Vanzacaftor-tezacaftor-deutivacaftor versus elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older (SKYLINE Trials VX20-121-102 and VX20-121-103): results from two randomised, active-controlled, phase 3 trials.

Background: The goal of cystic fibrosis transmembrane conductance regulator (CFTR) modulators is to reach normal CFTR function in people with cystic fibrosis. Vanzacaftor-tezacaftor-deutivacaftor restored CFTR function in vitro and in phase 2 trials in participants aged 18 years and older resulting in improvements in CFTR function, as measured by sweat chloride concentrations and lung function as measured by spirometry. We aimed to evaluate the efficacy and safety of vanzacaftor-tezacaftor-deutivacaftor compared with standard of care elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older.

Polymyxin B and ethylenediaminetetraacetic acid act synergistically against and .

Polymyxin B and ethylenediaminetetraacetic acid are antimicrobials possessing antibiofilm activity. They act by displacement and chelation, respectively, of divalent cations in bacterial membranes and may therefore act synergistically when applied in combination. If so, this combination of agents may be useful for the treatment of diseases like cystic fibrosis (CF), in which biofilms are present on the respiratory epithelium.

Advanced Cystic Fibrosis Lung Disease and Lung Transplantation in the Era of Cystic Fibrosis Transmembrane Conductance Regulator Modulators.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have changed the clinical landscape of cystic fibrosis (CF) by improving clinically significant outcome measures and quality of life of people with CF (pwCF). There are now long-term data showing improved 5-year survival with the use of ivacaftor, and the field continues to evolve at a rapid pace with the continued development of highly effective CFTR modulators. While the randomized controlled trials of CFTR modulators excluded patients with severe lung disease (forced expiratory volume in 1 second <40% predicted), observational data based on case reports and registry data show similar benefits in those with advanced lung disease.

Hybrid reconstruction of bronchial dehiscence following lung transplant.

Surgical repair of right-sided bronchial dehiscence post lung transplant is challenging. We report a hybrid reconstruction of the bronchus using an aortic homograft patch with stenting as a novel technique of management of ischemic airway injury following lung transplantation.

Hair cell α9α10 nicotinic acetylcholine receptor functional expression regulated by ligand binding and deafness gene products.

Auditory hair cells receive olivocochlear efferent innervation, which refines tonotopic mapping, improves sound discrimination, and mitigates acoustic trauma. The olivocochlear synapse involves α9α10 nicotinic acetylcholine receptors (nAChRs), which assemble in hair cells only coincident with cholinergic innervation and do not express in recombinant mammalian cell lines. Here, genome-wide screening determined that assembly and surface expression of α9α10 require ligand binding.

Lung transplant graft salvage using aortic homograft for bronchial dehiscence.

The use of aortic homograft in infective pathology is well described. Its use in the repair of post-transplant airway complications has been seldom reported. Herein, we report our experience with the successful use of aortic homograft in the management of post-transplant large airway complications in two patients.

Lung transplant in a recipient with tracheal bronchus.

We describe the intraoperative surgical management of tracheal bronchus encountered in a lung transplant recipient.

Socioeconomic deprivation is not associated with reduced survival of lung transplant recipients.

Background: Important risk factors for long-term survival of lung transplant (LT) recipients are infection, acute graft rejection (AR) and chronic lung allograft dysfunction (CLAD). Socioeconomic deprivation (SED) is associated with increased graft failure rate after heart and kidney transplantation, but has not been investigated in LT recipients. The aim of this study was to evaluate an association between LT recipients' SED status and development of AR, CLAD, and long-term survival.

Brain Tumours: Rise in Glioblastoma Multiforme Incidence in England 1995-2015 Suggests an Adverse Environmental or Lifestyle Factor.

Objective: To investigate detailed trends in malignant brain tumour incidence over a recent time period.

Methods: UK Office of National Statistics (ONS) data covering 81,135 ICD10 C71 brain tumours diagnosed in England (1995-2015) were used to calculate incidence rates (ASR) per 100k person-years, age-standardised to the European Standard Population (ESP-2013).

Results: We report a sustained and highly statistically significant ASR rise in glioblastoma multiforme (GBM) across all ages.

An international, multicentre evaluation and description of Burkholderia pseudomallei infection in cystic fibrosis.

Background: Several cases of Burkholderia pseudomallei infection in CF have been previously reported. We aimed to identify all cases globally, risk factors for acquisition, clinical consequences, and optimal treatment strategies.

Methods: We performed a literature search to identify all published cases of B.

Closure of a broncho-pleural fistula using an atrial septal defect occluder.

Broncho-pleural fistulae (BPF) are recognised as a rare complication following pneumonectomy. We describe a patient, who after failing conservative treatment, underwent closure of a persistent fistula with an atrial septal defect (ASD) occluder. Additionally we review the literature regarding management of BPF and the emerging role of cardiac defect closure devices as a possible treatment option.

Newborn transepidermal water loss values: a reference dataset.

Transepidermal water loss (TEWL) is a simple noninvasive measurement of inside-out skin barrier function. The goal of this research was to establish normal values for TEWL in early life using data gathered from the Cork BASELINE Birth Cohort Study. TEWL was recorded in a standardized fashion using a well-validated open-chamber system.

Rituximab-induced interstitial lung disease in a patient with immune thrombocytopenia purpura.

We report the case of an 84-year-old man with refractory immune thrombocytopenia purpura (ITP) who was treated with rituximab and subsequently developed severe interstitial lung disease. There has been increasing use of rituximab in the treatment of ITP with success rates of up to 62% in adult patients with recurrent ITP. Interstitial lung disease is a rare but recognised complication of rituximab but has been rarely reported in the setting of ITP.

Diagnostic yield of bronchoscopic sampling in febrile neutropenic patients with pulmonary infiltrate and haematological disorders.

Background: The development of pulmonary infiltrate in neutropenic patients is potentially life-threatening, and requires early diagnosis and treatment. Bronchoscopic sampling is an established form of investigation in such patients.

Aim: The aim of the study is to determine the diagnostic yield and complication rate of bronchoscopic sampling in patients with a haematological disorder presenting with febrile neutropenia and pulmonary infiltrate.

Drug-sensitive DNA polymerase δ reveals a role for mismatch repair in checkpoint activation in yeast.

We have used a novel method to activate the DNA damage S-phase checkpoint response in Saccharomyces cerevisiae to slow lagging-strand DNA replication by exposing cells expressing a drug-sensitive DNA polymerase δ (L612M-DNA pol δ) to the inhibitory drug phosphonoacetic acid (PAA). PAA-treated pol3-L612M cells arrest as large-budded cells with a single nucleus in the bud neck. This arrest requires all of the components of the S-phase DNA damage checkpoint: Mec1, Rad9, the DNA damage clamp Ddc1-Rad17-Mec3, and the Rad24-dependent clamp loader, but does not depend on Mrc1, which acts as the signaling adapter for the replication checkpoint.

Sexual and reproductive health in men with cystic fibrosis: consistent preferences, inconsistent practices.

Background: Sexual and reproductive health (SRH) is increasingly relevant for men with CF. However, the extent of similarities or differences in SRH clinical practices across different centres or states is unknown as single clinic studies are not informative about variations in male preferences or clinical practices. We wished to determine the variability of male SRH knowledge and preferences, and clinical practices across different CF clinics.

Aggregating disparate epidemiological evidence: comparing two seminal EMF reviews.

Two seminal reviews (IARC, 2002; CDHS, 2002) of possible health effects from power-frequency EMFs reached partly different conclusions from similar epidemiological evidence. These differences have an impact on precautionary policy. We examine the statistical aggregation of results from individual disparate studies.

Befriending patients with medication-resistant schizophrenia: can psychotic symptoms predict treatment response?

Objectives: Supportive interventions are used in schizophrenia, but little research has been conducted into whether any baseline variable predicts treatment response. The aim of this study was to establish if baseline delusions or hallucinations are associated with changes in overall symptoms in patients who received a befriending intervention.

Design: The sample consisted of 44 patients with schizophrenia.

The global regulator H-NS acts directly on the transpososome to promote Tn10 transposition.

The histone-like nucleoid structuring (H-NS) protein is a global transcriptional regulator that is known to regulate stress response pathways and virulence genes in bacteria. It has also been implicated in the regulation of bacterial transposition systems, including Tn10. We demonstrate here that H-NS promotes Tn10 transposition by binding directly to the transposition complex (or transpososome).