The SLaM Brain Health Clinic: remote biomarker enhanced memory clinic for people with mild cognitive impairment within a National Health Service mental health trust.

Background: The novel South London and Maudsley Brain Health Clinic (SLaM BHC) leverages advances in remote consultations and biomarkers to provide a timely, cost-efficient and accurate diagnosis in mild cognitive impairment (MCI).

Aims: To describe the organisation, patient cohort and acceptability of the remote diagnostic and interventional procedures.

Method: We describe the recruitment, consultation set-up, the clinical and biomarker programme, and the two online group interventions for cognitive wellbeing and lifestyle change.

Glioblastoma cells increase expression of notch signaling and synaptic genes within infiltrated brain tissue.

Glioblastoma remains one of the deadliest brain malignancies. First-line therapy consists of maximal surgical tumor resection, accompanied by chemotherapy and radiotherapy. Malignant cells escape surgical resection by migrating into the surrounding healthy brain tissue, where they give rise to the recurrent tumor.

Evaluation of in silico model predictions for mammalian acute oral toxicity and regulatory application in pesticide hazard and risk assessment.

The United States Environmental Protection Agency (USEPA) uses the lethal dose 50% (LD) value from in vivo rat acute oral toxicity studies for pesticide product label precautionary statements and environmental risk assessment (RA). The Collaborative Acute Toxicity Modeling Suite (CATMoS) is a quantitative structure-activity relationship (QSAR)-based in silico approach to predict rat acute oral toxicity that has the potential to reduce animal use when registering a new pesticide technical grade active ingredient (TGAI). This analysis compared LD values predicted by CATMoS to empirical values from in vivo studies for the TGAIs of 177 conventional pesticides.

A Review of Cyclic Imines in Shellfish: Worldwide Occurrence, Toxicity and Assessment of the Risk to Consumers.

Cyclic imines are a class of lipophilic shellfish toxins comprising gymnodimines, spirolides, pinnatoxins, portimines, pteriatoxins, prorocentrolides, spiro-prorocentrimine, symbiomines and kabirimine. They are structurally diverse, but all share an imine moiety as part of a bicyclic ring system. These compounds are produced by marine microalgal species and are characterized by the rapid death that they induce when injected into mice.

Diversity and distribution of benthic dinoflagellates in Tonga include the potentially harmful genera Gambierdiscus and Fukuyoa.

Benthic dinoflagellates that can cause illness, such as ciguatera poisoning (CP), are prevalent around the Pacific but are poorly described in many locations. This study represents the first ecological assessment of benthic harmful algae species in the Kingdom of Tonga, a country where CP occurs regularly. Surveys were conducted in June 2016 in the Tongatapu island group, and in June 2017 across three island groups: Ha'apai, Vava'u, and Tongatapu.

Directional characteristics of two gamelan gongs.

The distinctive geometry and structural characteristics of Balinese gamelan gongs lead to the instrument's unique sound and musical style. This work presents high-resolution directivity measurements of two types of gamelan gongs to quantify and better understand their acoustic behavior. The measured instruments' structural modes clearly impact their far-field directivity patterns, with the number of directional lobes corresponding to the associated structural mode shapes.

A tool for safer prescribing in vulnerable adults: the continuing development of the Medichec app and website.

Aims And Method: Adverse effects are a common concern when prescribing and reviewing medication, particularly in vulnerable adults such as older people and those with intellectual disability. This paper describes the development of an app giving information on side-effects, called Medichec, and provides a description of the processes involved in its development and how drugs were rated for each side-effect. Medications with central anticholinergic action, dizziness, drowsiness, hyponatraemia, QTc prolongation, bleeding and constipation were identified using the British National Formulary (BNF) and frequency of occurrence of these effects was determined using the BNF, product information and electronic searches, including PubMed.

A Sub-Acute Dosing Study of Saxitoxin and Tetrodotoxin Mixtures in Mice Suggests That the Current Paralytic Shellfish Toxin Regulatory Limit Is Fit for Purpose.

Paralytic shellfish poisoning is a worldwide problem induced by shellfish contaminated with paralytic shellfish toxins. To protect human health, a regulatory limit for these toxins in shellfish flesh has been adopted by many countries. In a recent study, mice were dosed with saxitoxin and tetrodotoxin mixtures daily for 28 days showing toxicity at low concentrations, which appeared to be at odds with other work.

Climate-controlled submarine landslides on the Antarctic continental margin.

Antarctica's continental margins pose an unknown submarine landslide-generated tsunami risk to Southern Hemisphere populations and infrastructure. Understanding the factors driving slope failure is essential to assessing future geohazards. Here, we present a multidisciplinary study of a major submarine landslide complex along the eastern Ross Sea continental slope (Antarctica) that identifies preconditioning factors and failure mechanisms.

The Effect of Experimental Protocol on the Toxicity of Saxitoxin in Mice.

Regulatory limits for toxins in shellfish are required to ensure the health of consumers. However, these limits also impact the profitability of shellfish industries making it critical that they are fit for purpose. Since human toxicity data is rarely available, the setting of regulatory limits is dependent on animal data which can then be extrapolated for use in the assessment of human risk.

Ostreopsis Schmidt and Coolia Meunier (Dinophyceae, Gonyaulacales) from Cook Islands and Niue (South Pacific Ocean), including description of Ostreopsis tairoto sp. nov.

It is important to decipher the diversity and distribution of benthic dinoflagellates, as there are many morphologically indistinct taxa that differ from one another in production of potent toxins. To date, the genus Ostreopsis comprises twelve described species, of which seven are potentially toxic and produce compounds presenting a threat to human and environmental health. In this study, isolates previously identified as "Ostreopsis sp.

Evaluation of the fish acute toxicity test for pesticide registration.

The U.S. Environmental Protection Agency (USEPA) uses the in vivo fish acute toxicity test to assess potential risk of substances to non-target aquatic vertebrates.

Interlaboratory Evaluation of Multiple LC-MS/MS Methods and a Commercial ELISA Method for Determination of Tetrodotoxin in Oysters and Mussels.

Background: Given the recent detection of tetrodotoxin (TTX) in bivalve molluscs but the absence of a full collaborative validation study for TTX determination in a large number of shellfish samples, interlaboratory assessment of method performance was required to better understand current capabilities for accurate and reproducible TTX quantitation using chemical and immunoassay methods.

Objective: The aim was to conduct an interlaboratory study with multiple laboratories, using results to assess method performance and acceptability of different TTX testing methods.

Methods: Homogenous and stable mussel and oyster materials were assessed by participants using a range of published and in-house detection methods to determine mean TTX concentrations.

Purification of Recombinant Human PARP-3.

The purification of poly(ADP-ribose) polymerase-3 (PARP-3) from overexpressing cells (Sf9 insect cells, Escherichia coli) has been updated to a fast and reproducible two-chromatographic-step protocol. After cell lysis, PARP-3 protein from the crude extract is affinity purified on a 3-aminobenzamide Sepharose™ chromatographic step. The last contaminants and the 3-methoxybenzamide used to elute PARP-3 from the previous affinity column are removed on the high-performance strong cation exchanger MonoQ™ matrix.

Comparison of clinical outcomes of VISIONAIRE patient-specific instrumentation with conventional instrumentation in total knee arthroplasty: a systematic literature review and meta-analysis.

Introduction: Malalignment and resulting complications are major challenges in total knee arthroplasty (TKA) which patient-specific instrumentation (PSI) is proposed to alleviate. Previous PSI meta-analyses of TKA outcomes typically do not differentiate between PSI systems and assess relatively few outcomes, so the value of their findings is limited. VISIONAIRE cutting guides (Smith + Nephew Inc.

Antipsychotic monitoring in dementia: quality of completion of antipsychotic monitoring forms in an older adult mental health service.

Aims And Method: To support safe prescribing of antipsychotics in dementia, antipsychotic monitoring forms were embedded into our electronic health records. We present a review of the data collected on these forms to assess prescribing and identify areas for improvement in our practice and processes. Data were extracted from the structured fields of antipsychotic initiation and review forms completed between 1 January 2018 and 31 January 2020.

Structural Characterization of Maitotoxins Produced by Toxic Species.

Identifying compounds responsible for the observed toxicity of the species is a critical step to ascertaining whether they contribute to ciguatera poisoning. Macroalgae samples were collected during research expeditions to Rarotonga (Cook Islands) and North Meyer Island (Kermadec Islands), from which two new species were characterized, CAWD232 and CAWD242. Previous chemical and toxicological investigations of these species demonstrated that they did not produce the routinely monitored Pacific ciguatoxins nor maitotoxin-1 (MTX-1), yet were highly toxic to mice via intraperitoneal (i.

A large West Antarctic Ice Sheet explains early Neogene sea-level amplitude.

Early to Middle Miocene sea-level oscillations of approximately 40-60 m estimated from far-field records are interpreted to reflect the loss of virtually all East Antarctic ice during peak warmth. This contrasts with ice-sheet model experiments suggesting most terrestrial ice in East Antarctica was retained even during the warmest intervals of the Middle Miocene. Data and model outputs can be reconciled if a large West Antarctic Ice Sheet (WAIS) existed and expanded across most of the outer continental shelf during the Early Miocene, accounting for maximum ice-sheet volumes.

Acute toxicity of decarbamoyl gonyautoxin 1&4 to mice by various routes of administration.

Saxitoxin and its derivatives, the paralytic shellfish toxins (PSTs), are well known to be toxic to humans, and maximum permitted levels in seafood have been established by regulatory authorities in many countries. Monitoring of PSTs is typically performed using chemical methods which quantify the concentration of the individual PST analogues, of which there are many. However, since the toxicities of analogues are different, they do not equally contribute to the overall toxicity of the sample.

Update of the Planktonic Diatom Genus in Aotearoa New Zealand Coastal Waters: Genetic Diversity and Toxin Production.

Domoic acid (DA) is produced by almost half of the species belonging to the diatom genus and causes amnesic shellfish poisoning (ASP). It is, therefore, important to investigate the diversity and toxin production of species for ASP risk assessments. Between 2018 and 2020, seawater samples were collected from various sites around Aotearoa New Zealand, and 130 clonal isolates of were established.

Sub-Acute Feeding Study of Saxitoxin to Mice Confirms the Effectiveness of Current Regulatory Limits for Paralytic Shellfish Toxins.

Regulatory limits for shellfish toxins are required to protect human health. Often these limits are set using only acute toxicity data, which is significant, as in some communities, shellfish makes up a large proportion of their daily diet and can be contaminated with paralytic shellfish toxins (PSTs) for several months. In the current study, feeding protocols were developed to mimic human feeding behaviour and diets containing three dose rates of saxitoxin dihydrochloride (STX.

Tumor-Associated Microglia and Macrophages in the Glioblastoma Microenvironment and Their Implications for Therapy.

Glioblastoma is the most frequent and malignant primary brain tumor. Standard of care includes surgery followed by radiation and temozolomide chemotherapy. Despite treatment, patients have a poor prognosis with a median survival of less than 15 months.

Centrally Acting Anticholinergic Drugs Used for Urinary Conditions Associated with Worse Outcomes in Dementia.

Objectives: To investigate the associations between central anticholinergic burden and mortality, hospitalization, and cognitive impairment in people with dementia prescribed anticholinergic drugs for urinary symptoms.

Design: Retrospective cohort study.

Setting And Participants: Patients diagnosed with dementia receiving anticholinergic medication for bladder conditions (N = 540), assembled from a large healthcare database.

Centrally-acting anticholinergic drugs- associations with mortality, hospitalisation and cognitive decline following dementia diagnosis in people receiving antidepressant and antipsychotic drugs.

Objectives: Long-term use of anticholinergic medication in older people is associated with increased risk of cognitive decline and mortality, but this relationship could be confounded by the underlying illness the drugs are treating. To investigate associations between central anticholinergic antidepressants or antipsychotics and mortality, hospitalisation and cognitive decline in people with dementia.

Method: In cohorts of patients with a dementia diagnosis receiving antidepressant and/or antipsychotic medication ( = 4,380 and  = 2,335 respectively), assembled from a large healthcare database, central anticholinergic burden scores were estimated using the Anticholinergic Effect on Cognition (AEC) scale.