Genetic and epigenetic alterations of the EGFR and mutually independent association with BRCA1, MGMT,and RASSF1A methylations in Vietnamese lung adenocarcinomas

Genetic and epigenetic alterations importantly contribute to the pathogenesis of lung cancer. In the study, we measured the frequency and distribution of molecular abnormalities of EGFR as well as the aberrant promoter methylations of BRCA1, MGMT, MLH1, and RASSF1A in Vietnamese lung adenocarcinomas. We investigated the association between genetic and epigenetic alteration, and between each abnormality with clinicopathologic parameters. Somatic EGFR mutation that was found in 49/139 (35.3%) lung adenocarcinomas showed a significant association with young age, female gender, and non-smokers. EGFR overexpression was identified in 82 tumors (59.0%) and statistical relationships with EGFR or BRCA1 methylation but not EGFR mutation. In addition, EGFR, BRCA1, MGMT, MLH1, and RASSF1A methylations were found in 33 (23.7%), 41 (29.5%), 46 (33.1%), 28 (20.1%), and 41 (29.5%) cases of a total of 139 lung adenocarcinomas, respectively. The RASSF1A methylation was found to be linked to the smoking habit. Methylations in MGMT and RASSF1A were also found to correlate with metastasis status. Furthermore, the distribution of EGFR mutation and that of BRCA1, MGMT or RASSF1A methylation were significantly exclusive in lung adenocarcinomas. The main finding of our study demonstrate that epigenetic abnormalities might play a critical role for the lung tumorigenesis in patients with smoking history and metastasis, and partly affect the predictive value of EGFR mutations through blocking expression due to promoter EGFR hypermethylation. Mutually exclusive distribution of genetic and epigenetic alterations reflects differently biological characteristics in the etiology of lung adenocarcinomas.     

Implementation of amplitude-integrated electroencephalography in tertiary Canadian Neonatal Intensive Care Units—a longitudinal study

AimTo investigate the implementation of amplitude-integrated electroencephalography (aEEG) as bedside monitoring tool of cerebral function in tertiary Canadian Neonatal Intensive Care Units (NICU) over the past decade.MethodsLongitudinal study consisting of online surveys of neonatologists on the use of aEEG in 2009 and 2018.ResultsThe response rate to the survey was 72 of 149 (49%) in 2009 and 18 of 30 (60%) in 2018, respectively. aEEG has been implemented in almost all (2009: 62.5%; 2018: 94%) tertiary Canadian NICUs. Two-thirds (2009: 67%; 2018: 71%) of the respondents considered information from aEEG tracing helpful in clinical practice. The main indications for aEEG were term neonates with hypoxic ischemic encephalopathy (2009 and 2018: 76%) and seizure detection/surveillance (2009: 88%; 2018: 94%). Teaching on aEEG has been implemented for neonatologists (2018: 100%) and health care providers (2018: 50%) in tertiary Canadian NICUs but there is a lack of standardization of training. Use of aEEG in preterm neonates (2009: 37%, 2018: 33%) and application of aEEG in research (18% reported occasional use) is less common.ConclusionaEEG is well established in tertiary Canadian NICUs to monitor cerebral function and detect seizure activity. There is a need to develop formalized aEEG training programs and methods to assess competence. Further implementation of aEEG in preterm neonates and research is desirable.     

Computational pathology definitions,best practices,and recommendations for regulatory guidance: a white paper from the Digital Pathology Association

In this white paper, experts from the Digital Pathology Association (DPA) define terminology and concepts in the emerging field of computational pathology, with a focus on its application to histology images analyzed together with their associated patient data to extract information. This review offers a historical perspective and describes the potential clinical benefits from research and applications in this field, as well as significant obstacles to adoption. Best practices for implementing computational pathology workflows are presented. These include infrastructure considerations, acquisition of training data, quality assessments, as well as regulatory, ethical, and cyber-security concerns. Recommendations are provided for regulators, vendors, and computational pathology practitioners in order to facilitate progress in the field. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

An analysis of reflective writing early in the medical curriculum: The relationship between reflective capacity and academic achievement

Objective: To examine the relationship between reflection, gender, residency choice, word count, and academic achievement among medical students.

Methods: A modified version of the Reflection Evaluation for Learners’ Enhanced Competencies Tool (REFLECT) was developed and used for this study (Cronbach’s alpha of 0.86 with an intraclass correlation coefficient [ICC] of 0.68). This was applied to writing samples about professionalism in gross anatomy from first-year medical students between 2005 and 2011. Four analysts reviewed and scored written reflections independently. Composite reflection scores were compared with gender, residency choice, length of written reflection, NBME® Gross Anatomy and Embryology Subject Examination scores, and final gross anatomy course.

Results: Total of 319 written reflections were evaluated. Female students who pursued medicine specialties had the highest composite reflection scores (87 [27.2%]). Word count frequently correlated with reflection score (p?<?0.0001). Students who performed well on the NBME® Gross Anatomy and Embryology Subject Examination tended to achieve high anatomy course grades (p?<?0.0001). There was no statistically significant relationship between composite reflection scores and NBME® Gross Anatomy and Embryology Subject Examination scores (p?=?0.16) or anatomy course grades (p?=?0.90).

Conclusions: This study suggests there are likely no correlations between reflective capacity and academic performance on tests of medical knowledge administered early in the medical curriculum.     

Genetic and Environmental Variances of Bone Microarchitecture and Bone Remodeling Markers: A Twin Study

All genetic and environmental factors contributing to differences in bone structure between individuals mediate their effects through the final common cellular pathway of bone modeling and remodeling. We hypothesized that genetic factors account for most of the population variance of cortical and trabecular microstructure, in particular intracortical porosity and medullary size – void volumes (porosity), which establish the internal bone surface areas or interfaces upon which modeling and remodeling deposit or remove bone to configure bone microarchitecture. Microarchitecture of the distal tibia and distal radius and remodeling markers were measured for 95 monozygotic (MZ) and 66 dizygotic (DZ) white female twin pairs aged 40 to 61 years. Images obtained using high‐resolution peripheral quantitative computed tomography were analyzed using StrAx1.0, a nonthreshold‐based software that quantifies cortical matrix and porosity. Genetic and environmental components of variance were estimated under the assumptions of the classic twin model. The data were consistent with the proportion of variance accounted for by genetic factors being: 72% to 81% (standard errors ～18%) for the distal tibial total, cortical, and medullary cross‐sectional area (CSA); 67% and 61% for total cortical porosity, before and after adjusting for total CSA, respectively; 51% for trabecular volumetric bone mineral density (vBMD; all p < 0.001). For the corresponding distal radius traits, genetic factors accounted for 47% to 68% of the variance (all p ≤ 0.001). Cross‐twin cross‐trait correlations between tibial cortical porosity and medullary CSA were higher for MZ (r_MZ = 0.49) than DZ (r_DZ = 0.27) pairs before (p = 0.024), but not after (p = 0.258), adjusting for total CSA. For the remodeling markers, the data were consistent with genetic factors accounting for 55% to 62% of the variance. We infer that middle‐aged women differ in their bone microarchitecture and remodeling markers more because of differences in their genetic factors than differences in their environment. © 2014 American Society for Bone and Mineral Research.     

Clinical and histological evaluation of immediate-loaded posterior implants in nonhuman primates

PURPOSE: To evaluate a square-thread design implant and compare the bone-implant contact percentage between immediate-loaded and nonloaded implants (controls) in nonhuman primates. MATERIALS: Five nonhuman primates each received 3 implants, with a total of 5 control implants and 10 immediate-loaded implants in posterior regions of the mouth. Ninety days after surgery (and function was appropriate), block sections of the implants were removed and sectioned in 200-mum thick pieces. The block sections were stained with modified Masson for evaluation of the bone-implant contact percentage. RESULTS: One of the immediate-loaded implants failed. The bone-implant contact percentage of control implants ranged from 50.34% to 64.13% and averaged 56.3%. The bone-implant contact percentage of immediate-loaded implants ranged from 43.23% to 75.72%, with an average of 62.4%. Two implants had lower bone-implant contact percentage than the others, and when these are not included in the evaluation, the bone-implant contact percentage average increased to 67.6%. CONCLUSIONS: Immediate-loaded implants in the nonhuman primates often have a higher bone-implant contact percentage at 90 days than unloaded implants. The bone remodeling is different for loaded implant-bone interfaces than for unloaded conditions. However, 1 immediate-loaded implant failed, and 2 implants had lower bone-implant contact percentage than controls. Therefore, although there are benefits of immediate loading, there appear to also be some risks.