Is reduction in appetite beneficial for body weight management in the context of overweight and obesity? Yes, according to the SATIN (Satiety Innovation) study

New dietary-based concepts are needed for treatment and effective prevention of overweight and obesity. The primary objective was to investigate if reduction in appetite is associated with improved weight loss maintenance. This cohort study was nested within the European Commission project Satiety Innovation (SATIN). Participants achieving ≥8% weight loss during an initial 8-week low-energy formula diet were included in a 12-week randomised double-blind parallel weight loss maintenance intervention. The intervention included food products designed to reduce appetite or matching controls along with instructions to follow national dietary guidelines. Appetite was assessed by ad libitum energy intake and self-reported appetite evaluations using visual analogue scales during standardised appetite probe days. These were evaluated at the first day of the maintenance period compared with baseline (acute effects after a single exposure of intervention products) and post-maintenance compared with baseline (sustained effects after repeated exposures of intervention products) regardless of randomisation. A total of 181 participants (forty-seven men and 134 women) completed the study. Sustained reduction in 24-h energy intake was associated with improved weight loss maintenance (R 0·37; P = 0·001), whereas the association was not found acutely (P = 0·91). Suppression in self-reported appetite was associated with improved weight loss maintenance both acutely (R −0·32; P = 0·033) and sustained (R −0·33; P = 0·042). Reduction in appetite seems to be associated with improved body weight management, making appetite-reducing food products an interesting strategy for dietary-based concepts

Feasibility Study of a Wearable Exoskeleton for Children: Is the Gait Altered by Adding Masses on Lower Limbs?

We are designing a pediatric exoskeletal ankle robot (pediatric Anklebot) to promote gait habilitation in children with Cerebral Palsy (CP). Few studies have evaluated how much or whether the unilateral loading of a wearable exoskeleton may have the unwanted effect of altering significantly the gait. The purpose of this study was to evaluate whether adding masses up to 2.5 kg, the estimated overall added mass of the mentioned device, at the knee level alters the gait kinematics. Ten healthy children and eight children with CP, with light or mild gait impairment, walked wearing a knee brace with several masses. Gait parameters and lower-limb joint kinematics were analyzed with an optoelectronic system under six conditions: without brace (natural gait) and with masses placed at the knee level (0.5, 1.0, 1.5, 2.0, 2.5 kg). T-tests and repeated measures ANOVA tests were conducted in order to find noteworthy differences among the trial conditions and between loaded and unloaded legs. No statistically significant differences in gait parameters for both healthy children and children with CP were observed in the five “with added mass” conditions. We found significant differences among “natural gait” and “with added masses” conditions in knee flexion and hip extension angles for healthy children and in knee flexion angle for children with CP. This result can be interpreted as an effect of the mechanical constraint induced by the knee brace rather than the effect associated with load increase. The study demonstrates that the mechanical constraint induced by the brace has a measurable effect on the gait of healthy children and children with CP and that the added mass up to 2.5 kg does not alter the lower limb kinematics. This suggests that wearable devices weighing 25 N or less will not noticeably modify the gait patterns of the population examined here.Cerebral Palsy International Research FoundationStavros S. Niarchos Foundatio

Optimized Hydrophobic Interactions and Hydrogen Bonding at the Target-Ligand Interface Leads the Pathways of Drug-Designing

Weak intermolecular interactions such as hydrogen bonding and hydrophobic interactions are key players in stabilizing energetically-favored ligands, in an open conformational environment of protein structures. However, it is still poorly understood how the binding parameters associated with these interactions facilitate a drug-lead to recognize a specific target and improve drugs efficacy. To understand this, comprehensive analysis of hydrophobic interactions, hydrogen bonding and binding affinity have been analyzed at the interface of c-Src and c-Abl kinases and 4-amino substituted 1H-pyrazolo [3, 4-d] pyrimidine compounds.In-silico docking studies were performed, using Discovery Studio software modules LigandFit, CDOCKER and ZDOCK, to investigate the role of ligand binding affinity at the hydrophobic pocket of c-Src and c-Abl kinase. Hydrophobic and hydrogen bonding interactions of docked molecules were compared using LigPlot program. Furthermore, 3D-QSAR and MFA calculations were scrutinized to quantify the role of weak interactions in binding affinity and drug efficacy.The in-silico method has enabled us to reveal that a multi-targeted small molecule binds with low affinity to its respective targets. But its binding affinity can be altered by integrating the conformationally favored functional groups at the active site of the ligand-target interface. Docking studies of 4-amino-substituted molecules at the bioactive cascade of the c-Src and c-Abl have concluded that 3D structural folding at the protein-ligand groove is also a hallmark for molecular recognition of multi-targeted compounds and for predicting their biological activity. The results presented here demonstrate that hydrogen bonding and optimized hydrophobic interactions both stabilize the ligands at the target site, and help alter binding affinity and drug efficacy

Structure-Based Development of Small Molecule PFKFB3 Inhibitors: A Framework for Potential Cancer Therapeutic Agents Targeting the Warburg Effect

Cancer cells adopt glycolysis as the major source of metabolic energy production for fast cell growth. The HIF-1-induced PFKFB3 plays a key role in this adaptation by elevating the concentration of Fru-2,6-BP, the most potent glycolysis stimulator. As this metabolic conversion has been suggested to be a hallmark of cancer, PFKFB3 has emerged as a novel target for cancer chemotherapy. Here, we report that a small molecular inhibitor, N4A, was identified as an initial lead compound for PFKFB3 inhibitor with therapeutic potential. In an attempt to improve its potency, we determined the crystal structure of the PFKFB3•N4A complex to 2.4 Å resolution and, exploiting the resulting molecular information, attained the more potent YN1. When tested on cultured cancer cells, both N4A and YN1 inhibited PFKFB3, suppressing the Fru-2,6-BP level, which in turn suppressed glycolysis and, ultimately, led to cell death. This study validates PFKFB3 as a target for new cancer therapies and provides a framework for future development efforts

Change in basic motor abilities, quality of movement and everyday activities following intensive, goal-directed, activity-focused physiotherapy in a group setting for children with cerebral palsy

Background: The effects of intensive training for children with cerebral palsy (CP) remain uncertain. The aim of the study was to investigate the impact on motor function, quality of movements and everyday activities of three hours of goal-directed activity-focused physiotherapy in a group setting, five days a week for a period of three weeks. Methods: A repeated measures design was applied with three baseline and two follow up assessments; immediately and three weeks after intervention. Twenty-two children with hemiplegia (n = 7), diplegia (n = 11), quadriplegia (n = 2) and ataxia (n = 2) participated, age ranging 3-9 y. All levels of Gross Motor Function Classification System (GMFCS) and Manual Ability Classification System (MACS) were represented. Parents and professionals participated in goal setting and training. ANOVA was used to analyse change over repeated measures. Results: A main effect of time was shown in the primary outcome measure; Gross Motor Function Measure-66 (GMFM- 66), mean change being 4.5 (p < 0.01) from last baseline to last follow up assessment. An interaction between time and GMFCS-levels was found, implying that children classified to GMFCS-levels I-II improved more than children classified to levels III-V. There were no main or interaction effects of age or anti-spastic medication. Change scores in the Pediatric Evaluation of Disability Inventory (PEDI) ranged 2.0-6.7, p < 0.01 in the Self-care domain of the Functional Skills dimension, and the Self-care and Mobility domains of the Caregiver Assistance dimension. The children's individual goals were on average attained, Mean Goal Attainment Scaling (GAS) T-score being 51.3. Non-significant improved scores on the Gross Motor Performance Measure (GMPM) and the Quality of Upper Extremities Skills Test (QUEST) were demonstrated. Significant improvement in GMPM scores were found in improved items of the GMFM, not in items that maintained the same score. Conclusions: Basic motor abilities and self-care improved in young children with CP after goal-directed activityfocused physiotherapy with involvement of their local environment, and their need for caregiver assistance in self-care and mobility decreased. The individualized training within a group context during a limited period of time was feasible and well-tolerated. The coherence between acquisition of basic motor abilities and quality of movement should be further examined

‘Better late than never’: the interplay between green technology and age for firm growth

This paper investigates the relationship between green/non-green technologies and firm growth. By combining the literature on eco-innovations, industrial organisation and entrepreneurial studies, we examine the dependence of this relationship on the pace at which firms grow and the age of the firm. From a dataset of 5498 manufacturing firms in Italy for the period of 2000–2008, longitudinal fixed effects quantile models are estimated, in which the firm’s age is set to moderate the effects of green and non-green patents on employment growth. We find that the positive effect of green technologies on growth is greater than that of non-green technologies. However, this result does not apply to struggling and rapidly growing firms. With fast-growing (above the median) firms, age moderates the growth effect of green technologies. Inconsistent with the extant literature, this moderation effect is positive: firm experience appears important for the growth benefits of green technologies, possibly relative to the complexity of their management

Characterization techniques for studying the properties of nanocarriers for systemic delivery

Nanocarriers have attracted a huge interest in the last decade as efficient drug delivery systems and diagnostic tools. They enable effective, targeted, controlled delivery of therapeutic molecules while lowering the side effects caused during the treatment. The physicochemical properties of nanoparticles determine their in vivo pharmacokinetics, biodistribution and tolerability. The most analyzed among these physicochemical properties are shape, size, surface charge and porosity and several techniques have been used to characterize these specific properties. These different techniques assess the particles under varying conditions, such as physical state, solvents etc. and as such probe, in addition to the particles themselves, artifacts due to sample preparation or environment during measurement. Here, we discuss the different methods to precisely evaluate these properties, including their advantages or disadvantages. In several cases, there are physical properties that can be evaluated by more than one technique. Different strengths and limitations of each technique complicate the choice of the most suitable method, while often a combinatorial characterization approach is needed

Early improvement in food cravings are associated with long-term weight loss success in a large clinical sample

Correction to: International Journal of Obesity (2017) 41,1232–1236; doi:10.1038/ijo.2017.89 Since publication the authors of this paper have requested that it be made open access under the CC BY licence

Cytoskeletal control of B cell responses to antigens.

The actin cytoskeleton is essential for cell mechanics and has increasingly been implicated in the regulation of cell signalling. In B cells, the actin cytoskeleton is extensively coupled to B cell receptor (BCR) signalling pathways, and defects of the actin cytoskeleton can either promote or suppress B cell activation. Recent insights from studies using single-cell imaging and biophysical techniques suggest that actin orchestrates BCR signalling at the plasma membrane through effects on protein diffusion and that it regulates antigen discrimination through the biomechanics of immune synapses. These mechanical functions also have a role in the adaptation of B cell subsets to specialized tasks during antibody responses

Following the genes: a framework for animal modeling of psychiatric disorders

The number of individual cases of psychiatric disorders that can be ascribed to identified, rare, single mutations is increasing with great rapidity. Such mutations can be recapitulated in mice to generate animal models with direct etiological validity. Defining the underlying pathogenic mechanisms will require an experimental and theoretical framework to make the links from mutation to altered behavior in an animal or psychopathology in a human. Here, we discuss key elements of such a framework, including cell type-based phenotyping, developmental trajectories, linking circuit properties at micro and macro scales and definition of neurobiological phenotypes that are directly translatable to humans