Single-cell transcriptomics reveals the molecular basis of human iPS cell differentiation into ectodermal ocular lineages.

The generation of a self-formed, ectodermal, autonomous multi-zone (SEAM) from human induced pluripotent stem cells (hiPSCs) offers a unique perspective to study the dynamics of ocular cell differentiation over time. Here, by utilising single-cell transcriptomics, we have (i) identified, (ii) molecularly characterised and (iii) ascertained the developmental trajectories of ectodermally-derived ocular cell populations which emerge within SEAMs as they form. Our analysis reveals interdependency between tissues of the early eye and delineates the sequential formation and maturation of distinct cell types over a 12-week period.

Application of quasimetagenomics methods to define microbial diversity and subtype in dairy and seafood production facilities.

In developed countries, the human diet is predominated by food commodities, which have been manufactured, processed, and stored in a food production facility. Little is known about the application of metagenomic sequencing approaches for detecting foodborne pathogens, such as , and characterizing microbial diversity in food production ecosystems. In this work, we investigated the utility of 16S rRNA amplicon and quasimetagenomic sequencing for the taxonomic and phylogenetic classification of culture enrichments of environmental swabs collected from dairy and seafood production facilities.

Gastrointestinal conditions related to tooth wear.

Gastro-oesophageal reflux disease (GORD) is a relatively common condition that occurs in adults and less commonly in children. It develops when the reflux of stomach contents into the oesophagus causes troublesome symptoms and/or complications. Signs and symptoms include heartburn, retrosternal discomfort, epigastric pain and hoarseness, dental erosion, chronic cough, burning mouth syndrome, halitosis and laryngitis.

Clinical and radiographic assessment and restoration of maxillary sinus function in relation to oro-antral fistula closure: a systematic review.

Background: The purpose of this study was to determine current practice in assessment of maxillary sinus health during oro-antral fistula closure.

Method: A systematic review using specific MeSH headings between 1990 and September 2021 on Medline, Ovid, and PubMed was performed. The inclusion criterion was closure of oro-antral fistula in adult patients.

Modeling the catarrhal stage of Bordetella pertussis upper respiratory tract infections in mice.

Pertussis (whooping cough) is a highly transmissible human respiratory disease caused by Bordetella pertussis, a human-restricted pathogen. Animal models generally involve pneumonic infections induced by depositing large numbers of bacteria in the lungs of mice. These models have informed us about the molecular pathogenesis of pertussis and guided development of vaccines that successfully protect against severe disease.

Bbvac: A Live Vaccine Candidate That Provides Long-Lasting Anamnestic and Th17-Mediated Immunity against the Three Classical spp.

Acute pathogens such as Bordetella pertussis can cause severe disease but are ultimately cleared by the immune response. This has led to the accepted paradigm that convalescent immunity is optimal and therefore broadly accepted as the "gold standard" against which vaccine candidates should be compared. However, successful pathogens like B.

Modeling Immune Evasion and Vaccine Limitations by Targeted Nasopharyngeal Bordetella pertussis Inoculation in Mice.

Conventional pertussis animal models deliver hundreds of thousands of Bordetella pertussis bacteria deep into the lungs, rapidly inducing severe pneumonic pathology and a robust immune response. However, human infections usually begin with colonization and growth in the upper respiratory tract. We inoculated only the nasopharynx of mice to explore the course of infection in a more natural exposure model.

Neuregulin-4 contributes to the establishment of cutaneous sensory innervation.

Recent work has shown that neuregulin-4 (NRG4) is a physiological regulator of the growth of sympathetic axons and CNS dendrites in the developing nervous system. Here, we have investigated whether NRG4 plays a role in sensory axon growth and the establishment of cutaneous sensory innervation. Imaging early nerve fibers in the well-characterized cutaneous trigeminal territory, the brachial plexus, and thorax revealed very marked and highly significant decreases in nerve fiber length and branching density in Nrg4 embryos compared with Nrg4 littermates.

BET 1: is the patient's perception of shortness of breath a useful triage tool in exacerbations of COPD?

A shortcut review was carried out to establish whether the degree of breathlessness in patients with an acute exacerbation of COPD is indicative of the severity of the exacerbation. Three hundred and forty-seven papers were found using the reported searches, of which five presented the best available evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these five papers are tabulated.

Enhancement of immune response against Bordetella spp. by disrupting immunomodulation.

Well-adapted pathogens must evade clearance by the host immune system and the study of how they do this has revealed myriad complex strategies and mechanisms. Classical bordetellae are very closely related subspecies that are known to modulate adaptive immunity in a variety of ways, permitting them to either persist for life or repeatedly infect the same host. Exploring the hypothesis that exposure to immune cells would cause bordetellae to induce expression of important immunomodulatory mechanisms, we identified a putative regulator of an immunomodulatory pathway.

CD40 forward signalling is a physiological regulator of early sensory axon growth.

Multiple members of the tumour necrosis factor superfamily (TNFSF) regulate the growth and branching of neural processes late in development, when neurons are establishing and refining connections. Here, we present the first evidence that a TNFSF member acts much earlier in development, when axons are growing to their targets. CD40L transiently enhanced axon growth from embryonic mouse DRG neurons cultured at this early stage.

BET 1: The role of topical phenylephrine in non-traumatic epistaxis.

A short cut review of the literature was carried out to establish whether topical phenylephrine was an effective treatment for non-traumatic epistaxis. A single paper looked at this modality comparing it to another topical treatment. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses are tabulated.

Adipocyte-secreted BMP8b mediates adrenergic-induced remodeling of the neuro-vascular network in adipose tissue.

Activation of brown adipose tissue-mediated thermogenesis is a strategy for tackling obesity and promoting metabolic health. BMP8b is secreted by brown/beige adipocytes and enhances energy dissipation. Here we show that adipocyte-secreted BMP8b contributes to adrenergic-induced remodeling of the neuro-vascular network in adipose tissue (AT).

Microbiomes Associated With Foods From Plant and Animal Sources.

Food microbiome composition impacts food safety and quality. The resident microbiota of many food products is influenced throughout the farm to fork continuum by farming practices, environmental factors, and food manufacturing and processing procedures. Currently, most food microbiology studies rely on culture-dependent methods to identify bacteria.

TWE-PRIL reverse signalling suppresses sympathetic axon growth and tissue innervation.

TWE-PRIL is a naturally occurring fusion protein of components of two TNF superfamily members: the extracellular domain of APRIL; and the intracellular and transmembrane domains of TWEAK with no known function. Here, we show that mice (which lack APRIL and TWE-PRIL) exhibited overgrowth of sympathetic fibres , and sympathetic neurons cultured from these mice had significantly longer axons than neurons cultured from wild-type littermates. Enhanced axon growth from sympathetic neurons cultured from mice was prevented by expressing full-length TWE-PRIL in these neurons but not by treating them with soluble APRIL.

Enhanced triage for patients with suspected cardiac chest pain: the History and Electrocardiogram-only Manchester Acute Coronary Syndromes decision aid.

Objectives: Several decision aids can 'rule in' and 'rule out' acute coronary syndromes (ACS) in the Emergency Department (ED) but all require measurement of blood biomarkers. A decision aid that does not require biomarker measurement could enhance risk stratification at triage and could be used in the prehospital environment. We aimed to derive and validate the History and ECG-only Manchester ACS (HE-MACS) decision aid using only the history, physical examination and ECG.

Blood or Serum Exposure Induce Global Transcriptional Changes, Altered Antigenic Profile, and Increased Cytotoxicity by Classical Bordetellae.

The classical bordetellae sense and respond to a variety of environments outside and within their mammalian hosts. By causing inflammation and tissue damage, we reasoned that bordetellae are likely to encounter components of blood and/or serum during the course of a respiratory infection, and that detecting and responding to these would be advantageous. Therefore, we hypothesized that classical bordetellae have the ability to sense and respond to blood or serum.

How events in emergency medicine impact doctors' psychological well-being.

Background: Emergency medicine is a high-pressured specialty with exposure to disturbing events and risk. We conducted a qualitative study to identify which clinical events resulted in emotional disruption and the impact of these events on the well-being of physicians working in an ED.

Methods: We used the principles of naturalistic inquiry to conduct narrative interviews with physicians working in the ED at Central Manchester University Hospitals NHS Foundation Trust, between September and October 2016.

Cross-sectional interview study of fertility, pregnancy, and urogenital schistosomiasis in coastal Kenya: Documented treatment in childhood is associated with reduced odds of subfertility among adult women.

Background: Previous research has documented an increased risk of subfertility in areas of sub-Saharan Africa, as well as an ecological association between urogenital schistosomiasis prevalence and decreased fertility. This pilot project examined reproductive patterns and the potential effects of childhood urogenital Schistosoma haematobium infection and individual treatment experience on adult subfertility among women who were long-term residents in an S. haematobium-endemic region of coastal Kenya.

Social-media-enabled learning in emergency medicine: a case study of the growth, engagement and impact of a free open access medical education blog.

Background: Clinicians are increasingly using social media for professional development and education. In 2012, we developed the St.Emlyn's blog, an open access resource dedicated to providing free education in the field of emergency medicine.

TNF superfamily member APRIL enhances midbrain dopaminergic axon growth and contributes to the nigrostriatal projection in vivo.

We have studied the role of the tumor necrosis factor superfamily member APRIL in the development of embryonic mouse midbrain dopaminergic neurons in vitro and in vivo. In culture, soluble APRIL enhanced axon growth during a window of development between E12 and E14 when nigrostriatal axons are growing to their targets in the striatum in vivo. April transcripts were detected in both the striatum and midbrain during this period and at later stages.

Zeb2 is a negative regulator of midbrain dopaminergic axon growth and target innervation.

Neural connectivity requires neuronal differentiation, axon growth, and precise target innervation. Midbrain dopaminergic neurons project via the nigrostriatal pathway to the striatum to regulate voluntary movement. While the specification and differentiation of these neurons have been extensively studied, the molecular mechanisms that regulate midbrain dopaminergic axon growth and target innervation are less clear.

BET 1: Lidocaine with propofol to reduce pain on injection.

A short review was carried out to see if mixing lidocaine with propofol is a safe and effective method in reducing the commonly reported pain at the injection site. Four relevant papers were found using the described search strategy. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated.