IRF3 inhibits inflammatory signaling pathways in macrophages to prevent viral pathogenesis.

Viral inflammation contributes to pathogenesis and mortality during respiratory virus infections. IRF3, a critical component of innate antiviral immune responses, interacts with pro-inflammatory transcription factor NF-κB, and inhibits its activity. This mechanism helps suppress inflammatory gene expression in virus-infected cells and mice.

The effectiveness and safety of proton beam radiation therapy in children and young adults with Central Nervous System (CNS) tumours: a systematic review.

Background: Central nervous system (CNS) tumours account for around 25% of childhood neoplasms. With multi-modal therapy, 5-year survival is at around 75% in the UK. Conventional photon radiotherapy has made significant contributions to survival, but can be associated with long-term side effects.

Retinoic Acid-Mediated Inhibition of Mouse Coronavirus Replication Is Dependent on IRF3 and CaMKK.

The ongoing COVID-19 pandemic has revealed the shortfalls in our understanding of how to treat coronavirus infections. With almost 7 million case fatalities of COVID-19 globally, the catalog of FDA-approved antiviral therapeutics is limited compared to other medications, such as antibiotics. All-trans retinoic acid (RA), or activated vitamin A, has been studied as a potential therapeutic against coronavirus infection because of its antiviral properties.

SARS-CoV-2 Monitoring in Wastewater Reveals Novel Variants and Biomarkers of Infection.

Wastewater-based epidemiology (WBE) is a popular tool for the early indication of community spread of infectious diseases. WBE emerged as an effective tool during the COVID-19 pandemic and has provided meaningful information to minimize the spread of infection. Here, we present a combination of analyses using the correlation of viral gene copies with clinical cases, sequencing of wastewater-derived RNA for the viral mutants, and correlative analyses of the viral gene copies with the bacterial biomarkers.

Gallstone Ileus with Cholecystogastric Fistula in an Older Female.

Unlabelled: Cholecystogastric fistulas are a rare but life-threatening complication of cholelithiasis. This medical condition has been explained in detail in several cases in the medical literature. However, there is still conflicting debate on how well to effectively manage patients with such a complex medical condition.

Comparing Treatment Outcomes Between In-Hospital and Emergency Department Management of Patients With Transient Ischemic Attacks.

Introduction A transient ischemic attack (TIA) is a medical emergency, as it is a sudden neurological episode caused by ischemia in a vascular territory in the brain, which lasts less than one hour. TIA definition has shifted from time-based to tissue-based according to modern literature. It is considered a warning sign for an impending stroke.

The Sea Was Angry That Day My Friends: An Inland Case of Acute Scombroid Poisoning With a Twist.

Scombroid poisoning is a common form of food poisoning related to fresh, canned, or smoked fish ingestion with high histamine content as a result of improper handling and storage. The incubation period for this type of fish poisoning is relatively short (ranges from a few minutes to hours). We present a case of a 53-year-old male who developed severe symptoms of scombroid poisoning minutes after ingesting an ahi tuna salad in a local restaurant.

Discovery of Icenticaftor (QBW251), a Cystic Fibrosis Transmembrane Conductance Regulator Potentiator with Clinical Efficacy in Cystic Fibrosis and Chronic Obstructive Pulmonary Disease.

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel are established as the primary causative factor in the devastating lung disease cystic fibrosis (CF). More recently, cigarette smoke exposure has been shown to be associated with dysfunctional airway epithelial ion transport, suggesting a role for CFTR in the pathogenesis of chronic obstructive pulmonary disease (COPD). Here, the identification and characterization of a high throughput screening hit as a potentiator of mutant human F508del and wild-type CFTR channels is reported.

A Case of Trazodone Overdose Successfully Rescued With Lipid Emulsion Therapy.

Trazodone is a very common medication prescribed to patients who suffer from insomnia. The toxic effects of trazodone remain ill-defined with no current known antidote therapy. Lipid emulsion therapy has been described as general rescue therapy in toxicology.

Outcomes of non-anaplastic stage III and 'inoperable' Wilms tumour treated in the UKW3 trial.

Background And Purpose: To describe the outcome of patients with stage III Wilms tumours (WT) treated in the UKW3 trial.

Material And Methods: Patients with a pathologically confirmed stage III non-anaplastic WT at nephrectomy (Group A) or with an 'inoperable' tumour at diagnosis managed by biopsy and pre-operative chemotherapy (Actinomycin D-Vincristine-Doxorubicin) but stage I or II at subsequent nephrectomy (Group B) were included.

Results: The 4-year overall (OS)/event free survival (EFS) for Group A (n = 117) patients was 90%(95%CI:83-94)/81%(CI:73-87) and for Group B (n = 32) 94%(CI:77-98)/88%(CI:70-95).

Picomolar, selective, and subtype-specific small-molecule inhibition of TRPC1/4/5 channels.

The concentration of free cytosolic Ca and the voltage across the plasma membrane are major determinants of cell function. Ca-permeable non-selective cationic channels are known to regulate these parameters, but understanding of these channels remains inadequate. Here we focus on transient receptor potential canonical 4 and 5 proteins (TRPC4 and TRPC5), which assemble as homomers or heteromerize with TRPC1 to form Ca-permeable non-selective cationic channels in many mammalian cell types.

The effectiveness and safety of proton beam radiation therapy in children with malignant central nervous system (CNS) tumours: protocol for a systematic review.

Background: The aim of this study is to use a systematic review framework to identify and synthesise the evidence on the use of proton beam therapy (PBT) for the treatment of children with CNS tumours and where possible compare this to the use of photon radiotherapy (RT).

Methods: Standard systematic review methods aimed at minimising bias will be employed for study identification, selection and data extraction. Twelve electronic databases have been searched, and further citation, hand searching and reference checking will be employed.