A Concurrent Validity Study of the Mullen Scales of Early Learning (MSEL) and the MacArthur-Bates Communicative Developmental Inventory (CDI) in Infants with an Elevated Likelihood or Diagnosis of Autism.

Infants at elevated likelihood for or later diagnosed with autism typically have smaller vocabularies than their peers, as shown by the Mullen Scales of Early Learning (MSEL) and the MacArthur-Bates Communicative Developmental Inventory (CDI). However, the extent to which MSEL and CDI scores align remains unclear, especially across clinical and non-clinical populations. This study examined whether the concurrent validity of the MSEL and CDI differs based on autism likelihood and diagnosis.

Infant responses to direct gaze and associations to autism: A live eye-tracking study.

When other people look directly towards us, we often respond by looking back at them, and such direct-gaze responses are important for establishing eye contact. Atypical eye contact is common in autism, but how and when this aspect of autism develops is not well understood. Here, we studied whether how much and how quickly infants respond to others' direct gaze is associated with autism in toddlerhood.

Stable eye versus mouth preference in a live speech-processing task.

Looking at the mouth region is thought to be a useful strategy for speech-perception tasks. The tendency to look at the eyes versus the mouth of another person during speech processing has thus far mainly been studied using screen-based paradigms. In this study, we estimated the eye-mouth-index (EMI) of 38 adult participants in a live setting.

Pre-pragmatic language use in toddlerhood: Developmental antecedents, aetiological factors, and associations to autism.

Background: Pragmatic language is key for adaptive communication, but often compromised in neurodevelopmental conditions such as autism spectrum disorder (ASD). Decontextualized language-to talk about events and things beyond here and now-develops early in childhood and can be seen as a pre-pragmatic ability. Little is known about the factors that contribute to decontextualized language use in toddlers and whether these are different from factors contributing to general language development.

Preferential looking to eyes versus mouth in early infancy: heritability and link to concurrent and later development.

Background: From birth, infants orient preferentially to faces, and when looking at the face, they attend primarily to eyes and mouth. These areas convey different types of information, and earlier research suggests that genetic factors influence the preference for one or the other in young children.

Methods: In a sample of 535 5-month-old infant twins, we assessed eye (relative to mouth) preference in early infancy, i.

Larger pupil dilation to nonsocial sounds in infants with subsequent autism diagnosis.

Background: Studies of infants with an elevated likelihood of autism spectrum disorder can identify basic developmental processes that are associated with subsequently emerging clinical symptoms. Atypical responsiveness to sounds in infancy is such a potential early marker of autism. Here, we used pupillometry to quantify reactivity to social and nonsocial sounds in infants with a subsequent diagnosis.

A Physiology-Based Model of Bile Acid Distribution and Metabolism Under Healthy and Pathologic Conditions in Human Beings.

Background & Aims: Disturbances of the enterohepatic circulation of bile acids (BAs) are seen in a number of clinically important conditions, including metabolic disorders, hepatic impairment, diarrhea, and gallstone disease. To facilitate the exploration of underlying pathogenic mechanisms, we developed a mathematical model built on quantitative physiological observations across different organs.

Methods: The model consists of a set of kinetic equations describing the syntheses of cholic, chenodeoxycholic, and deoxycholic acids, as well as time-related changes of their respective free and conjugated forms in the systemic circulation, the hepatoportal region, and the gastrointestinal tract.

Of mice and men: murine bile acids explain species differences in the regulation of bile acid and cholesterol metabolism.

Compared with humans, rodents have higher synthesis of cholesterol and bile acids (BAs) and faster clearance and lower levels of serum LDL-cholesterol. Paradoxically, they increase BA synthesis in response to bile duct ligation (BDL). Another difference is the production of hydrophilic 6-hydroxylated muricholic acids (MCAs), which may antagonize the activation of FXRs, in rodents versus humans.

Regulation of bile acid metabolism in biliary atresia: reduction of FGF19 by Kasai portoenterostomy and possible relation to early outcome.

Background: Fibroblast growth factor 19 (FGF19) is produced in the small intestine and is involved in suppression of hepatic bile acid (BA) synthesis. FGF19 is also expressed in the liver and serum levels are elevated in adults with cholestatic liver disease. This may reflect a rescue mechanism to dampen liver injury caused by increased intrahepatic BAs.

Energy restriction in obese women suggest linear reduction of hepatic fat content and time-dependent metabolic improvements.

Energy restriction reduces liver fat, improves hepatic insulin resistance and lipid metabolism. However, temporal data in which these metabolic improvements occur and their interplay is incomplete. By performing repeated MRI scans and blood analysis at day 0, 3, 7, 14 and 28 the temporal changes in liver fat and related metabolic factors were assessed at five times during a low-calorie diet (LCD, 800-1100 kcal/day) in ten obese non-diabetic women (BMI 41.

Overeating Saturated Fat Promotes Fatty Liver and Ceramides Compared With Polyunsaturated Fat: A Randomized Trial.

Context: Saturated fatty acid (SFA) vs polyunsaturated fatty acid (PUFA) may promote nonalcoholic fatty liver disease by yet unclear mechanisms.

Objective: To investigate if overeating SFA- and PUFA-enriched diets lead to differential liver fat accumulation in overweight and obese humans.

Design: Double-blind randomized trial (LIPOGAIN-2).

Gallbladder bile supersaturated with cholesterol in gallstone patients preferentially develops from shortage of bile acids.

Gallstone (GS) formation requires that bile is supersaturated with cholesterol, which is estimated by a cholesterol saturation index (CSI) calculated from gallbladder (GB) total lipids and the mol% (mole percent) of bile acids (BAs), cholesterol, and phospholipids (PLs). Whereas CSI indicates GS risk, we hypothesized that additional comparisons of GB lipid mol% data are inappropriate to identify why CSI is increased in GS disease. We anticipated that GB lipid mmol/l (millimole per liter) levels should instead identify that, and therefore retrieved GB mmol/l data for BAs, cholesterol, and PLs from a study on 145 GS and 87 GS-free patients and compared them with the corresponding mol% data.

Asynchronous rhythms of circulating conjugated and unconjugated bile acids in the modulation of human metabolism.

Background And Objectives: Bile acids (BAs) traversing the enterohepatic circulation (EHC) influence important metabolic pathways. By determining individual serum BAs in relation to markers of metabolic activity, we explored how diurnal variations in their EHC relate to hepatic metabolism in normal humans.

Methods: Serum BAs, fibroblast growth factor 19 (FGF19), lipoproteins, glucose/insulin and markers of cholesterol and BA syntheses were monitored for 32 h in 8 healthy males.

An FXR Agonist Reduces Bile Acid Synthesis Independently of Increases in FGF19 in Healthy Volunteers.

Bile acid (BA) synthesis is regulated through suppression of hepatic cholesterol 7α-hydroxylase via farnesoid X receptor (FXR) activation in hepatocytes and/or enterocytes; in enterocytes, this process requires FGF19 signaling. To study these pathways, we quantified markers of BA synthesis (7α-hydroxy-4-cholesten-3-one [C4]) and cholesterol production (lathosterol), fibroblast growth factor (FGF)19, and BAs in serum from healthy male volunteers given 1 oral dose of the nonsteroidal FXR agonist Px-102 (0.15 mg/kg, 0.

Cholestyramine treatment of healthy humans rapidly induces transient hypertriglyceridemia when treatment is initiated.

Bile acid (BA) production in mice is regulated by hepatic farnesoid X receptors and by intestinal fibroblast growth factor (FGF)-15 (in humans, FGF-19), a suppressor of BA synthesis that also reduces serum triglycerides and glucose. Cholestyramine treatment reduces FGF-19 and induces BA synthesis, whereas plasma triglycerides may increase from unclear reasons. We explored whether FGF-19 may suppress BA synthesis and plasma triglycerides in humans by modulation of FGF-19 levels through long-term cholestyramine treatment at increasing doses.

Acute caloric restriction counteracts hepatic bile acid and cholesterol deficiency in morbid obesity.

Background: Bile acid (BA) synthesis is regulated by BA signalling in the liver and by fibroblast growth factor 19 (FGF19), synthesized and released from the intestine. In morbid obesity, faecal excretion and hepatic synthesis of BAs and cholesterol are strongly induced and caloric restriction reduces their faecal excretion considerably. We hypothesized that the high intestinal food mass in morbidly obese subjects promotes faecal excretion of BAs and cholesterol, thereby creating a shortage of both BAs and cholesterol in the liver.

Treatment with the natural FXR agonist chenodeoxycholic acid reduces clearance of plasma LDL whilst decreasing circulating PCSK9, lipoprotein(a) and apolipoprotein C-III.

Background: The natural farnesoid X receptor (FXR) agonist chenodeoxycholic acid (CDCA) suppresses hepatic cholesterol and bile acid synthesis and reduces biliary cholesterol secretion and triglyceride production. Animal studies have shown that bile acids downregulate hepatic LDL receptors (LDLRs); however, information on LDL metabolism in humans is limited.

Methods: Kinetics of autologous I-LDL were determined in 12 male subjects at baseline and during treatment with CDCA (15 mg kg day ).

Impaired Cholesterol Efflux Capacity of High-Density Lipoprotein Isolated From Interstitial Fluid in Type 2 Diabetes Mellitus-Brief Report.

Objective: Patients with type 2 diabetes mellitus (T2D) have an increased risk of cardiovascular disease, the mechanism of which is incompletely understood. Their high-density lipoprotein (HDL) particles in plasma have been reported to have impaired cholesterol efflux capacity. However, the efflux capacity of HDL from interstitial fluid (IF), the starting point for reverse cholesterol transport, has not been studied.

Circulating Hepcidin-25 Is Reduced by Endogenous Estrogen in Humans.

Objective: Hepcidin reduces iron absorption by binding to the intestinal iron transporter ferroportin, thereby causing its degradation. Although short-term administration of testosterone or growth hormone (GH) has been reported to decrease circulating hepcidin levels, little is known about how hepcidin is influenced in human endocrine conditions associated with anemia.

Research Design And Methods: We used a sensitive and specific dual-monoclonal antibody sandwich immunoassay to measure hepcidin-25 in patients (a) during initiation of in vitro fertilization when endogenous estrogens were elevated vs.

Mice Abundant in Muricholic Bile Acids Show Resistance to Dietary Induced Steatosis, Weight Gain, and to Impaired Glucose Metabolism.

High endogenous production of, or treatment with muricholic bile acids, strongly reduces the absorption of cholesterol. Mice abundant in muricholic bile acids may therefore display an increased resistance against dietary induced weight gain, steatosis, and glucose intolerance due to an anticipated general reduction in lipid absorption. To test this hypothesis, mice deficient in steroid 12-alpha hydroxylase (Cyp8b1-/-) and therefore abundant in muricholic acids were monitored for 11 weeks while fed a high fat diet.

Specific inhibition of bile acid transport alters plasma lipids and GLP-1.

Background: Elobixibat is a minimally absorbed ileal bile acid (BA) transporter (IBAT) inhibitor in development against chronic constipation (CC) and constipation-predominant Irritable Bowel Syndrome (IBS-C). CC is associated with an increased risk for cardiovascular disease and type2 diabetes mellitus. The objectives of this study were to evaluate metabolic effects of elobixibat.

Levels of atherogenic lipoproteins are unexpectedly reduced in interstitial fluid from type 2 diabetes patients.

At a given level of serum cholesterol, patients with T2D have an increased risk of developing atherosclerosis compared with nondiabetic subjects. We hypothesized that T2D patients have an increased interstitial fluid (IF)-to-serum gradient ratio for LDL, due to leakage over the vascular wall. Therefore, lipoprotein profiles in serum and IF from 35 T2D patients and 35 healthy controls were assayed using fast performance liquid chromatography.