A grounded theory analysis of the functions of pro-ana social media accounts

Anorexia nervosa is an extremely dangerous eating disorder whose etiology has recently been examined in relation to difficulties in emotion regulation. The phenomenon of pro-anorexia (pro-ana) on social media sites and websites has also received recent attention; however, the functions served by these pro-ana accounts are not well understood. Thus, the present study aimed to examine the possible functions of these accounts, particularly with regard to emotion regulation, through the use of a Grounded Theory analysis. An emotion expression function was supported in this analysis, in addition to seven other functions: defining anorexia as a lifestyle, identity, or disease; discussion of anorexia as cyclically relapsing and recovering; defining what it means to be thin; defining the self as either fat or thin and thus worthless or good; motivating continued engagement in disordered eating; soliciting positive or negative attention from others; and the importance of images in the service of other functions. These functions of pro-ana social media sites can be used to improve treatment and support for those affected by anorexia nervosa both online and offline

Screening for energy restriction in middle and late life

The most commonly used screening tools for disordered eating, the Eating Attitudes Test (EAT-26) and Eating Disorders Examination–Questionnaire (EDE-Q), rely on the detection of shape and weight concerns to identify potentially dangerous caloric restriction among adolescent girls and young adult women. It is unclear how accurate these measures are at detecting restriction among adults 40 years and older. These adults may be vulnerable to developing or maintaining restrictive eating patterns when healthcare providers recommend weight loss as a preventative health measure or when acute or chronic illnesses (e.g., diabetes or cancers) impact eating. The present online study (a) evaluated the accuracy of and suggested optimal cut-scores for the EAT-26 and EDE-Q in this age group and (b) examined the accuracy of a measure of restricted energy intake for health-related reasons, i.e., the Orthorexia Nervosa Inventory (ONI). Of 145 participants, 60 completed demographic and health history surveys, EAT-26, EDE-Q, and ONI, and dietary recalls to examine energy intake. Receiver operating characteristics analyses used dietary recall data as an index criterion to determine the three measures’ accuracy at detecting participants who restricted their energy intake below estimated individual requirements. Results indicated that, contrary to initial hypotheses, the number of medical conditions did not affect energy restriction. Instead, participants who restricted their energy intake below requirements (n = 18) had higher BMIs and were more likely to have a medically prescribed diet than non-restrictors (n = 42). The EAT-26 and EDE-Q performed at the level of chance for detecting individuals whose dietary recalls indicated energy restriction, and the ONI performed in the acceptable range, using the cutoff score of ≥ 30 identified in the present study. Consequently, measures emphasizing altered eating patterns because of health concerns such as the ONI should be considered in clinical practice with middle and late life adults

DNA Einzelmolekül-Mechanik

DNA ist als Trägermolekül der Erbinformation von zentraler biologischer Bedeutung. Die vielfältigen Strukturen, die DNA bildet, werden dabei durch molekulare Erkennungsmechanismen gesteuert, die für jede Sequenz einzigartig sind. So bietet DNA auch die Möglichkeit gezielt und selbstorganisiert Strukturen aufzubauen, die als Grundlage für nanotechnologische Systeme dienen können. Um die Funktion einer Zelle sicher zu stellen treten viele verschiedene Moleküle mit DNA in Wechselwirkung. Dabei wird die DNA kompaktiert, entwunden, aufgetrennt und komplexiert. Im Rahmen dieser Arbeit wurden Kraftmessungen an einzelnen DNA-Molekülen durchgeführt. Dabei wurde sowohl das Entfalten (Unzipping), als auch das Überstrecken und kraftinduzierte Schmelzen untersucht. Insbesondere wurden die mechanischen Aspekte der Wirkung DNA-bindender Pharmaka auf molekularer Ebene studiert

Adipose tissue depot specific expression and regulation of fibrosis-related genes and proteins in experimental obesity

Transforming growth factor beta (Tgfb) is a well-studied pro-fibrotic cytokine, which upregulates cellular communication network factor 2 (Ccn2), collagen, and actin alpha 2, smooth muscle (Acta2) expression. Obesity induces adipose tissue fibrosis, which contributes to metabolic diseases. This work aimed to analyze the expression of Tgfb, Ccn2, collagen1a1 (Col1a1), Acta2 and BMP and activin membrane-bound inhibitor (Bambi), which is a negative regulator of Tgfb signaling, in different adipose tissue depots of mice fed a standard chow, mice fed a high fat diet (HFD) and ob/ob mice. Principally, these genes were low expressed in brown adipose tissues and this difference was less evident for the ob/ob mice. Ccn2 and Bambi protein as well as mRNA expression, and collagen1a1 mRNA were not induced in the adipose tissues upon HFD feeding whereas Tgfb and Acta2 mRNA increased in the white fat depots. Immunoblot analysis showed that Acta2 protein was higher in subcutaneous and perirenal fat of these mice. In the ob/ob mice, Ccn2 mRNA and Ccn2 protein were upregulated in the fat depots. Here, Tgfb, Acta2 and Col1a1 mRNA levels and serum Tgfb protein were increased. Acta2 protein was, however, not higher in subcutaneous and perirenal fat of these mice. Col6a1 mRNA was shown before to be higher in obese fat tissues. Current analysis proved the Col6a1 protein was induced in subcutaneous fat of HFD fed mice. Notably, Col6a1 was reduced in perirenal fat of ob/ob mice in comparison to the respective controls. 3T3-L1 cells express Ccn2 and Bambi protein, whose levels were not changed by fatty acids, leptin, lipopolysaccharide, tumor necrosis factor and interleukin-6. All of these factors led to higher Tgfb in 3T3-L1 adipocyte media but did not increase its mRNA levels. Free fatty acids induced necrosis whereas apoptosis did not occur in any of the in vitro incubations excluding cell death as a main reason for higher Tgfb in cell media. In summary, Tgfb mRNA is consistently induced in white fat tissues in obesity but this is not paralleled by a clear increase of its target genes. Moreover, discrepancies between mRNA and protein expression of Acta2 were observed. Adipocytes seemingly do not contribute to higher Tgfb mRNA levels in obesity. These cells release more Tgfb protein when challenged with obesity-related metabolites connecting metabolic dysfunction and fibrosis

Vertebrate lonesome kinase modulates the hepatocyte secretome to prevent perivascular liver fibrosis and inflammation

Vertebrate lonesome kinase (VLK) is the only known extracellular tyrosine kinase, but its physiological functions are largely unknown. We show that VLK is highly expressed in hepatocytes of neonatal mice, but downregulated during adulthood. To determine the role of VLK in liver homeostasis and regeneration, we generated mice with a hepatocyte-specific knockout of the VLK gene (Pkdcc). Cultured progenitor cells established from primary hepatocytes of Pkdcc knockout mice produced a secretome, which promoted their own proliferation in 3D spheroids and proliferation of cultured fibroblasts. In vivo, Pkdcc knockout mice developed liver steatosis with signs of inflammation and perivascular fibrosis upon aging, combined with expansion of liver progenitor cells. In response to chronic CCl4-induced liver injury, the pattern of deposited collagen was significantly altered in these mice. The liver injury marker alpha-fetoprotein (AFP) was increased in the secretome of VLK-deficient cultured progenitor cells and in liver tissues of aged or CCl4-treated knockout mice. These results support a key role for VLK and extracellular protein phosphorylation in liver homeostasis and repair through paracrine control of liver cell function and regulation of appropriate collagen deposition. This article has an associated First Person interview with the first author of the paper

Overexpression of Hepatocyte Chemerin-156 Lowers Tumor Burden in a Murine Model of Diethylnitrosamine-Induced Hepatocellular Carcinoma

The tumor inhibitory potential of the highly active chemerin-156 isoform was described in orthotopic models of hepatocellular carcinoma (HCC). The majority of HCC arises in the fibrotic liver, which was not reproduced in these studies. Here, a potential therapeutic activity of chemerin-156 was evaluated in diethylnitrosamine (DEN)-induced liver cancer, which mimics fibrosis-associated HCC. Mice were infected with adeno-associated virus (AAV) six months after DEN injection to overexpress chemerin-156 in the liver, and animals injected with non-recombinant-AAV served as controls. Three months later, the animals were killed. Both groups were comparable with regard to liver steatosis and fibrosis. Of note, the number of very small tumors was reduced by chemerin-156. Anyhow, the expression of inflammatory and profibrotic genes was similar in larger tumors of control and chemerin-156-AAV-infected animals. Although genes with a role in lipid metabolism, like 3-hydroxy-3-methylglutaryl-coenzym-A--reductase, were overexpressed in tumors of animals with high chemerin-156, total hepatic cholesterol, diacylglycerol and triglyceride levels, and distribution of individual lipid species were normal. Chemerin-156-AAV-infected mice had elevated hepatic and systemic chemerin. Ex vivo activation of the chemerin receptor chemokine-like receptor 1 increased in parallel with serum chemerin, illustrating the biological activity of the recombinant protein. In the tumors, chemerin-155 was the most abundant variant. Chemerin-156 was not detected in tumors of the controls and was hardly found in chemerin-156-AAV infected animals. In conclusion, the present study showed that chemerin-156 overexpression caused a decline in the number of small lesions but did not prevent the growth of pre-existing neoplasms

Accurate Lipid Quantification of Tissue Homogenates Requires Suitable Sample Concentration, Solvent Composition, and Homogenization Procedure—A Case Study in Murine Liver

Lipidomics aim to quantify lipid species in all kinds of samples, including tissues. To subject a fixed amount of sample to various workflows, tissue homogenates were frequently prepared at defined concentrations in water or by addition of organic solvents. Here, we investigated this first step of tissue lipidomics by quantitative flow injection analysis coupled to Fourier-Transform mass spectrometry (FTMS). The influence of sample concentration, solvent composition, and homogenization procedure on the recovery of lipids was studied in murine liver. Liver homogenates were prepared either by grinding tissue in liquid nitrogen or by bead-based homogenization. Ground samples were dissolved at different concentrations in water, methanol, and water/methanol = 1/1 (v/v). Here, lipid recovery depends on solvent composition and sample concentration. The recovery of nonpolar lipid classes, including triglycerides and cholesteryl ester, was decreased in methanolic homogenates. In contrast, due to superior dispersion of precipitates, bead-based homogenization resulted in efficient lipid recovery independent of the solvent composition. However, lipid distribution within samples, i.e., lipid content of supernatant and pellet following centrifugation, was altered substantially by solvent composition. In conclusion, accurate lipid quantification of tissue homogenates requires evaluation of solvent composition, sample concentration, as well as the homogenization method to guarantee efficient lipid recovery. Due to a potential loss of lipids, removal of precipitates by centrifugation prior to lipid extraction should be avoided

Accurate quantification of lipid species affected by isobaric overlap in Fourier-Transform mass spectrometry

Lipidomics data require consideration of ions with near-identical masses, which comprises amongst others the Type-II isotopic overlap. This overlap occurs in series of lipid species differing only by number of double bonds (DB) mainly due to the natural abundance of 13C-atoms. High-resolution mass spectrometry, such as Fourier-Transform mass spectrometry (FTMS), is capable of resolving Type-II overlap depending on mass resolving power. In this work, we evaluated FTMS quantification accuracy of lipid species affected by Type-II overlap. Spike experiments with lipid species pairs of various lipid classes were analyzed by flow-injection-analysis (FIA)-FTMS. Accuracy of quantification was evaluated without and with Type-II correction (using relative isotope abundance) as well as utilizing the first isotopic peak (M+1). Isobaric peaks, which were sufficiently resolved, were most accurate without Type-II correction. In cases of partially resolved peaks, we observed peak interference causing distortions in mass and intensity, which is a well described phenomenon in FTMS. Concentrations of respective species were more accurate when calculated from M+1. Moreover, some minor species, affected by considerable Type-II overlap, could only be quantified by M+1. Unexpectedly, even completely unresolved peaks were substantially overcorrected by Type-II correction due to peak interference. The described method was validated including intra and inter-day precisions for human serum and fibroblast samples. Taken together, our results show that accurate quantification of lipid species by FTMS requires resolution-depended data analysis

Gender-Specific Differences in Serum Sphingomyelin Species in Patients with Hepatitis C Virus Infection—Sphingomyelin Species Are Related to the Model of End-Stage Liver Disease (MELD) Score in Male Patients

Hepatitis C virus (HCV) replication depends on cellular sphingomyelin (SM), but serum SM composition in chronic HCV infection has been hardly analyzed. In this work, 18 SM species could be quantified in the serum of 178 patients with chronic HCV infection before therapy with direct-acting antivirals (DAAs) and 12 weeks later, when therapy was completed. Six SM species were higher in the serum of females than males before therapy and nine at the end of therapy; thus, sex-specific analysis was performed. Type 2 diabetes was associated with lower serum levels of SM 36:2;O2 and 38:2;O2 in men. Serum SM species did not correlate with the viral load in both sexes. Of note, three SM species were lower in males infected with HCV genotype 3 in comparison to genotype 1 infection. These SM species normalized after viral cure. SM 38:1;O2, 40:1;O2, 41:1;O2, and 42:1;O2 (and, thus, total SM levels) were higher in the serum of both sexes at the end of therapy. In males, SM 39:1;O2 was induced in addition, and higher levels of all of these SM species were already detected at 4 weeks after therapy has been started. Serum lipids are related to liver disease severity, and in females 15 serum SM species were low in patients with liver cirrhosis before initiation of and after treatment with DAAs. The serum SM species did not correlate with the model of end-stage liver disease (MELD) score in the cirrhosis and the non-cirrhosis subgroups in females. In HCV-infected male patients, nine SM species were lower in the serum of patients with cirrhosis before DAA treatment and eleven at the end of the study. Most of the SM species showed strong negative correlations with the MELD score in the male cirrhosis patients before DAA treatment and at the end of therapy. Associations of SM species with the MELD score were not detected in the non-cirrhosis male subgroup. In summary, the current analysis identified sex-specific differences in the serum levels of SM species in HCV infection, in liver cirrhosis, and during DAA therapy. Correlations of SM species with the MELD score in male but not in female patients indicate a much closer association between SM metabolism and liver function in male patients

Sex-specific changes in triglyceride profiles in liver cirrhosis and hepatitis C virus infection

Background Hepatitis C virus (HCV) infection is associated with serum lipid abnormalities, which partly normalize following direct-acting antiviral (DAA) therapy. Here, associations of serum triglycerides (TGs) with viral genotype and markers of liver disease severity were evaluated in patients with chronic HCV. Methods The study included the serum of 177 patients with chronic HCV. TGs were quantified by flow injection analysis Fourier transform mass spectrometry. Laboratory values and noninvasive scores for liver fibrosis assessment were determined. The nonparametric Kruskal‒Wallis test, one-way ANOVA, multiple linear regression and Student’s t test were used as appropriate. P values were adjusted for multiple comparisons. Results HCV-infected women had lower serum TGs than men, and thus, a sex-specific analysis was performed. None of the 46 TG species analyzed differed in the serum of female patients with and without liver cirrhosis. In contrast, in the serum of male patients with liver cirrhosis, TGs with 53, 56 and 58 carbon atoms and three to eight double bonds were diminished. These polyunsaturated TGs were also low in males with a high fibrosis-4 score. TGs with 7 or 8 double bonds negatively correlated with the model of end-stage liver disease score in males. In addition, TGs with 49, 51 and 53 carbon atoms were reduced in male patients infected with genotype 3a in comparison to genotype 1a. TGs with 56 carbon atoms were lower in genotype 3a-infected males than in genotype 1b-infected males. TGs did not differ in females by genotype. Genotype 3-related changes disappeared at the end of therapy with DAAs. Overall, the levels of serum TGs did not change during DAA therapy in either sex. Consequently, the serum TGs of males with liver cirrhosis were lower than those of males without cirrhosis at the end of therapy. Such a difference was not apparent in females. Conclusions The decline in TGs observed only in male patients with liver cirrhosis and male patients infected with genotype 3 illustrates sex-specific changes in lipid metabolism in chronic HCV