Bariatric-induced microbiome changes alter MASLD development in association with changes in the innate immune system

IntroductionMetabolic dysfunction-associated steatotic liver disease (MASLD) affects nearly 25% of the population and is the leading cause for liver-related mortality. Bariatric surgery is a well-known treatment for MASLD and obesity. Understanding the fundamental mechanisms by which bariatric surgery can alter MASLD can lead to new avenues of therapy and research. Previous studies have identified the microbiome's role in bariatric surgery and in inflammatory immune cell populations. The host innate immune system modulates hepatic inflammation and fibrosis, and thus the progression of MASLD. The precise role of immune cell types in the pathogenesis of MASLD remains an active area of investigation. The aim of this study was to understand the interplay between microbiota composition post-bariatric surgery and the immune system in MASLD.MethodsEighteen morbidly obese females undergoing sleeve gastrectomy were followed pre-and post-surgery. Stool from four patients, showing resolved MASLD post-surgery with sustained weight loss, was transplanted into antibiotic treated mice. Mice received pre-or post-surgery stool and were fed a standard or high-fat diet. Bodyweight, food intake, and physiological parameters were tracked weekly. Metabolic parameters were measured post-study termination.ResultsThe human study revealed that bariatric surgery led to significant weight loss (p > 0.05), decreased inflammatory markers, and improved glucose levels six months post-surgery. Patients with weight loss of 20% or more showed distinct changes in blood metabolites and gut microbiome composition, notably an increase in Bacteroides. The mouse model confirmed surgery-induced microbiome changes to be a major factor in the reduction of markers and attenuation of MASLD progression. Mice receiving post-surgery fecal transplants had significantly less weight gain and liver steatosis compared to pre-surgery recipients. There was also a significant decrease in inflammatory cytokines interferon gamma, interleukin 2, interleukin 15, and mig. This was accompanied by alterations in liver immunophenotype, including an increase in natural killer T cells and reduction of Kupfer cells in the post-surgery transplant group.DiscussionOur findings suggest surgery induced microbial changes significantly reduce inflammatory markers and fatty liver progression. The results indicate a potential causal link between the microbiome and the host immune system, possibly mediated through modulation of liver NKT and Kupffer cells

Information science and cognitive psychology: a theoretical approach

Information, as a human and social phenomenon, is the object of study of an emergent scientific field named Information Science (IS), which we put forward as unitary and transdisciplinary and open to a rich interdisciplinarity with other fields of knowledge. In face of the new reality, baptized the Information Society', and the emergence of a new paradigm, that we name "post-custodial, scientific and informational", as opposed to the previous one, "historicist, custodial and technicist", it is urgent to consolidate the theoretical and methodological foundations of IS in order to develop research, both pure and applied, and to contribute to a definition of its boundaries as a scientific area, in the scope of Social Sciences. Starting from an operative definition of Information, this paper aims to discuss the cognitive and emotional dimension of the info-communicational phenomenon and, for that, it is crucial to start a profound and hard dialogue with Cognitive Sciences. The label of 'cognitivist' given, in IS literature, to some authors like Bertram Brookes, because of the emphasis he put on the passage from a state of knowledge to a new state through an addition of knowledge coming from an increase of information, sounds quite equivocal, because knowledge and cognition are not synonymous and cognitive and emotional activity is not reducible to formalities. It is necessary to compare concepts and to understand the neuropsychological roots of the production, the organization and the info-communicational behaviour, so the contribution of Neurosciences and Cognitive Sciences, namely Cognitive Psychology, is indispensable

A Methodology for Detecting Field Potentials from the External Ear Canal: NEER and EVestG

An algorithm called the neural event extraction routine (NEER) and a method called Electrovestibulography (EVestG) for extracting field potentials (FPs) from artefact rich and noisy ear canal recordings is presented. Averaged FP waveforms can be used to aid detection of acoustic and or vestibular pathologies. FPs were recorded in the external ear canal proximal to the ear drum. These FPs were extracted using an algorithm called NEER. NEER utilises a modified complex Morlet wavelet analysis of phase change across multiple scales and a template matching (matched filter) methodology to detect FPs buried in noise and biological and environmental artefacts. Initial simulation with simulated FPs shows NEER detects FPs down to −30 dB SNR (power) but only 13–23% of those at SNR’s <−6 dB. This was deemed applicable to longer duration recordings wherein averaging could be applied as many FPs are present. NEER was applied to detect both spontaneous and whole body tilt evoked FPs. By subtracting the averaged tilt FP response from the averaged spontaneous FP response it is believed this difference is more representative of the vestibular response. Significant difference (p < 0.05) between up and down whole body (supine and sitting) movements was achieved. Pathologic and physiologic evidence in support of a vestibular and acoustic origin is also presented

Staggering of the Nuclear Charge Radii in a Superfluid Model with Good Particle Number

A simple superfluid model with an effective four body interaction of monopole pairing type is used to explain the staggering of the charge radii in the isotope chains. The contribution of deformation and of the particle number projection are analyzed for the Sn isotopes. Good results are obtained for the staggering parameters and neutron pairing energies.Comment: RevTex, 19 pages and 4 postscript figures uuencoded and attached. To appear in Phys. Rev.

Across-Channel Timing Differences as a Potential Code for the Frequency of Pure Tones

When a pure tone or low-numbered harmonic is presented to a listener, the resulting travelling wave in the cochlea slows down at the portion of the basilar membrane (BM) tuned to the input frequency due to the filtering properties of the BM. This slowing is reflected in the phase of the response of neurons across the auditory nerve (AN) array. It has been suggested that the auditory system exploits these across-channel timing differences to encode the pitch of both pure tones and resolved harmonics in complex tones. Here, we report a quantitative analysis of previously published data on the response of guinea pig AN fibres, of a range of characteristic frequencies, to pure tones of different frequencies and levels. We conclude that although the use of across-channel timing cues provides an a priori attractive and plausible means of encoding pitch, many of the most obvious metrics for using that cue produce pitch estimates that are strongly influenced by the overall level and therefore are unlikely to provide a straightforward means for encoding the pitch of pure tones

Long-Term Follow-Up After Gene Therapy for Canavan Disease

Canavan disease is a hereditary leukodystrophy caused by mutations in the aspartoacylase gene (ASPA), leading to loss of enzyme activity and increased concentrations of the substrate N-acetylaspartate (NAA) in the brain. Accumulation of NAA results in spongiform degeneration of white matter and severe impairment of psychomotor development. The goal of this prospective cohort study was to assess long-term safety and preliminary efficacy measures after gene therapy with an adeno-associated viral vector carrying the ASPA gene (AAV2-ASPA). Using noninvasive magnetic resonance imaging and standardized clinical rating scales, we observed Canavan disease in 28 patients, with a subset of 13 patients being treated with AAV2-ASPA. Each patient received 9 × 1011 vector genomes via intraparenchymal delivery at six brain infusion sites. Safety data collected over a minimum 5-year follow-up period showed a lack of long-term adverse events related to the AAV2 vector. Posttreatment effects were analyzed using a generalized linear mixed model, which showed changes in predefined surrogate markers of disease progression and clinical assessment subscores. AAV2-ASPA gene therapy resulted in a decrease in elevated NAA in the brain and slowed progression of brain atrophy, with some improvement in seizure frequency and with stabilization of overall clinical status

Diabetes susceptibility in ethnic minority groups from Turkey, Vietnam, Sri Lanka and Pakistan compared with Norwegians - the association with adiposity is strongest for ethnic minority women

<p>Abstract</p> <p>Background</p> <p>The difference in diabetes susceptibility by ethnic background is poorly understood. The aim of this study was to assess the association between adiposity and diabetes in four ethnic minority groups compared with Norwegians, and take into account confounding by socioeconomic position.</p> <p>Methods</p> <p>Data from questionnaires, physical examinations and serum samples were analysed for 30-to 60-year-olds from population-based cross-sectional surveys of Norwegians and four immigrant groups, comprising 4110 subjects born in Norway (n = 1871), Turkey (n = 387), Vietnam (n = 553), Sri Lanka (n = 879) and Pakistan (n = 420). Known and screening-detected diabetes cases were identified. The adiposity measures BMI, waist circumference and waist-hip ratio (WHR) were categorized into levels of adiposity. Gender-specific logistic regression models were applied to estimate the risk of diabetes for the ethnic minority groups adjusted for adiposity and income-generating work, years of education and body height used as a proxy for childhood socioeconomic position.</p> <p>Results</p> <p>The age standardized diabetes prevalence differed significantly between the ethnic groups (women/men): Pakistan: 26.4% (95% CI 20.1-32.7)/20.0% (14.9-25.2); Sri Lanka: 22.5% (18.1-26.9)/20.7% (17.3-24.2), Turkey: 11.9% (7.2-16.7)/12.0% (7.6-16.4), Vietnam: 8.1% (5.1-11.2)/10.4% (6.6-14.1) and Norway: 2.7% (1.8-3.7)/6.4% (4.6-8.1). The prevalence increased more in the minority groups than in Norwegians with increasing levels of BMI, WHR and waist circumference, and most for women. Highly significant ethnic differences in the age-standardized prevalence of diabetes were found for both genders in all categories of all adiposity measures (<it>p </it>< 0.001). The Odds Ratio (OR) for diabetes adjusted for age, WHR, body height, education and income-generating work with Norwegians as reference was 2.9 (1.30-6.36) for Turkish, 2.7 (1.29-5.76) for Vietnamese, 8.0 (4.19-15.14) for Sri Lankan and 8.3 (4.37-15.58) for Pakistani women. Men from Sri Lanka and Pakistan had identical ORs (3.0 (1.80-5.12)).</p> <p>Conclusions</p> <p>A high prevalence of diabetes was found in 30-to 60-year-olds from ethnic minority groups in Oslo, with those from Sri Lanka and Pakistan at highest risk. For all levels of adiposity, a higher susceptibility for diabetes was observed for ethnic minority groups compared with Norwegians. The association persisted after adjustment for socioeconomic position for all minority women and for men from Sri Lanka and Pakistan.</p