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ntibodies before their use in mechanistic studies and as diagnostic tools or therapeutic agents. This will not only improve the quality and reproducibility of research and reduce costs but will also reduce the number of therapeutic antibody failures in the clinic.
Whether gastric emptying tests predict longitudinal outcomes in patients with symptoms of gastroparesis is unclear. We aimed to determine whether baseline gastric emptying tests and gut motility parameters could impact longitudinal symptom(s) and quality of life (QOL) in a prospective, observational cohort study of patients with symptoms of gastroparesis.

One hundred fifty patients with gastroparesis symptoms underwent simultaneous scintigraphy (GES) and wireless motility capsule (WMC) measurement of gastric emptying and other motility parameters. Patient Assessment of Upper Gastrointestinal Symptoms and Quality of Life were administered at baseline, and 3 and 6 months after testing. #link# Multivariable generalized linear marginal models were fit to determine which baseline parameters predict longitudinal changes in symptoms and QOL.

Overall upper GI symptoms and QOL scores were moderate in severity at baseline and significantly improved over 6 months. Clinical variables, including female gender, harder stoolof life outcomes. These factors may help to risk stratify patients and guide treatment decisions. ClinicalTrials.gov no NCT02022826.
Studies have suggested marked increases in transplant delisting due to clinical improvement for patients with hepatitis C virus (HCV) associated cirrhosis in the era of direct acting antivirals (DAAs). This study provides a 'real world' assessment of waitlist dynamics for HCV transplant candidates in the current era.

This was a retrospective cohort study of adults waitlisted for liver transplant (LT) alone between 1/1/2005-12/31/2018 using national US data. The post-DAA era included all listings occurring after 1/1/2013. Temporal trends in waitlisting, patient characteristics and outcomes with decompensated cirrhosis were evaluated. Adjusted competing risks models assessed the interaction of DAA-era and HCV history on (i) waitlist mortality, and (ii) delisting due to clinical improvement.

Overall listing rates for HCV patients have decreased in the DAA era and particularly with Model for End-stage Liver Disease score ≥15 and ≥30. Rates of refractory ascites and severe encephalopathy at listing have increased. Delisting due to clinical improvement remains low (6.1% for 2013-2017 versus 5.2% for 2009-2012 versus 4% for 2005-2008; p < .001) and, for many, ascites (46.5%) and encephalopathy (30.5%) persist at delisting. Waitlist recovery is more frequent for HCV patients post-DAA (adjusted SHR 1.78 vs pre-DAA, 95% CI 1.58-2.02; p<.001), while improvements in waitlist mortality by era are similar to non-HCV candidates (adjusted SHR 0.74 [95% CI 0.7-0.78; p < .001] and 0.77 [95% CI 0.74-0.8; p < .001], respectively).

Listing rates for decompensated HCV cirrhosis have decreased in the DAA era. Delisting of HCV patients for clinical improvement has increased, but remains infrequent and many continue to experience considerable morbidity.
Listing rates for decompensated HCV cirrhosis have decreased in the DAA era. Delisting of HCV patients for clinical improvement has increased, but remains infrequent and many continue to experience considerable morbidity.The current study sought to characterize the pro-survival effects of erythropoietin (EPO) in a toxicant model of Parkinson's disease (PD). EPO treatment induced time-dependent elevations of antioxidant glutathione peroxidase (GPx) and anti-apoptotic factors (pAkt and pBad/Bad) within the striatum and substantia nigra pars compacta (SNc). Intriguingly, our results indicated a region- and lesion size- dependence of pro-survival effects of EPO. Indeed, intra-striatal (but not intra-nigral) infusion of EPO was effective at preventing dopaminergic terminal degeneration and sSNc neuronal loss induced by two different doses of 6-OHDA. These neuroprotective consequences were paralleled by a diminution of microglial morphological changes, along with enhanced motor functioning seen through a reduction in apomorphine-induced rotational behaviour. Finally, in the context of the 6-OHDA lesion, EPO again induced anti-apoptotic (Bcl-2) and antioxidant (GPx) factors within the striatum. Taken together, these results raise the possibility of EPO's potential use as an adjuvant therapy in the treatment of PD, or at least, suggest possible brain-region specific targets for the protective effects of EPO.Effective evaluation and prediction of aerosol transport deposition in the human respiratory tracts are critical to aerosol drug delivery and evaluation of inhalation products. Establishment of an in vitro-in vivo correlation (IVIVC) requires the understanding of flow and aerosol behaviour and underlying mechanisms at the microscopic scale. The achievement of the aim can be facilitated via computational fluid dynamics (CFD) based in silico modelling which treats the aerosol delivery as a two-phase flow. CFD modelling research, in particular coupling with discrete phase model (DPM) and discrete element method (DEM) approaches, has been rapidly developed in the past two decades. link2 This paper reviews the recent development in this area. The paper covers the following aspects geometric models of the respiratory tract, CFD turbulence models for gas phase and its coupling with DPM/DEM for aerosols, and CFD investigation of the effects of key factors associated with geometric variations, flow and powder characteristics. The review showed that in silico study based on CFD models can effectively evaluate and predict aerosol deposition pattern in human respiratory tracts. The review concludes with recommendations on future research to improve in silico prediction to achieve better IVIVC.Drug development is a critical step in the development pipeline of pharmaceutical industry, commonly performed in traditional cell culture and animal models. Though, those models hold critical gapsin the prediction and the translation of human pharmacokinetic (PK) and pharmacodynamics (PD) parameters. The advances in tissue engineering have allowed the combination of cell biology with microengineering techniques, offering alternatives to conventional preclinical models. Organ-on-a-chips and three-dimensional (3D) bioprinting models present the potentialityof simulating the physiological and pathological microenvironment of living organs and tissues, constituting this way,more realistic models for the assessment of absorption, distribution, metabolism and excretion (ADME) of drugs. Therefore, this review will focus on lung-on-a-chip and 3D bioprinting techniques for developing lung models that can be usedfor predicting PK/PD parameters.The regulation of food intake and eating behaviours involves interactions between different systems. The endocannabinoidome, comprising several fatty acid-derived mediators, plays a central role in the regulation of food intake. Alterations of this system have been suggested to intervene in the aetiology of eating disorders. This study aimed to examine the associations between non-pathological eating behaviours and circulating endocannabinoidome mediators in a heterogeneous human population. Plasma 2-monoacyl-glycerol and N-acyl-ethanolamine congeners were measured by LC-MS/MS in a sample of 190 men and women. Eating behaviours were assessed using the Three-Factor Eating Questionnaire (TFEQ) and the Intuitive Eating Scale-2 (IES-2). Following adjustment for body mass index and age, plasma levels of omega-3 polyunsaturated fatty acid-derived 2-monoacyl-glycerols, 2-eicosapentaenoyl-glycerol (2-EPG) and 2-docosapentaenoyl-glycerol (2-DPG), were associated with higher intuitive eating scores (0.15 ≤ rho ≤ 0.20; p less then 0.05). These associations were independent of the dietary intake of the fatty acid precursors of these 2-monoacyl-glycerols. However, almost no association was found between plasma levels of N-acyl-ethanolamine congeners and the TFEQ or the IES-2 scores. The results of the present study suggest the association of 2-monoacyl-glycerols, especially 2-EPG and 2-DPG, in the regulation of intuitive eating and the potential implication therein of bioactive lipids.Eating problems are common among children with Autism Spectrum Disorder (ASD), but it is unknown to what extent infant eating behavior is associated with later autistic traits. As eating selleck products is currently not included in ASD screening instruments, it is important to evaluate whether infant eating behavior predicts later autistic traits and might therefore be used to enhance the early detection of ASD. We investigated the association of breastfeeding and eating behavior during infancy with later autistic traits in the population-based Generation R cohort. We included 3546 mother-child dyads with maternal reports on feeding and eating at age two months and autistic traits at six years. Eating behavior was assessed with seven items on specific eating habits and the Social Responsiveness Scale was used to evaluate autistic traits. Covariates included child sex, and maternal psychopathology and autistic traits. Linear regression analyses showed that being formula fed at two months was associated with a higher autistic trait score at six years (adjusted B = 0.07; 95% CI 0.00-0.14). Children who were drinking only small quantities (adjusted B = 0.17, 95% CI 0.04-0.30) and were hungry/not satisfied (adjusted B = 0.23, 95% CI 0.08-0.39) at age two months also had a higher autistic traits score at age six years. We found no interactions with sex or breastfeeding. This study shows that eating behavior during infancy is related with autistic traits in childhood. Although the associations were fairly small, these findings suggest that early-life eating problems might be relevant for early detection of ASD and a potential addition to ASD-specific screening instruments.Ontogeny of audible and ultrasonic calls is poorly studied in Gerbillinae rodents. In this study, analysis of calls, emitted by pup and adult fat-tailed gerbils Pachyuromys duprasi during 420-s isolation-and-handling procedures, allowed testing two hypotheses. Hypothesis1 predicted that audible squeaks and clicks follow the same ontogenetic pathway (towards higher-frequency and shorter calls) that has been previously documented for the ultrasonic calls of fat-tailed gerbil. Hypothesis2 predicted that the audible call types would alternate with the ultrasonic call types along ontogeny in this species. Hypothesis1 was tested with comparison of acoustic variables of audible calls (squeaks and clicks), emitted by 1-10-day old pups and by adults. Clicks of 8.3-8.7 kHz and high-frequency squeaks of 1.92-3.57 kHz were present in pups and adults, whereas mid-frequency squeaks of 0.31-0.67 kHz and low-frequency squeaks of 0.04-0.11 kHz were only present in pups. In agreement with Hypothesis1, pup high-frequency squeak leaping rodents.Few studies of animal escape behaviour simultaneously investigate behavioural and physiological responses. Differences between these response types, however, have consequences for the way in which habituation or tolerance is interpreted - behavioural habituation may incur physiological costs. We simultaneously measured heart rate (HR) and behavioural responses during standardised approaches to incubating Masked Lapwings Vanellus miles, an urban-frequenting ground-nesting bird. We describe the existence of a distinct Physiological-Initiation Distance (PID) that precedes Flight-Initiation Distance (FID) but does not necessarily precede Alert Distance (AD). Two distinct response types occurred 'startle', where a behavioural or physiological response coincided with the appearance of a person (always the investigator; 75.9 % of 58 birds) and 'non-startle' responses, where a behavioural or physiological response occurred after the appearance of, and commencement of the approach by, the person (24.1 % or 14 birds). link3 For birds which were not startled, the interval between the initial heart rate increase and heart rate peak increased with clutch age.
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