Computational investigation of missense somatic mutations in cancer and potential links to pH-dependence and proteostasis.

Metabolic changes during tumour development lead to acidification of the extracellular environment and a smaller increase of intracellular pH. Searches for somatic missense mutations that could reveal adaptation to altered pH have focussed on arginine to histidine changes, part of a general arginine depletion that originates from DNA mutational mechanisms. Analysis of mutations to histidine, potentially a simple route to the introduction of pH-sensing, shows no clear biophysical separation overall of subsets that are more and less frequently mutated in cancer genomes.

Assessing the Pathogenicity of In-Frame CACNA1F Indel Variants Using Structural Modeling.

Small in-frame insertion-deletion (indel) variants are a common form of genomic variation whose impact on rare disease phenotypes has been understudied. The prediction of the pathogenicity of such variants remains challenging. X-linked incomplete congenital stationary night blindness type 2 (CSNB2) is a nonprogressive, inherited retinal disorder caused by variants in CACNA1F, encoding the Ca1.

Design, characterization and in vivo performance of solid lipid nanoparticles (SLNs)-loaded mucoadhesive buccal tablets for efficient delivery of Lornoxicam in experimental inflammation.

Lornoxicam (LRX) is a potent nonsteroidal anti-inflammatory drug (NSAID) used extensively to manage pain and inflammatory conditions. However, the drug possesses poor aqueous solubility (i.e.

Improving the clinical interpretation of missense variants in X linked genes using structural analysis.

Background: Improving the clinical interpretation of missense variants can increase the diagnostic yield of genomic testing and lead to personalised management strategies. Currently, due to the imprecision of bioinformatic tools that aim to predict variant pathogenicity, their role in clinical guidelines remains limited. There is a clear need for more accurate prediction algorithms and this study aims to improve performance by harnessing structural biology insights.

Using an integrative machine learning approach utilising homology modelling to clinically interpret genetic variants: CACNA1F as an exemplar.

Advances in DNA sequencing technologies have revolutionised rare disease diagnostics and have led to a dramatic increase in the volume of available genomic data. A key challenge that needs to be overcome to realise the full potential of these technologies is that of precisely predicting the effect of genetic variants on molecular and organismal phenotypes. Notably, despite recent progress, there is still a lack of robust in silico tools that accurately assign clinical significance to variants.

Variability in Gene Expression is Associated with Incomplete Penetrance in Inherited Eye Disorders.

Inherited eye disorders (IED) are a heterogeneous group of Mendelian conditions that are associated with visual impairment. Although these disorders often exhibit incomplete penetrance and variable expressivity, the scale and mechanisms of these phenomena remain largely unknown. Here, we utilize publicly-available genomic and transcriptomic datasets to gain insights into variable penetrance in IED.

Intergenerational accumulation of impairments in maternal behavior following postnatal social stress.

Early adversity such as depressed maternal care can have long-term physiological and behavioral effects on offspring and future generations. Exposure to chronic social stress (CSS), an ethologically model of postpartum depression and anxiety, during lactation impairs maternal care and exerts similar effects on the F1 dam offspring of the stressed F0 dams. These changes associate with increased corticosterone and neuroendocrine alterations.

Data Collection and Management in Community Engaged Research: Lessons Learned From Two Community-Based Participatory Research Partnerships.

Background: Data collection and data management (DCDM) within community-engaged research (CEnR) requires special considerations that differ from those of traditional research. To date, little guidance exists to preemptively help community-academic partnerships anticipate and resolve DCDM issues that may arise.

Objective: We sought to provide recommendations for DCDM based on two CEnR research projects.

Hemophilia A and hemophilia B: focus on arthropathy and variables affecting bleeding severity and prophylaxis.

Hemophilia A (HA) and hemophilia B (HB) are X-linked, recessive disorders. Although their clinical manifestations are essentially indistinguishable, it has been suggested that bleeding episodes in patients with HA are generally more severe and occur at higher frequency than in patients with HB. Nevertheless, considerable debate remains regarding the relative severity of HA and HB.

Altered glucose metabolism during chemoradiation for head and neck cancer.

Unlabelled: Platinum-based chemotherapy has been reported to induce diabetes and hyperosmolar coma in nondiabetic patients. The aim of the present study was to determine whether the administration of chemoradiation for head and neck carcinoma alters glucose metabolism during and after treatment.

Patients And Methods: Weekly nonfasting serum glucose level was obtained during treatment of one hundred and six patients with locally advanced head and neck cancer who underwent chemoradiationt.

Analysis of factors influencing Dysphagia severity following treatment of head and neck cancer.

The aim was to assess the influence of treatment, tumor stages and sites on the severity of dysphagia following treatment. Sequential modified barium swallow (MBS) examinations were performed in patients who complained of chronic dysphagia following treatment of their head and neck cancer. Patients were selected if they were cancer free at their last MBS and had 2 or more MBS studies.

Analysis of factors influencing aspiration risk following chemoradiation for oropharyngeal cancer.

Our aim was to identify risk factors for aspiration following concurrent chemoradiation for oropharyngeal cancer. 46 patients with locally advanced oropharyngeal carcinoma underwent concurrent chemoradiation at our institution. All patients underwent modified barium swallow to assess dysphagia severity and to determine the need for continued tube feedings after treatment.

Aspiration risk and postoperative radiation for head and neck cancer.

The aim of the study was to assess the aspiration risk following postoperative radiation for head and neck cancer. Thirty-seven patients had Modified Barium Swallow before and following treatment. Dysphagia severity was graded from 1 to 7.

Risk of aspiration following radiation for non-nasopharyngeal head and neck cancer.

Objective: We assessed the rate of aspiration following radiation for non-nasopharyngeal head and neck cancer.

Design: Retrospective study.

Setting: Veterans Administration Hospital.

Prevalence of pharyngeal and esophageal stenosis following radiation for head and neck cancer.

Objective: To evaluate the risk and outcome of pharyngoesophageal stenosis in patients who complained of dysphagia following radiation for head and neck cancer.

Design: Retrospective study.

Setting: Veterans Administration hospital.

Long-term aspiration following treatment for head and neck cancer.

Background: Dysphagia and aspiration are long-term complications with life-threatening consequences following treatment of head and neck cancer. We would like to assess the prevalence of aspiration in patients with long-term persistence of dysphagia (1 year or more) following treatment for head and neck cancer and to identify potential risk factors of aspiration.

Methods: Modified barium swallow (MBS) examinations were performed in cancer-free patients who complained of dysphagia following treatment for head and neck cancer.

Analysis of the factors influencing dysphagia severity upon diagnosis of head and neck cancer.

Our aim was to assess the influence of age, co-morbidity factors and tumour characteristics on dysphagia severity in the diagnosis of head and neck cancer. Modified barium swallow (MBS) examinations were performed in patients at diagnosis of head and neck cancer. Dysphagia was graded on a scale of 1 to 7 of increasing severity.

Dysphagia severity and aspiration following postoperative radiation for locally advanced oropharyngeal cancer.

Unlabelled: The aim of the present study was to assess dysphagia severity following postoperative radiation for locally advanced oropharyngeal cancer.

Patients And Methods: Eighteen patients with oropharyngeal carcinoma had undergone postoperative radiation. There were eight base of tongue, eight tonsils, and two soft palate carcinomas.

Effectiveness of the cough reflex in patients with aspiration following radiation for head and neck cancer.

The effectiveness of the cough reflex in patients who aspirated following radiation for head and neck cancer was evaluated in 89 patients (49 chemoradiation, 33 postoperative radiation, and 7 radiation alone). All patients had modified barium swallow because of dysphagia. The cough reflex was graded as present and effective, ineffective, intermittently effective, or absent.

Aspiration occurence during chemoradiation for head and neck cancer.

Aim: To assess the risk of developing aspiration during chemoradiation for head and neck cancer.

Patients And Methods: A retrospective review of 114 patients who underwent concurrent chemoradiation for locally advanced head and neck cancer was undertaken. Patients were determined as having aspiration if they had pneumonia on chest-X-ray (CXR) and/or had documented aspiration on the modified barium swallow (MBS) during their treatment.

Quality of life following chemoradiation and postoperative radiation for locally advanced head and neck cancer.

Background: To evaluate the impact of chemoradiation and postoperative radiation on patients' quality of life (QOL) in a single institution.

Methods: A retrospective analysis of 101 patients who had treatment for locally advanced head and neck cancer in a single institution. Forty-seven patients had chemotherapy and radiation, 54 patients underwent postoperative radiation.

Evaluation and management of swallowing dysfunction following chemoradiation for head and neck cancer.

Purpose Of Review: Concurrent chemoradiation offers excellent local control and survival for patients with locally advanced head and neck cancer while allowing anatomic organ preservation. Treatment toxicity is significant, however, often resulting in long-term dysphagia and aspiration. We review the prevalence of post-treatment swallowing dysfunction, describe current thinking about its pathogenesis and management, and signal possible directions for future research.

Safety and effectiveness of prophylactic gastrostomy tubes for head and neck cancer patients undergoing chemoradiation.

Background: We would like to assess the safety and effectiveness of prophylactic percutaneous endoscopic gastrostomy (PEG) tube feedings during concurrent chemoradiation for head and neck cancer.

Methods: Patients who underwent chemotherapy and radiation for head and neck malignancies were evaluated for their ability to resume oral feeding following treatment. All patients underwent PEG tube placement prior to the treatment because of the expected mucositis.