Divergent toxin alleles are suppressed by distinct mechanisms.

Toxin-antidote elements (TAs) are selfish DNA sequences that bias their transmission to the next generation. TAs typically consist of two linked genes: a toxin and an antidote. The toxin kills progeny that do not inherit the TA, while the antidote counteracts the toxin in progeny that inherit the TA.

Influences of Specialist Palliative Care Team Input, Advance Care Planning, Non-Invasive Ventilation and Gastrostomy Status on Unscheduled Hospital Admissions and Place of Death for People with Motor Neuron Disease: A Retrospective Cohort Analysis.

Motor neuron disease is a rapidly progressing neurological condition. People with life-limiting conditions generally prefer to die at home and avoid hospital admissions, with Specialist Palliative Care Team involvement often pivotal. Our aim was to investigate the role of advance care planning, Specialist Palliative Care Team input and other relevant variables on place of death and unscheduled hospital admissions in a Scottish population of people with motor neuron disease.

Clinicopathological analysis of NEK1 variants in amyotrophic lateral sclerosis.

Many genes have been linked to amyotrophic lateral sclerosis (ALS), including never in mitosis A (NIMA)-related kinase 1 (NEK1), a serine/threonine kinase that plays a key role in several cellular functions, such as DNA damage response and cell cycle regulation. Whole-exome sequencing studies have shown that NEK1 mutations are associated with an increased risk for ALS, where a significant enrichment of NEK1 loss-of-function (LOF) variants were found in individuals with ALS compared to controls. In particular, the p.

Humoral and cellular response induced by a second booster of an inactivated SARS-CoV-2 vaccine in adults.

Background: The Omicron variant has challenged the control of the COVID-19 pandemic due to its immuno-evasive properties. The administration of a booster dose of a SARS-CoV-2 vaccine showed positive effects in the immunogenicity against SARS-CoV-2, effect that is even enhanced after the administration of a second booster.

Methods: During a phase-3 clinical trial, we evaluated the effect of a second booster of CoronaVac®, an inactivated vaccine administered 6 months after the first booster, in the neutralization of SARS-CoV-2 (n = 87).

Systematic, comprehensive, evidence-based approach to identify neuroprotective interventions for motor neuron disease: using systematic reviews to inform expert consensus.

Objectives: Motor neuron disease (MND) is an incurable progressive neurodegenerative disease with limited treatment options. There is a pressing need for innovation in identifying therapies to take to clinical trial. Here, we detail a systematic and structured evidence-based approach to inform consensus decision making to select the first two drugs for evaluation in Motor Neuron Disease-Systematic Multi-arm Adaptive Randomised Trial (MND-SMART: NCT04302870), an adaptive platform trial.

Genotype-phenotype characterisation of long survivors with motor neuron disease in Scotland.

Background: We investigated the phenotypes and genotypes of a cohort of 'long-surviving' individuals with motor neuron disease (MND) to identify potential targets for prognostication.

Methods: Patients were recruited via the Clinical Audit Research and Evaluation for MND (CARE-MND) platform, which hosts the Scottish MND Register. Long survival was defined as > 8 years from diagnosis.

Island-specific evolution of a sex-primed autosome in a sexual planarian.

The sexual strain of the planarian Schmidtea mediterranea, indigenous to Tunisia and several Mediterranean islands, is a hermaphrodite. Here we isolate individual chromosomes and use sequencing, Hi-C and linkage mapping to assemble a chromosome-scale genome reference. The linkage map reveals an extremely low rate of recombination on chromosome 1.

Clinical trials in amyotrophic lateral sclerosis: a systematic review and perspective.

Amyotrophic lateral sclerosis is a progressive and devastating neurodegenerative disease. Despite decades of clinical trials, effective disease-modifying drugs remain scarce. To understand the challenges of trial design and delivery, we performed a systematic review of Phase II, Phase II/III and Phase III amyotrophic lateral sclerosis clinical drug trials on trial registries and PubMed between 2008 and 2019.

A Multisite Preregistered Paradigmatic Test of the Ego-Depletion Effect.

We conducted a preregistered multilaboratory project ( = 36; = 3,531) to assess the size and robustness of ego-depletion effects using a novel replication method, termed the . Each laboratory implemented one of two procedures that was intended to manipulate self-control and tested performance on a subsequent measure of self-control. Confirmatory tests found a nonsignificant result ( = 0.

Disparities of SARS-CoV-2 Nucleoprotein-Specific IgG in Healthcare Workers in East London, UK.

SARS-CoV-2 antibody detection serves as an important diagnostic marker for past SARS-CoV-2 infection and is essential to determine the spread of COVID-19, monitor potential COVID-19 long-term effects, and to evaluate possible protection from reinfection. A study was conducted across three hospital sites in a large central London NHS Trust in the UK, to evaluate the prevalence and duration of SARS-CoV-2 IgG antibody positivity in healthcare workers. A matrix equivalence study consisting of 228 participants was undertaken to evaluate the Abbott Panbio™ COVID-19 IgG/IgM rapid test device.

Relationship between neuropsychiatric disorders and cognitive and behavioural change in MND.

Objective: In this population-based study, we aimed to determine whether neuropsychiatric history, medication or family history of neuropsychiatric disorders predicted cognitive and/or behavioural impairment in motor neuron disease (MND).

Methods: People with MND (pwMND) on the Scottish Clinical, Audit, Research and Evaluation of MND (CARE-MND) register, diagnosed from January 2015 to January 2018, with cognitive and/or behavioural data measured using the Edinburgh Cognitive and Behavioural ALS Screen were included. Data were extracted on patient neuropsychiatric, medication and family history of neuropsychiatric disorders.

Affective and enjoyment responses to 12 weeks of high intensity interval training and moderate continuous training in adults with Crohn's disease.

The aim was to undertake secondary data analysis from a three-arm randomised feasibility trial of high intensity interval training (HIIT), moderate intensity continuous training (MICT), and usual care control in adults with Crohn's disease (CD; n = 36), with a primary focus on exploring affective and enjoyment responses. Twenty-five participants with quiescent or mildly-active CD were randomised to one of the two exercise groups: HIIT (n = 13) and MICT (n = 12). Both groups were offered thrice weekly sessions for 12 weeks.

Clinical audit research and evaluation of motor neuron disease (CARE-MND): a national electronic platform for prospective, longitudinal monitoring of MND in Scotland.

: Launched in 1989, the Scottish Motor Neuron Disease Register (SMNDR) has provided a resource for prospective clinical data collection. However, in 2015 we aimed to evolve a system to allow: i) A patient-centered approach to care based on recognized standards, ii) Harmonized data sharing between Scottish health professionals in "real-time", iii) Regular audit of care to facilitate timely improvements in service delivery, and iv) Patient participation in a diverse range of observational and interventional research studies including clinical trials. : We developed a standardized national electronic data platform-Clinical Audit Research and Evaluation of MND (CARE-MND) which integrates clinical audit and research data fields.

Improved survival and 30-day mortality after gastrostomy in Scottish motor neurone disease patients: evidence from a national retrospective cohort study using STROBE criteria.

: Defining historical changes and outcomes in the use of gastrostomy in the management of Scottish MND patients. : The 1989-1998 and 2015-2016 Scottish national MND cohorts were used to examine the frequency, timing, and survival related to gastrostomy. The cohorts were censored for survival analysis.

Changing epidemiology of motor neurone disease in Scotland.

Objectives: Scotland benefits from an integrated national healthcare team for motor neurone disease (MND) and a tradition of rich clinical data capture using the Scottish MND Register (launched in 1989; one of the first national registers). The Scottish register was re-launched in 2015 as Clinical Audit Research and Evaluation of MND (CARE-MND), an electronic platform for prospective, population-based research. We aimed to determine if incidence of MND is changing over time.

High-intensity interval training and moderate-intensity continuous training in adults with Crohn's disease: a pilot randomised controlled trial.

Background: This study assessed the feasibility and acceptability of two common types of exercise training-high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT)-in adults with Crohn's disease (CD).

Methods: In this mixed-methods pilot trial, participants with quiescent or mildly-active CD were randomly assigned 1:1:1 to HIIT, MICT or usual care control, and followed up for 6 months. The HIIT and MICT groups were offered three exercise sessions per week for the first 12 weeks.

Size, growth, and density data for shallow-water sea urchins from Mexico to the Aleutian Islands, Alaska, 1956-2016.

Size, growth, and density have been studied for North American Pacific coast sea urchins Strongylocentrotus purpuratus, S. droebachiensis, S. polyacanthus, Mesocentrotus (Strongylocentrotus) franciscanus, Lytechinus pictus, Centrostephanus coronatus, and Arbacia stellata by various workers at diverse sites and for varying lengths of time from 1956 to present.

Synapse loss in the prefrontal cortex is associated with cognitive decline in amyotrophic lateral sclerosis.

In addition to motor neurone degeneration, up to 50% of amyotrophic lateral sclerosis (ALS) patients present with cognitive decline. Understanding the neurobiological changes underlying these cognitive deficits is critical, as cognitively impaired patients exhibit a shorter survival time from symptom onset. Given the pathogenic role of synapse loss in other neurodegenerative diseases in which cognitive decline is apparent, such as Alzheimer's disease, we aimed to assess synaptic integrity in the ALS brain.

The Female-Like State: Decoupling the Transcriptomic Effects of Aging and Sperm Status.

Understanding genome and gene function in a whole organism requires us to fully comprehend the life cycle and the physiology of the organism in question. XX animals are hermaphrodites that exhaust their sperm after 3 d of egg-laying. Even though can live for many days after cessation of egg-laying, the molecular physiology of this state has not been as intensely studied as other parts of the life cycle, despite documented changes in behavior and metabolism.

Genetic epidemiology of motor neuron disease-associated variants in the Scottish population.

Genetic understanding of motor neuron disease (MND) has evolved greatly in the past 10 years, including the recent identification of association between MND and variants in TBK1 and NEK1. Our aim was to determine the frequency of pathogenic variants in known MND genes and to assess whether variants in TBK1 and NEK1 contribute to the burden of MND in the Scottish population. SOD1, TARDBP, OPTN, TBK1, and NEK1 were sequenced in 441 cases and 400 controls.

A comparison of the neuropsychological profiles of people living in squalor without hoarding to those living in squalor associated with hoarding.

Objective: Squalor affects 1 in 1000 older people and is regarded as a secondary condition to other primary disorders such as dementia, intellectual impairment and alcohol abuse. Squalor frequently is associated with hoarding behaviour. We compared the neuropsychological profile of people living in squalor associated with hoarding to those presenting with squalor only.

Present-day oxidative subsidence of organic soils and mitigation in the Sacramento-San Joaquin Delta, California, USA.

Subsidence of organic soils in the Sacramento-San Joaquin Delta threatens sustainability of the California (USA) water supply system and agriculture. Land-surface elevation data were collected to assess present-day subsidence rates and evaluate rice as a land use for subsidence mitigation. To depict Delta-wide present-day rates of subsidence, the previously developed SUBCALC model was refined and calibrated using recent data for CO emissions and land-surface elevation changes measured at extensometers.