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Objective: Prevention of eating disorders (EDs) is of high importance. However, digital programs with human moderation are unlikely to be disseminated widely. The aim of this study was to test whether a chatbot (i.e., computer program simulating human conversation) would significantly reduce ED risk factors (i.e., weight/shape concerns, thin‐ideal internalization) in women at high risk for an ED, compared to waitlist control, as well as whether it would significantly reduce overall ED psychopathology, depression, and anxiety and prevent ED onset. Method: Women who screened as high risk for an ED were randomized (N = 700) to (1) chatbot based on the StudentBodies© program; or (2) waitlist control. Participants were followed for 6 months. Results: For weight/shape concerns, there was a significantly greater reduction in intervention versus control at 3‐ (d = −0.20; p =.03) and 6‐m‐follow‐up (d = −0.19; p =.04). There were no differences in change in thin‐ideal internalization. The intervention was associated with significantly greater reductions than control in overall ED psychopathology at 3‐ (d = −0.29; p =.003) but not 6‐month follow‐up. There were no differences in change in depression or anxiety. The odds of remaining nonclinical for EDs were significantly higher in intervention versus control at both 3‐ (OR = 2.37, 95% CI [1.37, 4.11]) and 6‐month follow‐ups (OR = 2.13, 95% CI [1.26, 3.59]). Discussion: Findings provide support for the use of a chatbot‐based EDs prevention program in reducing weight/shape concerns through 6‐month follow‐up, as well as in reducing overall ED psychopathology, at least in the shorter‐term. Results also suggest the intervention may reduce ED onset. Public Significance: We found that a chatbot, or a computer program simulating human conversation, based on an established, cognitive‐behavioral therapy‐based eating disorders prevention program, was successful in reducing women's concerns about weight and shape through 6‐month follow‐up and that it may actually reduce eating disorder onset. These findings are important because this intervention, which uses a rather simple text‐based approach, can easily be disseminated in order to prevent these deadly illnesses. Trial registration: OSF Registries; https://osf.io/7zmbv [ABSTRACT FROM AUTHOR]

The novel identity of gem-dialkyl succinic acids as inhibitors for carboxypeptidases was established through utilization of X-ray crystallography. Results have shown that the presence of hydrophobic cavity in the enzyme accommodates the crucial catalytic residue glu-270 as well as the possible interactions with the methyl group of the inhibitor, thus, enhancing the binding.

The mechanism of subunit assembly of aspartate transcarbamoylase from Escherichia coli was studied by following the kinetics of reassociation. The isolated trimetric catalytic subunit (c3) and dimeric regulatory subunit (r2) were mixed together and formation of the dodecameric native enzyme (c6r6) was monitored by measuring changes in activity. Under appropriate conditions the reassociation was second order with respect to the c3 concentration and the effects of varying r2 concentration on the second-order rate constant were examined. An optimum r2 concentration of about 0.07 μM was observed. A scheme of the assembly pathways is proposed and is based on the reversible formation of c3r2n (n = 0, 1, 2 or 3) as intermediates. Various combinations of two such c3r2n species are considered as possible rate-limiting steps. This model yields an expression which relates the experimentally determined (overall) second-order rate constant to the equilibrium constant (Kd) governing the formation of c3r2n, the r2 concentration, and four coefficients which reflect the contribution of different types of assembly processes. Using previously determined values of Kd, the above expression for each r2 concentration reduces to a linear equation with four unknowns. The experimental data were subjected to multiple linear-regression analysis and values for the four coefficients were found which gave an excellent fit. Our results show that reassociation of the subunits is a fast bimolecular reaction with rate constants in excess of 106 M-1 s-1. Our analysis also suggests that interactions involving a total of more than three r2 subunits (e.g. the combination of c3r2 with c3r6) might contribute significantly to the overall assembly. The influence of various ligands on the reassociation rate profile was also studied. All ligands examined were partially inhibitory to the formation of native enzyme. The effects of substrates were similar to those of CTP whereas the effects of ATP were substantially different. These observations can be readily interpreted by postulating different conformational changes induced by the ligands. These changes should alter the relative orientation of the subunit contacts which must be formed in the reassociation process. The interpretation is consistent with our previous model of the allosteric mechanism. [ABSTRACT FROM AUTHOR]

Individual subunits of yeast transaldolase were studied by the method of matrix-bound derivatives. Native dimeric transaldolase was bound to Sepharose activated with low amounts of cyanogen bromide to give matrix-bound transaldolase in which the majority of molecules were bound covalently via only one subunit. Exhaustive washing with 6 M guanidinium chloride and renaturation in triethanolamine-EDTA buffer resulted in a derivative (bound-subunit transaldolase) which retained 65% of the original protein and 63% of the original activity. This active form of transaldolase is more sensitive to 2 M urea than bound-dimeric transaldolase. Bound-subunit transaldolase is able to associate with "nascent" soluble transaldolase subunits generated in situ by diluting a small aliquot of guanidinium-chloride-denatured transaldolase into a much larger volume of buffer. The ability of bound-subunit derivative to pick up soluble "nascent" transaldolase subunits is highly specific and reaches a plateau level close to the original protein and activity content of bound transaldolase. The product of such treatment (bound-renatured transaldolase) has properties virtually indistinguishable from those of bound transaldolase. These results indicate that individual subunits of transaldolase are catalytically active. Bound-subunit transaldolase has Km values similar to those of the bound-dimeric derivatives and can be inactivated with sodium borohydride in the presence of the substrate fructose 6-phosphate. However, the pH profile of the subunit form is substantially altered suggesting a shift in the pKa of an essential protonated group from 9.2 to 8.6. [ABSTRACT FROM AUTHOR]

Aim: To analyze whether high-intensity focused ultrasound (HIFU) ablation is an effective bridging therapy for patients with hepatocellular carcinoma (HCC)., Methods: From January 2007 to December 2010, 49 consecutive HCC patients were listed for liver transplantation (UCSF criteria). The median waiting time for transplantation was 9.5 mo. Twenty-nine patients received transarterial chemoembolization (TACE) as a bringing therapy and 16 patients received no treatment before transplantation. Five patients received HIFU ablation as a bridging therapy. Another five patients with the same tumor staging (within the UCSF criteria) who received HIFU ablation but not on the transplant list were included for comparison. Patients were comparable in terms of Child-Pugh and model for end-stage liver disease scores, tumor size and number, and cause of cirrhosis., Results: The HIFU group and TACE group showed no difference in terms of tumor size and tumor number. One patient in the HIFU group and no patient in the TACE group had gross ascites. The median hospital stay was 1 d (range, 1-21 d) in the TACE group and two days (range, 1-9 d) in the HIFU group (P < 0.000). No HIFU-related complication occurred. In the HIFU group, nine patients (90%) had complete response and one patient (10%) had partial response to the treatment. In the TACE group, only one patient (3%) had response to the treatment while 14 patients (48%) had stable disease and 14 patients (48%) had progressive disease (P = 0.00). Seven patients in the TACE group and no patient in the HIFU group dropped out from the transplant waiting list (P = 0.559)., Conclusion: HIFU ablation is safe and effective in the treatment of HCC for patients with advanced cirrhosis. It may reduce the drop-out rate of liver transplant candidate.