Use of gene expression profiling to identify candidate genes for pretherapeutic patient classification in acute appendicitis

Background: Phlegmonous and gangrenous appendicitis represent independent pathophysiological entities with different clinical courses ranging from spontaneous resolution to septic disease. However, reliable predictive methods for these clinical phenotypes have not yet been established. In an attempt to provide pathophysiological insights into the matter, a genomewide gene expression analysis was undertaken in patients with acute appendicitis. Methods: Peripheral blood mononuclear cells were isolated and, after histological confirmation of PA or GA, analysed for genomewide gene expression profiling using RNA microarray technology and subsequent pathway analysis. Results: Samples from 29 patients aged 7–17 years were included. Genomewide gene expression analysis was performed on 13 samples of phlegmonous and 16 of gangrenous appendicitis. From a total of 56 666 genes, 3594 were significantly differently expressed. Distinct interaction between T and B cells in the phlegmonous appendicitis group was suggested by overexpression of T cell receptor α and β subunits, CD2, CD3, MHC II, CD40L, and the B cell markers CD72 and CD79, indicating an antiviral mechanism. In the gangrenous appendicitis group, expression of genes delineating antibacterial mechanisms was found. Conclusion: These results provide evidence for different and independent gene expression in phlegmonous and gangrenous appendicitis in general, but also suggest distinct immunological patterns for the respective entities. In particular, the findings are compatible with previous evidence of spontaneous resolution in phlegmonous and progressive disease in gangrenous appendicitis

A metilglioxál metabolizmus szerepe 2-es típusú cukorbetegségben és szövődményeiben = The Role of Methylglyoxal Metabolism in Type-2 Diabetes and Its Complications

Az átmeneti, illetve a tartós hyperglykaemia következménye a sejten belüli reaktív oxigéngyökök mellett a reaktív aldehidek felszaporodása. A reaktív aldehidek kóroki tényezőként szerepelhetnek a cukorbetegség késői szövődményeinek kialakulásában. Ezen csoportból kiemelkedő jelentőséggel bír a glükózfüggő α-dikarbonil, a metilglioxál. Elsőként cukorbetegségben igazolták a metilglioxál sejten belüli felhalmozódását és a szérumszint emelkedését. A felhalmozódó metilglioxál káros hatással bír a hasnyálmirigy β-sejtjeinek inzulintermelésére, a fehérjék és nukleinsavak működésére, valamint az egyik legfontosabb prekurzora a késői glikációs végtermékeknek (advanced glycation end-products). A metilglioxál-akkumuláció elleni védelmet jelentő katabolikus rendszer, a glioxaláz enzimrendszer minden emlőssejtben megtalálható. Jelen közlemény áttekintést ad a metilglioxál anyagcseréjéről normális, valamint hyperglykaemiás körülmények között, és tárgyalja a metilglioxál szerepét a diabeteses késői, microvascularis szövődmények kórélettanában. Transient or chronic hyperglycaemia increases the formation of intracellular reactive oxygen species and aldehydes. The accumulation of reactive aldehydes is implicated in the development of diabetic complications. Methylglyoxal, a glucose dependent α-dicarbonyl might be the most important reactive aldehyde in diabetes and its complications. Diabetes was the first disease in which evidence emerged for the increased formation of methylglyoxal in the cells and in the serum. Methylglyoxal has a toxic effect on insulin secretion from pancreatic beta-cells, and on modifications of proteins and nucleic acids. Moreover, methylglyoxal is one of the major precursors of advanced glycation end-products. The glyoxalase enzyme system that exists in all mammalian cells is catalyzing the detoxification of methylglyoxal. This review summarizes the methylglyoxal metabolism in normoglycaemic and hyperglycamic conditions and the role of methylglyoxal in the development of late diabetic microvascular complications

Optimal Resting-Growth Strategies of Microbial Populations in Fluctuating Environments

Bacteria spend most of their lifetime in non-growing states which allow them to survive extended periods of stress and starvation. When environments improve, they must quickly resume growth to maximize their share of limited nutrients. Cells with higher stress resistance often survive longer stress durations at the cost of needing more time to resume growth, a strong disadvantage in competitive environments. Here we analyze the basis of optimal strategies that microorganisms can use to cope with this tradeoff. We explicitly show that the prototypical inverse relation between stress resistance and growth rate can explain much of the different types of behavior observed in stressed microbial populations. Using analytical mathematical methods, we determine the environmental parameters that decide whether cells should remain vegetative upon stress exposure, downregulate their metabolism to an intermediate optimum level, or become dormant. We find that cell-cell variability, or intercellular noise, is consistently beneficial in the presence of extreme environmental fluctuations, and that it provides an efficient population-level mechanism for adaption in a deteriorating environment. Our results reveal key novel aspects of responsive phenotype switching and its role as an adaptive strategy in changing environments

“I should have …”:A Photovoice Study With Women Who Have Lost a Man to Suicide

While the gendered nature of suicide has received increased research attention, the experiences of women who have lost a man to suicide are poorly understood. Drawing on qualitative photovoice interviews with 29 women who lost a man to suicide, we completed a narrative analysis, focused on describing the ways that women constructed and accounted for their experiences. We found that women’s narratives drew upon feminine ideals of caring for men’s health, which in turn gave rise to feelings of guilt over the man’s suicide. The women resisted holding men responsible for the suicide and tended to blame themselves, especially when they perceived their efforts to support the man as inadequate. Even when women acknowledged their guilt as illogical, they were seemingly unable to entirely escape regret and self-blame. In order to reformulate and avoid reifying feminine ideals synonymous with selflessly caring for others regardless of the costs to their own well-being, women’s postsuicide bereavement support programs  hould integrate a critical gender approach

Toll-like receptor 4 signaling in liver injury and hepatic fibrogenesis

Toll-like receptors (TLRs) are a family of transmembrane pattern recognition receptors (PRR) that play a key role in innate and adaptive immunity by recognizing structural components unique to bacteria, fungi and viruses. TLR4 is the most studied of the TLRs, and its primary exogenous ligand is lipopolysaccharide, a component of Gram-negative bacterial walls. In the absence of exogenous microbes, endogenous ligands including damage-associated molecular pattern molecules from damaged matrix and injured cells can also activate TLR4 signaling. In humans, single nucleotide polymorphisms of the TLR4 gene have an effect on its signal transduction and on associated risks of specific diseases, including cirrhosis. In liver, TLR4 is expressed by all parenchymal and non-parenchymal cell types, and contributes to tissue damage caused by a variety of etiologies. Intact TLR4 signaling was identified in hepatic stellate cells (HSCs), the major fibrogenic cell type in injured liver, and mediates key responses including an inflammatory phenotype, fibrogenesis and anti-apoptotic properties. Further clarification of the function and endogenous ligands of TLR4 signaling in HSCs and other liver cells could uncover novel mechanisms of fibrogenesis and facilitate the development of therapeutic strategies

Undiagnosed Phenylketonuria Can Exist Everywhere: Results From an International Survey

peer reviewedMany countries do not have a newborn screening (NBS) program, and immigrants from such countries are at risk for late diagnosis of phenylketonuria (PKU). In this international survey, 52 of 259 patients (20%) with late diagnosed PKU were immigrants, and 145 of the 259 (55%) were born before NBS or in a location without NBS. © 2021 The Author