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EGFR-mutant lung adenocarcinoma transformation to squamous cell carcinoma appears to be a mechanism of acquired EGFR tyrosine kinase inhibitor (TKI) resistance. It is challenging for treatment, because the therapeutic strategies to adopt in these cases are still unclear. The prognosis after transformation is generally poor, and treatment is largely ineffective. This article is protected by copyright. All rights reserved.DISEASE OVERVIEW Epstein Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) is an entity included in the 2016 WHO classification of lymphoid neoplasms. https://www.selleckchem.com/products/Temsirolimus.html EBV+ DLBCL, NOS, is an aggressive B-cell lymphoma associated with chronic EBV infection, and a poor prognosis with standard chemotherapeutic approaches. DIAGNOSIS The diagnosis is made through a careful pathological evaluation. Detection of EBV-encoded RNA (EBER) is considered standard for diagnosis; however, a clear cutoff for positivity has not been defined. The differential diagnosis includes plasmablastic lymphoma (PBL), DLBCL associated with chronic inflammation and primary effusion lymphoma (PEL), among others. RISK-STRATIFICATION The International Prognostic Index (IPI) and the Oyama score can be used for risk-stratification. The Oyama score includes age >70 years and presence of B symptoms. The expression of CD30 and PD-1/PD-L1 are emerging as potential adverse but targetable biomarkers. MANAGEMENT Patients with EBV+ DLBCL, NOS, should be staged and managed following similar guidelines than patients with EBV-negative DLBCL. EBV+ DLBCL, NOS, however, might have a worse prognosis than EBV-negative DLBCL in the era of chemoimmunotherapy. There is an opportunity to study and develop targeted therapy in the management of patients with EBV+ DLBCL, NOS. © 2020 Wiley Periodicals, Inc.Estrogen toxicity has been an area of priority in aquatic toxicology over the last 20 years. Currently, the estrogen toxicity is primarily linked to classical estrogen signalling, ERα and ERβ, interaction. Recent evidence has indicated that a rapid, non-genomic, non-classical estrogen signaling pathway exists via the G protein coupled estrogen receptor (GPER). GPER is expressed in many biological systems, with roles in the cardiovascular system. The objective of this research was to investigate the effect of 17α-ethinylestradiol (EE2) on the heart rate of embryonic Japanese medaka (Oryzias latipes). A significant decrease (bradycardia) in embryonic heart rate was observed in all treatment concentrations (0.1 ng/L, 1 ng/L, 10 ng/L, 100 ng/L, and 1000 ng/L EE2) at 144 hpf, 168 hpf, and 192 hpf (P≤0.05). While 120 hpf and 216 hpf embryos experienced a significant a decrease from the control at 10 ng/L, 100 ng/L, and 1000 ng/L EE2, and 0.1 ng/L, 100 ng/L, and 1000 ng/L EE2 respectively (P≤0.05). Additionally, using select estrogen receptor modulators (ERMs) it was demonstrated that estrogen induced bradycardia appears to be linked to GPER and not ERα and ERβ. This research highlights GPER as a novel and alternative mode of action for EE2 toxicity at environmentally relevant concentrations. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.BACKGROUND Current web-based educational approaches about living kidney donation (LKD) are complex, lengthy, and/or text-laden, which may impair accurate interpretation of information, thereby limiting kidney transplant access. PURPOSE This paper describes the process of developing animation-based LKD education designed to be suitable for and acceptable to kidney transplant candidates and their support networks. METHODS Based on formative work, early animation prototypes were designed by a transplant surgeon and a health communication expert. In qualitative focus groups and individual interviews, animation prototypes were shown to 46 kidney transplant recipients, 28 kidney transplant candidates, 32 previous or potential kidney donors, 10 caregivers, 32 transplant providers, 24 dialysis providers, and 4 cultural and community advisors for their input regarding animation suitability, acceptability, and potential usability/feasibility. Viewer feedback was used to iteratively refine the animations. Animation design to facilitate adult learning was guided by elaboration theory, Bandura's self-efficacy theory, and Mayer's cognitive theory of multimedia learning. RESULTS KidneyTIME currently consists of 12 animations about LKD process, benefits, and risks. CONCLUSIONS Patients/friends/family members, experts, and stakeholders provided valuable feedback to the research team that was integrated into the development of KidneyTIME with the goal of enhancing suitability, acceptability, engagement, usability, and feasibility of dissemination. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.Many obese patients are exposed to hypolipidemic and serotonin-norepinephrine reuptake inhibitor (SNRI) drugs. Statins are one of the most marketed drugs in the world to treat dyslipidemia, while sibutramine, a SNRI drug, is prescribed in some countries to treat obesity and is detected as an additive in many adulterated weight loss supplements marketed worldwide. Previous studies reported adverse effects of isolated exposure to these drugs on male rat reproductive parameters. In the present work, we further investigated male reproductive toxicity of these drugs, administered in isolation or combination in adult rats for a longer period of treatment. Adult male rats (90 days) were treated (gavage) for 70 days with saline and dimethyl sulfoxide (control), sibutramine (10 mg/kg), rosuvastatin (5 mg/kg), or rosuvastatin combined with sibutramine. Sibutramine alone or with rosuvastatin, promoted a reduction in food intake and body weight gain, weight of the epididymis, ventral prostate and seminal vesicle; as well as decreased sperm reserves and transit time through the epididymis; androgen depletion; and increased index of cytoplasmic droplet. The rosuvastatin-treated group showed reduced frequency of ejaculation. Exposure to this drug alone or combined with sibutramine impaired epididymal morphology. Co-exposed rats had altered epididymal morphometry, and seminal vesicle and testis weights. The rats also showed decreased fertility after natural mating and a trend toward a delay in ejaculation, suggesting a small synergistic effect of these drugs. Given the greater reproductive efficiency of rodents, the results obtained in the present study raise concern regarding possible fertility impairment in men taking statins and SNRI drugs. © 2020 John Wiley & Sons, Ltd.Performing toxicity testing on multiple species with differing degrees of evolutionary relatedness can provide important information on how chemical sensitivity varies among species and can help pinpoint the biological drivers of species sensitivity. Such knowledge could ultimately be used to design better multi-species predictive ecological risk assessment models and identify particularly sensitive species. However, laboratory toxicity tests involving multiple species can also be resource intensive, especially when each species has unique husbandry conditions. Here, we perform lethality tests with two metals, copper chloride and zinc chloride, on five different nematode species, which are nested in their degree of evolutionary relatedness Caenorhabditis briggsae, Caenorhabditis elegans, Oscheius myriophila, Oscheius tipulae, and Pristionchus pacificus. All species were successfully cultured and tested concurrently with limited resources, demonstrating that inexpensive, multi-species nematode toxicity testing systems are achievable. The results indicate that P. pacificus is most sensitive to both metals. Conversely, C. elegans was the least sensitive species to copper, but the second most sensitive to zinc, indicating that species relationships do not necessarily predict species sensitivity. Toxicity testing with additional nematode species and types of chemicals is feasible and will help form more generalizable conclusions about relative species sensitivity. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.OBJECTIVE Clinical trials in amyotrophic lateral sclerosis (ALS) continue to rely on survival or functional scales as endpoints, despite the emergence of quantitative biomarkers. Neuroimaging-based biomarkers in ALS have been shown to detect ALS-associated pathology in vivo, although anatomical patterns of disease spread are poorly characterized. The objective of this study is to simulate disease propagation using network analyses of cerebral magnetic resonance imaging (MRI) data to predict disease progression. METHODS Using brain networks of ALS patients (n = 208) and matched controls across longitudinal time points, network-based statistics unraveled progressive network degeneration originating from the motor cortex and expanding in a spatiotemporal manner. We applied a computational model to the MRI scan of patients to simulate this progressive network degeneration. Simulated aggregation levels at the group and individual level were validated with empirical impairment observed at later time points of white matter and clinical decline using both internal and external datasets. RESULTS We observe that computer-simulated aggregation levels mimic true disease patterns in ALS patients. Simulated patterns of involvement across cortical areas show significant overlap with the patterns of empirically impaired brain regions on later scans, at both group and individual levels. These findings are validated using an external longitudinal dataset of 30 patients. INTERPRETATION Our results are in accordance with established pathological staging systems and may have implications for patient stratification in future clinical trials. Our results demonstrate the utility of computational models in ALS to predict disease progression and underscore their potential as a prognostic biomarker. ANN NEUROL 2020. © 2020 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.Medical technologies of various kinds play an increasingly important role in medical treatment, but may also increase health inequalities if they are primarily used by high-status patients. While many have problematised inequalities in the material access to medical technologies, differences in use and perception are also salient for explaining the relationship between medical technologies and health inequalities. This article attempts to theorise these inequalities by bringing health inequality research into dialogue with social constructivist perspectives on user-technology relations. Based on qualitative interview data from a case study of the technological self-management of type 1 diabetes, I construct three clusters of technological practices and perceptions corresponding to three broad user types. These user types are then discussed in the context of patient empowerment and the promotion of the active, autonomous and self-reflective 'expert' patient in European health care systems. To the extent that they materialise and enforce institutional expectations which only the most resourceful patients will be able to live up to, medical technologies may serve to entrench and legitimate social inequalities in health and medical care. Research therefore needs not only to consider how medical technologies are distributed, but also their design and appropriation by users. © 2020 The Author. Sociology of Health & Illness published by John Wiley & Sons Ltd on behalf of Foundation for SHIL.
