The gut microbiome-brain crosstalk in neurodegenerative diseases

The gut-brain axis (GBA) is a complex interactive network linking the gut to the brain. It involves the bidirectional communication between the gastrointestinal and the central nervous system, mediated by endocrinological, immunological, and neural signals. Perturbations of the GBA have been reported in many neurodegenerative diseases, suggesting a possible role in disease pathogenesis, making it a potential therapeutic target. The gut microbiome is a pivotal component of the GBA, and alterations in its composition have been linked to GBA dysfunction and CNS inflammation and degeneration. The gut microbiome might influence the homeostasis of the central nervous system homeostasis through the modulation of the immune system and, more directly, the production of molecules and metabolites. Small clinical and preclinical trials, in which microbial composition was manipulated using dietary changes, fecal microbiome transplantation, and probiotic supplements, have provided promising outcomes. However, results are not always consistent, and large-scale randomized control trials are lacking. Here, we give an overview of how the gut microbiome influences the GBA and could contribute to disease pathogenesis in neurodegenerative diseases

New Diagnostic and Prognostic Models for the Development of Alcoholic Cirrhosis Based on Genetic Predisposition and Alcohol History

Liver cirrhosis development is a multifactorial process resulting from a combination of environmental and genetic factors. The aim of the study was to develop accurate non-invasive diagnostic and prognostic models for alcoholic cirrhosis. Consecutive subjects with at-risk alcohol intake were retrospectively enrolled (110 cirrhotic patients and 411 non-cirrhotics). At enrollment, the data about lifetime drinking history were collected and all patients were tested for Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409, Transmembrane 6 Superfamily 2 (TM6SF2) rs58542926, and hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) rs72613567 variants. In cross-sectional analyses, models for the diagnosis of cirrhosis were developed using multivariate logistic regression. A predictive score for cirrhosis development over 24 years was built by evaluating time-dependent AUC curves. The best diagnostic accuracy was demonstrated by the model, which also includes daily alcohol consumption, duration of hazardous alcohol use, and genetic variants, with AUCs of 0.951 (95% CI 0.925–0.977) and 0.887 (95% CI 0.925–0.977) for cirrhosis and compensated cirrhosis, respectively. The predictive model for future cirrhosis development (AUC of 0.836 95% CI: 0.769–0.904) accounted for age at onset of at-risk alcohol consumption and the number of PNPLA3 and HSD17B13 variant alleles. We have developed accurate genetic and alcohol consumption models for the diagnosis of alcoholic cirrhosis and the prediction of its future risk

Motivational enhancement therapy versus cognitive behavioral therapy in a cohort of men and women with alcohol use disorder

The clinical manifestations of alcohol dependence are not homogeneous. Many studies described both cognitive impairments and psychiatric disorders among people with Alcohol use disorder (AUD). However, AUD can be present without comorbid psychiatric disorders or severe cognitive deficits, namely, “pure alcoholics”. Until now, knowledge about effective treatments for this typology of AUD patients remains unknown. The aim of the present study was to assess two psychological methods of intervention: Cognitive-behavioral treatment (CBT) in the short format and the Motivational enhancement therapy (MET). We then opted to compare the efficacy of methods in treating AUD in both men and women pure alcoholics. We performed a controlled and randomized study consisting of 325 people affected by AUD (244 men, 81 women). 72.3% (n=235; 181 men 54 women) were excluded according to selection criteria. The major percentage of exclusion (38.7%; n=91; 63 men 28 women) regarded patients with comorbid psychiatric disorders. Only the 90 remaining test subjects (27.7% of the sample population; 63 men and 27 women) classified as pure alcoholics were eligible for this study. The test subjects were divided into two groups. One group underwent MET (n=47; 35 men and 12 women) and the other underwent CBT (n=43; 28 men and 15 women). We found a significant adherence to the treatment in the CBT group (19 men and 9 women) compared to the MET group (3 men and 1 woman). At the end of treatment, the dropout rates for the CBT and MET therapy groups were 34.9% and 91.5%, respectively. Moreover, we found no differences in the percentage of abstinent days between CBT and MET groups at three months (CBT: n=36; mean 91.40±15.34; MET: n=18; mean 93.90±11.95; t(52)= 0.605, p=0.550), at six months (CBT: N=30; mean 85.00±30.71; MET: n=9; mean 87.78±33.08; t(37)=-0.234, p=0.820) and at twelve months from the beginning of treatment (CBT: n=28; mean 90.14±22.06; MET: n=4; mean 100±0; t(30)=-0.881, p=0.838). In conclusion, we disclose that CBT in the short format could be an effective treatment strategy for pure alcoholics without psychiatric disorders or severe cognitive deficits

A longitudinal study on BIO14.6 hamsters with dilated cardiomyopathy: micro-echocardiographic evaluation

<p>Abstract</p> <p>Background</p> <p>In recent years, several new technologies for small-animal imaging have been developed. In particular, the use of ultrasound in animal imaging has focused on the investigation of accessible biological structures such as the heart, of which it provides a morphological and functional assessment. The purpose of this study was to investigate the role of micro-ultrasonography (μ-US) in a longitudinal study on BIO14.6 cardiomyopathic hamsters treated with gene therapy.</p> <p>Methods</p> <p>Thirty hamsters were divided into three groups (n = 10): Group I, untreated BIO 14.6 hamsters; Group II, BIO 14.6 hamsters treated with gene therapy; Group III, untreated wild type (WT) hamsters. All hamsters underwent serial μ-US sessions and were sacrificed at predetermined time points.</p> <p>Results</p> <p>μ-US revealed: in Group I, progressive dilation of the left ventricle with a change in heart morphology from an elliptical to a more spherical shape, altered configuration of the mitral valve and subvalvular apparatus, and severe reduction in ejection fraction; in Group II, mild decrease in contractile function and ejection fraction; in Group III, normal cardiac chamber morphology and function. There was a negative correlation between the percentage of fibrosis observed at histology and the ejection fraction obtained on μ-echocardiography (Spearman r: -0.839; p < 0.001).</p> <p>Conclusions</p> <p>Although histological examination remains indispensable for a conclusive diagnosis, high-frequency μ-echocardiography, thanks to the high spatial and contrast resolution, can be considered sufficient for monitoring therapeutic efficacy and/or the progression of dilated cardiomyopathy, providing an alternative tool for repeatable and noninvasive evaluation.</p

Observation of J/ψpJ/\psi p resonances consistent with pentaquark states in Λb0→J/ψK−p{\Lambda_b^0\to J/\psi K^-p} decays

Observations of exotic structures in the $J/\psi p$ channel, that we refer to as pentaquark-charmonium states, in $\Lambda_b^0\to J/\psi K^- p$ decays are presented. The data sample corresponds to an integrated luminosity of 3/fb acquired with the LHCb detector from 7 and 8 TeV pp collisions. An amplitude analysis is performed on the three-body final-state that reproduces the two-body mass and angular distributions. To obtain a satisfactory fit of the structures seen in the $J/\psi p$ mass spectrum, it is necessary to include two Breit-Wigner amplitudes that each describe a resonant state. The significance of each of these resonances is more than 9 standard deviations. One has a mass of $4380\pm 8\pm 29$ MeV and a width of $205\pm 18\pm 86$ MeV, while the second is narrower, with a mass of $4449.8\pm 1.7\pm 2.5$ MeV and a width of $39\pm 5\pm 19$ MeV. The preferred $J^P$ assignments are of opposite parity, with one state having spin 3/2 and the other 5/2.Comment: 48 pages, 18 figures including the supplementary material, v2 after referee's comments, now 19 figure

Quantum numbers of the X(3872)X(3872) state and orbital angular momentum in its ρ0Jψ\rho^0 J\psi decay

Angular correlations in $B^+\to X(3872) K^+$ decays, with $X(3872)\to \rho^0 J/\psi$, $\rho^0\to\pi^+\pi^-$ and $J/\psi \to\mu^+\mu^-$, are used to measure orbital angular momentum contributions and to determine the $J^{PC}$ value of the $X(3872)$ meson. The data correspond to an integrated luminosity of 3.0 fb$^{-1}$ of proton-proton collisions collected with the LHCb detector. This determination, for the first time performed without assuming a value for the orbital angular momentum, confirms the quantum numbers to be $J^{PC}=1^{++}$. The $X(3872)$ is found to decay predominantly through S wave and an upper limit of $4\%$ at $95\%$ C.L. is set on the fraction of D wave.Comment: 16 pages, 4 figure

Precise measurements of the properties of the B-1(5721)(0,+) and B-2*(5747)(0,+) states and observation of B-+,B-0 pi(-,+) mass structures

Invariant mass distributions of B+π− and B0π+ combinations are investigated in order to study excited B mesons. The analysis is based on a data sample corresponding to 3.0 fb−1 of pp collision data, recorded by the LHCb detector at centre-of-mass energies of 7 and 8 TeV. Precise measurements of the masses and widths of the B1(5721)0,+ and B2(5747)0,+ states are reported. Clear enhancements, particularly prominent at high pion transverse momentum, are seen over background in the mass range 5850-6000 MeV in both B+π− and B0π+ combinations. The structures are consistent with the presence of four excited B mesons, labelled BJ (5840)0,+ and BJ (5960)0,+, whose masses and widths are obtained under different hypotheses for their quantum numbers

COVID-19 in rheumatic diseases in Italy: first results from the Italian registry of the Italian Society for Rheumatology (CONTROL-19)

OBJECTIVES: Italy was one of the first countries significantly affected by the coronavirus disease 2019 (COVID-19) epidemic. The Italian Society for Rheumatology promptly launched a retrospective and anonymised data collection to monitor COVID-19 in patients with rheumatic and musculoskeletal diseases (RMDs), the CONTROL-19 surveillance database, which is part of the COVID-19 Global Rheumatology Alliance. METHODS: CONTROL-19 includes patients with RMDs and proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) updated until May 3rd 2020. In this analysis, only molecular diagnoses were included. The data collection covered demographic data, medical history (general and RMD-related), treatments and COVID-19 related features, treatments, and outcome. In this paper, we report the first descriptive data from the CONTROL-19 registry. RESULTS: The population of the first 232 patients (36% males) consisted mainly of elderly patients (mean age 62.2 years), who used corticosteroids (51.7%), and suffered from multi-morbidity (median comorbidities 2). Rheumatoid arthritis was the most frequent disease (34.1%), followed by spondyloarthritis (26.3%), connective tissue disease (21.1%) and vasculitis (11.2%). Most cases had an active disease (69.4%). Clinical presentation of COVID-19 was typical, with systemic symptoms (fever and asthenia) and respiratory symptoms. The overall outcome was severe, with high frequencies of hospitalisation (69.8%), respiratory support oxygen (55.7%), non-invasive ventilation (20.9%) or mechanical ventilation (7.5%), and 19% of deaths. Male patients typically manifested a worse prognosis. Immunomodulatory treatments were not significantly associated with an increased risk of intensive care unit admission/mechanical ventilation/death. CONCLUSIONS: Although the report mainly includes the most severe cases, its temporal and spatial trend supports the validity of the national surveillance system. More complete data are being acquired in order to both test the hypothesis that RMD patients may have a different outcome from that of the general population and determine the safety of immunomodulatory treatments

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions

CMS physics technical design report : Addendum on high density QCD with heavy ions

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