Tuneable Recombinant Spider Silk Protein Hydrogels for Drug Release and 3D Cell Culture.

Hydrogels are useful drug release systems and tissue engineering scaffolds. However, synthetic hydrogels often require harsh gelation conditions and can contain toxic by-products while naturally derived hydrogels can transmit pathogens and in general have poor mechanical properties. Thus, there is a need for a hydrogel that forms under ambient conditions, is non-toxic, xeno-free, and has good mechanical properties.

Understanding How Contingency Staffing Programs Can Support Mental Health Services in the Veterans Health Administration.

Beginning in 2019, the Department of Veterans Affairs (VA) prioritized improving access to care nationally to deliver virtual care and implemented 18 regionally based Clinical Resource Hubs (CRHs) to meet this priority. This observational study describes the quantity and types of care delivered by CRH Mental Health teams, and the professions of those hired to deliver it. A retrospective cohort study, based on national VA CRH mental health care utilization data and CRH staffing data for CRH's first 3 years, was conducted.

Prosaposin maintains lipid homeostasis in dopamine neurons and counteracts experimental parkinsonism in rodents.

Prosaposin (PSAP) modulates glycosphingolipid metabolism and variants have been linked to Parkinson's disease (PD). Here, we find altered PSAP levels in the plasma, CSF and post-mortem brain of PD patients. Altered plasma and CSF PSAP levels correlate with PD-related motor impairments.

Feasibility and therapeutical potential of local intracerebral encapsulated cell biodelivery of BDNF to App knock-in Alzheimer mice.

Background: Alzheimer's disease (AD) is an age-related disease characterized by altered cognition, neuroinflammation, and neurodegeneration against which there is presently no effective cure. Brain-derived neurotrophic factor (BDNF) is a key neurotrophin involved in the learning and memory process, with a crucial role in synaptic plasticity and neuronal survival. Several findings support that a reduced BDNF expression in the human brain is associated with AD pathogenesis.

Microglia Impairs Proliferation and Induces Senescence In-Vitro in NGF Releasing Cells Used in Encapsulated Cell Biodelivery for Alzheimer's Disease Therapy.

There is no cure yet available for Alzheimer's disease (AD). We recently optimized encapsulated cell biodelivery (ECB) devices releasing human mature nerve growth factor (hmNGF), termed ECB-NGF, to the basal forebrain of AD patients. The ECB-NGF delivery resulted in increased CSF cholinergic markers, improved glucose metabolism, and positive effects on cognition in AD patients.

Fast Alpha Activity in EEG of Patients With Alzheimer's Disease Is Paralleled by Changes in Cognition and Cholinergic Markers During Encapsulated Cell Biodelivery of Nerve Growth Factor.

Background: Basal forebrain cholinergic neurons are dependent on nerve growth factor (NGF) for growth and survival and these cells are among the first to degenerate in Alzheimer's disease (AD). Targeted delivery of NGF has been suggested as a potential therapy for AD. This hypothesis was tested in a clinical trial with encapsulated cell biodelivery of NGF (NGF-ECB) in AD patients.

Certainty and systematicity of practice-derived evidence matter for its relative importance in professional decision-making: Survey results on the role of proven experience in Swedish medicine, nursing, OT, dentistry, and dental hygiene.

Background: High-quality healthcare decisions need to balance input from science and clinical practice. When two sources of evidence - such as scientific and practice-derived evidence - are compared, integrated, or need to stand-in for one another, they need to be comparable on similar dimensions. Since 1891, Swedish physicians have been operating under a legal requirement to base their healthcare decisions on science and "proven experience" (approximately clinical expertise), and today all healthcare personnel in Sweden fall under this legal requirement.

Amyloid-Beta Peptides and Activated Astroglia Impairs Proliferation of Nerve Growth Factor Releasing Cells In Vitro: Implication for Encapsulated Cell Biodelivery-Mediated AD Therapy.

Alzheimer's disease (AD) treatment is constrained due to the inability of peripherally administered therapeutic molecules to cross the blood-brain barrier. Encapsulated cell biodelivery (ECB) devices, a tissue-targeted approach for local drug release, was previously optimized for human mature nerve growth factor (hmNGF) delivery in AD patients but was found to have reduced hmNGF release over time. To understand the reason behind reduced ECB efficacy, we exposed hmNGF-releasing cells (NGC0211) in vitro to human cerebrospinal fluid (CSF) obtained from Subjective Cognitive Impairment (SCI), Lewy Body Dementia (LBD), and AD patients.

Psychological Adaptive Mechanism Maturity Predicts Good Outcomes in Treatment for Refractory PTSD.

Post-traumatic Stress Disorder (PTSD) severity follows a bell-shaped curve ranging from mild to severe. Those in the severe range often receive the most intensive treatments, including targeted residential rehabilitation stays. These are expensive and welcome ways to improve their effectiveness.

A Review of Techniques for Biodelivery of Nerve Growth Factor (NGF) to the Brain in Relation to Alzheimer's Disease.

Age-dependent progressive neurodegeneration and associated cognitive dysfunction represent a serious concern worldwide. Currently, dementia accounts for the fifth highest cause of death, among which Alzheimer's disease (AD) represents more than 60% of the cases. AD is associated with progressive cognitive dysfunction which affects daily life of the affected individual and associated family.

Where Dopaminergic and Cholinergic Systems Interact: A Gateway for Tuning Neurodegenerative Disorders.

Historically, many investigations into neurodegenerative diseases have focused on alterations in specific neuronal populations such as, for example, the loss of midbrain dopaminergic neurons in Parkinson's disease (PD) and loss of cholinergic transmission in Alzheimer's disease (AD). However, it has become increasingly clear that mammalian brain activities, from executive and motor functioning to memory and emotional responses, are strictly regulated by the integrity of multiple interdependent neuronal circuits. Among subcortical structures, the dopaminergic nigrostriatal and mesolimbic pathways as well as cholinergic innervation from basal forebrain and brainstem, play pivotal roles in orchestrating cognitive and non-cognitive symptoms in PD and AD.

The epistemic roles of clinical expertise: An empirical study of how Swedish healthcare professionals understand proven experience.

Clinical expertise has since 1891 a Swedish counterpart in proven experience. This study aims to increase our understanding of clinicians' views of their professional expertise, both as a source or body of knowledge and as a skill or quality. We examine how Swedish healthcare personnel view their expertise as captured by the (legally and culturally relevant) Swedish concept of "proven experience," through a survey administered to a simple random sample of Swedish physicians and nurses (2018, n = 560).

Perceptions of Older Adult Care Among Ambulatory Oncology Nurses.

Background: Most cancer treatment is provided in the ambulatory setting; thus, it is important to know what issues ambulatory oncology nurses identify in their practice with older cancer patients as well as resources that are helpful or are needed.

Objective: The aim of this study was to capture ambulatory oncology nurses' perceptions of the unique aspects of caring for older patients and to present the development process, content validity testing, and psychometric evaluation of a survey designed to denote nurse perceptions of older adult care.

Methods: An expert panel and 2 focus groups informed the development of a 34-item survey scored on a 5-point Likert-type agreement scale and 2 open-ended questions.

"Science and proven experience": How should the epistemology of medicine inform the regulation of healthcare?

The Swedish medico-legal concept of "science and proven experience" is both legally important and ambiguous. The conceptual uncertainty associated with it can hamper effective assessment of medical evidence in legal proceedings and encourage medical professionals to distrust legal regulation. We examine normative criteria a functioning medico-legal notion should presumably meet, e.

The cholinergic system in subtypes of Alzheimer's disease: an in vivo longitudinal MRI study.

Background: The heterogeneity within Alzheimer's disease (AD) seriously challenges the development of disease-modifying treatments. We investigated volume of the basal forebrain, hippocampus, and precuneus in atrophy subtypes of AD and explored the relevance of subtype stratification in a small clinical trial on encapsulated cell biodelivery (ECB) of nerve growth factor (NGF) to the basal forebrain.

Methods: Structural MRI data was collected for 90 amyloid-positive patients and 69 amyloid-negative healthy controls at baseline, 6-, 12-, and 24-month follow-up.

Long-term, stable, targeted biodelivery and efficacy of GDNF from encapsulated cells in the rat and Goettingen miniature pig brain.

Delivering glial cell line-derived neurotrophic factor (GDNF) to the brain is a potential treatment for Parkinson's Disease (PD). Here we use an implantable encapsulated cell technology that uses modified human clonal ARPE-19 ​cells to deliver of GDNF to the brain. I studies demonstrated sustained delivery of GDNF to the rat striatum over 6 months.

Widespread Striatal Delivery of GDNF from Encapsulated Cells Prevents the Anatomical and Functional Consequences of Excitotoxicity.

Methods: Human ARPE-19 cells engineered to secrete high levels of the glial cell line-derived neurotrophic factor (GDNF) were encapsulated into hollow fiber membranes. The devices were implanted into the rat striatum 1 week prior to striatal quinolinic acid injections. Animals were evaluated using a battery of validated motor tests, and histology was performed to determine the extent of GDNF diffusion and associated prevention of neuronal cell loss and behavioral deficits.

Long-Term, Targeted Delivery of GDNF from Encapsulated Cells Is Neuroprotective and Reduces Seizures in the Pilocarpine Model of Epilepsy.

Neurotrophic factors are candidates for treating epilepsy, but their development has been hampered by difficulties in achieving stable and targeted delivery of efficacious concentrations within the desired brain region. We have developed an encapsulated cell technology that overcomes these obstacles by providing a targeted, continuous, synthesized source of high levels of neurotrophic molecules from human clonal ARPE-19 cells encapsulated into hollow fiber membranes. Here we illustrate the potential of this approach for delivering glial cell line-derived neurotrophic factor (GDNF) directly to the hippocampus of epileptic rats.

Unilateral ex vivo gene therapy by GDNF in epileptic rats.

Temporal lobe epilepsy (TLE) is the most common type of epilepsy in adults. This neurological disorder is characterized by focal seizures originating in the temporal lobe, often with secondary generalization. A variety of pharmacological treatments exist for patients suffering from focal seizures, but systemically administered drugs offer only symptomatic relief and frequently cause unwanted side effects.

Seizure-Suppressant and Neuroprotective Effects of Encapsulated BDNF-Producing Cells in a Rat Model of Temporal Lobe Epilepsy.

Brain-derived neurotrophic factor (BDNF) may represent a therapeutic for chronic epilepsy, but evaluating its potential is complicated by difficulties in its delivery to the brain. Here, we describe the effects on epileptic seizures of encapsulated cell biodelivery (ECB) devices filled with genetically modified human cells engineered to release BDNF. These devices, implanted into the hippocampus of pilocarpine-treated rats, highly decreased the frequency of spontaneous seizures by more than 80%.

The feasibility of an encapsulated cell approach in an animal deafness model.

For patients with profound hearing loss a cochlear implant (CI) is the only treatment today. The function of a CI depends in part of the function and survival of the remaining spiral ganglion neurons (SGN). It is well known from animal models that inner ear infusion of neurotrophic factors prevents SGN degeneration and maintains electrical responsiveness in deafened animals.

Encapsulated cell device approach for combined electrical stimulation and neurotrophic treatment of the deaf cochlea.

Profound hearing impairment can be overcome by electrical stimulation (ES) of spiral ganglion neurons (SGNs) via a cochlear implant (CI). Thus, SGN survival is critical for CI efficacy. Application of glial cell line-derived neurotrophic factor (GDNF) has been shown to reduce SGN degeneration following deafness.

Distress and Coping Self-Efficacy in Inpatient Oncology Nurses.

Purpose/objectives: To examine distress and coping self-efficacy in inpatient oncology nurses. 
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Design: Cross-sectional survey design.

Cholinergic profiles in the Goettingen miniature pig (Sus scrofa domesticus) brain.

Central cholinergic structures within the brain of the even-toed hoofed Goettingen miniature domestic pig (Sus scrofa domesticus) were evaluated by immunohistochemical visualization of choline acetyltransferase (ChAT) and the low-affinity neurotrophin receptor, p75 . ChAT-immunoreactive (-ir) perikarya were seen in the olfactory tubercle, striatum, medial septal nucleus, vertical and horizontal limbs of the diagonal band of Broca, and the nucleus basalis of Meynert, medial habenular nucleus, zona incerta, neurosecretory arcuate nucleus, cranial motor nuclei III and IV, Edinger-Westphal nucleus, parabigeminal nucleus, pedunculopontine nucleus, and laterodorsal tegmental nucleus. Cholinergic ChAT-ir neurons were also found within transitional cortical areas (insular, cingulate, and piriform cortices) and hippocampus proper.