Notes

Gene along with miRNA phrase adjustments to squamous cell carcinoma involving larynx and hypopharynx.
The purpose of the meeting was to develop international expert consensus recommendations on the use of such tumour-agnostic treatments in patients with solid tumours. The aim was to generate a reference document for clinical practice, for pharmaceutical companies in the design of clinical trials, for ethics committees in the approval of clinical trial protocols and for regulatory authorities in relation to drug approvals, with a particular emphasis on diagnostic testing and patient selection. BACKGROUND Aspirin has been associated with a reduced risk of colorectal cancer, and possibly of a few other digestive tract cancers. find more The quantification of risk reduction and the optimal dose and duration of aspirin use for the prevention of colorectal and other digestive tract cancers remains unclear. METHODS To provide an up-to-date quantification of this association, we conducted a systematic review and meta-analysis of all observational studies on aspirin and cancers of the digestive tract sites published through March 2019. We estimated the pooled relative risk (RR) of cancer for regular aspirin use versus non-use using random-effects models, and, whenever data were available, we investigated the dose- and duration-risk relations. RESULTS Regular aspirin use is associated with a reduced risk of colorectal cancer [RR = 0.73, 95% confidence interval (CI) = 0.69-0.78, 45 studies], squamous-cell esophageal cancer (RR = 0.67, 95% CI = 0.57-0.79, 13 studies), adenocarcinoma of the esophagus and gastric cardia some rare ones. The favorable effect of aspirin increases with longer duration of use, and, for colorectal cancer, with increasing dose. Physiological equilibrium in the retina depends on coordinated work between rod and cone photoreceptors and can be compromised by the expression of mutant proteins leading to inherited retinal degeneration (IRD). IRD is a diverse group of retinal dystrophies with multifaceted molecular mechanisms that are not fully understood. In this review, we focus on the contribution of chronically activated unfolded protein response (UPR) to inherited retinal pathogenesis, placing special emphasis on studies employing genetically modified animal models. As constitutively active UPR in degenerating retinas may activate pro-apoptotic programs associated with oxidative stress, pro-inflammatory signaling, dysfunctional autophagy, free cytosolic Ca2+ overload, and altered protein synthesis rate in the retina, we focus on the regulatory mechanisms of translational attenuation and approaches to overcoming translational attenuation in degenerating retinas. We also discuss current research on the role of the UPR mediator PERK and its downstream targets in degenerating retinas and highlight the therapeutic benefits of reprogramming PERK signaling in preclinical animal models of IRD. Finally, we describe pharmacological approaches targeting UPR in ocular diseases and consider their potential applications to IRD. link2 BACKGROUND Under the Affordable Care Act, states were given the option to expand Medicaid in 2014. By the end of 2014, 32 states had opted to expand Medicaid while 19 did not. Previous quasi-experimental studies took advantage of this state-specific policy implementation and found increased insurance coverage in expansion compared to non-expansion states. With longer-term data now available, we studied the effect of Medicaid expansion on changes in insurance coverage and mammography rates in expansion and non-expansion states. STUDY DESIGN Seven states which expanded Medicaid eligibility in 2014 and six non-expansion states were selected based on available data. The U.S. Census American Community Survey was queried for insurance coverage from 2011-2016 and the Centers for Disease Control and Prevention Behavioral Risk Factor Surveillance System from 2010-2018. Difference-in-difference linear mixed models were used to estimate and compare insurance coverage and screening mammogram rates between expansion and non-expansion states before and after 2014. RESULTS The increase in insurance rates for all persons covered by some type of health insurance after Medicaid expansion was significantly different in expansion than non-expansion states (p=0.001). The increase in Medicaid coverage was significant in expansion compared to non-expansion states (p less then 0.001). A similar trend was seen in screening mammogram rates in women from low income households in expansion versus non-expansion states (p=0.049). CONCLUSION Medicaid expansion states saw greater improvement in total insurance and Medicaid coverage, and in mammogram rates in lower income women, when compared to non-expansion states after Medicaid legislation was passed. Our study demonstrates that people do take advantage of expanded eligibility by acquiring insurance and this may improve access to preventive measures such as screening mammography. BACKGROUND Previously, we demonstrated that lumpectomy (L) patients reported higher appearance satisfaction (AS), appreciation of a pleasurable breast caress (PBC), and persistence of the breast during intimacy (BI) than mastectomy with reconstruction (MR) which we used to describe breast specific sensuality (BSS). Our current objective is to compare BSS between L and nipple-sparing mastectomy (NSM). DESIGN An anonymous, cross-sectional survey was distributed to breast cancer survivors between 2014 and 2016. Eligible patients underwent surgery between 2000 and 2014, were >18 years old, English speaking, and >1 year past surgery. Demographics, treatment details, Female Sexual Function Index metrics, and investigator generated questions regarding AS and BSS were collected. RESULTS Of the 600 women who participated, 585 surveys were eligible. Surgical modality was reported as L by 406 (69.4%), mastectomy alone (M) by 50 (8.5%), and MR by 129 (22.1%). link3 Nipple preservation data was available for 47 of 129 (36.4%) of MR, with 21 NSM and 26 non-nipple-sparing mastectomy (nNSM). Favorable post-operative AS was reported by 76.2% of L and 71.4% of NSM (p=0.039). L was more comfortable being seen undressed than NSM (82.4% vs. 71.4%, p=0.0003). The chest remained a part of intimacy for 65.4% of L vs. 42.9% of NSM (p=0.0009). PBC was reported more frequently by L than NSM (66.2% vs. 20%, p= less then 0.0001). The breast caress was unpleasant for 40% of NSM, nearly four-fold higher than L (11.3%, p less then 0.0001). CONCLUSION NSM was significantly less satisfied with appearance, less comfortable being seen undressed, had decreased persistence of breast intimacy, and experienced a less pleasurable breast caress than lumpectomy. Counseling patients regarding these findings will empower informed decision making, optimize expectations, and may enhance postoperative satisfaction. BACKGROUND Hepatocellular carcinoma (HCC) constitutes 0.5% of childhood malignancies and exhibits poor prognosis. Complete tumor extirpation either by partial liver resection (LR) or liver transplantation (LT) is the only curative treatment. Due to the poor initial outcomes of LT, LR has remained the mainstay of treatment for all but select children fulfilling the Milan criteria (originally designed for adults). METHODS Retrospective cohort study of pediatric HCC patients ( less then 18 years) registered in the Surveillance, Epidemiology, and End Results database between 2004-2015. Survival analysis was performed by means of Kaplan-Meier methods, two-sided stratified log-rank tests, and Cox regression models. RESULTS Out of 127 children with HCC, 46 did not undergo surgery (36.2%), 32 underwent LT (25.2%), and 49 underwent LR (38.6%). Using Kaplan-Meier method, the 5-year cancer-specific survival (CSS) rates for LT and LR were 87%, and 63%, respectively. LT exhibited superior CSS vs. LR (log-rank, P=0.007). For T1 stage, LT showed equivalent CSS when compared to LR (log-rank, P=0.23), while for T2 and T3 stage, LT exhibited superior CSS (log-rank, P=0.047, and P=0.01, respectively). On multivariable Cox regression model, T3/T4 stage (adjusted HR 13.63, 95%CI 2.9-64.07; P=0.001), and LR (adjusted HR 7.51, 95%CI 2.07-27.29; P=0.002) were found to be independently associated with cancer-specific mortality. Fibrolamellar histology and lymph node status were not found to be associated with mortality. CONCLUSIONS Our findings suggest that children diagnosed with non-metastatic advanced-stage HCC shows a favorable prognosis after LT when compared to LR. Early inclusion of a LT consultation after initial diagnosis is warranted, especially in children with unresectable HCC or when complete tumor extirpation with LR is not feasible. Embryonic diapause is a conserved reproductive strategy in which development arrests at the blastocyst phase. Recently mammalian target of rapamycin (mTOR) inhibition was shown to induce diapause on mouse blastocysts and a paused-like state on mouse embryonic stem cells (mESCs). In this work, we aimed to further characterize this new paused-pluripotent state, focusing on its glycolytic and oxidative metabolic function. We therefore exposed mESCs, to the mTOR inhibitor INK-128 and evaluated proliferation, pluripotency status and energy-related metabolism, as well as the mTOR inhibition status and translational function. Unexpectedly, in our hands INK-128 did not inhibit the phosphorylation of mTOR or its downstream targets after 48 h. Accordingly, no alterations on protein translational function were observed. Nonetheless, INK-128 could still successfully induce a paused-like state in naïve mESCs regardless of their culturing conditions, by greatly slowing proliferation without affecting pluripotency status. This effect was more prevalent in 2i cultured cells. Interestingly, in this paused-like state, mESCs present a glucose-related hypometabolic profile, which is a hallmark of diapaused blastocysts, with decreased glycolytic and oxidative metabolism and decreased nutrient uptake. Despite the lack of mTOR inhibition and translational suppression, INK-128 still induced a paused-like pluripotent state through cell cycle and metabolic modulation, rather than by translational suppression, suggesting more than one avenue for this type of pluripotent phenotype. BACKGROUND In recent years, there has been a growing interest in the formation of copolymer-lipid hybrid self-assemblies, which allow combining and improving the main features of pure lipid-based and copolymer-based systems known for their potential applications in the biomedical field. As the most common method used to obtain giant vesicles is electroformation, most systems so far used low Tg polymers for their flexibility at room temperature. METHODS Copolymers used in the hybrid vesicles have been synthesized by a modified version of the ATRP, namely the Activators ReGenerated by Electron Transfer ATRP and characterized by NMR and DSC. Giant hybrid vesicles have been obtained using electroformation and droplet transfer method. Confocal fluorescence microscopy was used to image the vesicles. RESULTS Electroformation enabled to obtain hybrid vesicles in a narrow range of compositions (15 mol% was the maximum copolymer content). This range could be extended by the use of a droplet transfer method, which enabled obtaining hybrid vesicles incorporating a methacrylate-based polymer in a wide range of compositions.
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