Fetal hypoplastic lungs have multilineage inflammation that is reversed by amniotic fluid stem cell extracellular vesicle treatment.

Antenatal administration of extracellular vesicles from amniotic fluid stem cells (AFSC-EVs) reverses features of pulmonary hypoplasia in models of congenital diaphragmatic hernia (CDH). However, it remains unknown which lung cellular compartments and biological pathways are affected by AFSC-EV therapy. Herein, we conducted single-nucleus RNA sequencing (snRNA-seq) on rat fetal CDH lungs treated with vehicle or AFSC-EVs.

Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study.

Background: Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare and aggressive cancer predisposition syndrome. Because a scarcity of data on this condition contributes to management challenges and poor outcomes, we aimed to describe the clinical spectrum, cancer biology, and impact of genetics on patient survival in CMMRD.

Methods: In this cohort study, we collected cross-sectional and longitudinal data on all patients with CMMRD, with no age limits, registered with the International Replication Repair Deficiency Consortium (IRRDC) across more than 50 countries.

Sleep deprivation drives brain-wide changes in cholinergic presynapse abundance in .

Sleep is an evolutionarily conserved state that supports brain functions, including synaptic plasticity, in species across the animal kingdom. Here, we examine the neuroanatomical and cell-type distribution of presynaptic scaling in the fly brain after sleep loss. We previously found that sleep loss drives accumulation of the active zone scaffolding protein Bruchpilot (BRP) within cholinergic Kenyon cells of the mushroom body (MB), but not in other classes of MB neurons.

Characterization of the congenital diaphragmatic hernia model in C57BL/6J fetal mice: a step toward lineage tracing experiments.

Purpose: Lineage tracing is key to study the fate of individual cells and their progeny especially in developmental biology. To conduct these studies, we aimed to establish a reproducible model of CDH in the most commonly used genetic background strain that is C57BL/6J mice.

Methods: CDH was induced in C57BL/6J dams by maternal administration of nitrofen + bisdiamine at E8.

Anti-inflammatory effects of antenatal administration of stem cell derived extracellular vesicles in the brain of rat fetuses with congenital diaphragmatic hernia.

Purpose: Congenital diaphragmatic hernia (CDH) survivors may experience neurodevelopmental impairment, whose etiology remains elusive. Preclinical evidence indicates that amniotic fluid stem cell extracellular vesicle (AFSC-EV) administration promotes lung development but their effects on other organs are unknown. Herein, we investigated the brain of rat fetuses with CDH for signs of inflammation and response to AFSC-EVs.

The Emerging Cloud: a survey of vapers, their health and utilization of healthcare within the UK.

Background: Recent work in the UK estimated the prevalence of current cannabinoid-based vaping to be higher than in the USA, a factor previously associated with e-cigarette or vaping-associated lung injury (EVALI). Research in the USA has demonstrated that attendances to emergency departments relating to e-cigarettes began to rise before the EVALI outbreak, suggesting that vapers also experience milder forms of vaping-related illness.

Aim: Quantify symptom prevalence and healthcare utilization amongst current UK vapers.

Proteome Changes Resulting from Malting in Hordein-Reduced Barley Lines.

L., commonly known as barley, is primarily used for animal feed and malting. The major storage proteins in barley are hordeins, known triggers of celiac disease (CD).

From grain to malt: Tracking changes of ultra-low-gluten barley storage proteins after malting.

Barley (Hordeum vulgare L.) is a major cereal crop produced globally. Hordeins, the major storage proteins in barley, can trigger immune responses leading to celiac disease or symptoms associated with food allergy.

The unseen cloud: a survey of vaping practices and the acquisition of vaping products within the UK.

Background: Vaping of cannabinoid-based products and informal acquisition of vaping products were associated with the outbreak of E-cigarette or vaping associated lung injury (EVALI) in the USA. Current prevalence of cannabinoid-based vaping within the UK is not known and literature regarding the acquisition of vaping products is limited.

Aim: To estimate the prevalence of nicotine-based, nicotine-free and cannabinoid-based product vaping within the UK and to determine where vaping products are acquired.

Abnormal sensory perception masks behavioral performance of Grin1 knockdown mice.

The development and function of sensory systems require intact glutamatergic neurotransmission. Changes in touch sensation and vision are common symptoms in autism spectrum disorders, where altered glutamatergic neurotransmission is strongly implicated. Further, cortical visual impairment is a frequent symptom of GRIN disorder, a rare genetic neurodevelopmental disorder caused by pathogenic variants of GRIN genes that encode NMDA receptors.

Isotonitazene, a novel psychoactive substance opioid, detected in two cases following a local surge in opioid overdoses.

Background: Isotonitazene is a novel opioid that was first reported in Europe in 2019. There have been no reports of the detection of isotonitazene in patients presenting to the emergency department with acute drug toxicity.

Aim: There was an increase in presentations to our emergency department with acute opioid toxicity in August 2021.

Proteome and Nutritional Shifts Observed in Hordein Double-Mutant Barley Lines.

Lysine is the most limiting essential amino acid in cereals, and efforts have been made over the decades to improve the nutritional quality of these grains by limiting storage protein accumulation and increasing lysine content, while maintaining desired agronomic traits. The single mutation in barley has been shown to significantly increase lysine content but also reduces grain size. Herein, the regulatory effect of the mutation that controls storage protein accumulation as well as a plethora of critically important processes in cereal seeds was investigated in double mutant barley lines.

Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance.

Purpose: Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals.

Patients And Methods: Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium.

Flow Cytometry as an Important Tool in Proteomic Profiling.

Flow cytometry enables the simultaneous detection of multiple surface and intracellular antigens for proteomic profiling of cells. This allows characterization and identification of specific cell subtypes within a heterogeneous population and is usually called immunophenotyping. Antigen-specific antibodies, conjugated to various fluorophores, are incubated with the sample to identify each marker.

Proteome Analysis of Hordein-Null Barley Lines Reveals Storage Protein Synthesis and Compensation Mechanisms.

Hordeins are the major barley seed storage proteins and are elicitors of celiac disease. Attempts to reduce the hordein level in barley have been made; however, the resultant pleiotropic effects are less understood. Here, data-independent acquisition mass spectrometry was used to measure proteome-wide abundance differences between wild-type and single hordein-null barley lines.

The role of pectoral nerve blocks in a day-case mastectomy service: A prospective cohort study.

Background: It is now recognised that the majority of breast surgery can be safely undertaken as day case procedures. We aimed to evaluate the effect of pectoral nerve (Pecs2) blocks on recovery parameters and day case rates in patients undergoing mastectomy for breast cancer.

Methods: A prospective cohort study was performed in a single NHS Foundation trust between 1st April 2014 and 31st December 2016.

In Utero Gene Therapy (IUGT) Using GLOBE Lentiviral Vector Phenotypically Corrects the Heterozygous Humanised Mouse Model and Its Progress Can Be Monitored Using MRI Techniques.

In utero gene therapy (IUGT) to the fetal hematopoietic compartment could be used to treat congenital blood disorders such as β-thalassemia. A humanised mouse model of β-thalassemia was used, in which heterozygous animals are anaemic with splenomegaly and extramedullary hematopoiesis. Intrahepatic in utero injections of a β globin-expressing lentiviral vector (GLOBE), were performed in fetuses at E13.

Catcher of the Rye: Detection of Rye, a Gluten-Containing Grain, by LC-MS/MS.

Rye, wheat, and barley contain gluten, proteins that trigger immune-mediated inflammation of the small intestine in people with celiac disease (CD). The only treatment for CD is a lifelong gluten-free diet. To be classified as gluten-free by the World Health Organization the gluten content must be below 20 mg/kg, but Australia has a more rigorous standard of no detectable gluten and not made from wheat, barley, rye, or oats.

Hordein Accumulation in Developing Barley Grains.

The temporal pattern of accumulation of hordein storage proteins in developing barley grains was studied by enzyme-linked immunosorbent assay (ELISA), western blot and liquid chromatography tandem mass spectrometry (LC-MS/MS). Hordein accumulation was compared to the pattern seen for two abundant control proteins, serpin Z4 (an early accumulator) and lipid transferase protein (LTP1, a late accumulator). Hordeins were detected from 6 days post-anthesis (DPA) and peaked at 30 DPA.

Molecular Evidence of Genome Editing in a Mouse Model of Immunodeficiency.

Genome editing is the introduction of directed modifications in the genome, a process boosted to therapeutic levels by designer nucleases. Building on the experience of ex vivo gene therapy for severe combined immunodeficiencies, it is likely that genome editing of haematopoietic stem/progenitor cells (HSPC) for correction of inherited blood diseases will be an early clinical application. We show molecular evidence of gene correction in a mouse model of primary immunodeficiency.