Are We Missing Obstructive Sleep Apnea in Patients With Non-traumatic Subglottic Stenosis?

Objective: To investigate the association between subglottic stenosis (SGS) and obstructive sleep apnea (OSA).

Methods: This is a cross-sectional pilot cohort study conducted at a single tertiary academic center from 2022 to 2023. Subjects with non-traumatic SGS were recruited for enrollment.

Association between Swallowing Outcomes and Dose to Critical Swallow Structures in Patients Undergoing Transoral Robotic Surgery and Post-Operative Radiation Therapy.

Background: The radiation dose to dysphagia and aspiration-related structures (DARS) for patients undergoing transoral robotic surgery (TORS) and post-operative radiation therapy (PORT) for primary oropharyngeal carcinoma is unknown.

Methods: This prospective study measured swallowing using the MD Anderson Dysphagia Inventory at baseline and then 12-months after PORT. Dosimetric parameters were collected.

Identification of Src as a Therapeutic Target in Oesophageal Adenocarcinoma through Functional Genomic and High-Throughput Drug Screening Approaches.

Drug resistance limits the effectiveness of oesophageal adenocarcinoma (OAC) chemotherapies, leading to a poor prognosis for this disease. Elucidation of the underlying resistance mechanisms is key to enabling the identification of more effective treatments. This study, therefore, aims to identify novel therapeutic and/or chemotherapy sensitising drug targets in OAC.

Design and synthesis of multifunctional microtubule targeting agents endowed with dual pro-apoptotic and anti-autophagic efficacy.

Autophagy is a lysosome dependent cell survival mechanism and is central to the maintenance of organismal homeostasis in both physiological and pathological situations. Targeting autophagy in cancer therapy attracted considerable attention in the past as stress-induced autophagy has been demonstrated to contribute to both drug resistance and malignant progression and recently interest in this area has re-emerged. Unlocking the therapeutic potential of autophagy modulation could be a valuable strategy for designing innovative tools for cancer treatment.

Functional swallowing outcomes related to radiation exposure to dysphagia and aspiration-related structures in patients with head and neck cancer undergoing definitive and postoperative intensity-modulated radiotherapy.

Background: The relationship between swallowing outcomes and radiotherapy dose to dysphagia and aspiration-related structures (DARS) may be different following definitive versus postoperative radiotherapy (PORT) for mucosal head and neck cancer (HNC) and has not been well-studied.

Method: Patient- and clinician-reported swallowing measures were prospectively collected at six time points from baseline to 24 months postradiotherapy HNC. Radiotherapy plans were retrospectively analyzed to assess dose delivered to DARS.

ATM Kinase Inhibition Preferentially Sensitises PTEN-Deficient Prostate Tumour Cells to Ionising Radiation.

Radical radiotherapy, often in combination with hormone ablation, is a safe and effective treatment option for localised or locally-advanced prostate cancer. However, up to 30% of patients with locally advanced PCa will go on to develop biochemical failure, within 5 years, following initial radiotherapy. Improving radiotherapy response is clinically important since patients exhibiting biochemical failure develop castrate-resistant metastatic disease for which there is no curative therapy and median survival is 8-18 months.

Spiroindoline-Capped Selective HDAC6 Inhibitors: Design, Synthesis, Structural Analysis, and Biological Evaluation.

Histone deacetylase inhibitors (HDACi) have emerged as promising therapeutics for the treatment of neurodegeneration, cancer, and rare disorders. Herein, we report the development of a series of spiroindoline-based HDAC6 isoform-selective inhibitors based on the X-ray crystal studies of the hit . We identified compound as the most potent and selective HDAC6 inhibitor of the series.

The tumour microenvironment of the upper and lower gastrointestinal tract differentially influences dendritic cell maturation.

Background: Only 10-30% of oesophageal and rectal adenocarcinoma patients treated with neoadjuvant chemoradiotherapy have a complete pathological response. Inflammatory and angiogenic mediators in the tumour microenvironment (TME) may enable evasion of anti-tumour immune responses.

Methods: The TME influence on infiltrating dendritic cells (DCs) was modelled by treating immature monocyte-derived DCs with Tumour Conditioned Media (TCM) from distinct gastrointestinal sites, prior to LPS-induced maturation.

miR-191 promotes radiation resistance of prostate cancer through interaction with RXRA.

Radiation therapy is a common treatment for prostate cancer, however recurrence remains a problem. MicroRNA expression is altered in prostate cancer and may promote therapy resistance. Through bioinformatic analyses of TCGA and CPC-GENE patient cohorts, we identified higher miR-191 expression in tumor versus normal tissue, and increased expression in higher Gleason scores.

Defining the molecular evolution of extrauterine high grade serous carcinoma.

Objective: High grade serous carcinoma (HGSC) is the most common and most aggressive, subtype of epithelial ovarian cancer. It presents as advanced stage disease with poor prognosis. Recent pathological evidence strongly suggests HGSC arises from the fallopian tube via the precursor lesion; serous tubal intraepithelial carcinoma (STIC).

Increasing Chance-Based Uncertainty Reduces Heavy Drinkers' Cognitive Reactance to Web-Based Personalized Normative Feedback.

Objective: Despite its prominence in the health communication literature, psychological reactance has rarely been considered as a factor that may undermine web-based Personalized Normative Feedback (PNF) alcohol interventions for college students. This study built on recent gamification work to examine how chance-based uncertainty, a popular game mechanic associated with motivation and attention in digital games for learning, might be leveraged to reduce the psychological reactance experienced by heavy drinking students receiving alcohol PNF, thereby leading to larger reductions in their alcohol consumption.

Method: Psychological reactance, perceptions of norms, and drinking behaviors were assessed during a 3-week period following random assignment of binge drinking students (N = 141, 51% female) into one of four web-based PNF conditions.

Glucose transporter 1 expression as a marker of prognosis in oesophageal adenocarcinoma.

Background: The current TNM staging system for oesophageal adenocarcinoma (OAC) has limited ability to stratify patients and inform clinical management following neo-adjuvant chemotherapy and surgery.

Results: Functional genomic analysis of the gene expression data using Gene Set Enrichment Analysis (GSEA) identified GLUT1 as putative prognostic marker in OAC.In the discovery cohort GLUT1 positivity was observed in 114 patients (80.

FES-related tyrosine kinase activates the insulin-like growth factor-1 receptor at sites of cell adhesion.

IGF-1 receptor (IGF-1R) and integrin cooperative signaling promotes cancer cell survival, proliferation, and motility, but whether this influences cancer progression and therapy responses is largely unknown. Here we investigated the non-receptor tyrosine adhesion kinase FES-related (FER), following its identification as a potential mediator of sensitivity to IGF-1R kinase inhibition in a functional siRNA screen. We found that FER and the IGF-1R co-locate in cells and can be co-immunoprecipitated.

Activation of MAPK signalling results in resistance to saracatinib (AZD0530) in ovarian cancer.

SRC tyrosine kinase is frequently overexpressed and activated in late-stage, poor prognosis ovarian tumours, and preclinical studies have supported the use of targeted SRC inhibitors in the treatment of this disease. The SAPPROC trial investigated the addition of the SRC inhibitor saracatinib (AZD0530) to weekly paclitaxel for the treatment of platinum resistant ovarian cancer; however, this drug combination did not provide any benefit to progression free survival (PFS) of women with platinum resistant disease. In this study we aimed to identify mechanisms of resistance to SRC inhibitors in ovarian cancer cells.

A novel and dedicated multidisciplinary service to manage breech presentation at term; 3 years of experience in a tertiary care maternity unit.

Objective: In order to provide uniform and unbiased multidisciplinary counselling on the options available, including vaginal breech delivery (VBD) and external cephalic version (ECV), the latter of which could then be performed, a weekly Breech Clinic was introduced to a tertiary care maternity unit in Northern Ireland in June 2013, replacing the traditional ECV Clinic introduced in June 2012.

Methods: Retrospective data collection was undertaken using clinic proformas, Northern Ireland Maternity System data and case notes of women who attended the clinics (ECV and Breech) from June 2012 to May 2015.

Results: There were 434 referrals to the clinic over the 3-year period; 356 women attended.

Evidence for Therapeutic Patient Education Interventions to Promote Cardiovascular Patient Self-Management: A Scientific Statement for Healthcare Professionals From the American Heart Association.

Background: The burden of cardiovascular disease as a chronic illness increasingly requires patients to assume more responsibility for their self-management. Patient education is believed to be an essential component of cardiovascular care; however, there is limited evidence about specific therapeutic patient education approaches used and the impact on patient self-management outcomes.

Methods And Results: An integrative review of the literature was conducted to critically analyze published research studies of therapeutic patient education for self-management in selected cardiovascular conditions.

Six-minute walk distance predicts 30-day readmission after acute heart failure hospitalization.

Objectives: To determine the relationship between 6-min walk test distance (6MWD) and 30-day readmission in hospitalized heart failure (HF) patients.

Background: 6MWD is known to predict hospitalizations in outpatients with HF, but its ability to predict recidivism in hospitalized HF patients is relatively unknown.

Methods: Seventy-one hospitalized HF patients with NYHA Class II/III (mean age 52.

Activation of STING-Dependent Innate Immune Signaling By S-Phase-Specific DNA Damage in Breast Cancer.

Background: Previously we identified a DNA damage response-deficient (DDRD) molecular subtype within breast cancer. A 44-gene assay identifying this subtype was validated as predicting benefit from DNA-damaging chemotherapy. This subtype was defined by interferon signaling.

IGF-1R inhibition sensitizes breast cancer cells to ATM-related kinase (ATR) inhibitor and cisplatin.

The complexity of the IGF-1 signalling axis is clearly a roadblock in targeting this receptor in cancer therapy. Here, we sought to identify mediators of resistance, and potential co-targets for IGF-1R inhibition. By using an siRNA functional screen with the IGF-1R tyrosine kinase inhibitor (TKI) BMS-754807 in MCF-7 cells we identified several genes encoding components of the DNA damage response (DDR) pathways as mediators of resistance to IGF-1R kinase inhibition.

Prior knowledge transfer across transcriptional data sets and technologies using compositional statistics yields new mislabelled ovarian cell line.

Here, we describe gene expression compositional assignment (GECA), a powerful, yet simple method based on compositional statistics that can validate the transfer of prior knowledge, such as gene lists, into independent data sets, platforms and technologies. Transcriptional profiling has been used to derive gene lists that stratify patients into prognostic molecular subgroups and assess biomarker performance in the pre-clinical setting. Archived public data sets are an invaluable resource for subsequent in silico validation, though their use can lead to data integration issues.

When the guardian becomes the enemy: Targeting ATM in PTEN-deficient cancers.

Ataxia telangiectasia mutated (ATM) is an important signaling molecule in the DNA damage response and inhibitors of ATM are under clinical development. We identified a synthetic lethal interaction between ATM inhibition and phosphatase and tensin homolog (PTEN) loss that was the result of increased oxidative stress. Inhibition of ATM therefore represents a novel strategy to target PTEN-associated cancers.

Autonomic Testing in Women with Chronic Pelvic Pain.

Purpose: We determined whether abnormal autonomic nervous system innervation of the bladder underlies IC (interstitial cystitis)/BPS (bladder pain syndrome) differently than other chronic pelvic pain.

Materials And Methods: In this institutional review board approved protocol 39 healthy controls and 134 subjects were enrolled, including 36 with IC/BPS, 14 with myofascial pelvic pain and 42 with IC/BPS plus myofascial pelvic pain. Three subjects were excluded from study.