Therapeutic alliance in Enhanced Cognitive Behavioural Therapy for bulimia nervosa: Probably necessary but definitely insufficient

The present paper assessed therapeutic alliance over the course of Enhanced Cognitive Behavioural Therapy (CBT-E) in a community-based sample of 112 patients with a diagnosis of bulimia nervosa (BN) or atypical BN. Temporal assessment of alliance was conducted at three time points (the start, middle and end of treatment) and the relationship between alliance and treatment retention and outcome was explored. Results indicated that the alliance between patient and therapist was strong at all stages of CBT-E, and even improved in the early stages of treatment when behaviour change was initiated (weekly in-session weighing, establishing regular eating, and ceasing binge-eating and compensatory behaviours).The present study found no evidence that alliance was related to treatment retention or outcomes, or that symptom severity or problematic interpersonal styles interacted with alliance to influence outcomes. Alliance was also unrelated to baseline emotional or interpersonal difficulties. The study provides no evidence that alliance has clinical utility for the prediction of treatment retention or outcome in CBT-Efor BN, even for individuals with severe symptoms or problematic interpersonal styles. Early symptom change was the best predictor of outcome in CBT-E. Further research is needed to determine whether these results are generalizable to patients with anorexia nervosa

A model of a small open economy integrated in a monetary union

This paper develops a model of a small open economy integrated in a monetary union, which is a nontrivial technical extension of the existing small open economy model. The model is used to study the monetary transmission mechanism in Portugal.info:eu-repo/semantics/publishedVersio

Uphill walking at iso-efficiency speeds

Uphill walking gait has been extensively studied, but the optimal uphill speed able to enhance the metabolic demand without increasing fatigability has so far received little attention. Therefore, the aim of this study was to assess the metabolic/kinematic demand at constant speed (6 km\ub7h 121 G0 level, G2 2% uphill, G7 7% uphill) and at iso-efficiency speeds (G2IES 5.2 km\ub7h 121 2% uphill and G7IES 3.9 km\ub7h 121 7% uphill). For this aim, physically active women (n:24, Age 33.40 \ub1 4.97 years, BMI 21.62 \ub1 2.06 kg/m-2) after an 8-min warm-up were studied on a treadmill for 10\u2b9 for every walking condition with a 5\u2b9 rest in between. Average heart rate (AVG-HR), rating of perceived exertion (RPE) and kinematic variables (stance time, swing time, stride length, stride cycle, stride-length variability, stride-cycle variability and internal work) were studied. Modif\ufeffications in stance time, stride length and stride cycle (p<0.005), and lower internal-work values (p<0.001) occurred in G7IES in comparison to the other conditions. Swing time was significantly modified only in G7IES compared to G0 and G7 (p<0.001 and p<0.005, respectively). Stride-length variability and stride-cycle variability were higher in G7IES compared to the other conditions (p<0.001). G7 induced the highest AVG-HR (p<0.005) and RPE (p<0.001) compared to the other conditions. This study demonstrates that by applying the equation for uphill walking gait, it is possible to maintain a similar metabolic demand and RPE at iso-efficiency speeds during uphill compared to level walking, inducing at the same time a modification of the kinematic parameters of walking gait performed at the same slope condition

The progression of deoxynivalenol-induced growth suppression in nursery pigs and the potential of an algae-modified montmorillonite clay to mitigate these effects

Citation: Frobose, H. L., Erceg, J. A., Fowler, S. Q., Tokach, M. D., DeRouchey, J. M., Woodworth, J. C., . . . Goodband, R. D. (2016). The progression of deoxynivalenol-induced growth suppression in nursery pigs and the potential of an algae-modified montmorillonite clay to mitigate these effects. Journal of Animal Science, 94(9), 3746-3759. doi:10.2527/jas2016-0663Two experiments were conducted to characterize the progression of deoxynivalenol (DON)-induced growth suppression and to investigate algae-modified montmorillonite clay (AMMC) as a means to alleviate the effects of DON in nursery pigs. In both experiments, naturally DON-contaminated wheat was used to produce diets with desired DON levels. In Exp. 1, 280 barrows and gilts (10.0 +/- 0.2 kg BW) were used in a 28-d experiment arranged in a 2 x 2 + 1 factorial design with 8 replicates per treatment. The 5 treatments consisted of 2 positive control (PC) diets with DON below detection limits and with or without 0 or 0.50% AMMC and 3 negative control (NC) diets with 5 mg/kg of DON and containing 0, 0.25, or 0.50% AMMC. No DON x AMMC interactions were observed. Overall, pigs fed DON had decreased (P < 0.001) ADG and final BW regardless of AMMC addition. Feeding DON-contaminated diets elicited the most severe depression (P < 0.001) in ADFI and G:F from d 0 to 3, remaining poorer overall (P < 0.01) but lessening in severity as exposure time increased. Pigs fed DON diets had greater (P < 0.05) within pen BW variation (CV) on d 28. Although the addition of 0.50% AMMC to diets restored (P < 0.05) ADFI from d 14 to 21 to levels similar to the PC, no other differences were observed for AMMC inclusion. In Exp. 2, 360 barrows (11.4 +/- 0.2 kg BW) were used in a 21-d experiment with 9 dietary treatments arranged in a 3 x 3 factorial design with DON and AMMC inclusion as main effects. There were 8 replicate pens per treatment. Treatments consisted of 3 PC diets without DON, 3 low-DON (1.5 mg/kg DON) NC diets, and 3 high-DON (3 mg/kg DON) NC diets with 0, 0.17, or 0.50% AMMC incorporated at each DON level. No DON x AMMC interactions were observed. As DON level increased, ADG and final BW decreased (quadratic, P < 0.05), driven by decreased (quadratic, P < 0.01) ADFI and poorer (quadratic; P < 0.05) G:F. At both 1.5 and 3 mg/kg DON, reductions in ADG were most marked from d 0 to 7 (15 to 22% lower) and were least distinct from d 14 to 21 (5 to 6% lower). Incorporating AMMC at increasing levels had no effect on ADG, ADFI, G:F, or final BW. Overall, these experiments reinforce DON effects on feed intake but also indicate that the effects of DON on G: F may be more severe than previously thought. Furthermore, some pigs appear to develop tolerance to DON, as effects on ADFI and G: F lessen over time. However, the addition of AMMC did not offset the deleterious effects of DON

Comparison of Proliferation and Differentiation of Calvarial Osteoblast Cultures Derived from Msx2 Deficient and Wild Type Mice

We analyzed proliferation and differentiation of calvarial osteoblasts derived from Msx2 deficient in comparison with wild type mice. Calvarial osteoblast cultures from five to eight days old Msx2 deficient, heterozygous and wild type mice were studied for difference in proliferation and differentiation. Proliferation rate was assessed by counting cell number, BrdU and Calcein AM labeling. Differentiation was assessed by Von Kossa and alkaline phosphatase staining, northern blot hybridization with bone differentiation markers, infection of cell cultures with retrovirus expressing GFP under the control of type I collagen promoter fragment. At day six, cell number in cell culture derived from Msx2 deficient mice was 20% lower then in culture from wild type mice. There were 16.8% BrdU labeled cells in cell culture from Msx2 deficient mice, 20.9% in culture from heterozygous mice and 21.6% in culture from wild type mice. Cell cultures from Msx2 deficient mice showed lower intensity of fluorescence when marked with Calcein AM then cultures from wild type mice. Von Kossa staining showed increased mineralization and northern blot analysis showed increased levels of bone differentiation markers in cell cultures derived from Msx2 deficient mice. GFP came on earlier in Msx2 deficient cultures after infection with Col2.3 GFP retrovirus. We conclude that calvarial osteoblasts derived from Msx2 deficient mice have a lower rate of proliferation and demonstrate increased osteoblastic differentiation when compared to osteoblasts derived from wild type mice

Unraveling the developmental roadmap toward human brown adipose tissue

Increasing brown adipose tissue (BAT) mass and activation is a therapeutic strategy to treat obesity and complications. Obese and diabetic patients possess low amounts of BAT, so an efficient way to expand their mass is necessary. There is limited knowledge about how human BAT develops, differentiates, and is optimally activated. Accessing human BAT is challenging, given its low volume and anatomical dispersion. These constraints make detailed BAT-related developmental and functional mechanistic studies in humans virtually impossible. We have developed and characterized functionally and molecularly a new chemically defined protocol for the differentiation of human pluripotent stem cells (hPSCs) into brown adipocytes (BAs) that overcomes current limitations. This protocol recapitulates step by step the physiological developmental path of human BAT. The BAs obtained express BA and thermogenic markers, are insulin sensitive, and responsive to β-adrenergic stimuli. This new protocol is scalable, enabling the study of human BAs at early stages of development

New generalized fuzzy metrics and fixed point theorem in fuzzy metric space

In this paper, in fuzzy metric spaces (in the sense of Kramosil and Michalek (Kibernetika 11:336-344, 1957)) we introduce the concept of a generalized fuzzy metric which is the extension of a fuzzy metric. First, inspired by the ideas of Grabiec (Fuzzy Sets Syst. 125:385-389, 1989), we define a new G-contraction of Banach type with respect to this generalized fuzzy metric, which is a generalization of the contraction of Banach type (introduced by M Grabiec). Next, inspired by the ideas of Gregori and Sapena (Fuzzy Sets Syst. 125:245-252, 2002), we define a new GV-contraction of Banach type with respect to this generalized fuzzy metric, which is a generalization of the contraction of Banach type (introduced by V Gregori and A Sapena). Moreover, we provide the condition guaranteeing the existence of a fixed point for these single-valued contractions. Next, we show that the generalized pseudodistance J:X×X→[0,∞) (introduced by Włodarczyk and Plebaniak (Appl. Math. Lett. 24:325-328, 2011)) may generate some generalized fuzzy metric NJ on X. The paper includes also the comparison of our results with those existing in the literature

Expression and function of Dlx genes in the osteoblast lineage

AbstractOur laboratory and others have shown that overexpression of Dlx5 stimulates osteoblast differentiation. Dlx5−/−/Dlx6−/− mice have more severe craniofacial and limb defects than Dlx5−/−, some of which are potentially due to defects in osteoblast maturation. We wished to investigate the degree to which other Dlx genes compensate for the lack of Dlx5, thus allowing normal development of the majority of skeletal elements in Dlx5−/− mice. Dlx gene expression in cells from different stages of the osteoblast lineage isolated by FACS sorting showed that Dlx2, Dlx5 and Dlx6 are expressed most strongly in less mature osteoblasts, whereas Dlx3 is very highly expressed in differentiated osteoblasts and osteocytes. In situ hybridization and Northern blot analysis demonstrated the presence of endogenous Dlx3 mRNA within osteoblasts and osteocytes. Dlx3 strongly upregulates osteoblastic markers with a potency comparable to Dlx5. Cloned chick or mouse Dlx6 showed stimulatory effects on osteoblast differentiation. Our results suggest that Dlx2 and Dlx6 have the potential to stimulate osteoblastic differentiation and may compensate for the absence of Dlx5 to produce relatively normal osteoblastic differentiation in Dlx5 knockout mice, while Dlx3 may play a distinct role in late stage osteoblast differentiation and osteocyte function

Pharmacological screening identifies SHK242 and SHK277 as novel arginase inhibitors with efficacy against allergen-induced airway narrowing in vitro and in vivo

Arginase is a potential target for asthma treatment. However, there are currently no arginase inhibitors available for clinical use. Here, a novel class of arginase inhibitors was synthesized, and their efficacy was pharmacologically evaluated. The reference compound 2(S)-amino-6-boronohexanoic acid (ABH) and >200 novel arginase inhibitors were tested for their ability to inhibit recombinant human arginase 1 and 2 in vitro. The most promising compounds were separated as enantiomers. Enantiomer pairs SHK242 and SHK243, and SHK277 and SHK278 were tested for functional efficacy by measuring their effect on allergen-induced airway narrowing in lung slices of ovalbumin-sensitized guinea pigs ex vivo. A guinea pig model of acute allergic asthma was used to examine the effect of the most efficacious enantiopure arginase inhibitors on allergen-induced airway hyper-responsiveness (AHR), early and late asthmatic reactions (EAR and LAR), and airway inflammation in vivo. The novel compounds were efficacious in inhibiting arginase 1 and 2 in vitro. The enantiopure SHK242 and SHK277 fully inhibited arginase activity, with IC50 values of 3.4 and 10.5 μM for arginase 1 and 2.9 and 4.0 µM for arginase 2, respectively. Treatment of slices with ABH or novel compounds resulted in decreased ovalbumin-induced airway narrowing compared with control, explained by increased local nitric oxide production in the airway. In vivo, ABH, SHK242, and SHK277 protected against allergen-induced EAR and LAR but not against AHR or lung inflammation. We have identified promising novel arginase inhibitors for the potential treatment of allergic asthma that were able to protect against allergen-induced early and late asthmatic reactions. SIGNIFICANCE STATEMENT: Arginase is a potential drug target for asthma treatment, but currently there are no arginase inhibitors available for clinical use. We have identified promising novel arginase inhibitors for the potential treatment of allergic asthma that were able to protect against allergen-induced early and late asthmatic reactions. Our new inhibitors show protective effects in reducing airway narrowing in response to allergens and reductions in the early and late asthmatic response