Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
6,405
result(s) for
"Wilkinson, John"
Sort by:
Dysphagia: Evaluation and Collaborative Management
Dysphagia is common but may be underreported. Specific symptoms, rather than their perceived location, should guide the initial evaluation and imaging. Obstructive symptoms that seem to originate in the throat or neck may actually be caused by distal esophageal lesions. Oropharyngeal dysphagia manifests as difficulty initiating swallowing, coughing, choking, or aspiration, and it is most commonly caused by chronic neurologic conditions such as stroke, Parkinson disease, or dementia. Symptoms should be thoroughly evaluated because of the risk of aspiration. Patients with esophageal dysphagia may report a sensation of food getting stuck after swallowing. This condition is most commonly caused by gastroesophageal reflux disease and functional esophageal disorders. Eosinophilic esophagitis is triggered by food allergens and is increasingly prevalent; esophageal biopsies should be performed to make the diagnosis. Esophageal motility disorders such as achalasia are relatively rare and may be overdiagnosed. Opioid-induced esophageal dysfunction is becoming more common. Esophagogastroduodenoscopy is recommended for the initial evaluation of esophageal dysphagia, with barium esophagography as an adjunct. Esophageal cancer and other serious conditions have a low prevalence, and testing in low-risk patients may be deferred while a four-week trial of acid-suppressing therapy is undertaken. Many frail older adults with progressive neurologic disease have significant but unrecognized dysphagia, which significantly increases their risk of aspiration pneumonia and malnourishment. In these patients, the diagnosis of dysphagia should prompt a discussion about goals of care before potentially harmful interventions are considered. Speech-language pathologists and other specialists, in collaboration with family physicians, can provide structured assessments and make appropriate recommendations for safe swallowing, palliative care, or rehabilitation.
Journal Article
Transcription Factors OVOL1 and OVOL2 Induce the Mesenchymal to Epithelial Transition in Human Cancer
Cell plasticity regulated by the balance between the mesenchymal to epithelial transition (MET) and the opposite program, EMT, is critical in the metastatic cascade. Several transcription factors (TFs) are known to regulate EMT, though the mechanisms of MET remain unclear. We demonstrate a novel function of two TFs, OVOL1 and OVOL2, as critical inducers of MET in human cancers. Our findings indicate that the OVOL-TFs control MET through a regulatory feedback loop with EMT-inducing TF ZEB1, and the regulation of mRNA splicing by inducing Epithelial Splicing Regulatory Protein 1 (ESRP1). Using mouse prostate tumor models we show that expression of OVOL-TFs in mesenchymal prostate cancer cells attenuates their metastatic potential. The role of OVOL-TFs as inducers of MET is further supported by expression analyses in 917 cancer cell lines, suggesting their role as crucial regulators of epithelial-mesenchymal cell plasticity in cancer.
Journal Article
Practice variation and practice guidelines: Attitudes of generalist and specialist physicians, nurse practitioners, and physician assistants
To understand clinicians' beliefs about practice variation and how variation might be reduced.
We surveyed board-certified physicians (N = 178), nurse practitioners (N = 60), and physician assistants (N = 12) at an academic medical center and two community clinics, representing family medicine, general internal medicine, and cardiology, from February-April 2016. The Internet-based questionnaire ascertained clinicians' beliefs regarding practice variation, clinical practice guidelines, and costs.
Respondents agreed that practice variation should be reduced (mean [SD] 4.5 [1.1]; 1 = strongly disagree, 6 = strongly agree), but agreed less strongly (4.1 [1.0]) that it can realistically be reduced. They moderately agreed that variation is justified by situational differences (3.9 [1.2]). They strongly agreed (5.2 [0.8]) that clinicians should help reduce healthcare costs, but agreed less strongly (4.4 [1.1]) that reducing practice variation would reduce costs. Nearly all respondents (234/249 [94%]) currently depend on practice guidelines. Clinicians rated differences in clinician style and experience as most influencing practice variation, and inaccessibility of guidelines as least influential. Time to apply standards, and patient decision aids, were rated most likely to help standardize practice. Nurse practitioners and physicians assistants (vs physicians) and less experienced (vs senior) clinicians rated more favorably several factors that might help to standardize practice. Differences by specialty and academic vs community practice were small.
Clinicians believe that practice variation should be reduced, but are less certain that this can be achieved. Accessibility of guidelines is not a significant barrier to practice standardization, whereas more time to apply standards is viewed as potentially helpful.
Journal Article
Pharmaceutical pollution of the world’s rivers
Significance Despite growing evidence of the deleterious effects on ecological and human health, little is known regarding the global occurrence of pharmaceuticals in rivers. Studies assessing their occurrence are available for 75 of 196 countries, with most research conducted in North America and Western Europe. This leaves large geographical regions relatively unstudied. Here, we present the findings of a global reconnaissance of pharmaceutical pollution in rivers. The study monitored 1,052 sampling sites along 258 rivers in 104 countries of all continents, thus representing the pharmaceutical fingerprint of 471.4 million people. We show that the presence of these contaminants in surface water poses a threat to environmental and/or human health in more than a quarter of the studied locations globally.
Journal Article
A gene–environment-induced epigenetic program initiates tumorigenesis
Tissue damage increases the risk of cancer through poorly understood mechanisms
1
. In mouse models of pancreatic cancer, pancreatitis associated with tissue injury collaborates with activating mutations in the
Kras
oncogene to markedly accelerate the formation of early neoplastic lesions and, ultimately, adenocarcinoma
2
,
3
. Here, by integrating genomics, single-cell chromatin assays and spatiotemporally controlled functional perturbations in autochthonous mouse models, we show that the combination of
Kras
mutation and tissue damage promotes a unique chromatin state in the pancreatic epithelium that distinguishes neoplastic transformation from normal regeneration and is selected for throughout malignant evolution. This cancer-associated epigenetic state emerges within 48 hours of pancreatic injury, and involves an ‘acinar-to-neoplasia’ chromatin switch that contributes to the early dysregulation of genes that define human pancreatic cancer. Among the factors that are most rapidly activated after tissue damage in the pre-malignant pancreatic epithelium is the alarmin cytokine interleukin 33, which recapitulates the effects of injury in cooperating with mutant
Kras
to unleash the epigenetic remodelling program of early neoplasia and neoplastic transformation. Collectively, our study demonstrates how gene–environment interactions can rapidly produce gene-regulatory programs that dictate early neoplastic commitment, and provides a molecular framework for understanding the interplay between genetic and environmental cues in the initiation of cancer.
In mouse models of pancreatic cancer, a cooperative interaction between tissue damage and
Kras
gene mutation rapidly induces cancer-associated chromatin states in pre-malignant tissue, leading to gene dysregulation and neoplastic transformation.
Journal Article