Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00306932607174,00302841026182,alsfakia@gmail.com
Mastectomy skin flap necrosis poses significant challenges to both patients and surgeons, potentially resulting in clinical and psychological comorbidities, delays in adjuvant therapy, and increased health care costs. The Breast Reconstruction Risk Assessment Score was expanded to estimate complication risk after tissue expander placement up to 1 year postoperatively.
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Planta Med
DOI: 10.1055/a-0626-7426
Cardamonin exhibits a variety of pharmacological activities including anti-inflammatory and antitumor, which are correlated with the inhibition of nuclear factor-kappaB and the mammalian target of rapamycin, respectively. However, whether the anti-inflammatory effects of cardamonin are mediated by the mammalian target of rapamycin remains unknown. In this study, ovarian cancer SKOV3 cells were cultured with lipopolysaccharide to induce inflammation, and the inhibitory effects and underlying molecular mechanisms of cardamonin were investigated using specific inhibitors of the mammalian target of rapamycin and the nuclear factor-kappaB pathway (rapamycin and pyrrolidine dithiocarbamate, respectively). Our results indicated that cardamonin inhibited the viability of normal and lipopolysaccharide-pretreated SKOV3 cells in a concentration-dependent manner. In accordance with rapamycin, the activation of the mammalian target of rapamycin and its downstream target, ribosomal protein S6 kinase 1, was inhibited by cardamonin, while pyrrolidine dithiocarbamate substantially blocked nuclear factor-kappaB activation and mildly inhibited the phosphorylation of the mammalian target of rapamycin and ribosomal protein S6 kinase 1. Pretreated with pyrrolidine dithiocarbamate, the effect of cardamonin on the mammalian target of rapamycin signalling was not affected, but the expression of inflammatory factors was further reduced. In cells pretreated with rapamycin, the inhibitory effects of cardamonin were completely suppressed with regards to the phosphorylation of the mammalian target of rapamycin, ribosomal protein S6 kinase 1, TNF-α, and interleukin-6, and nuclear factor-kappaB p65 protein expression was decreased. In conclusion, our findings indicate that the anti-inflammatory effects of cardamonin are correlated with mammalian target of rapamycin inhibition.
[…]
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
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On May 11, 2018, the US administration released American Patients First, its blueprint for cutting drug prices and reducing out-of-pocket payments. “Other countries use socialised health care to command unfairly low prices from US drug makers”, stated the White House, in an accompanying briefing. “This places the burden of financing drug development largely on American patients and taxpayers”.
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We, the editors of surgery journals, believe that conducting sex-inclusive biomedical and clinical research is imperative to improving health outcomes of men and women. Recent studies have shown that the majority of biomedical research in the field of surgery and related topics is conducted on male animals and male cells, even when studying diseases prevalent in women.1 Human clinical research suffers from a lack of sex-based reporting and sex-based analysis of the results.2,3 Given these findings, the National Institutes of Health (NIH) has now asked that sex be considered as a biologic variable in all NIH-funded research.
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The intricacy of different organs and tissues, along with confounding factors linked with disease or trauma fundamentally requiring repair, is a challenge for regenerative medicine. Biomaterials, cells and growth factors are used to design a construct for tissue replacement but not all tissues are same architecturally or functionally (1). New manufacturing techniques that fall under the banner of 3D printing enables designing of construct architecturally closer to native tissue (2). These techniques allow fabrication of tubular tissues (heart, urethra, blood vessel), viscus organs (pancreas) and solid system (bones) to be printed in the lab (3-4).
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Purohit, in the Indian religious context (Hindu), means priest. Purohits are professional voice users who use their voice while performing regular worships and rituals in temples and homes. Any deviations in their voice can have an impact on their profession. Hence, there is a need to investigate the voice characteristics of purohits using perceptual and acoustic analyses. (Source: Journal of Voice)
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We report a case of sudden-onset vocal tremor that impeded a young professional singer’s ability to perform and record her album. The etiology was determined to be a medication side effect of lamotrigine; a reaction that has not been previously reported. (Source: Journal of Voice)
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Publication date: Available online 17 May 2018
Source:Cell Stem Cell
Author(s): Anna M. Nicholson, Cora Olpe, Alice Hoyle, Ann-Sofie Thorsen, Teja Rus, Mathilde Colombé, Roxanne Brunton-Sim, Richard Kemp, Kate Marks, Phil Quirke, Shalini Malhotra, Rogier ten Hoopen, Ashraf Ibrahim, Cecilia Lindskog, Meagan B. Myers, Barbara Parsons, Simon Tavaré, Mark Wilkinson, Edward Morrissey, Douglas J. Winton
We investigated the means and timing by which mutations become fixed in the human colonic epithelium by visualizing somatic clones and mathematical inference. Fixation requires two sequential steps. First, one of approximately seven active stem cells residing within each colonic crypt has to be mutated. Second, the mutated stem cell has to replace neighbors to populate the entire crypt in a process that takes several years. Subsequent clonal expansion due to crypt fission is infrequent for neutral mutations (around 0.7% of all crypts undergo fission in a single year). Pro-oncogenic mutations subvert both stem cell replacement to accelerate fixation and clonal expansion by crypt fission to achieve high mutant allele frequencies with age. The benchmarking of these behaviors allows the advantage associated with different gene-specific mutations to be compared irrespective of the cellular mechanisms by which they are conferred.
Winton and colleagues describe stem cell dynamics in normal human colon to identify the efficiency of clone fixation within the epithelium and the rate of subsequent lateral expansion. Against these benchmarks biased stem cell behaviors advantaged in both fixation and expansion can be quantified to predict the age-related burden of pro-oncogenic mutation.
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Publication date: Available online 17 May 2018
Source:Cell Stem Cell
Author(s): Stefan M. Czerniecki, Nelly M. Cruz, Jennifer L. Harder, Rajasree Menon, James Annis, Edgar A. Otto, Ramila E. Gulieva, Laura V. Islas, Yong Kyun Kim, Linh M. Tran, Timothy J. Martins, Jeffrey W. Pippin, Hongxia Fu, Matthias Kretzler, Stuart J. Shankland, Jonathan Himmelfarb, Randall T. Moon, Neal Paragas, Benjamin S. Freedman
Organoids derived from human pluripotent stem cells are a potentially powerful tool for high-throughput screening (HTS), but the complexity of organoid cultures poses a significant challenge for miniaturization and automation. Here, we present a fully automated, HTS-compatible platform for enhanced differentiation and phenotyping of human kidney organoids. The entire 21-day protocol, from plating to differentiation to analysis, can be performed automatically by liquid-handling robots, or alternatively by manual pipetting. High-content imaging analysis reveals both dose-dependent and threshold effects during organoid differentiation. Immunofluorescence and single-cell RNA sequencing identify previously undetected parietal, interstitial, and partially differentiated compartments within organoids and define conditions that greatly expand the vascular endothelium. Chemical modulation of toxicity and disease phenotypes can be quantified for safety and efficacy prediction. Screening in gene-edited organoids in this system reveals an unexpected role for myosin in polycystic kidney disease. Organoids in HTS formats thus establish an attractive platform for multidimensional phenotypic screening.
Organoids derived from human iPSCs have great potential for drug screening, but their complexity poses a challenge for miniaturization and automation. Freedman and colleagues establish a robotic pipeline to manufacture and analyze kidney organoids in microwell arrays. They apply this system to improve differentiation, measure toxicity, and comprehend disease.
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Publication date: Available online 17 May 2018
Source:Cell Stem Cell
Author(s): David Petrik, Michael H. Myoga, Sofia Grade, Niklas J. Gerkau, Melanie Pusch, Christine R. Rose, Benedikt Grothe, Magdalena Götz
One hallmark of adult neurogenesis is its adaptability to environmental influences. Here, we uncovered the epithelial sodium channel (ENaC) as a key regulator of adult neurogenesis as its deletion in neural stem cells (NSCs) and their progeny in the murine subependymal zone (SEZ) strongly impairs their proliferation and neurogenic output in the olfactory bulb. Importantly, alteration of fluid flow promotes proliferation of SEZ cells in an ENaC-dependent manner, eliciting sodium and calcium signals that regulate proliferation via calcium-release-activated channels and phosphorylation of ERK. Flow-induced calcium signals are restricted to NSCs in contact with the ventricular fluid, thereby providing a highly specific mechanism to regulate NSC behavior at this special interface with the cerebrospinal fluid. Thus, ENaC plays a central role in regulating adult neurogenesis, and among multiple modes of ENaC function, flow-induced changes in sodium signals are critical for NSC biology.
Stem cells need to adapt to signals from the environment to regulate their output. Here, we show the key role of a flow-sensitive ion channel in regulating the activation of adult neural stem cells and their output.
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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00306932607174,00302841026182,alsfakia@gmail.com 