Project description:Rationale/statement of the problem Substantial evidence suggests conditions in intrauterine life may play a critical role in subsequent health and disease susceptibility related outcomes (i.e., the concept of fetal or developmental programming of health and disease). The elucidation of biological mechanisms underlying these effects is an area of active investigation. We suggest that telomere biology may represent a novel mechanism underlying the effects of a disparate set of suboptimal intrauterine exposures on various health and disease risk phenotypes. From an evolutionary-developmental perspective, energy substrate availability (i.e., nutrition) and challenges that have the potential to impact the structural or functional integrity and survival of the organism (i.e., stress) likely represent the most important environmental considerations underlying natural selection and developmental plasticity. Maternal stress and nutrition in pregnancy therefore represent attractive candidate processes in the context of fetal programming of telomere biology. Our previous work has established an important role for prenatal stress and stress-related processes in adult telomere biology Methods In two longitudinal birth cohorts, stress- and nutrition-related processes were assessed during pregnancy and telomere length (TL) was subsequently measured in newborns (cord blood) and infants (buccal cells). Results (1) Among the nutrition-related factors, maternal lower folate levels (an essential methyl donor) and higher triglyceride concentrations in early pregnancy were significantly and independently associated with shorter newborn TL. (2) Among psychosocial stress-related measures, higher maternal pregnancy-specific stress was associated with shorter newborn TL. (3) Maternal estrogen (E3) levels during early pregnancy were associated with longer infant TL. Conclusion Taken together, our findings provide the first evidence in humans that maternal nutrition and stress-related processes during pregnancy may exert a programming effect on the newborn and infant telomere biology system. In utero telomere biology represents a potential molecular mechanism whereby different exposures in this critical developmental period before birth could impact subsequent health and disease susceptibility related outcomes over the life span, including aging and longevity

Project description:E-JOURNAL LINKED ABSTRACT URL http://www.current-oncology.com/index.php/oncology/article/view/840/ Pseudocirrhosis is a rare form of liver disease that causes clinical symptoms and shows radiographic signs of cirrhosis, but that has histologic features suggesting a distinct pathologic process. In the setting of cancer, hepatic metastases and systemic chemotherapy are suspected causes of pseudocirrhosis. We present the case of a 49-year-old woman with medullary thyroid carcinoma metastatic to the liver who developed pseudocirrhosis. The patient was initially enrolled in a phase i clinical trial of 5-fluorouracil, leucovorin, and oxaliplatin (folfox) in combination with sunitinib (NCT00599924). After this patient’s liver metastases regressed measurably, she was switched to sunitinib maintenance. After 4 months of combination therapy with folfox–sunitinib and 15 months of sunitinib maintenance, she developed abdominal bloating, early satiety, and right upper quadrant pain that increased with inspiration. Computed tomography of the abdomen revealed cirrhotic morphology changes in the liver, including the appearance of a nodular surface and capsular retraction. The patient had no risk factors for cirrhosis and laboratory testing for causes of liver disease were normal or negative. Core-needle liver biopsy demonstrated sheets and nests of epithelioid and spindle cells resembling the primary tumor; septal fibrosis and regenerative nodules typical of cirrhosis were not observed. The background hepatic plate architecture was intact. Laboratory studies showed increased aminotransferases, alkaline phosphatase, and international normalized ratio, and decreased albumin. Portal hypertension, esophageal varices, portal hypertensive gastropathy, and hepatic hydrothorax developed as a result of advanced liver disease. Because of disease progression, sunitinib was discontinued, and the patient was managed with sorafenib. Pseudocirrhosis has often been attributed to chemotherapeutic agents, particularly in the context of metastatic breast cancer. The toxicity profiles of folfox and sunitinib include hepatic steatosis and other forms of hepatotoxicity, but cirrhotic-like disease has not been reported. Considering the transformation of discrete hepatic metastases into a diffuse carcinomatous infiltrate and the unrelated toxicities of folfox and sunitinib, we diagnosed this patient with carcinomatous pseudocirrhosis secondary to metastatic medullary thyroid carcinoma. We discuss the diagnosis of pseudocirrhosis in this case and review the literature regarding pseudocirrhosis in cancer.

Project description:BackgroundCochrane plain language summaries (PLSs) are an important format to present high-quality healthcare evidence to patients with cancer and their families. They should be written in a way everyone can understand, since they serve as a tool in decision-making and present a bridge to overcome the gap between the healthcare users and professionals.ObjectiveThe aim of the study was to assess the language characteristics of PLSs of Cochrane systematic reviews of oncology interventions in comparison with corresponding Cochrane scientific abstracts (SAs).MethodsIn this cross-sectional study, we included all Cochrane PLSs and SAs of systematic reviews of oncology interventions available in the Cochrane Database of Systematic Reviews. We assessed text readability, measured using the Simple Measure of Gobbledygook (SMOG) index, and the prevalence of words related to different language tones (clout, authenticity, emotions and analytical tones). Two independent assessors categorized the conclusiveness of the efficacy of interventions into nine categories.ResultsThe overall median SMOG index for 275 PLSs was 13.0 (95% confidence interval [CI] 12.8-13.3). Readability scores did not differ across Cochrane Review Groups. SAs had a higher readability index than the corresponding PLSs (median = 16.6, 95% CI = 16.4-16.8). Regarding linguistic characteristics, PLSs were shorter than SAs, with less use of analytical tone, but more use of a positive emotional tone and authenticity. Overall, the 'Unclear' category of conclusiveness was the most common among all PLSs. Also, PLSs with 'No evidence' conclusions were the shortest and had the lowest SMOG index.ConclusionPLSs of Cochrane systematic reviews of oncological interventions have low readability and most give unclear conclusions about the efficacy of interventions. PLSs should be simplified so that patients and their families can benefit from appropriate health information on evidence synthesis. Further research is needed into reasons for unclear language to describe evidence from oncology trials.

Dataset Information

Symposium Summaries.

Publications

Symposium Summaries.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets