Use of alternatives to animal testing for Environmental Safety Assessment (ESA): Report from the 2023 EPAA partners' forum.

Environmental Safety Assessments (ESA) are mandatory for several regulatory purposes and are an important component of stewardship/sustainability initiatives. Fish testing is used for assessing chemical toxicity and bioaccumulation potential; amphibians are included in some jurisdictions and their use is increasing to assess endocrine disruption. Alternative methods are becoming more available, covering the principles of the 3Rs (i.

Identifying Best Practices for Improving the Evaluation and Management of Stroke in Rural Lower-Resourced Settings: A Scientific Statement From the American Heart Association.

Considerable variation exists in the delivery of acute stroke care and stroke outcomes across settings and population groups. This is attributable in part to variation in resources among emergency departments in the United States, most notably in rural regions. Structural constraints of the US health care system, including the geographic distribution of where patients live relative to the location of hospitals and certified stroke centers, will continue to mean that many patients with stroke initially present to community emergency departments that have fewer stroke-related resources.

Prevalence and patterns of testing for anaemia in primary care in England.

Despite epidemiological data on anaemia being available on a global scale, its prevalence in the United Kingdom is not well described. To investigate anaemia prevalence and testing patterns for haemoglobin and other blood parameters. A population-based cohort study using data drawn from the Clinical Practice Research Datalink Aurum database in 2019.

The photosensitive endoplasmic reticulum-chloroplast contact site.

The endoplasmic reticulum (ER) forms contact sites with the chloroplast. Exposing contact sites that contain both the chloroplast and the ER to localised high-fluence, wavelength specific, 405 nm violet light, hereinafter referred to as photostimulation, induces multiple, potentially interacting intra- and intercellular responses. The responses vary depending on the tissue type of the cell and the chloroplast.

New insight into the molecular etiopathogenesis of konzo: Cyanate could be a plausible neurotoxin contributing to konzo, contrary to thiocyanate.

Introduction: Chronic cassava-derived cyanide poisoning is associated with the appearance of konzo, a tropical spastic paraparesis due to selective upper motor neuron damage. Whether the disease is caused by a direct action of cyanide or its metabolites is still an open question. This preliminary study assessed the neurotoxic effects of thiocyanate (SCN) and cyanate (OCN), two cyanide metabolites hypothesized to be plausible toxic agents in konzo.

Predicting population-level impacts of projected climate heating on a temperate freshwater fish.

Climate heating has the potential to drive changes in ecosystems at multiple levels of biological organization. Temperature directly affects the inherent physiology of plants and animals, resulting in changes in rates of photosynthesis and respiration, and trophic interactions. Predicting temperature-dependent changes in physiological and trophic processes, however, is challenging because environmental conditions and ecosystem structure vary across biogeographical regions of the globe.

The Utility of the Koala Scat: A Scoping Review.

The use of samples or scats to provide important ecological, genetic, disease and physiology details on free-range populations is gaining popularity as an alternative non-invasive methodology. Koala populations in SE Queensland and NSW have recently been listed as endangered and continue to face anthropomorphic and stochastic environmental impacts that could potentially lead to their extinction. This scoping review examines the current and potential utility of the koala scat to contribute data relevant to the assessment of koala conservation status and decision making.

Evaluation of the EMA log kow trigger for fish BCF testing based on data for several human pharmaceuticals.

In the European Medicines Agency (EMA) "Guideline for Environmental Risk Assessment of Medicinal Products for Human Use," a fish bioconcentration factor (BCF) study is triggered in Phase I for pharmaceuticals having log Kow >4.5, to support Persistence, Bioaccumulation and Toxicity (PBT) screening, and in Phase II to assess secondary poisoning and bioaccumulation ('B') potential when log Kow ≥3. The standard sampling schedule outlined in OECD Test Guideline 305 (TG305) may require assessment of approximately 200 fish following exposure to low- and high-test concentrations and a negative control.

Meiosis II spindle disassembly requires two distinct pathways.

During exit from meiosis II, cells undergo several structural rearrangements, including disassembly of the meiosis II spindles and cytokinesis. Each of these changes is regulated to ensure that they occur at the proper time. Previous studies have demonstrated that both which encodes a STE20-family GCKIII kinase, and , which encodes a meiosis-specific activator of the Anaphase Promoting Complex, are required for both meiosis II spindle disassembly and cytokinesis in the budding yeast .

Direct intranodal tonsil vaccination with modified vaccinia Ankara vaccine protects macaques from highly pathogenic SIVmac251.

Human immunodeficiency virus (HIV) is a mucosally transmitted virus that causes immunodeficiency and AIDS. Developing efficacious vaccines to prevent infection is essential to control the epidemic. Protecting the vaginal and rectal mucosa, the primary routes of HIV entry has been a challenge given the significant compartmentalization between the mucosal and peripheral immune systems.

Minimizing Experimental Testing on Fish for Legacy Pharmaceuticals.

There was no regulatory requirement for ecotoxicological testing of human pharmaceuticals authorized before 2006, and many of these have little or no data available to assess their environmental risk. Motivated by animal welfare considerations, we developed a decision tree to minimize in vivo fish testing for such legacy active pharmaceutical ingredients (APIs). The minimum no observed effect concentration (NOEC, the lowest NOEC from chronic and algal toxicity studies), the theoretical therapeutic water concentration (TWC, calculated using the fish plasma model), and the predicted environmental concentration (PEC) were used to derive API risk quotients (PEC/NOEC and PEC/TWC).

Identification of a stereotypic molecular arrangement of endogenous glycine receptors at spinal cord synapses.

Precise quantitative information about the molecular architecture of synapses is essential to understanding the functional specificity and downstream signaling processes at specific populations of synapses. Glycine receptors (GlyRs) are the primary fast inhibitory neurotransmitter receptors in the spinal cord and brainstem. These inhibitory glycinergic networks crucially regulate motor and sensory processes.

Advancing cell instructive biomaterials through increased understanding of cell receptor spacing and material surface functionalization.

Regenerative medicine is aimed at restoring normal tissue function and can benefit from the application of tissue engineering and nano-therapeutics. In order for regenerative therapies to be effective, the spatiotemporal integration of tissue engineered scaffolds by the native tissue, and the binding/release of therapeutic payloads by nano-materials, must be tightly controlled at the nanoscale in order to direct cell fate. However, due to a lack of insight regarding cell-material interactions at the nanoscale and subsequent downstream signaling, the clinical translation of many regenerative therapies is limited due to poor material integration, rapid clearance and complications such as graft-versus-host disease.

Dying for change: A roadmap to refine the fish acute toxicity test after 40 years of applying a lethal endpoint.

The fish acute toxicity test (TG203; OECD, 2019) is frequently used and highly embedded in hazard and risk assessment globally. The test estimates the concentration of a chemical that kills 50% of the fish (LC) over a 96 h exposure and is considered one of the most severe scientific procedures undertaken. Over the years, discussions at the Organisation for Economic Co-operation and Development (OECD) have resulted in changes to the test which reduce the number of fish used, as well as the development of a (potential) replacement test (TG236, OECD, 2013).

Investigating endocrine-disrupting properties of chemicals in fish and amphibians: Opportunities to apply the 3Rs.

Many regulations are beginning to explicitly require investigation of a chemical's endocrine-disrupting properties as a part of the safety assessment process for substances already on or about to be placed on the market. Different jurisdictions are applying distinct approaches. However, all share a common theme requiring testing for endocrine activity and adverse effects, typically involving in vitro and in vivo assays on selected endocrine pathways.

Light chain cast nephropathy caused by plasmablastic lymphoma of the bladder.

Introduction: Plasmablastic lymphoma (PBL) is a rare form of B-cell lymphoma typically seen in patients with underlying immunosuppression such as HIV, autoimmune disease, and organ transplantation. PBL in HIV-positive patients usually originates from the gastrointestinal tract, with a predilection for the oral cavity. Bladder involvement by PBL is exceedingly rare, and cast nephropathy due to κ light chain-secreting PBL has not been reported previously.

The human nucleoporin Tpr protects cells from RNA-mediated replication stress.

Although human nucleoporin Tpr is frequently deregulated in cancer, its roles are poorly understood. Here we show that Tpr depletion generates transcription-dependent replication stress, DNA breaks, and genomic instability. DNA fiber assays and electron microscopy visualization of replication intermediates show that Tpr deficient cells exhibit slow and asymmetric replication forks under replication stress.

Expansion of telehealth in primary care during the COVID-19 pandemic: benefits and barriers.

The novel coronavirus disease 2019 (COVID-19) pandemic remarkably accelerated the adoption of telemedicine in outpatient settings. Out of necessity, virtual care became a preferred and default modality of extending primary care services to health care consumers. Although telemedicine is not a new concept and had been used in many organizations and health systems, the COVID-19 pandemic scaled up its use in a variety of health care settings.