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This article presents the findings of a study conducted in Uruguay to determine the prevalence and endoscopic-histological correlation of premalignant gastric lesions. The study included 102 patients who underwent upper endoscopy and gastric biopsies. The prevalence of chronic atrophic gastritis (CAG) was found to be 38.2%, while intestinal metaplasia (IM) had a prevalence of 31.4%. The endoscopic-histological correlation for CAG and IM was low, indicating the need for biopsy for diagnosis in all cases. The study also identified a low proportion of high-risk stages of premalignant lesions. [Extracted from the article]

Purpose: Evaluate the efficacy of hydroxytyrosol in the local treatment of inflammatory colitis. Currently, the existing treatments for inflammatory bowel diseases does not cure the disease and it is associated with high rates of side effects and complications. Hydroxytyrosol is a phenyl-ethyl-alcohol derived from the hydrolysis of oleuropein and present in olive oil, previous studies have demonstrated the anti-inflammatory effect of dietary hydroxytyrosol supplement, with no toxicity. Materials & Methods: Colitis has been induced by using Trinitrobenzene Sulfonic Acid at 40 rats. They were divided into four groups randomly: 10 rats without treatment; 10 rats with pectin/alginate mixture; 10 rats treated with pectin/alginate + olive oil; 10 rats treated with pectin/alginate + olive oil + hydroxytyrosol. Animals were sacrificed 10 days after induction of trinitrobenzene sulfonic acid, receiving 5 days of continuous treatment. Samples of the rectal area were studied and observed under a microscope to determine the damage by Hunter scoring modified, assessing inflammatory infiltration, number of intestinal walls involved, damage to the mucosal architecture, and edema. Results: When the rectum was analyzed in a global way, nonsignificant differences were observed; however, when performing an individualized analysis, statistically significant differences in the inflammatory infiltrate are present in the samples, which were evaluated using the ANOVA and Student-T statistics. Conclusions: Local treatment with the natural antioxidant hydroxytyrosol combined with pectin/alginate and olive oil of inflammatory bowel disease has been shown to be effective against inflammatory infiltration of TNBS-induced colitis. [ABSTRACT FROM AUTHOR]

We have revisited the sky region delimited by 290° < l < 320° and 3° < b < 17°, which includes a large arc of neutral hydrogen (H I), and extended the study region using the Leiden-Argentine-Bonn HI survey. The HI arc is almost an open downward semi-circumference of ≈10° of radius, with the symmetry axis perpendicular to the Galactic plane and the vertex at (l, b) ≈ (308°, 11°). The velocity component in the spectra of the 21 cm HI line that reveals the HI arc has a mean radial velocity (local standard of rest) of -19 ± 2 km s-1. Analysing HI maps covering the region lying below the arc (b < 0), we have investigated whether the arc could be interpreted as the cap of an expanding shell originated by a strong explosion occurred below the Galactic plane. The lower cap of the shell would have been blown out into the Galactic halo. In these conditions, the evolution of the shock wave and the associated shell was calculated by means of the Kompaneets approximation. By comparing the model's predictions with the observations, we obtained that the distance, age and HI mass of the shell would be 640 pc, 9.3 × 106 yr and 3.4 × 105 M⊙, respectively. The shell's sizes along and perpendicular to the Galactic plane would be 295 pc and ≈540 pc, respectively. By means of the model, we obtained that the energy of the explosion that gave origin to the shell would be around 5 × 1050 erg. Data from future surveys and from Gaia are expected to help confirming the proposed model. Other interstellar complexes of the region are also considered in relation to the HI shell. [ABSTRACT FROM AUTHOR]

The velocity distribution of stars in the solar neighbourhood can be globally characterized by the presence of two stellar streams (I and II). Stream I contains kinematic substructures, named moving groups of stars, such us the Pleiades and Hyades groups. While Stream II is essentially associated with the Sirius group. The origin and nature of these two stellar streams are still not completely clear. We propose that Streams I and II were gravitationally linked to an old gas supercloud that was disintegrated in parts that formed new subsystems, viz., the Orion arm and Gould's belt. On the basis of this idea, we constructed a dynamical model of the supercloud in order to explain the kinematic and structural characteristics of the local system of gas and stars. For the study of the relative orbits of the two stellar streams with respect to the supercloud's centre and of the Galactic orbit of the supercloud, we developed appropriate epicyclic motion equations. The results of the model indicate the possibility that about 75- 100 Myr ago the supercloud crossed the Perseus arm and as a consequence was strongly braked. Besides, around 60 Myr ago, the position of the supercloud coincided approximately with that of the Big Dent, a huge depression of the Galactic disc. We suggest that the cause that originated the Big Dent could be the same that perturbed the supercloud starting the formation of the Orion arm and Gould's belt. In this context, we derived the theoretical distributions of positions and velocities for the stars of Streams I and II. [ABSTRACT FROM AUTHOR]

In the solar neighbourhood, there are moving groups of stars with similar ages and others of stars with heterogeneous ages as the field stars. To explain these facts, we have constructed a simple model of three phases. Phase A: a giant interstellar cloud is uniformly accelerated (or decelerated) with respect to the field stars during a relatively short period of time (10 Myr) and the cloud's mass is uniformly increased. As a result, a number of passing field stars is gravitationally captured by the cloud at the end of this phase; phase B: the acceleration (or deceleration) and mass accretion of the cloud cease. The star formation spreads throughout the cloud, giving origin to stellar groups of similar ages; and phase C: the cloud loses all its gaseous component at a constant rate and in parallel is uniformly decelerated (or accelerated) until reaching the initial velocity of phase A (case 1) or the velocity of the gas cloud remains constant (case 2). Both cases give equivalent results. The system equations for the star motions governed by a time-dependent gravitational potential of the giant cloud and referred to a coordinate system comoving with the cloud have been solved analytically. We have assumed a homogeneous spheroidal cloud of fixed semimajor axis a = 300 pc and of an initial density of 7 atoms cm− 3, with a density increment of 100 per cent and a cloud's velocity variation of 30 km s−1, from the beginning to the end of phase A. The result is that about 4 per cent of the field stars that are passing within the volume of the cloud at the beginning of phase A are captured. The Sun itself could have been captured by the same cloud that originated the moving groups of the solar neighbourhood. [ABSTRACT FROM AUTHOR]

BSTRACT We propose a scenario for the formation of DA white dwarfs with very thin helium buffers. For these stars we explore the possible occurrence of diffusion-induced CNO-flashes during their early cooling stage. In order to obtain very thin helium buffers, we simulate the formation of low-mass remnants through an asymptotic giant branch (AGB) final/late thermal pulse (AFTP/LTP scenario). Then we calculate the consequent white dwarf cooling evolution by means of a consistent treatment of element diffusion and nuclear burning. Based on physically sound white dwarf models, we find that the range of helium buffer masses for these diffusion-induced novae to occur is significantly smaller than that predicted by the only previous study of this scenario. As a matter of fact, we find that these flashes do occur only in some low-mass ( M ≲ 0.6 M⊙) and low-metallicity ( ZZAMS≲ 0.001) remnants about 106-107 yr after departing from the AGB. For these objects, we expect the luminosity to increase by about 4 orders of magnitude in less than a decade. We also show that diffusion-induced novae should display a very typical eruption light curve, with an increase of about a few magnitudes per year before reaching a maximum of MV ∼−5 to −6. Our simulations show that surface abundances after the outburst are characterized by log NH/ NHe∼−0.15 ... 0.6 and N > C ≳ O by mass fractions. Contrary to previous speculations we show that these events are not recurrent and do not change substantially the final H-content of the cool (DA) white dwarf. Finally, with the aid of model predictions we discuss the possibility that Nova Vul 1670 (CK Vul) and the recently proposed [WN/WC]-central stars of planetary nebulae could be observational counterparts of this diffusion-induced nova scenario. We conclude that, despite discrepancies with observations, the scenario offers one of the best available explanations for CK Vul and, with minor modifications, explains the observed properties of [WN/WC]-central stars of planetary nebulae. [ABSTRACT FROM AUTHOR]

The article discusses the use of positive capsule endoscopy to diagnose and treat the small-bowel disorders. Topics include the emergence of spiral enteroscopy as an alternate method for enteroscopy, the assessment of the impact of capsule endoscopy in patients with double-balloon enteroscopy (DBE) and obscure gastrointestinal bleeding (OGIB) conducted by L. C. Fry and colleagues, and the challenges posed by the diagnosis of Crohn's disease.

We have studied the kinematics and spatial distribution of the interstellar gas in the sky region , using the extensive Leiden–Dwingeloo Survey of H i emission and the Columbia Survey of CO emission. The spectra show two main velocity components, namely feature A that has a mean local standard of rest (LSR) velocity of and is due to the Lindblad ring of the Gould belt, and feature C that has a mean LSR velocity of and is associated to the local arm or Orion arm. The H i and CO distributions of feature A in the region trace a large complex of gas and dust known as the Cepheus Flare, which lies at a distance of 300 pc. The spectral line profiles of feature A, which are rather broad and often double-peaked, reveal that the Cepheus Flare forms part of a big expanding shell of interstellar matter that encloses an old supernova remnant associated with a void inside the Cepheus Flare. On the other hand, by analysing the distribution and velocity structure of feature C, we have detected a second large expanding shell in the region, located at a distance of 800 pc in the local arm. This shell surrounds the stellar association Cepheus OB4 and was probably generated by stellar winds and supernovae of Cepheus OB4. The radii, expansion velocities and H i masses of the two shells are approximately 50 pc, 4 km s−1 and for the Cepheus Flare shell and 100 pc, 4 km s−1 and for the Cepheus OB4 shell. Both shells have similar ages of the order of a few 106 yr. [ABSTRACT FROM AUTHOR]

We report here on the development and characterization of 15 microsatellite loci isolated from Mangifera indica L. These markers were evaluated using 59 Florida cultivars and four related species from the USDA germplasm collection for mango. Two loci were monomorphic and 13 polymorphic, with two to seven alleles per locus. Four loci departed significantly from Hardy–Weinberg equilibrium and have significant heterozygote deficiency. Nine loci exhibited significant linkage disequilibrium. Cross-species amplification was successful in four related species. These loci are being used to investigate patterns of genetic variation within M. indica and between closely related species. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 68-year-old man presented with obscure occult gastrointestinal bleeding and was referred to emergency department for capsule endoscopy. The patient developed melena after he underwent into capsule endoscopy and was required for blood transfusion. The article discusses enteroscopy, metastatic renal cell cancer, and intraluminal small-bowel metastases.

Production of cacao in tropical America has been severely affected by fungal pathogens causing diseases known as witches' broom (WB, caused by Moniliophthora perniciosa), frosty pod (FP, caused by M. roreri) and black pod (BP, caused by Phytophthora spp.). BP is pan-tropical and causes losses in all producing areas. WB is found in South America and parts of the Caribbean, while FP is found in Central America and parts of South America. Together, these diseases were responsible for over 700 million US dollars in losses in 2001 (4). Commercial cacao production in West Africa and South Asia are not yet affected by WB and FP, but cacao grown in these regions is susceptible to both. With the goal of providing new disease resistant cultivars the USDA-ARS and Mars, Inc. have developed a marker assisted selection (MAS) program. Quantitative trait loci have been identified for resistance to WB, FP, and BP. The potential usefulness of these markers in identifying resistant individuals has been confirmed in an experimental F1 family in Ecuador. [ABSTRACT FROM AUTHOR]

Objective: Functional dyspepsia (FD) is a gastrointestinal functional disorder of the upper gastrointestinal tract that affects the quality of life of patients and poses a significant economic burden. It has been proposed that the local inflammatory immune response at the duodenum is associated with an increase in intestinal permeability, favoring the recruitment of Th2 cells and granulocyte degranulation. Moreover, systemic immune response could also be related to the symptoms of FD. The objective of this study was to evaluate the systemic immune response in Uruguayan patients with FD by analyzing the cytokine levels in plasma and the frequency of circulating T cells associated with duodenal recruitment., Patients and Methods: An analytic and cross-sectional study in 30 patients with FD and 15 healthy controls (HCs) was carried out. Patients were diagnosed with FD according to the Roma IV Committee definition. Cytokine levels were measured in plasma by a specific assay. Expression of α4β7 and CC chemokine receptor9 in circulating T cells was evaluated by flow cytometry., Results: Higher levels of interleukin (IL)-5, IL-13, and IL-8 and lower levels of IL-10 and IL-12p70 were detected in patients with FD than in HC. Furthermore, a positive linear correlation between IL-13 and the severity of FD symptoms was found. CD4 + T cells from patients with FD expressed higher levels of α4β7 and CC chemokine receptor9 than those from HC., Conclusions: An increase of Th2-like cytokines and a positive correlation between the levels of plasma IL-13 and the severity of symptoms in patients with FD from Uruguay were detected., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Cardiovascular disease is the main cause of mortality in industrialized countries, with over 500 million people affected worldwide. In this work, the roles of low-molecular-weight metabolites originating from the gut microbiome, such as short-chain fatty acids, hydrogen sulfide, trimethylamine, phenylacetic acid, secondary bile acids, indoles, different gases, neurotransmitters, vitamins, and complex lipids, are discussed in relation to their CVD-promoting or preventing activities. Molecules of mixed microbial and human hepatic origin, such as trimethylamine N-oxide and phenylacetylglutamine, are also presented. Finally, dietary agents with cardioprotective effects, such as probiotics, prebiotics, mono- and poly-unsaturated fatty acids, carotenoids, and polyphenols, are also discussed. A special emphasis is given to their gut microbiota-modulating properties.

Natural products play a crucial role in drug development, addressing the escalating microbial resistance to antibiotics and the treatment of emerging diseases. Progress in genome sequencing techniques, coupled with the development of bioinformatics tools and the exploration of uncharted habitats, has highlighted the biosynthetic potential of actinomycetes. By in silico screening for diazo-related gene genomes from twelve Streptomyces strains isolated from Attini leaf-cutting ants, the new crx biosynthetic gene cluster (BGC) was identified in Streptomyces sp. CS057. This cluster, highly conserved in several Streptomyces strains, contains genes related to diazo group formation and genes for the biosynthesis of 3,4-AHBA. By overexpressing the LuxR-like regulatory gene crxR1 , we were able to activate the crx cluster, which encodes the biosynthesis of three 3,4-AHBA-derived compounds that we named crexazones (CRXs). The chemical structure of crexazones (CRXs) was determined by LC-DAD-HRMS-based dereplication and NMR spectroscopic analyses and was found to correspond to two known compounds, 3-acetamido-4-hydroxybenzoic acid (CRX1) and the phenoxazinone texazone (CRX3), and a novel 3,4-AHBA-containing compound herein designated as CRX2. Experimental proof linking the crx BGC to their encoded compounds was achieved by generating mutants in selected crx genes.

Objective: In patients with iron deficiency anaemia (IDA), the diagnostic yield of gastroscopy and colonoscopy (bidirectional endoscopy) in detecting neoplastic lesions is low. This study aimed to develop and validate a faecal immunochemical test (FIT)-based model to optimise the work-up of patients with IDA., Methods: Outpatients with IDA were enrolled in a prospective, multicentre study from April 2016 to October 2019. One FIT was performed before bidirectional endoscopy. Significant gastrointestinal lesions were recorded and a combined model developed with variables that were independently associated with significant colorectal lesions in the multivariate analysis. The model cut-off was selected to provide a sensitivity of at least 95% for colorectal cancer (CRC) detection, and its performance was compared to different FIT cut-offs. The data set was randomly split into two groups (developed and validation cohorts). An online calculator was developed for clinical application., Results: The development and validation cohorts included 373 and 160 patients, respectively. The developed model included FIT value, age, and sex. In the development and validation cohorts, a model cut-off of 0.1375 provided a negative predictive value of 98.1 and 96.7% for CRC and 90.7 and 88.3% for significant colorectal lesions, respectively. This combined model reduced the rate of missed significant colorectal lesions compared to FIT alone and could have avoided more than one-fourth of colonoscopies., Conclusion: The FIT-based combined model developed in this study may serve as a useful diagnostic tool to triage IDA patients for early endoscopic referral, resulting in considerable reduction of unnecessary colonoscopies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hernández, Quintero, Morales-Arraez, Rayado, Hijos-Mallada, Fernández, Castro-Parga, Álvarez-Sánchez, Olano, Rodríguez-Alcalde, Amaral-González, Alonso-Abreu, Nicolás-Pérez, Carrillo-Palau, González-Dávila and Gimeno-García.)

Background: Volatile compounds are key elements in the interaction and communication between organisms at both interspecific and intraspecific levels. In complex bacterial communities, the emission of these fast-acting chemical messengers allows an exchange of information even at a certain distance that can cause different types of responses in the receiving organisms. The changes in secondary metabolism as a consequence of this interaction arouse great interest in the field of searching for bioactive compounds since they can be used as a tool to activate silenced metabolic pathways. Regarding the great metabolic potential that the Actinobacteria group presents in the production of compounds with attractive properties, we evaluated the reply the emitted volatile compounds can generate in other individuals of the same group., Results: We recently reported that volatile compounds released by different streptomycete species trigger the modulation of biosynthetic gene clusters in Streptomyces spp. which finally leads to the activation/repression of the production of secondary metabolites in the recipient strains. Here we present the application of this rationale in a broader bacterial community to evaluate volatiles as signaling effectors that drive the activation of biosynthesis of bioactive compounds in other members of the Actinobacteria group. Using cocultures of different actinobacteria (where only the volatile compounds reach the recipient strain) we were able to modify the bacterial secondary metabolism that drives overproduction (e.g., granaticins, actiphenol, chromomycins) and/or de novo production (e.g., collismycins, skyllamycins, cosmomycins) of compounds belonging to different chemical species that present important biological activities., Conclusions: This work shows how the secondary metabolism of different Actinobacteria species can vary significantly when exposed in co-culture to the volatile compounds of other phylum-shared bacteria, these effects being variable depending on strains and culture media. This approach can be applied to the field of new drug discovery to increase the battery of bioactive compounds produced by bacteria that can potentially be used in treatments for humans and animals., (© 2024. The Author(s).)

Antimicrobial resistance is one of the main global threats to human health in the 21st century due to the rapid appearance of bacterial resistance and the lack of novel bioactive compounds. Natural products, especially from Actinomycetes, remain the best source to refill the drug industry pipeline. Different strategies have been pursued to increase the chances of discovering new molecules, such as studying underexplored environments like arthropod symbionts, which represent a relevant reservoir for active metabolites. This review summarizes recent research on the identification of bioactive molecules produced by Actinomycetes associated with arthropods' microbiome. The metabolites have been categorized based on their structural properties and host, highlighting that multidisciplinary approaches will be the key to fully understanding this complex relationship.

Piperazic acid is a cyclic nonproteinogenic amino acid that contains a hydrazine N-N bond formed by a piperazate synthase (KtzT-like). This amino acid, found in bioactive natural products synthesized by non-ribosomal peptide synthetases (NRPSs), confers conformational constraint to peptides, an important feature for their biological activities. Genome mining of Streptomyces strains has been revealed as a strategy to identify biosynthetic gene clusters (BGCs) for potentially active compounds. Moreover, the isolation of new strains from underexplored habitats or associated with other organisms has allowed to uncover new BGCs for unknown compounds. The in-house "Carlos Sialer (CS)" strain collection consists of seventy-one Streptomyces strains isolated from the cuticle of leaf-cutting ants of the tribe Attini . Genomes from twelve of these strains have been sequenced and mined using bioinformatics tools, highlighting their potential to encode secondary metabolites. In this work, we have screened in silico those genomes, using KtzT as a hook to identify BGCs encoding piperazic acid-containing compounds. This resulted in uncovering the new BGC dpn in Streptomyces sp. CS113, which encodes the biosynthesis of the hybrid polyketide-depsipeptide diperamycin. Analysis of the diperamycin polyketide synthase (PKS) and NRPS reveals their functional similarity to those from the aurantimycin A biosynthetic pathway. Experimental proof linking the dpn BGC to its encoded compound was achieved by determining the growth conditions for the expression of the cluster and by inactivating the NRPS encoding gene dpnS2 and the piperazate synthase gene dpnZ . The identity of diperamycin was confirmed by High-Resolution Mass Spectrometry (HRMS) and Nuclear Magnetic Resonance (NMR) and by analysis of the domain composition of modules from the DpnP PKS and DpnS NRPS. The identification of the dpn BGC expands the number of BGCs that have been confirmed to encode the relatively scarcely represented BGCs for depsipeptides of the azinothricin family of compounds and will facilitate the generation of new-to-nature analogues by combinatorial biosynthesis.

In recent years, the study of volatile compounds has sparked interest due to their implications in signaling and the enormous variety of bioactive properties attributed to them. Despite the absence of analysis methods standardization, there are a multitude of tools and databases that allow the identification and quantification of volatile compounds. These compounds are chemically heterogeneous and their diverse properties are exploited by various fields such as cosmetics, the food industry, agriculture and medicine, some of which will be discussed here. In virtue of volatile compounds being ubiquitous and fast chemical messengers, these molecules mediate a large number of interspecific and intraspecific interactions, which are key at an ecological level to maintaining the balance and correct functioning of ecosystems. This review briefly summarized the role of volatile compounds in inter- and intra-specific relationships as well as industrial applications associated with the use of these compounds that is emerging as a promising field of study., (Copyright © 2024. Published by Elsevier Inc.)

Competing Interests: The authors declare that they have no conflict of interest.

Three novel lipopeptides, PM130391 (1), PM130392 (2), and PM140293 (3) were obtained from cultures of Streptomyces tuirus PHM034 isolated from a marine sediment. Structural elucidation of the three compounds showed they belong to the nonribosomal peptides family, and they all contain an acylated alanine, three piperazic acids, a methylated glycine, and an N-hydroxylated alanine. The difference between the three compounds resides in the acyl chain bound to the alanine residue. All three compounds showed cytotoxic activity against human cancer cell lines. Genome sequence and bioinformatics analysis allowed the identification of the gene cluster responsible for the biosynthesis. Inactivation of a nonribosomal peptide synthase of this cluster abolished the biosynthesis of the three compounds, thus demonstrating the involvement of this cluster in the biosynthesis of these lipopeptides.

There is an urgent need to develop new antifungals due to the increasing prevalence of multidrug-resistant fungal infections and the recent emergence of COVID-19-associated candidiasis. A good study model for evaluating new antifungal compounds is Candida glabrata , an opportunistic fungal pathogen with intrinsic resistance to azoles (the most common clinical drugs for treating fungal infections). The aim of the current contribution was to conduct in vitro tests of antifungal metabolites produced by the bacteria Streptomyces albidoflavus Q, identify their molecular structures, and utilize several techniques to provide evidence of their therapeutic target. S. albidoflavus was isolated from maize rhizospheric soil in Mexico and identified by phylogenomic analysis using a 92-gene core. Of the 66 metabolites identified in S. albidoflavus Q by a liquid chromatography-high resolution mass spectrometry (LC-HRMS) metabolomic analysis of the lyophilized supernatant, six were selected by the Way2drug server based on their in silico binding to the likely target, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR, the key enzyme in the ergosterol biosynthesis pathway). Molecular modeling studies show a relatively high binding affinity for the Cg HMGR enzyme by two secondary metabolites: isogingerenone B (diaryl heptanoid) and notoginsenoside J (polycyclic triterpene). These secondary metabolites were able to inhibit ergosterol synthesis and affect yeast viability in vitro . They also caused alterations in the ultrastructure of the yeast cytoplasmic membrane, as evidenced by transmission electron microscopy. The putative target of isogingerenone B and notoginsenoside J is distinct from that of azole drugs (the most common clinical antifungals). The target for the latter is the lanosterol 14 alpha-demethylase enzyme (Erg11). IMPORTANCE Multidrug resistance has emerged among yeasts of the genus Candida , posing a severe threat to global health. The problem has been exacerbated by the pandemic associated with COVID-19, during which resistant strains of Candida auris and Candida glabrata have been isolated from patients infected with the SARS-CoV-2 virus. To confront this challenge, the World Health Organization has invoked scientists to search for new antifungals with alternative molecular targets. This study identified 66 metabolites produced by the bacteria Streptomyces albidoflavus Q, 6 of which had promising properties for potential antifungal activity. The metabolites were tested in vitro as inhibitors of ergosterol synthesis and C. glabrata growth, with positive results. They were also found to damage the cytoplasmic membrane of the fungus. The corresponding molecular structures and their probable therapeutic target were established. The target is apparently distinct from that of azole drugs.

The study of volatile organic compounds (VOCs) has expanded because of the growing need to search for new bioactive compounds that could be used as therapeutic alternatives. These small molecules serve as signals to establish interactions with other nearby organisms in the environment. In this work, we evaluated the antifungal effect of VOCs produced by different Streptomyces spp. This study was performed using VOC chamber devices that allow for the free exchange of VOCs without physical contact between microorganisms or the diffusible compounds they produce. Antifungal activity was tested against Escovopsis weberi, a fungal pathogen that affects ant nest stability, and the results showed that Streptomyces spp. CS014, CS057, CS131, CS147, CS159, CS207, and CS227 inhibit or reduce the fungal growth with their emitted VOCs. A GS-MS analysis of volatiles produced and captured by activated charcoal suggested that these Streptomyces strains synthesize several antifungal VOCs, many of them produced because of the presence of E. weberi, with the accumulation of various VOCs determining the growth inhibition effect.

The search for novel bioactive compounds to overcome resistance to current therapeutics has become of utmost importance. Streptomyces spp. are one of the main sources of bioactive compounds currently used in medicine. In this work, five different global transcriptional regulators and five housekeeping genes, known to induce the activation or overproduction of secondary metabolites in Streptomyces coelicolor , were cloned in two separated constructs and expressed in 12 different strains of Streptomyces spp. from the in-house CS collection. These recombinant plasmids were also inserted into streptomycin and rifampicin resistant Streptomyces strains (mutations known to enhance secondary metabolism in Streptomyces ). Different media with diverse carbon and nitrogen sources were selected to assess the strains' metabolite production. Cultures were then extracted with different organic solvents and analysed to search for changes in their production profiles. An overproduction of metabolites already known to be produced by the biosynthesis wild-type strains was observed such as germicidin by CS113, collismycins by CS149 and CS014, or colibrimycins by CS147. Additionally, the activation of some compounds such as alteramides in CS090a pSETxkBMRRH and CS065a pSETxkDCABA or inhibition of the biosynthesis of chromomycins in CS065a in pSETxkDCABA when grown in SM10 was demonstrated. Therefore, these genetic constructs are a relatively simple tool to manipulate Streptomyces metabolism and explore their wide secondary metabolites production potential.

Genome mining using standard bioinformatics tools has allowed for the uncovering of hidden biosynthesis gene clusters for specialized metabolites in Streptomyces genomes. In this work, we have used an alternative approach consisting in seeking " Streptomyces Antibiotic Regulatory Proteins" (SARP) encoding genes and analyzing their surrounding DNA region to unearth cryptic gene clusters that cannot be identified using standard bioinformatics tools. This strategy has allowed the unveiling of the new ahb cluster in Streptomyces argillaceus , which had not been retrieved before using antiSMASH. The ahb cluster is highly preserved in other Streptomyces strains, which suggests a role for their encoding compounds in specific environmental conditions. By combining overexpression of three regulatory genes and generation of different mutants, we were able to activate the ahb cluster, and to identify and chemically characterize the encoded compounds that we have named ahbamycins (AHBs). These constitute a new family of metabolites derived from 3-amino-4-hydroxybenzoate (3,4-AHBA) known for having antibiotic and antitumor activity. Additionally, by overexpressing three genes of the cluster ( ahbH , ahbI, and ahbL2 ) for the synthesis and activation of 3,4-AHBA, a new hybrid compound, AHB18, was identified which had been produced from a metabolic crosstalk between the AHB and the argimycin P pathways. The identification of this new BGC opens the possibility to generate new compounds by combinatorial biosynthesis.

The increasing appearance of multiresistant pathogens, as well as emerging diseases, has highlighted the need for new strategies to discover natural compounds that can be used as therapeutic alternatives, especially in the genus Streptomyces , which is one of the largest producers of bioactive metabolites. In recent years, the study of volatile compounds (VOCs) has raised interest because of the variety of their biological properties in addition to their involvement in cell communication. In this work, we analyze the implications of VOCs as mediating molecules capable of inducing the activation of biosynthetic pathways of bioactive compounds in surrounding Actinomycetes. For this purpose, several strains of Streptomyces were co-cultured in chamber devices that allowed VOC exchange while avoiding physical contact. In several of those strains, secondary metabolism was activated by VOCs emitted by companion strains, resulting in increased antibiotic production and synthesis of new VOCs. This study shows a novel strategy to exploit the metabolic potential of Actinomycetes as well as emphasizes the importance of studying the interactions between different microorganisms sharing the same ecological niche.

Competing Interests: The authors declare no conflicts of interest.

Coronavirus disease-19 (COVID-19) patients with severe complications present comorbidities like cardiovascular-disease, hypertension and type-2 diabetes mellitus (DM), sharing metabolic alterations like insulin resistance (IR) and dyslipidemia. Our objective was to evaluate the association among different components of the lipid-lipoprotein profile, such as remnant lipoprotein (RLP)-cholesterol, in patients with COVID-19, and to analyze their associations with the severity of the disease and death. We studied 193 patients (68 (29-96) years; 49.7% male) hospitalized for COVID-19 and 200 controls (46 (18-79) years; 52.5% male). Lipoprotein profile, glucose and procalcitonin were assessed. Patients presented higher glucose, TG, TG/HDL-cholesterol and RLP-cholesterol levels, but lower total, LDL, HDL and no-HDL-cholesterol levels (p < 0.001). When a binary logistic regression was performed, age, non-HDL-cholesterol, and RLP-cholesterol were associated with death (p = 0.005). As the COVID-19 condition worsened, according to procalcitonin tertiles, a decrease in all the cholesterol fractions (p < 0.03) was observed with no differences in TG, while levels of RLP-cholesterol and TG/HDL-cholesterol increased (p < 0.001). Lower levels of all the cholesterol fractions were related with the presence and severity of COVID-19, except for RLP-cholesterol levels and TG/HDL-cholesterol index. These alterations indicate a lipid metabolic disorder, characteristic of IR states in COVID-19 patients. RLP-cholesterol levels predicted severity and death in these patients., (© 2022. The Author(s).)

Cyclic vomiting syndrome is a benign, chronic, functional gastrointestinal pathology that manifests clinically with intense nausea and vomiting interspersed with asymptomatic periods. Its diagnosis is made according to the Rome IV criteria, which require the presence of at least 2 episodes of vomiting in the past 6 months or 3 or more episodes in the past year, with the corresponding exclusion of secondary causes that can explain the vomiting. We present the case of a 44-year-old man who consulted for intermittent nausea and vomiting of 1 year evolution with hydroelectrolytic repercussion and multiple emergency consultations. The diagnosis of cyclic vomiting syndrome was made and treatment with amitriptyline was started due to its neuromodulatory effect to prevent the recurrence of episodes. After 6 months of establishing it, the patient is asymptomatic.

Competing Interests: The authors declare that they have no conflict of interest.

The improvement of genome sequencing techniques has brought to light the biosynthetic potential of actinomycetes due to the large number of gene clusters they present compared to the number of known compounds. Genome mining is a recent strategy in the search for novel bioactive compounds, which involves the analysis of sequenced genomes to identify uncharacterized natural product biosynthetic gene clusters, many of which are cryptic or silent under laboratory conditions, and to develop experimental approaches to identify their products. Owing to the importance of halogenation in terms of structural diversity, bioavailability, and bioactivity, searching for new halogenated bioactive compounds has become an interesting issue in the field of natural product discovery. Following this purpose, a screening for halogenase coding genes was performed on 12 Streptomyces strains isolated from fungus-growing ants of the Attini tribe. Using the bioinformatics tools antiSMASH and BLAST, six halogenase coding genes were identified. Some of these genes were located within biosynthetic gene clusters (BGCs), which were studied by construction of several mutants for the identification of the putative halogenated compounds produced. The comparison of the metabolite production profile of wild-type strains and their corresponding mutants by ultrahigh-performance liquid chromatography-UV and high-performance liquid chromatography-mass spectrometry allowed us the identification of a novel family of halogenated compounds in Streptomyces sp. strain CS147, designated colibrimycins. IMPORTANCE Genome mining has proven its usefulness in the search for novel bioactive compounds produced by microorganisms, and halogenases comprise an interesting starting point. In this work, we have identified a new halogenase coding gene that led to the discovery of novel lipopetide nonribosomal peptide synthetase/polyketide synthase (NRPS/PKS)-derived natural products, the colibrimycins, produced by Streptomyces sp. strain CS147, isolated from the Attini ant niche. Some colibrimycins display an unusual α-ketoamide moiety in the peptide structure. Although its biosynthetic origin remains unknown, its presence might be related to a hypothetical inhibition of virus proteases, and, together with the presence of the halogenase, it represents a feature to be incorporated in the arsenal of structural modifications available for combinatorial biosynthesis.

The rapid emergence of bacterial resistance to antibiotics has urged the need to find novel bioactive compounds against resistant microorganisms. For that purpose, different strategies are being followed, one of them being exploring secondary metabolite production in microorganisms from uncommon sources. In this work, we have analyzed the genome of 12 Streptomyces sp. strains of the CS collection isolated from the surface of leaf-cutting ants of the Attini tribe and compared them to four Streptomyces model species and Pseudonocardia sp. Ae150A&#95;Ps1, which shares the ecological niche with those of the CS collection. We used a combination of phylogenetics, bioinformatics and dereplication analysis to study the biosynthetic potential of our strains. 51.5% of the biosynthetic gene clusters (BGCs) predicted by antiSMASH were unknown and over half of them were strain-specific, making this strain collection an interesting source of putative novel compounds.

Background: We recently demonstrated that the odds of contracting coronavirus disease 2019 (COVID-19) in patients with celiac disease (CeD) is similar to that of the general population. However, how patients with CeD perceive their COVID-19 risk may differ from their actual risk., Aim: To investigate risk perceptions of contracting COVID-19 in patients with CeD and determine the factors that may influence their perception., Methods: We distributed a survey throughout 10 countries between March and June 2020 and collected data on demographics, diet, COVID-19 testing, and risk perceptions of COVID-19 in patients with CeD. Participants were recruited through various celiac associations, clinic visits, and social media. Risk perception was assessed by asking individuals whether they believe patients with CeD are at an increased risk of contracting COVID-19 when compared to the general population. Logistic regression was used to determine the influencing factors associated with COVID-19 risk perception, such as age, sex, adherence to a gluten-free diet (GFD), and comorbidities such as cardiac conditions, respiratory conditions, and diabetes. Data was presented as adjusted odds ratios (aORs)., Results: A total of 10737 participants with CeD completed the survey. From them, 6019 (56.1%) patients with CeD perceived they were at a higher risk or were unsure if they were at a higher risk of contracting COVID-19 compared to the non-CeD population. A greater proportion of patients with CeD perceived an increased risk of contracting COVID-19 when compared to infections in general due to their CeD (56.1% vs 26.7%, P < 0.0001). Consequently, 34.8% reported taking extra COVID-19 precautions as a result of their CeD. Members of celiac associations were less likely to perceive an increased risk of COVID-19 when compared to non-members (49.5% vs 57.4%, P < 0.0001). Older age (aOR: 0.99; 95%CI: 0.99 to 0.99, P < 0.001), male sex (aOR: 0.84; 95%CI: 0.76 to 0.93, P = 0.001), and strict adherence to a GFD (aOR: 0.89; 95%CI: 0.82 to 0.96, P = 0.007) were associated with a lower perception of COVID-19 risk and the presence of comorbidities was associated with a higher perception of COVID-19 risk (aOR: 1.38; 95%CI: 1.22 to 1.54, P < 0.001)., Conclusion: Overall, high levels of risk perceptions, such as those found in patients with CeD, may increase an individual's pandemic-related stress and contribute to negative mental health consequences. Therefore, it is encouraged that public health officials maintain consistent communication with the public and healthcare providers with the celiac community. Future studies specifically evaluating mental health in CeD could help determine the consequences of increased risk perceptions in this population., Competing Interests: Conflict-of-interest statement: MIPS received in kind support for the Modulen formula from Nestle Canada, consultant honoraria from Takeda, Baxter and Frezenius Kabi unrelated to this manuscript. ASD has received honoraria from Janseen, Abbvie, Nestle and Sanofi unrelated to this manuscript. All other authors have no financial disclosures or relevant conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)