Sanderrosendahl3037

Debates in fields studying the biological aspects of aging and longevity, such as biogerontology, are often split between 'anti-aging' approaches aimed largely at treating diseases and those focusing more on maintaining, promoting, and even enhancing health. However, it is far from clear what this 'health' is that would be maintained, promoted, or enhanced. Interestingly, what few have yet to fully reflect on is that there is still no theory of health within the health or aging sciences that would provide an integrative explanatory framework akin to other scientific theories. After clarifying why such a theory could be useful, I discuss five general features of medical theories that could be used to evaluate the utility of a given proposal. With these features in hand, I suggest that philosophers and scientists work together on analyzing actual medical research (experimental analysis), and the ways in which a theoretical construct of 'health' is being progressively identified and measured therein. I conclude by suggesting that research fields studying stress and aging might be particularly helpful in developing candidates for theory construction due to their broad scope, increasing specificity, and potential for providing integrative explanations.NK cells have been seen as potential agents in adoptive immunotherapy for cancer. The main challenge for the success of this approach is to obtain a great quantity of activated NK cells for adoptive transfer. The present study had aimed to evaluate the effect of a feeder layer of irradiated MSCs in the in vitro expansion of NK cells. MSCs were obtained from the bone marrow (BM) cells remaining in the bag and filter used in the transplantation of hematopoietic stem cells. NK cells were obtained from peripheral blood (PB) of healthy volunteers. NK expansion and activation were stimulated by culture with artificial antigen-presenting cells (aAPCs) and IL-2, in the presence or absence of BM-MSCs. NK cell proliferation, phenotypic expression and cytotoxic activity were evaluated. Both culture conditions showed high NK purity with predominance of NK CD56brightCD16+ subset post expansion. However, cultures without the presence of MSCs showed higher NK proliferation, expression of activation markers (CD16 and NKG2D) and related cytotoxic activity. In this experimental study, the presence of a feeder layer of irradiated BM-MSCs interfered negatively in the expansion of PB-NKs, limiting their growth and activation. Further investigation is needed to understand the mechanisms of NK-MSC interaction and its implications.Epithelial cells form continuous sheets of cells that exist in tensional homeostasis. Homeostasis is maintained through cell-to-cell junctions that distribute tension and balance forces between cells and their underlying matrix. Disruption of tensional homeostasis can lead to epithelial-mesenchymal transition (EMT), a transdifferentiation process in which epithelial cells adopt a mesenchymal phenotype, losing cell-cell adhesion and enhancing cellular motility. This process is critical during embryogenesis and wound healing, but is also dysregulated in many disease states. To further understand the role of intercellular tension in spatial patterning of epithelial cell monolayers, we developed a multicellular computational model of cell-cell and cell-substrate forces. This work builds on a hybrid cellular Potts model (CPM)-finite element model to evaluate cell-matrix mechanical feedback of an adherent multicellular cluster. Cellular movement is governed by thermodynamic constraints from cell volume, cell-cell and cell-matrix contacts, and durotaxis, which arises from cell-generated traction forces on a finite element substrate. Junction forces at cell-cell contacts balance these traction forces, thereby producing a mechanically stable epithelial monolayer. Simulations were compared to in vitro experiments using fluorescence-based junction force sensors in clusters of cells undergoing EMT. Results indicate that the multicellular CPM model can reproduce many aspects of EMT, including epithelial monolayer formation dynamics, changes in cell geometry, and spatial patterning of cell-cell forces in an epithelial tissue.Terpenoids, one of the major components of essential oils, are known to exert potent antifungal activity against yeast Saccharomyces cerevisiae. They have been the subject of a considerable number of investigations that uncovered extensive pharmacological properties, including antifungal and antibacterial effects. However, their mechanism of action remains elusive. In order to use terpenoids as the antimicrobial and antifungal agents in food preservation in a rational way, a good knowledge of their mode of action is required. We hypothesized that the cellular membrane is the main target site for the antifungal agents, and that structural properties of these agents are key to penetrate and act upon phospholipid bilayers. In this study, we thus aimed to study the effect of terpenoids on the cell membrane integrity, with the focus on both their structural properties, such as the presence of aromatic ring or hydroxyl group; and their hydrophobicity, as a consequence of these structural features. We first uncovered the antifungal properties of phenolic terpenoids thymol, carvacrol and eugenol, cyclic terpenes limonene, carveol, and α-pinene, in addition to the closely related compounds of different chemical structures. We then examined the cell membrane deterioration upon the addition of these reagents. Our results demonstrate that the presence of a phenolic -OH moiety is crucial, and hydrophobicity gained by the aromatic ring structure contributes to the ability of penetration and damaging yeast plasma membrane to achieve high antifungal activity.PURPOSE OF REVIEW This review highlights recent work that will lead to near-term advances in the understanding and treatment of gastroparesis (Gp). RECENT FINDINGS Major current advancements in the pathophysiology of Gp, include recognition of the SIP syncytium as the pacemaking unit rather than ICC alone and that Gp may be part of a pan-enteric autoimmune and/or autonomic disorder with macrophage imbalance. The development of newer techniques to assess gastric emptying (gastric emptying breath test and wireless motility capsule) and pyloric distensibility (EndoFLIP®) are allowing clinicians better characterization of their patients. In addition to pharmaceutical compounds in the pipeline, neuromodulation and endosurgical techniques, such as G-POEM, may help address refractory Gp. We expect that the 2020 decade will witness exciting developments. Treatments targeting gastrointestinal motility, immunological dysfunction, and inflammatory mediators will be evaluated. We anticipate future studies will be guided by biomarkers correlated with patient outcomes and therapeutic efficacy to establish new paradigms in the management of Gp.PURPOSE OF REVIEW The purpose is to provide a review of cross-sectional imaging updates in the assessment of gastrointestinal diseases, relevant to clinical practice and research. RECENT FINDINGS New magnetic resonance imaging contrast agents (Eovist) are taken up by hepatocytes and excreted via the biliary tree. As such, a lesion will retain contrast only if hepatocytes are present, which aids in refining the differential diagnosis. Magnetic resonance enterography is a method for non-invasively diagnosing and following various GI conditions, predominantly inflammatory bowel disease. Contrast-enhanced ultrasound uses gas-filled microbubbles providing superb temporal resolution most notably in the arterial phase, which aids in differentiating lesions. Elastography is a new technique which assesses stiffness of liver for evaluating fibrosis. These new techniques provide more accurate diagnoses and information, often limiting ionizing radiation exposure from other modalities. While ultrasound will still remain the initial imaging modality, familiarity with these other options is valuable for appropriate pathology workup.Biochemical analysis of creatine kinase MB (CK-MB), which is a biomarker of myocardial damage, is used as a potential adjunct test in clinical and forensic medicine. However, there is no previous meta-analysis that summarizes the diagnostic value of postmortem biochemical analysis of CK-MB in cardiac death. The purpose of this study was to perform a systematic literature review and meta-analysis of postmortem CK-MB in cardiac death for forensic work. Six online databases, including PubMed, Embase, Cochrane Library, the China National Knowledge Infrastructure (CNKI), the China Biomedical Literature Database (CBM), and Wanfang Data, were used to search for related studies. The quality of the included literature was assessed according to the Newcastle-Ottawa Quality Assessment Scale (NOS). The meta-analysis was performed by Review Manager version 5.3 software to investigate the diagnostic role of postmortem CK-MB in cardiac death, especially in myocardial infarction. Sixteen pieces of related literature were identified, all of which were considered high quality. The results of the meta-analysis revealed that the postmortem CK-MB level in the pericardial fluid was significantly higher in the cardiac death group with a standard mean difference (SMD) = 0.63, 95% confidence interval (CI) = 0.09~1.17, p = 0.02. This was also the result in the myocardial infarction group (SMD = 0.83, 95% CI = 0.10~1.56, p = 0.03). No significant difference in CK-MB was found in serum for cardiac death (SMD = -0.31, 95% CI = -0.85~0.24, p = 0.27) or myocardial infarction (SMD = -0.10, 95% CI = -0.69~0.49, p = 0.74). The postmortem biochemical analysis of CK-MB in the pericardial fluid can be used as an auxiliary method in the postmortem diagnosis of cardiac death, along with autopsy and histological investigation.INTRODUCTION Evidence on the association between diabetes and risk of bladder cancer has been controversial. In addition, findings on the associations between duration of diabetes, diabetes treatment, and risk of bladder cancer have been inconsistent. METHODS A total of 148,208 participants in Women's Health Initiative study were included. Information on diabetes status, diabetes duration, and treatment was collected both at baseline and during follow-up. Information on potential confounders including age, race/ethnicity, education, occupation, family history of cancer, smoking status, alcohol consumption, total physical activity, body mass index, and daily dietary intake were collected at baseline. Bladder cancer cases were collected and confirmed by a centralized review of pathology reports. Cox proportional hazard models with time-varying covariates were used to examine associations of diabetes status, duration of diabetes, and diabetes treatment with bladder cancer risk. RESULTS During a median follow-up of 18.5 years, 865 bladder cancer cases were identified. There were no significant associations of diabetes, duration of diabetes, or diabetes treatment with risk of bladder cancer. Participants with prevalent diabetes did not have significantly higher risk of bladder cancer compared with those without diabetes. Pitstop 2 molecular weight CONCLUSION Diabetes was not significantly associated with risk of bladder cancer among postmenopausal women.