Lifestyle intervention for morbid obesity: effects on liver steatosis, inflammation, and fibrosis.

The prevalence of obesity-related nonalcoholic fatty liver disease (NAFLD) is rising. NAFLD may result in nonalcoholic steatohepatitis (NASH), progressing to liver cirrhosis. Weight loss is recommended to treat obesity-related NASH. Lifestyle intervention may improve NASH; however, pertinent trials have so far focused on overweight patients, whereas patients with obesity are at highest risk of developing NAFLD. Furthermore, reports of effects on liver fibrosis are scarce. We evaluated the effect of lifestyle intervention on NAFLD in a real-life cohort of morbidly obese patients. In our observational study, 152 patients underwent lifestyle intervention, with a follow-up of 52 weeks. Noninvasive measures of obesity, metabolic syndrome, liver steatosis, liver damage, and liver fibrosis were analyzed. Treatment response in terms of weight loss was achieved in 85.1% of patients. Dysglycemia and dyslipidemia improved. The proportion of patients with fatty liver dropped from 98.1 to 54.3% ( P < 0.001). Weight loss >10% was associated with better treatment response ( P = 0.0009). Prevalence of abnormal serum transaminases fell from 81.0 to 50.5% ( P < 0.001). The proportion fibrotic patients, as determined by the NAFLD fibrosis score, dropped from 11.8 to 0% ( P < 0.05). Low serum levels of adiponectin correlated with degree of liver damage, i.e., serum liver transaminases ( r = -0,32, P < 0.05). Serum levels of adiponectin improved with intervention. In conclusion, lifestyle intervention effectively targeted obesity and the metabolic syndrome. Liver steatosis, damage and fibrosis were ameliorated in this real-life cohort of morbidly obese patients, mediated in part by changes in the adipokine profile. Patients with weight loss of >10% seemed to benefit most. NEW & NOTEWORTHY We demonstrate new evidence that lifestyle intervention is effective in treating NAFLD in the important group of patients with (morbid) obesity. Although current guidelines on the therapy of NASH recommend weight loss of 5-7%, weight reduction >10% may be favorable in morbid obesity. Serum levels of adipokines correlate with liver damage, which is indicative of their pathogenetic importance in human NASH. Our study adds to the limited body of evidence that NAFLD-associated liver fibrosis may resolve with lifestyle intervention.

Assessing the effects of temporal coherence on auditory stream formation through comodulation masking release.

Recent studies of auditory streaming have suggested that repeated synchronous onsets and offsets over time, referred to as "temporal coherence," provide a strong grouping cue between acoustic components, even when they are spectrally remote. This study uses a measure of auditory stream formation, based on comodulation masking release (CMR), to assess the conditions under which a loss of temporal coherence across frequency can lead to auditory stream segregation. The measure relies on the assumption that the CMR, produced by flanking bands remote from the masker and target frequency, only occurs if the masking and flanking bands form part of the same perceptual stream. The masking and flanking bands consisted of sequences of narrowband noise bursts, and the temporal coherence between the masking and flanking bursts was manipulated in two ways: (a) By introducing a fixed temporal offset between the flanking and masking bands that varied from zero to 60 ms and (b) by presenting the flanking and masking bursts at different temporal rates, so that the asynchronies varied from burst to burst. The results showed reduced CMR in all conditions where the flanking and masking bands were temporally incoherent, in line with expectations of the temporal coherence hypothesis.

Effects of tonotopicity, adaptation, modulation tuning, and temporal coherence in "primitive" auditory stream segregation.

The perceptual organization of two-tone sequences into auditory streams was investigated using a modeling framework consisting of an auditory pre-processing front end [Dau et al., J. Acoust. Soc. Am. 102, 2892-2905 (1997)] combined with a temporal coherence-analysis back end [Elhilali et al., Neuron 61, 317-329 (2009)]. Two experimental paradigms were considered: (i) Stream segregation as a function of tone repetition time (TRT) and frequency separation (Δf) and (ii) grouping of distant spectral components based on onset/offset synchrony. The simulated and experimental results of the present study supported the hypothesis that forward masking enhances the ability to perceptually segregate spectrally close tone sequences. Furthermore, the modeling suggested that effects of neural adaptation and processing though modulation-frequency selective filters may enhance the sensitivity to onset asynchrony of spectral components, facilitating the listeners' ability to segregate temporally overlapping sounds into separate auditory objects. Overall, the modeling framework may be useful to study the contributions of bottom-up auditory features on "primitive" grouping, also in more complex acoustic scenarios than those considered here.

Helminths and COVID-19 susceptibility, disease progression, and vaccination efficacy.

Almost 2 years into the coronavirus disease 2019 (COVID-19) pandemic, it remains to be determined how helminths interact with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We discuss how helminths may alter susceptibility to infection, COVID-19 pathology, and the efficiency of vaccines by combined analysis of available COVID-19 data and previous investigations of the effect of helminths in viral infections.

Non-stationary aging dynamics in ant societies.

In recent experiments by Richardson et al. (2010) [Richardson, T.O., Robinson, E.J.H., Christensen, K., Jensen, H.J., Franks, N.R., Sendova-Franks, A.B., 2010. PLoS ONE 5, e9621.] ant motion out of the nest is shown to be a non-stationary process intriguingly similar to the dynamics encountered in physical aging of glassy systems. Specifically, exit events can be described as a Poisson process in logarithmic time, or, for short, a log-Poisson process. Nouvellet et al. (2010) [Nouvellet, P., Bacon, J.P.,Waxman, D., 2010. J. Theor. Biol. 266, 573.] criticized these conclusions and performed new experiments where the exit process could more simply be described by standard Poisson statistics. In their reply Richardson et al. (2011b) [Richardson, T.O., Robinson, E.J.H., Christensen, K., Jensen, J.H., Christensen, K., Jensen, H.J., Franks, N.R., Sendova-Franks, A.B., 2011b. J. Theor. Biol. 269, 356-358.] stressed that the two sets of experiments were performed under very different conditions and claimed that this was the likely source of the discrepancy. Ignoring any technical issues which are part of the above discussion, the focal point of this work is to ascertain whether or not both log-Poisson and Poisson statistics are possible in an ant society under different external conditions. To this end, a model is introduced where interacting ants move in a stochastic fashion from one site to a neighboring site on a finite 2D lattice. The probability of each move is determined by the ensuing changes of a utility function which is a sum of pairwise interactions between ants, weighted by distance. Depending on how the interactions are defined and on a control parameter dubbed 'degree of stochasticity' (DS), the dynamics either quickly converges to a stationary state, where movements are a standard Poisson process, or may enter a non-stationary regime, where exits can be described as suggested by Richardson et al. Other aspects of the model behavior are also discussed, i.e. the time dependence of the average value of the utility function, and the statistics of spatial re-arrangements happening anywhere in the system. Finally, we discuss the role of record events and their statistics in the context of ant societies and suggest the possibility that a transition from non-stationary to stationary dynamics can be triggered experimentally.

Thermal shifts and intermittent linear response of aging systems.

At time t after an initial quench, an aging system responds to a perturbation turned on at time tw