Limbic system synaptic dysfunctions associated with prion disease onset.

Misfolding of normal prion protein (PrP) to pathological isoforms (prions) causes prion diseases (PrDs) with clinical manifestations including cognitive decline and mood-related behavioral changes. Cognition and mood are linked to the neurophysiology of the limbic system. Little is known about how the disease affects the synaptic activity in brain parts associated with this system.

Sodium hypochlorite inactivation of human CJD prions.

Prion diseases are transmissible, fatal neurologic diseases of mammals caused by the accumulation of mis-folded, disease associated prion protein (PrPd). Creutzfeldt-Jakob Disease (CJD) is the most common human prion disease and can occur by sporadic onset (sCJD) (~85% of CJD cases), genetic mutations in the prion protein gene (10-15%) or iatrogenic transmission (rare). PrPd is difficult to inactivate and many methods to reduce prion infectivity are dangerous, caustic, expensive, or impractical.

Nettle-induced Urticaria Treatment Study (NUTS): demonstrating the joy of research through a randomised, blinded, placebo-controlled trial.

The use of dock leaves to ease the discomfort of nettle stings is a well-known folk remedy in the British Isles, yet has never been tested in a clinical trial. A group of Emergency Department doctors designed and conducted the Nettle-induced Urticaria Treatment Study (NUTS) as a research training and team-building exercise to address this gap in the Emergency Medicine evidence base.

Cleavage site-directed antibodies reveal the prion protein in humans is shed by ADAM10 at Y226 and associates with misfolded protein deposits in neurodegenerative diseases.

Proteolytic cell surface release ('shedding') of the prion protein (PrP), a broadly expressed GPI-anchored glycoprotein, by the metalloprotease ADAM10 impacts on neurodegenerative and other diseases in animal and in vitro models. Recent studies employing the latter also suggest shed PrP (sPrP) to be a ligand in intercellular communication and critically involved in PrP-associated physiological tasks. Although expectedly an evolutionary conserved event, and while soluble forms of PrP are present in human tissues and body fluids, for the human body neither proteolytic PrP shedding and its cleavage site nor involvement of ADAM10 or the biological relevance of this process have been demonstrated thus far.

Lack of Transmission of Chronic Wasting Disease Prions to Human Cerebral Organoids.

Chronic wasting disease (CWD) is a cervid prion disease with unknown zoonotic potential that might pose a risk to humans who are exposed. To assess the potential of CWD to infect human neural tissue, we used human cerebral organoids with 2 different prion genotypes, 1 of which has previously been associated with susceptibility to zoonotic prion disease. We exposed organoids from both genotypes to high concentrations of CWD inocula from 3 different sources for 7 days, then screened for infection periodically for up to 180 days.

Neural cell engraftment therapy for sporadic Creutzfeldt-Jakob disease restores neuroelectrophysiological parameters in a cerebral organoid model.

Background: Sporadic Creutzfeldt-Jakob disease (sCJD), the most common human prion disease, is a fatal neurodegenerative disease with currently no treatment options. Stem cell therapy for neurodegenerative diseases is emerging as a possible treatment option. However, while there are a few clinical trials for other neurodegenerative disorders such as Parkinson's disease, prion disease cell therapy research has so far been confined to animal models.

Bone health in rural Australia: a mixed methods study of consumer needs.

Unlabelled: This mixed methods study explores osteoporosis among adults living in a regional area of Victoria, Australia. Three major themes emerged from interviews, which reflected the findings of surveys, concerns regarding the adequacy of care in rural areas, a desire for tailored, local care, and a desire for hybrid telemedicine or in-person services.

Purpose: Osteoporosis or osteopenia affects over half of adults aged over 50 years.

A PrP EGFR signaling axis controls neural stem cell senescence through modulating cellular energy pathways.

Mis-folding of the prion protein (PrP) is known to cause neurodegenerative disease; however, the native function of this protein remains poorly defined. PrP has been linked with many cellular functions, including cellular proliferation and senescence. It is also known to influence epidermal growth factor receptor (EGFR) signaling, a pathway that is itself linked with both cell growth and senescence.

α-Synuclein seeding activity in duodenum biopsies from Parkinson's disease patients.

Abnormal deposition of α-synuclein is a key feature and biomarker of Parkinson's disease. α-Synuclein aggregates can propagate themselves by a prion-like seeding-based mechanism within and between tissues and are hypothesized to move between the intestine and brain. α-Synuclein RT-QuIC seed amplification assays have detected Parkinson's-associated α-synuclein in multiple biospecimens including post-mortem colon samples.

Temporary alteration of neuronal network communication is a protective response to redox imbalance that requires GPI-anchored prion protein.

Cellular prion protein (PrP) protects neurons against oxidative stress damage. This role is lost upon its misfolding into insoluble prions in prion diseases, and correlated with cytoskeletal breakdown and neurophysiological deficits. Here we used mouse neuronal models to assess how PrP protects the neuronal cytoskeleton, and its role in network communication, from oxidative stress damage.

The experiences of women from culturally and linguistically diverse backgrounds with gestational diabetes mellitus: A mixed methods systematic review.

Background: Gestational diabetes mellitus (GDM) is experienced at a higher rate in women from culturally and linguistically diverse (CALD) backgrounds. The aim of this systematic review is to describe the experiences of women with GDM from CALD backgrounds and compare their experiences to women with GDM from non-CALD backgrounds.

Materials And Methods: MEDLINE, EMBASE, PsycINFO, Scopus, WOS and CINAHL databases were searched for qualitative and quantitative studies which included data on the experiences of CALD background women with GDM during all stages of pregnancy.

Altered energy metabolism in Fatal Familial Insomnia cerebral organoids is associated with astrogliosis and neuronal dysfunction.

Fatal familial insomnia (FFI) is a rare neurodegenerative disease caused by a dominantly inherited single amino acid substitution (D178N) within the prion protein (PrP). No in vitro human brain tissue model for this disease has previously been available. Consequently, how this mutation exerts its damaging effect on brain cells is still unknown.

Stress and viral insults do not trigger E200K PrP conversion in human cerebral organoids.

Prion diseases are a group of rare, transmissible, and invariably fatal neurodegenerative diseases that affect both humans and animals. The cause of these diseases is misfolding of the prion protein into pathological isoforms called prions. Of all human prion diseases, 10-15% of cases are genetic and the E200K mutation, which causes familial Creutzfeldt-Jakob disease (CJD), is the most prevalent.

Hereditary E200K mutation within the prion protein gene alters human iPSC derived cardiomyocyte function.

Cardiomyopathy is a co-morbidity of some prion diseases including genetic disease caused by mutations within the PrP gene (PRNP). Although the cellular prion protein (PrP) has been shown to protect against cardiotoxicity caused by oxidative stress, it is unclear if the cardiomyopathy is directly linked to PrP dysfunction. We differentiated cardiomyocyte cultures from donor human induced pluripotent stem cells and found a direct influence of the PRNP E200K mutation on cellular function.

Hyperacute stroke and the specialist nursing impact: exploring the cause and context of feelings of secondary traumatic stress - a qualitative inquiry.

Background: Secondary traumatic stress (STS) has been defined as the stress resulting from helping or wanting to help a traumatised or suffering person. The hyperacute nature of stroke specialist nurses' work places them at risk of developing STS.

Aims: To explore the factors that are influential in stroke specialist nurses' experience of STS development within hyperacute practice.

Potential of Microneedle Systems for COVID-19 Vaccination: Current Trends and Challenges.

To prevent the coronavirus disease 2019 (COVID-19) pandemic and aid restoration to prepandemic normality, global mass vaccination is urgently needed. Inducing herd immunity through mass vaccination has proven to be a highly effective strategy for preventing the spread of many infectious diseases, which protects the most vulnerable population groups that are unable to develop immunity, such as people with immunodeficiencies or weakened immune systems due to underlying medical or debilitating conditions. In achieving global outreach, the maintenance of the vaccine potency, transportation, and needle waste generation become major issues.

Organoids for modeling prion diseases.

Human cerebral organoids are an exciting and novel model system emerging in the field of neurobiology. Cerebral organoids are spheres of self-organizing, neuronal lineage tissue that can be differentiated from human pluripotent stem cells and that present the possibility of on-demand human neuronal cultures that can be used for non-invasively investigating diseases affecting the brain. Compared with existing humanized cell models, they provide a more comprehensive replication of the human cerebral environment.

Reduced SOD2 expression does not influence prion disease course or pathology in mice.

Prion diseases are progressive, neurodegenerative diseases affecting humans and animals. Also known as the transmissible spongiform encephalopathies, for the hallmark spongiform change seen in the brain, these diseases manifest increased oxidative damage early in disease and changes in antioxidant enzymes in terminal brain tissue. Superoxide dismutase 2 (SOD2) is an antioxidant enzyme that is critical for life.

Rottlerin inhibits La Crosse virus-induced encephalitis in mice and blocks release of replicating virus from the Golgi body in neurons.

La Crosse virus (LACV) is a mosquito-borne orthobunyavirus that causes approximately 60 to 80 hospitalized pediatric encephalitis cases in the United States yearly. The primary treatment for most viral encephalitis, including LACV, is palliative care, and specific antiviral therapeutics are needed. We screened the National Center for Advancing Translational Sciences library of 3,833 FDA-approved and bioactive small molecules for the ability to inhibit LACV-induced death in SH-SY5Y neuronal cells.

Neuronal excitatory-to-inhibitory balance is altered in cerebral organoid models of genetic neurological diseases.

The neuro-physiological properties of individuals with genetic pre-disposition to neurological disorders are largely unknown. Here we aimed to explore these properties using cerebral organoids (COs) derived from fibroblasts of individuals with confirmed genetic mutations including PRNP, trisomy 21 (T21), and LRRK2, which are associated with Creutzfeldt Jakob disease, Down Syndrome, and Parkinson's disease. We utilized no known disease/healthy COs (HC) as normal function controls.

Virtual delivery: a panacea for the financial and ethical challenges associated with physiology laboratory classes?

There has been a gradual shift in the delivery of physiology laboratory classes over the last 30 years. For many, wet-lab demonstrations using animal tissues have been reduced or replaced with student-led investigations where students are both subjects and researchers. Despite these changes, expectations remain that physiology courses should include a practical component to encourage deeper and higher-order learning.

Corrigendum to "The psychosocial impact of surgical complications on the operating surgeon: A scoping review" [Ann. Med. Surg. 67 (July 2021) 102530].

[This corrects the article DOI: 10.1016/j.amsu.