The GC hexanucleotide repeat expansion in C9ORF72 is the major genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9-ALS/FTD). Despite considerable efforts, the development of mouse models of C9-ALS/FTD useful for therapeutic development has proven challenging due to the intricate interplay of genetic and molecular factors underlying this neurodegenerative disorder, in addition to species differences. This study presents a robust investigation of the cellular pathophysiology and behavioral outcomes in a previously described AAV mouse model of C9-ALS expressing 66 GC hexanucleotide repeats.
View Article and Find Full Text PDFBackground: Convenience, privacy, and cost-effectiveness associated with web-based data collection have facilitated the recent expansion of web-based survey research. Importantly, however, practical benefits of web-based survey research, to scientists and participants alike, are being overshadowed by the dramatic rise in suspicious and fraudulent survey submissions. Misinformation associated with survey fraud compromises data quality and data integrity with important implications for scientific conclusions, clinical practice, and social benefit.
View Article and Find Full Text PDFThe GC hexanucleotide repeat expansion in the major genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9-ALS/FTD). Despite considerable efforts, the development of mouse models of C9-ALS/FTD useful for therapeutic development has proven challenging due to the intricate interplay of genetic and molecular factors underlying this neurodegenerative disorder, in addition to species differences. This study presents a robust investigation of the cellular pathophysiology and behavioral outcomes in a previously described AAV mouse model of C9-ALS expressing 66 GC hexanucleotide repeats.
View Article and Find Full Text PDFObjective: To evaluate audiological outcomes of transcutaneous devices among individuals with mixed hearing loss (MHL) who underwent implantation with the Cochlear™ Osia® and Med-El Bonebridge™ devices.
Methods: Adults with MHL in at least one ear, including a best bone conduction (BBC) threshold of 30 dB HL or poorer, and air-bone gaps of 15 dB HL or more at one or more frequencies were implanted with the Cochlear™ Osia® or Med-El Bonebridge™ devices for MHL. Four-frequency pure tone average (PTA) was calculated for aided thresholds and compared to preoperative PTAs for BBC thresholds.
Importance: Lengthening waiting lists for organ transplant mandates the development of strategies to expand the deceased donor pool. Due to concerns regarding organ viability, most organ donation organizations internationally wait no longer than 1 to 2 hours for potential donation after circulatory death (DCD), possibly underutilizing an important organ source; UK policy mandates a minimum 3-hour wait time.
Objective: To assess whether time to death (TTD) from withdrawal of life-sustaining treatment (WLST) is associated with kidney transplant outcomes.
Background: Donor liver transaminases (ALT and AST) have been used to decline livers for transplant, despite evidence that they do not influence transplant outcomes. This study assesses the effect that raised donor transaminases have on the unnecessary decline of livers.
Methods: This retrospective cohort study used the National Health Service registry on adult liver transplantation (2016-2019).
Objectives: A recent study has provided empirical support for the use of remote microphone (RM) systems to improve listening-in-noise performance of autistic youth. It has been proposed that RM system effects might be achieved by boosting engagement in this population. The present study used behavioral coding to test this hypothesis in autistic and nonautistic youth listening in an ecologically valid, noisy environment.
View Article and Find Full Text PDFThe GC hexanucleotide repeat expansion in is the major genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9-ALS/FTD). Despite considerable efforts, the development of mouse models of C9-ALS/FTD useful for therapeutic development has proven challenging due to the intricate interplay of genetic and molecular factors underlying this neurodegenerative disorder, in addition to species differences. This study presents a robust investigation of the cellular pathophysiology and behavioral outcomes in a previously described AAV mouse model of C9-ALS expressing 66 GC hexanucleotide repeats.
View Article and Find Full Text PDFIntroduction: Despite the progress in reducing child mortality, the rate remains high, particularly in sub-Saharan African countries. Limited data exist on child survival and other birth outcomes by sex. This study compared survival rates and birth outcomes by sex among neonates and children under 2 in Ethiopia.
View Article and Find Full Text PDFBackground: Kidney transplantation is the optimal treatment for kidney failure. Donation, transport and transplant of kidney grafts leads to significant ischaemia reperfusion injury. Static cold storage (SCS), whereby the kidney is stored on ice after removal from the donor until the time of implantation, represents the simplest preservation method.
View Article and Find Full Text PDFThe relative amount of AMPA receptors expressed at the surface of neurons can be measured using superecliptic pHluorin (SEP) labeling at their N-terminus. However, the high signal variability resulting from protein overexpression in neurons and the low signal observed in intracellular vesicles make quantitative characterization of receptor trafficking difficult. Here, we establish a real-time live-cell assay of AMPAR trafficking based on fluorescence lifetime imaging (FLIM), which allows for simultaneous visualization of both surface and intracellular receptors.
View Article and Find Full Text PDFContext: As patients approach the end of life, discussion of their treatment goals is essential to avoid unnecessary suffering and deliver care in a manner consistent with their overall values.
Objectives: Implement a multipronged approach to improve the rates of advance care planning (ACP) documentation among providers admitting patients with cancer to the intensive care unit (ICU) from the emergency department (ED).
Methods: We developed multiple interventions including the development of a best-practice advisory to alert providers when patients had previous do-not-resuscitate orders; standardization of ACP documentation; early oncologist involvement in goals-of-care conversations with patients; a survey of ED providers to identify barriers to success; and positive reinforcement strategies aimed at improving the rates of ACP documentation in patients admitted from the ED to the ICU.
Simultaneous pancreas-kidney (SPK) transplantation improves quality of life and limits progression of diabetic complications. There is reluctance to accept pancreata from donors with abnormal blood tests, due to concern of inferior outcomes. We investigated whether donor amylase and liver blood tests (markers of visceral ischaemic injury) predict pancreas graft outcome using the UK Transplant Registry (2016-2021).
View Article and Find Full Text PDFCochrane Database Syst Rev
May 2024
Background: Waiting lists for kidney transplantation continue to grow. Live kidney donation significantly reduces waiting times and improves long-term outcomes for recipients. Major disincentives to potential kidney donors are the pain and morbidity associated with surgery.
View Article and Find Full Text PDFObjectives: This study aimed to systematically review evidence on the cost-effectiveness of chimeric antigen receptor T-cell (CAR-T) therapies for patients with cancer.
Methods: Electronic databases were searched in October 2022 and updated in September 2023. Systematic reviews, health technology assessments, and economic evaluations that compared costs and effects of CAR-T therapy in patients with cancer were included.
90% of the UK diabetic population are classified as T2DM. This study aims to compare outcomes after SPK transplant between recipients with T1DM or T2DM. Data on all UK SPK transplants from 2003-2019 were obtained from the NHSBT Registry ( = 2,236).
View Article and Find Full Text PDFObjectives: This study examined the neural mechanisms by which remote microphone (RM) systems might lead to improved behavioral performance on listening-in-noise tasks in autistic and non-autistic youth.
Design: Cortical auditory evoked potentials (CAEPs) were recorded in autistic (n = 25) and non-autistic (n = 22) youth who were matched at the group level on chronological age ( M = 14.21 ± 3.
Objectives: The purposes of this study were to compare (a) listening-in-noise (accuracy and effort) and (b) remote microphone (RM) system benefits between autistic and non-autistic youth.
Design: Groups of autistic and non-autistic youth that were matched on chronological age and biological sex completed listening-in-noise testing when wearing and not wearing an RM system. Listening-in-noise accuracy and listening effort were evaluated simultaneously using a dual-task paradigm for stimuli varying in type (syllables, words, sentences, and passages).
T cells are required to clear infection, and T cell motion plays a role in how quickly a T cell finds its target, from initial naive T cell activation by a dendritic cell to interaction with target cells in infected tissue. To better understand how different tissue environments affect T cell motility, we compared multiple features of T cell motion including speed, persistence, turning angle, directionality, and confinement of T cells moving in multiple murine tissues using microscopy. We quantitatively analyzed naive T cell motility within the lymph node and compared motility parameters with activated CD8 T cells moving within the villi of small intestine and lung under different activation conditions.
View Article and Find Full Text PDFIntroduction: Patients with either Idiopathic Hypersomnia or Narcolepsy demonstrate excessive daytime somnolence (EDS) with resultant inattention mimicking Attention Deficit Hyperactivity Disorder (ADHD). Patients with ADHD also often express sleep problems including EDS. Thus, patients with ADHD and patients with idiopathic hypersomnia or narcolepsy may share inattention and daytime drowsiness as common features.
View Article and Find Full Text PDFBackground: Liver transplantation is the only chance of cure for people with end-stage liver disease and some people with advanced liver cancers or acute liver failure. The increasing prevalence of these conditions drives demand and necessitates the increasing use of donated livers which have traditionally been considered suboptimal. Several novel machine perfusion preservation technologies have been developed, which attempt to ameliorate some of the deleterious effects of ischaemia reperfusion injury.
View Article and Find Full Text PDFThe group 7 complexes [M(κ-2,6-(RPO)CHN)(CO)L][BAr] [M = Mn, R = Pr, L = THF; M = Re, R = Bu, L = vacant site] undergo solid-gas reactivity with CO to form the products of THF substitution or CO addition respectively. There is a large, local, adaptive change of [BAr] anions for M = Mn, whereas for M = Re the changes are smaller and also remote to the site of reactivity.
View Article and Find Full Text PDFAims: The significance of subclonal expression of p53 (abrupt transition from wild-type to mutant-pattern staining) is not well understood, and the arbitrary diagnostic cut-off of 10% between NSMP and p53abn molecular subtypes of endometrial carcinoma (EC) has not been critically assessed. Our aim was to characterise subclonal p53 and discrepant p53 expression/TP53 sequencing results in EC and assess their clinical significance.
Methods And Results: Subclonal p53 immuostaining on whole sections from 957 ECs was recorded.
Cochrane Database Syst Rev
August 2023
Background: Liver resection is the optimal treatment for selected benign and malignant liver tumours, but it can be associated with significant blood loss. Numerous anaesthetic and surgical techniques have been developed to reduce blood loss and improve perioperative outcomes. One such technique is the application of topical fibrin-based haemostatic agents (FBHAs) to the resection surface.
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