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Numerous randomized clinical trials (RCTs) were conducted to evaluate dolutegravir based triple antiretroviral therapy (ART) compared to other triple antiretroviral regimens in naïve patients, and a summary of the available evidence is required to shed more light on safety and effectiveness issues. Systematic review and meta-analysis of RCTs comparing dolutegravir-containing ART to non-dolutegravir containing ART in HIV-infected naive patients. Primary outcomes: % of patients with viral load<50 copies/mL at 48 weeks, stratified according to baseline viral load levels (< or >100.000 copies/mL); overall rate of discontinuation and/or switching for any cause (virologic failure, clinical failure, adverse events). Measure of treatment effect: Risk Difference (RD) with 95% confidence intervals (CIs). The GRADE system was used to assess the certainty of the body of evidence. We included 7 RCTs (13 reports, 6407patients) comparing dolutegravir containing to non-dolutegravir containing ART, both in combination with 2 NRTIs. Controls were raltegravir or bictegravir (3 RCTs), boosted atazanavir or darunavir (2 RCTs) or efavirenz (2 RCTs). Rates of patients with VL <50 copies/ml were higher in dolutegravir recipients compared to controls at 48 weeks (RD, 0.05; 95% CIs, 0.03/0.08, p = 0.0002) and 96 weeks (RD, 0.06; 95% CIs, 0.03/0.10, p<0.0001); the average benefit of using dolutegravir was particularly evident at 48 weeks in the subgroup of patients with high baseline viral load (RD, 0.10; 95% CIs, 0.05/0.15; p< 0.0001; GRADE assessment: \"high certainty of evidence\"). Overall rate of discontinuation were lower in dolutegravir compared to controls (RD,-0.03, 95% CIs -0.05/-0.01; p = 0.007). No significant differences were observed in rates of discontinuation due to adverse events (RD, -0.02; 95% CIs, -0.05/0.00), virologic failure (RD, -0.01; 95% CIs, -0.02/0.01), and most common adverse events (GRADE assessment: from \"very-low\" to \"moderate certainty of evidence\"). Starting treatment in naive patients with dolutegravir containing ART has an increased likelihood of achieving viral suppression in the comparison with non-dolutegravir containing ART. The average benefit is particularly evident in those with high baseline viral load.

The present research studied the effect of a dietary inclusion with Hermetia illucens larvae meal (Hi) on rainbow trout’s fillets chemical composition. The effect of Hi inclusion in diets on rainbow trout chemical characteristics was evaluated. Trout were fed three different diets: control (C, no Hi inclusion), 25% and 50% of substitution of fish meal with Hi (Hi25 and Hi50, respectively). Fillets were analysed to quantify proximate composition, carbohydrates percentage, colour parameters, nucleotides concentration, fatty acids profile, volatile organic compounds (VOCs) and myofibrillar and sarcoplasmic concentrations. Diets did not affect proximate composition. Contrariwise, Hi50 diet decreased fillet yellowness and both substitution percentages affected negatively adenosine monophosphate concentration. Saturated fatty acids, mostly C12 : 0, increased their contents in relation with Hi inclusion at the expense of monounsaturated and polyunsaturated (both n-3 and n-6) fatty acids. Less modifications were reported in VOCs as only heptanal and octanal concentrations were affected, no new compounds appeared in relation with Hi inclusion. No modifications in proteins patterns were shown even if myofibrillar content decreased in trout fed Hi50. The results highlighted that chemical modifications occurred in fillets were related to the chemical composition of the H. illucens meal and to the percentage of inclusion in the diet. Substitution of fish meal with a precisely percentage of H. illucens meal could be a potential future solution in order to decrease the quantity of fish meal used in aquafeeds.

Soya bean is the main protein source in poultry feed but rising prices make an alternative protein source necessary. Insects, such as the black soldier fly (Hermetia illucens), may be an attractive solution for hens, although little information is available on their effect on egg quality. The present study aims to fill this gap by testing the effect of 100% replacement of soya bean with H. illucens larva meal in the diet of Lohmann Brown Classic laying hens for 21 weeks. At the end of the trial, the eggs were characterized for parameters such as weight, colour, proximate composition of albumen and yolk, and content of carotenoids, tocopherols and cholesterol. The fatty acid profile of yolks was also determined. Hens fed the insect-based diet produced eggs (HIM group) with a higher proportion of yolk than the group fed the soya bean-based diet (SBM group). HIM was associated with redder yolks (red index 5.63 v. 1.36) than SBM. HIM yolks were richer in γ-tocopherol (4.0 against 2.4 mg/kg), lutein (8.6 against 4.9 mg/kg), β-carotene (0.33 against 0.19 mg/kg) and total carotenoids (15 against 10.5 mg/kg) than SBM yolks. The fatty acid composition of HIM yolks was almost identical to that of SBM yolks. Finally, HIM yolks contained 11% less cholesterol than SBM yolks. These results suggest that H. illucens larva meal is a suitable total substitute for soya bean meal in the diet of Lohmann Brown Classic laying hens. A sustainable alternative to the plant protein source therefore seems feasible.

It is well know that systems with an interaction decaying as a power of the distance may have critical exponents that are different from those of short-range systems. The boundary between long-range and short-range is known, however the behavior in the crossover region is not well understood. In this paper we propose a general form for the crossover function and we compute it in a particular limit. We compare our predictions with the results of numerical simulations for two-dimensional long-range percolation.

Spin glasses (SGs) are paradigmatic models for physical, computer science, biological, and social systems. The problem of studying the dynamics for SG models is nondetermistic polynomial-time (NP) hard; that is, no algorithm solves it in polynomial time. Here we implement the optical simulation of an SG, exploiting the N segments of a wavefront-shaping device to play the role of the spin variables, combining the interference downstream of a scattering material to implement the random couplings between the spins (the Jij matrix) and measuring the light intensity on a number P of targets to retrieve the energy of the system. By implementing a plain Metropolis algorithm, we are able to simulate the spin model dynamics, while the degree of complexity of the potential energy landscape and the region of phase diagram explored are user defined, acting on the ratio P/N = α. We study experimentally, numerically, and analytically this Hopfield-like system displaying a paramagnetic, ferromagnetic, and SG phase, and we demonstrate that the transition temperature Tg to the glassy phase from the paramagnetic phase grows with α. We demonstrate the computational advantage of the optical SG where interaction terms are realized simultaneously when the independent light rays interfere on the detector’s surface. This inherently parallel measurement of the energy provides a speedup with respect to purely in silico simulations scaling with N.

Abstract The aim of this research was to study the effect of insect meal from Tenebrio molitor larvae (Tenebrio molitor larvae meal [TML]) as complete replacement of soybean meal (SBM) on growth performance, nutrient digestibility, and carcass and meat traits of broilers. A total of eighty 30-d-old male Shaver brown broilers were homogenously divided into 2 groups (each consisting of 8 replicates of 5 birds). Up to 62 d of age, the groups were fed 2 isoproteic and isoenergetic diets differing for the ingredient used as the main protein source: the control group was fed a corn–SBM–based diet, whereas in the TML group, the SBM was completely replaced by TML. Broiler growth performance was measured during the trial. At 62 d of age, 2 broilers per replicate (16 per group) were slaughtered and apparent ileal digestibility coefficients and carcass and meat traits were determined. The use of TML as the main protein source in the broiler diet had no significant effect on most growth performance and carcass traits and chemical and physical properties of meat, the latter being important for marketing purposes. The feed conversion ratio in the entire experimental period (from 30 to 62 d) was improved in the TML group compared with the SBM group (P < 0.05). The apparent ileal digestibility coefficients of DM, OM, and CP in broilers fed the SBM diet were greater (P < 0.01) than the other group. The full digestive system in broilers fed SBM had a lower (P < 0.05) absolute and relative weight than that of broilers fed TML. Also, the weight and the percentage of the spleen in the SBM group were lower (P < 0.05) than those in the TML group. The length of the entire intestine in the group fed TML was greater (P < 0.05) than the other group and the same happened when intestinal length was expressed as percentage of broiler BW (P < 0.05). Among the different intestinal tracts, the ileum and ceca of broilers fed TML had a greater (P < 0.05) length than that of broilers fed SBM. Also, ceca weight (as an absolute value or percentage on live weight) in broilers fed TML was greater (P < 0.05) than that of broilers fed SBM. Breast pH and cooking losses in broilers fed TML were greater (P < 0.05) than those of broilers fed SBM. Chemical characteristic of meat obtained from right breast of slaughtered broilers were unaffected by dietary treatments. Tenebrio molitor larvae meal can be a suitable alternative protein source for growing broilers and also when used as principal protein contributor to the diet.

Numerical models indicate that collective animal behavior may emerge from simple local rules of interaction among the individuals. However, very little is known about the nature of such interaction, so that models and theories mostly rely on aprioristic assumptions. By reconstructing the three-dimensional positions of individual birds in airborne flocks of a few thousand members, we show that the interaction does not depend on the metric distance, as most current models and theories assume, but rather on the topological distance. In fact, we discovered that each bird interacts on average with a fixed number of neighbors (six to seven), rather than with all neighbors within a fixed metric distance. We argue that a topological interaction is indispensable to maintain a flock's cohesion against the large density changes caused by external perturbations, typically predation. We support this hypothesis by numerical simulations, showing that a topological interaction grants significantly higher cohesion of the aggregation compared with a standard metric one.

A worldwide increase in the prevalence of coral diseases and mortality has been linked to ocean warming due to changes in coral-associated bacterial communities, pathogen virulence, and immune system function. In the Mediterranean basin, the worrying upward temperature trend has already caused recurrent mass mortality events in recent decades. To evaluate how elevated seawater temperatures affect the immune response of a thermophilic coral species, colonies of Astroides calycularis were exposed to environmental (23 °C) or elevated (28 °C) temperatures, and subsequently challenged with bacterial lipopolysaccharides (LPS). Using immunolabeling with specific antibodies, we detected the production of Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-kB), molecules involved in coral immune responses, and heat shock protein 70 (HSP70) activity, involved in general responses to thermal stress. A histological approach allowed us to characterize the tissue sites of activation (epithelium and/or gastroderm) under different experimental conditions. The activity patterns of the examined markers after 6 h of LPS stimulation revealed an up-modulation at environmental temperature. Under warmer conditions plus LPS-challenge, TLR4-NF-kB activation was almost completely suppressed, while constituent elevated values were recorded under thermal stress only. An HSP70 up-regulation appeared in both treatments at elevated temperature, with a significantly higher activation in LPS-challenge colonies. Such an approach is useful for further understanding the molecular pathogen-defense mechanisms in corals in order to disentangle the complex interactive effects on the health of these ecologically relevant organisms related to global climate change.

Antimicrobial peptides (AMPs) are important mediator molecules of the innate defense mechanisms in a wide range of living organisms, including bacteria, mammals, and plants. Among them, peptide protease inhibitors (PPIs) from plants play a central role in their defense mechanisms by directly attacking pathogens or by modulating the plant’s defense response. The growing prevalence of microbial resistance to currently available antibiotics has intensified the interest concerning these molecules as novel antimicrobial agents. In this scenario, PPIs isolated from a variety of plants have shown potential in inhibiting the growth of pathogenic bacteria, protozoans, and fungal strains, either by interfering with essential biochemical or physiological processes or by altering the permeability of biological membranes of invading organisms. Moreover, these molecules are active inhibitors of a range of proteases, including aspartic, serine, and cysteine types, with some showing particular efficacy as trypsin and chymotrypsin inhibitors. In this review, we provide a comprehensive analysis of the potential of plant-derived PPIs as novel antimicrobial molecules, highlighting their broad-spectrum antimicrobial efficacy, specificity, and minimal toxicity. These natural compounds exhibit diverse mechanisms of action and often multifunctionality, positioning them as promising molecular scaffolds for developing new therapeutic antibacterial agents.

We study the satisfiability of random Boolean expressions built from many clauses with K variables per clause (K-satisfiability). Expressions with a ratio α of clauses to variables less than a threshold α c are almost always satisfiable, whereas those with a ratio above this threshold are almost always unsatisfiable. We show the existence of an intermediate phase below α c , where the proliferation of metastable states is responsible for the onset of complexity in search algorithms. We introduce a class of optimization algorithms that can deal with these metastable states; one such algorithm has been tested successfully on the largest existing benchmark of K-satisfiability.