomic analysis of human ALS skeletal muscle reveals a disease-specific pattern of dysregulated circRNAs.

Circular RNAs are abundant, covalently closed transcripts that arise in cells through back-splicing and display distinct expression patterns across cells and developmental stages. While their functions are largely unknown, their intrinsic stability has made them valuable biomarkers in many diseases. Here, we set out to examine circRNA patterns in amyotrophic lateral sclerosis (ALS).

MicroRNA-183-5p regulates TAR DNA-binding protein 43 neurotoxicity via SQSTM1/p62 in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that selectively attacks motor neurons, and leads to progressive muscle weakness and death. A common pathological feature is the misfolding, aggregation, and cytoplasmic mislocalization of TAR DNA-binding protein 43 (TDP-43) proteins in more than 95% of ALS patients, suggesting a universal role TDP-43 proteinopathy in ALS. Mutations in SQSTM1/p62 have been identified in familial and sporadic cases of ALS.

Life-Long Steroid Responsive Familial Myopathy With Docking Protein 7 Mutation.

Docking protein 7 (DOK7) congenital myasthenic syndrome (CMS) is characterized by limb-girdle weakness and lack of fluctuating fatigability simulating many familial myopathies. Albuterol is the first line of therapy in view of consistent improvement. Two brothers with progressive predominant biceps weakness for 1-3 years responded to prednisone treatment for 40-50 years.

RNA regulation of inflammatory responses in glia and its potential as a therapeutic target in central nervous system disorders.

A major hallmark of neuroinflammation is the activation of microglia and astrocytes with the induction of inflammatory mediators such as IL-1β, TNF-α, iNOS, and IL-6. Neuroinflammation contributes to disease progression in a plethora of neurological disorders ranging from acute CNS trauma to chronic neurodegenerative disease. Posttranscriptional pathways of mRNA stability and translational efficiency are major drivers for the expression of these inflammatory mediators.

Targeting the TREM1-positive myeloid microenvironment in glioblastoma.

Background: Tumor cellular and molecular heterogeneity is a hallmark of glioblastoma and underlies treatment resistance and recurrence. This manuscript investigated the myeloid-derived microenvironment as a driver of glioblastoma heterogeneity and provided a pharmacological pathway for its suppression.

Methods: Transcriptomic signatures of glioblastoma infiltrated myeloid-derived cells were assessed using R2: genomic platform, Ivy Glioblastoma Spatial Atlas, and single-cell RNA-seq data of primary and recurrent glioblastomas.

Smad8 Is Increased in Duchenne Muscular Dystrophy and Suppresses miR-1, miR-133a, and miR-133b.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disease characterized by skeletal muscle instability, progressive muscle wasting, and fibrosis. A major driver of DMD pathology stems from aberrant upregulation of transforming growth factor β (TGFβ) signaling. In this report, we investigated the major transducers of TGFβ signaling, i.

Inhibition of the RNA Regulator HuR by SRI-42127 Attenuates Neuropathic Pain After Nerve Injury Through Suppression of Neuroinflammatory Responses.

Microglial activation with the production of pro-inflammatory mediators such as IL-6, TNF-α, and IL-1β, is a major driver of neuropathic pain (NP) following peripheral nerve injury. We have previously shown that the RNA binding protein, HuR, is a positive node of regulation for many of these inflammatory mediators in glia and that its chemical inhibition or genetic deletion attenuates their production. In this report, we show that systemic administration of SRI-42127, a novel small molecule HuR inhibitor, attenuates mechanical allodynia, a hallmark of NP, in the early and chronic phases after spared nerve injury in male and female mice.

High fidelity dialectical behaviour therapy online: Learning from experienced practitioners.

Dialectical behaviour therapy (DBT) is an effective treatment for borderline personality disorder and other problems underpinned by difficulties with emotional regulation. The main components of DBT are skills training groups and individual therapy. The COVID-19 outbreak forced a rapid adaptation to online delivery, which largely mirrored face-to-face programmes using videoconferencing technology.

Towards online delivery of Dialectical Behaviour Therapy: A scoping review.

Dialectical Behaviour Therapy (DBT) programmes are often the only available treatment for people diagnosed with borderline personality disorder and were rapidly converted to online delivery during the COVID-19 pandemic. Limited research exists surrounding how the major elements of DBT are delivered in an online environment. This scoping review considered the operationalization of online delivery of DBT and its effectiveness.

The versatile role of HuR in Glioblastoma and its potential as a therapeutic target for a multi-pronged attack.

Glioblastoma (GBM) is a malignant and aggressive brain tumor with a median survival of ∼15 months. Resistance to treatment arises from the extensive cellular and molecular heterogeneity in the three major components: glioma tumor cells, glioma stem cells, and tumor-associated microglia and macrophages. Within this triad, there is a complex network of intrinsic and secreted factors that promote classic hallmarks of cancer, including angiogenesis, resistance to cell death, proliferation, and immune evasion.

Breakthrough instruments and products: Investigation of atomic layer deposited Al:ZnO layer by spectroscopic ellipsometry from the deep-UV to the mid-IR in one instrument.

The Semilab SE-2000 spectroscopic ellipsometer is a versatile thin film characterization instrument capable of spectroscopic ellipsometry measurements covering a large spectral range from ultraviolet to near infrared within a few seconds and into the mid-infrared in a few minutes. It is suitable for characterizing thin films from monolayers to complex multi-layer laminates and bulk materials. This article demonstrates the unique capabilities of the SE-2000 system by the wide spectral range investigation of Al doped ZnO layers on different substrates and with different layer structures.

A Neuroscience Primer for Integrating Geroscience With the Neurobiology of Aging.

Neuroscience has a rich history of studies focusing on neurobiology of aging. However, much of the aging studies in neuroscience occur outside of the gerosciences. The goal of this primer is 2-fold: first, to briefly highlight some of the history of aging neurobiology and second, to introduce to geroscientists the broad spectrum of methodological approaches neuroscientists use to study the neurobiology of aging.