Translocation of Viable Gut Microbiota to Mesenteric Adipose Drives Formation of Creeping Fat in Humans.

A mysterious feature of Crohn's disease (CD) is the extra-intestinal manifestation of "creeping fat" (CrF), defined as expansion of mesenteric adipose tissue around the inflamed and fibrotic intestine. In the current study, we explore whether microbial translocation in CD serves as a central cue for CrF development. We discovered a subset of mucosal-associated gut bacteria that consistently translocated and remained viable in CrF in CD ileal surgical resections, and identified Clostridium innocuum as a signature of this consortium with strain variation between mucosal and adipose isolates, suggesting preference for lipid-rich environments. Single-cell RNA sequencing characterized CrF as both pro-fibrotic and pro-adipogenic with a rich milieu of activated immune cells responding to microbial stimuli, which we confirm in gnotobiotic mice colonized with C. innocuum. Ex vivo validation of expression patterns suggests C. innocuum stimulates tissue remodeling via M2 macrophages, leading to an adipose tissue barrier that serves to prevent systemic dissemination of bacteria.

Differential effects of acute versus chronic dietary fructose consumption on metabolic responses in FVB/N mice.

Increased human consumption of high-fructose corn syrup has been linked to the marked increase in obesity and metabolic syndrome. Previous studies on the rapid effects of a high-fructose diet in mice have largely been confined to the C57BL/6 strains. In the current study, the FVB/N strain of mice that are resistant to diet-induced weight gain were used and fed a control or high-fructose diet for 48 h or for 12 wk. Many of the previously reported changes that occurred upon high-fructose feeding for 48 h in C57BL/6 mice were recapitulated in the FVB/N mice. However, the acute increases in fructolytic and lipogenic gene expression were completely lost during the 12-wk dietary intervention protocol. Furthermore, there was no significant weight gain in FVB/N mice fed a high-fructose diet for 12 wk, despite an overall increase in caloric consumption and an increase in average epididymal adipocyte cell size. These findings may be in part explained by a commensurate increase in energy expenditure and in carbohydrate utilization in high-fructose-fed animals. Overall, these findings demonstrate that FVB/N mice are a suitable model for the study of the effects of dietary intervention on metabolic and molecular parameters. Furthermore, the rapid changes in hepatic gene expression that have been widely reported were not sustained over a longer time course. Compensatory changes in energy expenditure and utilization may be in part responsible for the differences obtained between acute and chronic high-fructose feeding protocols.

Continuous and simultaneous measurement of triple-oxygen and hydrogen isotopes of liquid and vapor during evaporation experiments.

RATIONALE: Oxygen and hydrogen isotopes are important tools for studying the modern and past hydrological cycle. Previous evaporation experiments used episodic measurement of liquid and/or vapor or did not measure all isotopologues of water. Here, we describe an evaporation experimental system that allows all isotopologues of liquid and water vapor to be measured simultaneously and near-continuously at high precision using cavity ring-down laser spectroscopy (CRDS). METHODS: Evaporating liquid is periodically sampled from a closed recirculating loop by a syringe pump that delivers a constant supply of water to the vaporizer, achieving a water vapor concentration of 20,000 ppmV H2 O (±132, 1σ). Vapor is sampled directly from the evaporation chamber. Isotope ratios are measured simultaneously with a Picarro L2140-i CRDS instrument. RESULTS: For liquid measurements, Allan variance analysis indicates an optimum data collection window of 34 min for oxygen isotopes and 27 min for hydrogen isotopes. During these periods, the mean standard error is ±0.0081‰ for δ17 O values, ±0.0081‰ for δ18 O values, and ±0.019‰ for δ2 H values. For the derived parameters 17 O-excess and d-excess, the standard error of the mean is 5.8 per meg and 0.07‰, respectively. For the vapor phase a 12.5 min data window for all isotopologues results in a mean standard error of ±0.012‰ for δ17 O values, ±0.011‰ for δ18 O values, and ±0.023‰ for δ2 H values. For the derived parameters, the standard error of the mean is 9.2 per meg for 17 O-excess and 0.099‰ for d-excess. These measurements result in consistently narrow 95% confidence limits for the slopes of ln(δ17 O + 1) vs ln(δ18 O + 1) and ln(δ2 H + 1) vs ln(δ18 O + 1). CONCLUSIONS: The experimental method permits measurement of fractionation of triple-oxygen and hydrogen isotopes of evaporating water under varying controlled conditions at high precision. Application of this method will be useful for testing theoretical models of evaporation and conducting experiments to simulate evaporation and isotopic equilibration in natural systems.

Halide Photoredox Chemistry.

Halide photoredox chemistry is of both practical and fundamental interest. Practical applications have largely focused on solar energy conversion with hydrogen gas, through HX splitting, and electrical power generation, in regenerative photoelectrochemical and photovoltaic cells. On a more fundamental level, halide photoredox chemistry provides a unique means to generate and characterize one electron transfer chemistry that is intimately coupled with X-X bond-breaking and -forming reactivity. This review aims to deliver a background on the solution chemistry of I, Br, and Cl that enables readers to understand and utilize the most recent advances in halide photoredox chemistry research. These include reactions initiated through outer-sphere, halide-to-metal, and metal-to-ligand charge-transfer excited states. Kosower's salt, 1-methylpyridinium iodide, provides an early outer-sphere charge-transfer excited state that reports on solvent polarity. A plethora of new inner-sphere complexes based on transition and main group metal halide complexes that show promise for HX splitting are described. Long-lived charge-transfer excited states that undergo redox reactions with one or more halogen species are detailed. The review concludes with some key goals for future research that promise to direct the field of halide photoredox chemistry to even greater heights.

Magnetic resonance angiography reveals increased arterial blood supply and tumorigenesis following high fat feeding in a mouse model of triple-negative breast cancer.

Breast cancer is the second most commonly diagnosed malignancy among women globally. Past MRI studies have linked a high animal fat diet (HAFD) to increased mammary cancer risk in the SV40Tag mouse model of triple-negative breast cancer. Here, serial MRI examines tumor progression and measures the arterial blood volume feeding mammary glands in low fat diet (LFD) or HAFD fed mice. Virgin female C3(1)SV40Tag mice (n = 8), weaned at 3 weeks old, were assigned to an LFD (n = 4, 3.7 kcal/g, 17.2% kcal from vegetable oil) or an HAFD (n = 4, 5.3 kcal/g, 60% kcal from lard) group. From ages 8 to 12 weeks, weekly fast spin echo MR images and time-of-flight (TOF) MR angiography of inguinal mammary glands were acquired at 9.4 T. Following in vivo MRI, mice were sacrificed. Inguinal mammary glands were excised and fixed for ex vivo MRI and histology. Tumor, blood, and mammary gland volumes for each time point were measured from manually traced regions of interest; tumors were classified as invasive by histopathology-blinded observers. Our analysis confirmed a strong correlation between total tumor volume and blood volume in the mammary gland. Tumor growth rates from weeks 8-12 were twice as high in HAFD-fed mice (0.42 ± 0.14/week) as in LFD-fed mice (0.21 ± 0.03/week), p < 0.004. Mammary gland blood volume growth rate was 2.2 times higher in HAFD mice (0.29 ± 0.11/week) compared with LFD mice (0.13 ± 0.06/week), p < 0.02. The mammary gland growth rate of HAFD-fed mice (0.071 ± 0.011/week) was 2.7 times larger than that of LFD-fed mice (0.026 ± 0.009/week), p < 0.01. This is the first non-invasive, in vivo MRI study to demonstrate a strong correlation between an HAFD and increased cancer burden and blood volume in mammary cancer without using contrast agents, strengthening the evidence supporting the adverse effects of an HAFD on mammary cancer. These results support the potential future use of TOF angiography to evaluate vasculature of suspicious lesions.

Effect of Needle Exchange Program on Maternal Hepatitis C Virus Prevalence.

OBJECTIVE: This study aimed to quantify the prevalence of maternal hepatitis C virus (HCV) before and after implementation of the needle exchange program (NEP) in Scioto County, Ohio. STUDY DESIGN: We conducted a population-based retrospective cohort study of all live births in Ohio (2006-2015). Frequency of maternal HCV was compared before (2006-2011) and after (2012-2015) the implementation of an NEP (2011) in Portsmouth, Ohio (Scioto County). Trends in maternal HCV prevalence in neighboring counties both physically adjacent and regional to Scioto County were also evaluated before and after NEP implementation. RESULTS: During the study period, there were 7,069 reported cases of maternal HCV infection at the time of delivery among 1,463,506 (0.5%) live births in Ohio. The rate of maternal HCV infection increased 137% in Scioto County between 2006 and 2011. After initiation of the NEP in Portsmouth, Ohio, in 2011, the rate of increase in the following 4 years (2012-2015) was 12%. The rate of increase in maternal HCV declined precipitously in counties physically adjacent to Scioto County, whereas regional counties continued to have substantial increases in maternal HCV. CONCLUSION: Rate of maternal HCV infection increased 137% versus 12% (rate difference: 125%) between pre- and post-NEP implementation time periods in Scioto County.

Barriers for interfacial back-electron transfer: A comparison between TiO2 and SnO2/TiO2 core/shell structures.

Temperature dependent kinetics for back-electron transfer (BET) from electrons in TiO2 or SnO2/TiO2 core/shell nanoparticles to oxidized donor-bridge-acceptor (D-B-A) sensitizers is reported over a 110° range. Two D-B-A sensitizers (CF3-p and CF3-x) were utilized that differed only by the nature of the bridging ligand: a xylyl spacer that largely insulated the two redox active centers and a phenyl bridge that promoted strong electronic coupling and an adiabatic electron transfer mechanism. An Arrhenius analysis revealed that the activation energies were significantly larger for the core/shell oxides, Ea = 32 ± 4 kJ/mol, compared to TiO2 alone, Ea = 22 ± 6 kJ/mol. The barriers for BET on sensitized TiO2 were within the same range as previous literature reports, while this study represents the first quantification for SnO2/TiO2 core/shell materials. Two different models were proposed to rationalize the larger barrier for the core/shell materials: (1) a band edge offset model and (2) a low energy trap state model with recombination from the TiO2 rutile polymorph shell. The latter model was preferred and is in better agreement with the experimental data. The kinetic analysis also afforded the forward and reverse rate constants for the intramolecular equilibrium. In accordance with theoretical predictions and previous research, the absolute value of the free energy change was smaller for the adiabatic equilibrium provided by the phenyl bridge, i.e., |ΔGo ad| <|ΔGo|.

Psychosocial Stress Exposure Disrupts Mammary Gland Development.

Exposure to psychosocial stressors and ensuing stress physiology have been associated with spontaneous invasive mammary tumors in the Sprague-Dawley rat model of human breast cancer. Mammary gland (MG) development is a time when physiologic and environmental exposures influence breast cancer risk. However, the effect of psychosocial stress exposure on MG development remains unknown. Here, in the first comprehensive longitudinal study of MG development in nulliparous female rats (from puberty through young adulthood; 8-25 wks of age), we quantify the spatial gradient of differentiation within the MG of socially stressed (isolated) and control (grouped) rats. We then demonstrate that social isolation increased stress reactivity to everyday stressors, resulting in downregulation of glucocorticoid receptor (GR) expression in the MG epithelium. Surprisingly, given that chemical carcinogens increase MG cancer risk by preventing normal terminal end bud (TEB) differentiation, chronic isolation stress did not alter TEBs. Instead, isolation blunted MG growth and alveolobular differentiation and reduced epithelial cell proliferation in these structures. Social isolation also enhanced corpora luteal progesterone at all ages but reduced estrogenization only in early adulthood, a pattern that precludes modulated ovarian function as a sufficient mechanism for the effects of isolation on MG development. This longitudinal study of natural variation provides an integrated view of MG development and the importance of increased GR activation in nulliparous ductal growth and alveolobular differentiation. Thus, social isolation and its physiological sequelae disrupt MG growth and differentiation and suggest a contribution of stress exposure during puberty and young adulthood to the previously observed increase in invasive MG cancer observed in chronically socially-isolated adult Sprague-Dawley rats.

Visible Light Driven Bromide Oxidation and Ligand Substitution Photochemistry of a Ru Diimine Complex.

The complex [Ru(deeb)(bpz)2]2+ (RuBPZ2+, deeb = 4,4'-diethylester-2,2'-bipyridine, bpz = 2,2'-bipyrazine) forms a single ion pair with bromide, [RuBPZ2+, Br-]+, with Keq = 8400 ± 200 M-1 in acetone. The RuBPZ2+ displayed photoluminescence (PL) at room temperature with a lifetime of 1.75 µs. The addition of bromide to a RuBPZ2+ acetone solution led to significant PL quenching and Stern-Volmer plots showed upward curvature. Time-resolved PL measurements identified two excited state quenching pathways, static and dynamic, which were operative toward [RuBPZ2+, Br-]+ and free RuBPZ2+, respectively. The single ion-pair [RuBPZ2+, Br-]+* had a lifetime of 45 ± 5 ns, consistent with an electron transfer rate constant, ket = (2.2 ± 0.3) × 107 s-1. In contrast, RuBPZ2+* was dynamically quenched by bromide with a quenching rate constant, kq = (8.1 ± 0.1) × 1010 M-1 s-1. Nanosecond transient absorption revealed that both the static and dynamic pathways yielded RuBPZ+ and Br2•- products that underwent recombination to regenerate the ground state with a second-order rate constant, kcr = (2.3 ± 0.5) × 1010 M-1 s-1. Kinetic analysis revealed that RuBPZ+ was a primary photoproduct, while Br2•- was secondary product formed by the reaction of a Br• with Br-, k = (1.1 ± 0.2) × 1010 M-1 s-1. Marcus theory afforded an estimate of the formal reduction potential for E0(Br•/-) in acetone, 1.42 V vs NHE. A 1H NMR analysis indicated that the ion-paired bromide was preferentially situated close to the RuII center. Prolonged steady state photolysis of RuBPZ2+ and bromide yielded two ligand-substituted photoproducts, cis- and trans-Ru(deeb)(bpz)Br2. A photochemical intermediate, proposed to be [Ru(deeb)(bpz)(κ1-bpz)(Br)]+, was found to absorb a second photon to yield cis- and trans-Ru(deeb)(bpz)Br2 photoproducts.

Dye-Sensitized Hydrobromic Acid Splitting for Hydrogen Solar Fuel Production.

Hydrobromic acid (HBr) has significant potential as an inexpensive feedstock for hydrogen gas (H2) solar fuel production through HBr splitting. Mesoporous thin films of anatase TiO2 or SnO2/TiO2 core-shell nanoparticles were sensitized to visible light with a new RuII polypyridyl complex that served as a photocatalyst for bromide oxidation. These thin films were tested as photoelectrodes in dye-sensitized photoelectrosynthesis cells. In 1 N HBr (aq), the photocatalyst undergoes excited-state electron injection and light-driven Br- oxidation. The injected electrons induce proton reduction at a Pt electrode. Under 100 mW cm-2 white-light illumination, sustained photocurrents of 1.5 mA cm-2 were measured under an applied bias. Faradaic efficiencies of 71 ± 5% for Br- oxidation and 94 ± 2% for H2 production were measured. A 12 µmol h-1 sustained rate of H2 production was maintained during illumination. The results demonstrate a molecular approach to HBr splitting with a visible light absorbing complex capable of aqueous Br- oxidation and excited-state electron injection.

Evidence of non-pancreatic beta cell-dependent roles of Tcf7l2 in the regulation of glucose metabolism in mice.

Non-coding variation within TCF7L2 remains the strongest genetic determinant of type 2 diabetes risk in humans. A considerable effort has been placed in understanding the functional roles of TCF7L2 in pancreatic beta cells, despite evidence of TCF7L2 expression in various peripheral tissues important in glucose homeostasis. Here, we use a humanized mouse model overexpressing Tcf7l2, resulting in glucose intolerance, to infer the contribution of Tcf7l2 overexpression in beta cells and in other tissues to the metabolic phenotypes displayed by these mice. Restoring Tcf7l2 expression specifically in beta cells to endogenous levels, in face of its overexpression elsewhere, results in impaired insulin secretion, reduced beta cell number and islet area, corroborating data obtained in humans showing similar phenotypes as a result of manipulations leading to Tcf7l2 loss of function. Interestingly, the persistent overexpression of Tcf7l2 in non-pancreatic tissues results in a significant worsening in glucose tolerance in vivo, indicating that Tcf7l2 overexpression in beta cells does not account for the glucose intolerance in the Tcf7l2 overexpression mouse model. Collectively, these data posit that Tcf7l2 plays key roles in glucose metabolism through actions beyond pancreatic beta cells, and further points to functionally opposing cell-type specific effects for Tcf7l2 on the maintenance of balanced glucose metabolism, thereby urging a careful examination of its role in non-pancreatic tissues as well as its composite metabolic effects across distinct tissues. Uncovering these roles may lead to new therapeutic targets for type 2 diabetes.

MRI reveals increased tumorigenesis following high fat feeding in a mouse model of triple-negative breast cancer.

High animal fat consumption is associated with an increase in triple-negative breast cancer (TNBC) risk. Based on previous MRI studies demonstrating the feasibility of detecting very early non-palpable mammary cancers in simian virus 40 large T antigen (SV40TAg) mice, we examined the effect of dietary fat fed from weaning to young adulthood in this model of TNBC. Virgin female C3(1)SV40TAg mice (n = 16) were weaned at 3-4 weeks of age and then fed either a low fat diet (LFD) (n = 8, 3.7 kcal/g; 17.2% kcal from vegetable oil) or a high animal fat diet (HAFD) (n = 8, 5.3 kcal/g; 60% kcal from lard). After 8 weeks on the diet (12 weeks of age), fast spin echo MR images of inguinal mammary glands were acquired at 9.4 T. Following in vivo MRI, mice were sacrificed and inguinal mammary glands were excised and formalin fixed for ex vivo MRI. 3D volume-rendered MR images were then correlated with mammary gland histology to assess the glandular parenchyma and tumor burden. Using in vivo MRI, an average of 3.88 ± 1.03 tumors were detected per HAFD-fed mouse compared with an average of 1.25 ± 1.16 per LFD-fed mouse (p < 0.007). Additionally, the average tumor volume was significantly higher following HAFD feeding (0.53 ± 0.45 mm3 ) compared with LFD feeding (0.20 ± 0.08 mm3 , p < 0.02). Analysis of ex vivo MR and histology images demonstrated that HAFD mouse mammary glands had denser parenchyma, irregular and enlarged ducts, dilated blood vessels, increased white adipose tissue, and increased tumor invasion. MRI and histological studies of the SV40TAg mice demonstrated that HAFD feeding also resulted in higher cancer incidence and larger mammary tumors. Unlike other imaging methods for assessing environmental effects on mammary cancer growth, MRI allows routine serial measurements and reliable detection of small cancers as well as accurate tumor volume measurements and assessment of the three-dimensional distribution of tumors over time.

Postoperative Venous Thromboembolism in Patients Undergoing Abdominal Surgery for IBD: A Common but Rarely Addressed Problem.

BACKGROUND: Venous thromboembolism after abdominal surgery occurs in 2% to 3% of patients with Crohn's disease and ulcerative colitis. However, no evidence-based guidelines currently exist to guide postdischarge prophylactic anticoagulation. OBJECTIVE: We sought to determine the use of postoperative postdischarge venous thromboembolism chemical prophylaxis, 90-day venous thromboembolism rates, and factors associated with 90-day thromboembolic events in IBD patients following abdominal surgery. DESIGN: This was a retrospective evaluation of an administrative database. DATA SOURCE: Data were obtained from Optum Labs Data Warehouse, a large administrative database containing claims on privately insured and Medicare Advantage enrollees. PATIENTS: Seven thousand seventy-eight patients undergoing surgery for Crohn's disease or ulcerative colitis were included in the study. MAIN OUTCOME MEASURES: Primary outcomes were rates of postdischarge venous thromboembolism prophylaxis and 90-day rates of postdischarge thromboembolic events. In addition, patient clinical characteristics were identified to determine predictors of postdischarge venous thromboembolism. RESULTS: Postdischarge chemical prophylaxis was given to only 0.6% of patients in the study. Two hundred thirty-five patients (3.3%) developed a postdischarge thromboembolic complication. Postdischarge thromboembolism was more common in patients with ulcerative colitis than with Crohn's disease (5.8% vs 2.3%; p < 0.001). Increased rates of venous thromboembolism were seen in patients undergoing colectomy or proctectomy with simultaneous stoma creation compared with colectomy or proctectomy alone (5.8% vs 2.1%; p < 0.001). The strongest predictors of thromboembolic complications were stoma creation (adjusted OR, 1.95; 95% CI, 1.34-2.84), J-pouch reconstruction (adjusted OR, 2.66; 95% CI, 1.65-4.29), preoperative prednisone use (adjusted OR, 1.57; 95% CI, 1.19-2.08), and longer length of stay (adjusted OR, 1.89; 95% CI, 1.41-2.52). LIMITATIONS: This study is limited by its retrospective design. CONCLUSIONS: The use of postdischarge venous thromboembolism prophylaxis in this patient sample was infrequent. Development of evidence-based guidelines, particularly for high-risk patients, should be considered to improve the outcomes of IBD patients undergoing abdominal surgery.

Use of noise cancellation earphones in out-of-booth audiometric evaluations.

OBJECTIVE: To assess the utility of noise cancelation earphones (NCE) in audiometric evaluations. DESIGN: Degree of noise reduction of Bose QuietComfort 15 NCE was assessed through probe-microphone measures and sound-field audiometry. Occlusion effects from NCE were assessed for potential effects on bone-conduction thresholds. STUDY SAMPLE: Twenty participants were tested to determine average occlusion effect values during bone-conduction testing with and without NCE. Noise reduction values of the NCE were assessed on a single subject through probe-microphone measures and sound-field testing. RESULTS: NCE sufficiently reduced ambient noise to levels acceptable for air-conduction testing as well as for bone-conduction testing for most patients when adding minimal adjustment to acceptable levels as outlined by the ANSI S3.1-1999 standard. In addition, NCE did not create a clinically significant change in the occlusion effect for bone-conduction testing. CONCLUSION: NCE placed over insert earphones provide a sound pressure level at the tympanic membrane that is below ANSI standards for routine air-conduction testing and result in sufficient ambient noise reduction for bone-conduction testing with most patients. There is no clinically significant occlusion effect from NCE during routine bone-conduction audiometry. These findings support the utility of using NCE for offsite audiometric testing.

Peripheral circadian misalignment: contributor to systemic insulin resistance and potential intervention to improve bariatric surgical outcomes.

Thirteen percent of the world's population suffers from obesity and 39% from being overweight, which correlates with an increase in numerous secondary metabolic complications, such as Type 2 diabetes mellitus. Bariatric surgery is the most effective treatment for severe obesity and results in significant weight loss and the amelioration of obesity-related comorbidities through changes in enteroendocrine activity, caloric intake, and alterations in gut microbiota composition. The circadian system has recently been found to be a critical regulatory component in the control of metabolism and, thus, may potentially play an important role in inappropriate weight gain. Indeed, some behaviors and lifestyle factors associated with an increased risk of obesity are also risk factors for misalignment in the circadian clock system and for the metabolic syndrome. It is thus possible that alterations in peripheral circadian clocks in metabolically relevant tissues are a contributor to the current obesity epidemic. As such, it is plausible that postsurgical alterations in central circadian alignment, as well as peripheral gene expression in metabolic tissues may represent another mechanism for the beneficial effects of bariatric surgery. Bariatric surgery may represent an opportunity to identify changes in the circadian expression of clock genes that have been altered by environmental factors, allowing for a better understanding of the mechanism of action of surgery. These studies could also reveal an overlooked target for behavioral intervention to improve metabolic outcomes following bariatric surgery.

Systemic regulation of adipose metabolism.

White adipose tissue serves as a critical energy storage depot and endocrine organ. Adipocytes are subject to numerous levels of regulation, including neuronal, endocrine and metabolic. While insulin is the classical endocrine regulator of lipid metabolism in adipose tissue, other important endocrine hormones also control adipose tissue physiology. In this review, we will focus on the contribution of the pituitary in the modulation of adipocyte function, through the direct release of growth hormone as well as via the regulation of the thyroid gland and release of thyroid hormone. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.

Assessing the Usability and Feasibility of Digital Assistant Tools for Direct Support Professionals: Participatory Design and Pilot-Testing.

BACKGROUND: The United States is experiencing a direct support professional (DSP) crisis, with demand far exceeding supply. Although generating documentation is a critical responsibility, it is one of the most wearisome aspects of DSPs' jobs. Technology that enables DSPs to log informal time-stamped notes throughout their shift could help reduce the burden of end-of-shift documentation and increase job satisfaction, which in turn could improve the quality of life of the individuals with intellectual and developmental disabilities (IDDs) whom DSPs support. However, DSPs, with varied ages, levels of education, and comfort using technology, are not likely to adopt tools that detract from caregiving responsibilities or increase workload; therefore, technological tools for them must be relatively simple, extremely intuitive, and provide highly valued capabilities. OBJECTIVE: This paper describes the development and pilot-testing of a digital assistant tool (DAT) that enables DSPs to create informal notes throughout their shifts and use these notes to facilitate end-of-shift documentation. The purpose of the pilot study was to assess the usability and feasibility of the DAT. METHODS: The research team applied an established user-centered participatory design process to design, develop, and test the DAT prototypes between May 2020 and April 2023. Pilot-testing entailed having 14 DSPs who support adults with IDDs use the first full implementation of the DAT prototypes during 2 or 3 successive work shifts and fill out demographic and usability questionnaires. RESULTS: Participants used the DAT prototypes to create notes and help generate end-of-shift reports. The System Usability Scale score of 81.79 indicates that they found the prototypes easy to use. Survey responses imply that using the DAT made it easier for participants to produce required documentation and suggest that they would adopt the DAT if this tool were available for daily use. CONCLUSIONS: Simple technologies such as the DAT prototypes, which enable DSPs to use mobile devices to log time-stamped notes throughout their shift with minimal effort and use the notes to help write reports, have the potential to both reduce the burden associated with producing documentation and enhance the quality (level of detail and accuracy) of this documentation. This could help to increase job satisfaction and reduce turnover in DSPs, both of which would help improve the quality of life of the individuals with IDDs whom they support. The pilot test results indicate that DSPs found the DAT easy to use. Next steps include (1) producing more robust versions of the DAT with additional capabilities, such as storing data locally on mobile devices when Wi-Fi is not available; and (2) eliciting input from agency directors, families, and others who use data about adults with IDDs to help care for them to ensure that data produced by DSPs are relevant and useful.

The novel endocrine disruptor tolylfluanid impairs insulin signaling in primary rodent and human adipocytes through a reduction in insulin receptor substrate-1 levels.

Emerging data suggest that environmental endocrine disrupting chemicals may contribute to the pathophysiology of obesity and diabetes. In a prior work, the phenylsulfamide fungicide tolylfluanid (TF) was shown to augment adipocyte differentiation, yet its effects on mature adipocyte metabolism remain unknown. Because of the central role of adipose tissue in global energy regulation, the present study tested the hypothesis that TF modulates insulin action in primary rodent and human adipocytes. Alterations in insulin signaling in primary mammalian adipocytes were determined by the phosphorylation of Akt, a critical insulin signaling intermediate. Treatment of primary murine adipose tissue in vitro with 100nM TF for 48h markedly attenuated acute insulin-stimulated Akt phosphorylation in a strain- and species-independent fashion. Perigonadal, perirenal, and mesenteric fat were all sensitive to TF-induced insulin resistance. A similar TF-induced reduction in insulin-stimulated Akt phosphorylation was observed in primary human subcutaneous adipose tissue. TF treatment led to a potent and specific reduction in insulin receptor substrate-1 (IRS-1) mRNA and protein levels, a key upstream mediator of insulin's diverse metabolic effects. In contrast, insulin receptor-ß, phosphatidylinositol 3-kinase, and Akt expression were unchanged, indicating a specific abrogation of insulin signaling. Additionally, TF-treated adipocytes exhibited altered endocrine function with a reduction in both basal and insulin-stimulated leptin secretion. These studies demonstrate that TF induces cellular insulin resistance in primary murine and human adipocytes through a reduction of IRS-1 expression and protein stability, raising concern about the potential for this fungicide to disrupt metabolism and thereby contribute to the pathogenesis of diabetes.

Impaired insulin signaling in human adipocytes after experimental sleep restriction: a randomized, crossover study.

BACKGROUND: Insufficient sleep increases the risk for insulin resistance, type 2 diabetes, and obesity, suggesting that sleep restriction may impair peripheral metabolic pathways. Yet, a direct link between sleep restriction and alterations in molecular metabolic pathways in any peripheral human tissue has not been shown. OBJECTIVE: To determine whether sleep restriction results in reduced insulin sensitivity in subcutaneous fat, a peripheral tissue that plays a pivotal role in energy metabolism and balance. DESIGN: Randomized, 2-period, 2-condition, crossover clinical study. SETTING: University of Chicago Clinical Resource Center. PARTICIPANTS: Seven healthy adults (1 woman, 6 men) with a mean age of 23.7 years (SD, 3.8) and mean body mass index of 22.8 kg/m(2) (SD, 1.6). INTERVENTION: Four days of 4.5 hours in bed or 8.5 hours in bed under controlled conditions of caloric intake and physical activity. MEASUREMENTS: Adipocytes collected from subcutaneous fat biopsy samples after normal and restricted sleep conditions were exposed to incremental insulin concentrations. The ability of insulin to increase levels of phosphorylated Akt (pAkt), a crucial step in the insulin-signaling pathway, was assessed. Total Akt (tAkt) served as a loading control. The insulin concentration for the half-maximal stimulation of the pAkt-tAkt ratio was used as a measure of cellular insulin sensitivity. Total body insulin sensitivity was assessed using a frequently sampled intravenous glucose tolerance test. RESULTS: The insulin concentration for the half-maximal pAkt-tAkt response was nearly 3-fold higher (mean, 0.71 nM [SD, 0.27] vs. 0.24 nM [SD, 0.24]; P = 0.01; mean difference, 0.47 nM [SD, 0.33]; P = 0.01), and the total area under the receiver-operating characteristic curve of the pAkt-tAkt response was 30% lower (P = 0.01) during sleep restriction than during normal sleep. A reduction in total body insulin sensitivity (P = 0.02) paralleled this impaired cellular insulin sensitivity. LIMITATION: This was a single-center study with a small sample size. CONCLUSION: Sleep restriction results in an insulin-resistant state in human adipocytes. Sleep may be an important regulator of energy metabolism in peripheral tissues. PRIMARY FUNDING SOURCE: National Institutes of Health.

Complete Hydatidiform Mole with a Coexisting Viable Male Fetus Detected by Cell-Free DNA.

Complete hydatidiform mole with coexisting fetus (CHMCF) is rare, and diagnosis is challenging due to limited data. Here, we present the case of a patient with noninvasive prenatal test (NIPT) resulting in "likely molar pregnancy" in the second trimester. Subsequent ultrasound confirmed a cystic appearing portion of the placenta. At 22 weeks, the patient delivered a demised fetus and two placentas. Pathology was consistent with CHMCF. This case is the first to show primary detection of a CHMCF with single-nucleotide polymorphism (SNP)-based NIPT prior to ultrasound identification. Our case suggests the use of SNP-based NIPT as an alternative noninvasive method to guide shared decision-making and clinical management for patients with this diagnosis.