Psychometric properties of the Turkish version of the moral distress-appraisal scale for nurses.

Moral distress causes frustration, guilt, anger, stress, sadness, anxiety, fear, burnout, insecurity, and depression in nurses, and this is reflected in their work performances. Therefore, internationally validated tools and methodological studies are needed to measure moral distress among nurses. This study aims to evaluate the psychometric properties of the Turkish version of the Moral Distress-Appraisal Scale (MD-APPS) among nurses in Turkey. Psychometric properties of the Turkish version of the Moral Distress-Appraisal Scale (MD-APPS), which included internal consistency reliability and construct validity with factor analysis, were examined in a sample of 420 nurses working in different hospitals in Turkey completed the study between February and July 2022. The content validity index of the Turkish version of the MD-APPS based on expert opinions was 0.90. Through exploratory factor analysis for construct validity, a two-factor structure was obtained as in the original scale. The variance explained by these two factors was 56.67 %. Confirmatory factor analysis showed that the scale was valid, while internal consistency coefficient and test-retest results demonstrated that the scale was reliable. The Turkish version of the MD-APPS is a valid and reliable tool for evaluating moral distress among nurses.

The effect of a video-assisted operating room promotion program on the anxiety levels of parents and their children: A randomized controlled trial protocol.

PURPOSE: Anxiety experienced by parents is an important predictor of anxiety experienced by children. Different interventions are used to reduce the anxiety levels of children and their parents during the preoperative period. Apart from conventional training methods, watching videos about real-life operating rooms can reduce parents' and their children's anxiety levels. Children scheduled for surgery are likely to experience less anxiety if their parents experience less anxiety. A video-assisted operating room promotion program will develop for parents. This study will be aimed to evaluate the effect of the program on the anxiety levels of parents and children. DESIGN AND METHODS: This study protocol is a single-center, single-blind, pre-test, post-test, follow-up parallel group randomized controlled trial. This study protocol was prepared with the Standard Protocol Items: Recommendations for Interventional Trials guidelines and will adhere to the Consolidated Standards of Reporting Trials Non-Pharmacologic Treatment Interventions checklist. A total of 100 eligible participants will be randomized into intervention and control groups. The intervention group will attend the program and receive standard care. CONCLUSION: If we obtain the expected results, we think that they will help healthcare professionals develop methods and strategies to reduce the anxiety levels of parents and children through content covering the pre-, peri-, and post-surgical processes. PRACTICE IMPLICATIONS: The results will assist healthcare professionals in the management of pain and guide them in developing technology-based nursing interventions. Trial registration It was registered at ClinicalTrials.gov in January 2022 (NCT05186766).

Relationship Between Quality of Care and Patient Care Outcomes for Postoperative Pain in Major Orthopedic Surgery: Analytical and Cross-Sectional Study.

The quality of care provided for the management of postoperative pain and patient outcomes are key criteria for healthcare institutions. This study aimed to determine the relationship between the quality of care provided for the alleviation of postoperative pain experienced among patients undergoing major orthopedic surgery and the patient care outcomes. The study was designed as an analytical and cross-sectional study. The rates of pain severity and sleep interference, activity interference, affective experiences, and adverse effects due to postoperative pain were higher in female patients than in male patients. A significant positive correlation was identified between the quality of postoperative pain care and the perception of care (p < .05). Implementing nursing interventions to improve pain management and increase the quality of care appears to be vital elements for reducing adverse effects caused by pain and increasing the satisfaction with postoperative pain care.

Egr1 mediates the effect of insulin on leptin transcription in adipocytes.

In mammals, leptin production in adipocytes is up-regulated by feeding and insulin. Although this regulatory connection is central to all physiological effects of leptin, its molecular mechanism remains unknown. Here, we show that the transcription factor early growth response 1, Egr1, is rapidly but transiently induced by insulin in adipose cells both in vitro and in vivo, and its induction is followed by an increase in leptin transcription. ChIP and luciferase assays demonstrate that Egr1 directly binds to and activates the leptin promoter. Interestingly, the lipid droplet protein FSP27 may work as a co-factor for Egr1 in regulating leptin expression. By using siRNA-mediated knockout of Egr1 along with its overexpression in adipocytes, we demonstrate that Egr1 is both necessary and sufficient for the stimulatory effect of insulin on leptin transcription.

Regulation of fatty acid trafficking in liver by thioesterase superfamily member 1.

Thioesterase superfamily member 1 (Them1) is an acyl-CoA thioesterase that is highly expressed in brown adipose tissue, where it functions to suppress energy expenditure. Lower Them1 expression levels in the liver are upregulated in response to high-fat feeding. Them1-/- mice are resistant to diet-induced obesity, hepatic steatosis, and glucose intolerance, but the contribution of Them1 in liver is unclear. To examine its liver-specific functions, we created conditional transgenic mice, which, when bred to Them1-/- mice and activated, expressed Them1 exclusively in the liver. Mice with liver-specific Them1 expression exhibited no changes in energy expenditure. Rates of fatty acid oxidation were increased, whereas hepatic VLDL triglyceride secretion rates were decreased by hepatic Them1 expression. When fed a high-fat diet, Them1 expression in liver promoted excess steatosis in the setting of reduced rates of fatty acid oxidation and preserved glycerolipid synthesis. Liver-specific Them1 expression did not influence glucose tolerance or insulin sensitivity, but did promote hepatic gluconeogenesis in high-fat-fed animals. This was attributable to the generation of excess fatty acids, which activated PPARα and promoted expression of gluconeogenic genes. These findings reveal a regulatory role for Them1 in hepatocellular fatty acid trafficking.

Thioesterase superfamily member 1 suppresses cold thermogenesis by limiting the oxidation of lipid droplet-derived fatty acids in brown adipose tissue.

OBJECTIVE: Non-shivering thermogenesis in brown adipose tissue (BAT) plays a central role in energy homeostasis. Thioesterase superfamily member 1 (Them1), a BAT-enriched long chain fatty acyl-CoA thioesterase, is upregulated by cold and downregulated by warm ambient temperatures. Them1 (-/-) mice exhibit increased energy expenditure and resistance to diet-induced obesity and diabetes, but the mechanistic contribution of Them1 to the regulation of cold thermogenesis remains unknown. METHODS: Them1 (-/-) and Them1 (+/+) mice were subjected to continuous metabolic monitoring to quantify the effects of ambient temperatures ranging from thermoneutrality (30 °C) to cold (4 °C) on energy expenditure, core body temperature, physical activity and food intake. The effects of Them1 expression on O2 consumption rates, thermogenic gene expression and lipolytic protein activation were determined ex vivo in BAT and in primary brown adipocytes. RESULTS: Them1 suppressed thermogenesis in mice even in the setting of ongoing cold exposure. Without affecting thermogenic gene transcription, Them1 reduced O2 consumption rates in both isolated BAT and primary brown adipocytes. This was attributable to decreased mitochondrial oxidation of endogenous but not exogenous fatty acids. CONCLUSIONS: These results show that Them1 may act as a break on uncontrolled heat production and limit the extent of energy expenditure. Pharmacologic inhibition of Them1 could provide a targeted strategy for the management of metabolic disorders via activation of brown fat.

Nonalcoholic fatty liver disease is an independent risk factor for atherosclerosis in young adult men.

INTRODUCTION: The possible cause of accelerated atherosclerosis in NAFLD may be the relationship with the MetS and its components. Our primary goal was to evaluate the relationship between NAFLD and subclinical atherosclerosis in adult male patients between 20 and 40 years of age. Moreover, we aimed to investigate the changes in this association according to the presence or absence of MetS. METHOD: Sixty-one male patients with biopsy-proven NAFLD and 41 healthy male volunteers were enrolled. In order to exclude any interference of confounding factors, we studied a specifically selected group with no additional cardiovascular risk. PWV, CIMT and FMD levels were measured in all patients and controls. RESULTS: The levels of cf-PWV were significantly higher in SS and NASH patients compared to the control group (P < 0.001); no significant difference was found between SS and NASH patients (P > 0.05). We found significantly decreased FMD levels in patients with SS and NASH compared with control subjects (P < 0.001). Subjects with NASH had significantly greater CIMT measurements than the SS and controls (P = 0.026, P < 0.001, respectively). Although, NAFLD patients with MetS had increased cf-PWV and CIMT and reduced FMD compared to healthy subjects (P < 0.05), no significant difference existed between NAFLD with Mets and NAFLD without MetS in terms of cf-PWV, CIMT and FMD (P > 0.05) CONCLUSION: The present study showed that the presence of NAFLD leads to increased risk of endothelial dysfunction and atherosclerosis in adult male patients, independent of MetS.

Food-associated stimuli enhance barrier properties of gastrointestinal mucus.

Orally delivered drugs and nutrients must diffuse through mucus to enter the circulatory system, but the barrier properties of mucus and their modulation by physiological factors are generally poorly characterized. The main objective of this study was to examine the impact of physicochemical changes occurring upon food ingestion on gastrointestinal (GI) mucus barrier properties. Lipids representative of postprandial intestinal contents enhanced mucus barriers, as indicated by a 10-142-fold reduction in the transport rate of 200 nm microspheres through mucus, depending on surface chemistry. Physiologically relevant increases in [Ca(2+)] resulted in a 2-4-fold reduction of transport rates, likely due to enhanced cross-linking of the mucus gel network. Reduction of pH from 6.5 to 3.5 also affected mucus viscoelasticity, reducing particle transport rates approximately 5-10-fold. Macroscopic visual observation and micro-scale lectin staining revealed mucus gel structural changes, including clumping into regions into which particles did not penetrate. Histological examination indicated food ingestion can prevent microsphere contact with and endocytosis by intestinal epithelium. Taken together, these results demonstrate that GI mucus barriers are significantly altered by stimuli associated with eating and potentially dosing of lipid-based delivery systems; these stimuli represent broadly relevant variables to consider upon designing oral therapies.

CXCR3 controls T-cell accumulation in fat inflammation.

OBJECTIVE: Obesity associates with increased numbers of inflammatory cells in adipose tissue (AT), including T cells, but the mechanism of T-cell recruitment remains unknown. This study tested the hypothesis that the chemokine (C-X-C motif) receptor 3 (CXCR3) participates in T-cell accumulation in AT of obese mice and thus in the regulation of local inflammation and systemic metabolism. APPROACH AND RESULTS: Obese wild-type mice exhibited higher mRNA expression of CXCR3 in periepididymal AT-derived stromal vascular cells compared with lean mice. We evaluated the function of CXCR3 in AT inflammation in vivo using CXCR3-deficient and wild-type control mice that consumed a high-fat diet. Periepididymal AT from obese CXCR3-deficient mice contained fewer T cells than obese controls after 8 and 16 weeks on high-fat diet, as assessed by flow cytometry. Obese CXCR3-deficient mice had greater glucose tolerance than obese controls after 8 weeks, but not after 16 weeks. CXCR3-deficient mice fed high-fat diet had reduced mRNA expression of proinflammatory mediators, such as monocyte chemoattractant protein-1 and regulated on activation, normal T cell expressed and secreted, and anti-inflammatory genes, such as Foxp3, IL-10, and arginase-1 in periepididymal AT, compared with obese controls. CONCLUSIONS: These results demonstrate that CXCR3 contributes to T-cell accumulation in periepididymal AT of obese mice. Our results also suggest that CXCR3 regulates the accumulation of distinct subsets of T cells and that the ratio between these functional subsets across time likely modulates local inflammation and systemic metabolism.

Thioesterase superfamily member 2/Acyl-CoA thioesterase 13 (Them2/Acot13) regulates adaptive thermogenesis in mice.

Members of the acyl-CoA thioesterase (Acot) gene family hydrolyze fatty acyl-CoAs, but their biological functions remain incompletely understood. Thioesterase superfamily member 2 (Them2; synonym Acot13) is enriched in oxidative tissues, associated with mitochondria, and relatively specific for long chain fatty acyl-CoA substrates. Using Them2(-/-) mice, we have demonstrated key roles for Them2 in regulating hepatic glucose and lipid metabolism. However, reduced body weights and decreased adiposity in Them2(-/-) mice observed despite increased food consumption were not well explained. To explore a role in thermogenesis, mice were exposed to ambient temperatures ranging from thermoneutrality (30 °C) to cold (4 °C). In response to short term (24-h) exposures to decreasing ambient temperatures, Them2(-/-) mice exhibited increased adaptive responses in physical activity, food consumption, and energy expenditure when compared with Them2(+/+) mice. By contrast, genotype-dependent differences were not observed in mice that were equilibrated (96 h) at each ambient temperature. In brown adipose tissue, the absence of Them2 was associated with reduced lipid droplets, alterations in the ultrastructure of mitochondria, and increased expression of thermogenic genes. Indicative of a direct regulatory role for Them2 in heat production, cultured primary brown adipocytes from Them2(-/-) mice exhibited increased norepinephrine-mediated triglyceride hydrolysis and increased rates of O2 consumption, together with elevated expression of thermogenic genes. At least in part by regulating intracellular fatty acid channeling, Them2 functions in brown adipose tissue to suppress adaptive increases in energy expenditure.

Other ways to skin a cat: activating SREBP without Scap.

The sterol regulatory element binding protein (SREBP) pathway plays a central role in the global regulation of lipid homeostasis. SREBPs are membrane-bound transcription factors whose proteolytic activation is regulated by cellular lipid levels; when demand for lipid rises, SREBP travels from the endoplasmic reticulum to the Golgi apparatus where it is cleaved by two distinct proteases. Cleavage releases the transcription factor domain of SREBP from the membrane-bound precursor and transcription of its target genes consequently rises. Previously, we isolated Drosophila mutants null for dsrebp and others lacking site-2 protease (ds2p), the second of two Golgi-resident proteases that cleave dSREBP. dScap is a protein needed to escort dSREBP from the ER to the Golgi apparatus. We recently characterized the phenotypes of dscap mutants as well. Here, we describe additional details of phenotypes arising from the inability to activate SREBP appropriately.

Activation of sterol regulatory element binding proteins in the absence of Scap in Drosophila melanogaster.

The escort factor Scap is essential in mammalian cells for regulated activation of sterol regulatory element binding proteins (SREBPs). SREBPs are membrane-bound transcription factors. Cells lacking Scap cannot activate SREBP. They are therefore deficient in the transcription of numerous genes involved in lipid synthesis and uptake; they cannot survive in the absence of exogenous lipid. Here we report that, in contrast to mammalian cells, Drosophila completely lacking dscap are viable. Flies lacking dscap emerge at approximately 70% of the expected rate and readily survive as homozygous stocks. These animals continue to cleave dSREBP in some tissues. Transcription of dSREBP target genes in dscap mutant larvae is reduced compared to wild type. It is greater than in mutants lacking dSREBP and remains responsive to dietary lipids in dscap mutants. Flies lacking dscap do not require the caspase Drice to activate dSREBP. This contrasts with ds2p mutants. ds2p encodes a protease that releases the transcription factor domain of dSREBP from the membrane. Larvae doubly mutant for dscap and ds2p exhibit phenotypes similar to those of ds2p single mutants. Thus, dScap and dS2P, essential components of the SREBP activation machinery in mammalian cells, are dispensable in Drosophila owing to different compensatory mechanisms.

Distinct roles of RalA and RalB in the progression of cytokinesis are supported by distinct RalGEFs.

The Ras family G-proteins RalA and RalB make critical non-overlapping contributions to the generation of a tumorigenic regulatory network, supporting bypass of the normal restraints on both cell proliferation and survival. The Sec6/8 complex, or exocyst, has emerged as a principal direct effector complex for Ral GTPases. Here, we show that RalA and RalB support mitotic progression through mobilization of the exocyst for two spatially and kinetically distinct steps of cytokinesis. RalA is required to tether the exocyst to the cytokinetic furrow in early cytokinesis. RalB is then required for recruitment of the exocyst to the midbody of this bridge to drive abscission and completion of cytokinesis. The collaborative action of RalA and RalB is specified by discrete subcellular compartmentalization and unique pairs of RalGEF proteins that provide inputs from both Ras-family protein-dependent and protein-independent regulatory cues. This suggests that Ral GTPases integrate diverse upstream signals to choreograph multiple roles for the exocyst in mitotic progression.

The closed structure of the MscS mechanosensitive channel. Cross-linking of single cysteine mutants.

Mechanosensitive channels must make a large conformational change during the transition from the closed to the open state. The crystal structure of the open form of the Escherichia coli MscS channel was recently solved and depicts a homoheptamer (1). In this study, cross-linking of site-specific cysteine substitutions demonstrates that residues up to 10-33 A apart in the crystal structure readily form disulfide bridges in the closed form and can also be cross-linked by a 10-A linker. Cross-linking between adjacent subunits stabilizes the heptameric form of the channel providing biochemical evidence to support the crystal structure. The data are consistent with the published model (1) in that the membrane domain is highly flexible and that the closed to open transition may involve a significant displacement of transmembrane helices 1 and 2, possibly by as much as 30 A. The data are also consistent with significant flexibility of the cytoplasmic domain.