The Quintero Bay, located along the central coast of Chile, has suffered different oil spills during the past 5 years, impacting marine ecosystems. This report describes the microbial community structure of seawater samples obtained from the Quintero Bay through 16S rRNA amplicon sequencing.

The β3 adrenergic receptor is raising as an important drug target for the treatment of pathologies such as diabetes, obesity, depression, and cardiac diseases among others. Several attempts to obtain selective and high affinity ligands have been made. Currently, Mirabegron is the only available drug on the market that targets this receptor approved for the treatment of overactive bladder. However, the FDA (Food and Drug Administration) in USA and the MHRA (Medicines and Healthcare products Regulatory Agency) in UK have made reports of potentially life-threatening side effects associated with the administration of Mirabegron, casting doubts on the continuity of this compound. Therefore, it is of utmost importance to gather information for the rational design and synthesis of new β3 adrenergic ligands. Herein, we present the first combined 2D-QSAR (two-dimensional Quantitative Structure-Activity Relationship) and 3D-QSAR/CoMSIA (three-dimensional Quantitative Structure-Activity Relationship/Comparative Molecular Similarity Index Analysis) study on a series of potent β3 adrenergic agonists of indole-alkylamine structure. We found a series of changes that can be made in the steric, hydrogen-bond donor and acceptor, lipophilicity and molar refractivity properties of the compounds to generate new promising molecules. Finally, based on our analysis, a summary and a regiospecific description of the requirements for improving β3 adrenergic activity is given.

Abstract Aims Dynamin‐2 is a large GTPase, a member of the dynamin superfamily that regulates membrane remodelling and cytoskeleton dynamics. Mutations in the dynamin‐2 gene ( DNM2 ) cause autosomal dominant centronuclear myopathy (CNM), a congenital neuromuscular disorder characterised by progressive weakness and atrophy of the skeletal muscles. Cognitive defects have been reported in some DNM2 ‐linked CNM patients suggesting that these mutations can also affect the central nervous system (CNS). Here we studied how a dynamin‐2 CNM‐causing mutation influences the CNS function. Methods Heterozygous mice harbouring the p.R465W mutation in the dynamin–2 gene (HTZ), the most common causing autosomal dominant CNM, were used as disease model. We evaluated dendritic arborisation and spine density in hippocampal cultured neurons, analysed excitatory synaptic transmission by electrophysiological field recordings in hippocampal slices, and evaluated cognitive function by performing behavioural tests. Results HTZ hippocampal neurons exhibited reduced dendritic arborisation and lower spine density than WT neurons, which was reversed by transfecting an interference RNA against the dynamin‐2 mutant allele. Additionally, HTZ mice showed defective hippocampal excitatory synaptic transmission and reduced recognition memory compared to the WT condition. Conclusion Our findings suggest that the dynamin‐2 p.R465W mutation perturbs the synaptic and cognitive function in a CNM mouse model and support the idea that this GTPase plays a key role in regulating neuronal morphology and excitatory synaptic transmission in the hippocampus.

Background This work presents a forecast model for non-typhoidal salmonellosis outbreaks. Method This forecast model is based on fitted values of multivariate regression time series that consider diagnosis and estimation of different parameters, through a very flexible statistical treatment called generalized auto-regressive and moving average models (GSARIMA). Results The forecast model was validated by analyzing the cases of Salmonella enterica serovar Enteritidis in Sydney Australia (2014–2016), the environmental conditions and the consumption of high-risk food as predictive variables. Conclusions The prediction of cases of Salmonella enterica serovar Enteritidis infections are included in a forecast model based on fitted values of time series modeled by GSARIMA, for an early alert of future outbreaks caused by this pathogen, and associated to high-risk food. In this context, the decision makers in the epidemiology field can led to preventive actions using the proposed model.

Purpose This paper aims to propose a supply model of periodic review with joint replenishment for multi-products grouped by several variables with random and time dependence demand. Design/methodology/approach The products are grouped by multivariate cluster analysis. The stochastic inventory model describes the random demand of each product, considering the temporal dependency through a generalized autoregressive moving average model. Stochastic programming for the total cost of inventory is obtained considering the expected value of the demand per unit of time. Findings The total costs for the products grouped with the proposed model are 6% lower than for the individual inventory policy. The expected shortage units decrease significantly in the proposed grouped model with temporary dependence. In addition, the proposal with temporary dependency has lower costs than when the independent and identically distributed demand is considered. Originality/value The proposed policy is exemplified with real-world data from a Chilean hospital, where the products (drugs) are segmented by grouping variables, forming clusters of drugs with homogeneous behavior within the groups and heterogeneous behavior between groups.

Most studies of inventory consolidation effects assume time-independent random demand. In this article, we consider time-dependence by incorporating an autoregressive moving average structure to model the demand for products. With this modeling approach, we analyze the effect of consolidation on inventory costs compared to a system without consolidation. We formulate an inventory setting based on continuous-review using allocation rules for regular transshipment and centralization, which establishes temporal structures of demand. Numerical simulations demonstrate that, under time-dependence, the demand conditional variance, based on past data, is less than the marginal variance. This finding favors dedicated locations for inventory replenishment. Additionally, temporal structures reduce the costs of maintaining safety stocks through regular transshipments when such temporal patterns exist. The obtained results are illustrated with an example using real-world data. Our investigation provides information for managing supply chains in the presence of time-patterned demands that can be of interest to decision-makers in the supply chain.

Here we describe modified syntheses of o-acetylbenzoic acids­ and o-acetylphenylacetic acids by Heck palladium-catalysed aryl­ation of n-butyl vinyl ether with o-iodobenzoic acids or with o-iodo­phenylacetic acids, respectively. General syntheses of benzo[b]naphtho[2,3-b]furan-6,11-diones from o-acetylbenzoic acids and 2-benzyl-3-hydroxynaphthalene-1,4-diones from o-acetylphenylacetic acids are also reported.

Biocatalyst systems based on biofilms were developed to remove nitrogen and sulfur-containing heterocyclic hydrocarbons using Cobetia sp. strain MM1IDA2H-1 and Rhodococcus rhodochrous. The curli overproducers mutants CM1 and CM4 were derived from Cobetia sp. strain and used to build monostrain biofilms to remove quinoline; and together with R. rhodochrous to simultaneously remove quinoline and dibenzothiophene using mixed biofilms. The quinoline removal using biofilms were 96% and 97% using CM1 or CM4 curli overproducers respectively, whereas bacterial suspensions assays yielded 19% and 24% with the same strains. At the other hand, the simultaneous removal of quinoline and dibenzothiophene using mixed biofilms were respectively 50% and 58% using strains R. rhodochrous with CM1 and 75% and 50% using R. rhodochrous with CM4. Results show that biofilms were more efficient than bacterial suspension assays and that in mixed biofilms the shared surface area by two or more bacteria could affect the final yield.

This review discusses the contribution of the use of the isolated rat aorta (IRA) as a model for the evaluation of extracts and metabolites produced by plants with a vasodilator effect in animals. This model continues to be a valuable approach for the search and development of new phytochemicals consumed as medicinal plants or foods. In most cases, the sources of phytochemicals have been used in folk medicine to treat ailments that include hypertension. In this model, the endothelium is emphasized as a key component that modulates the vessel contractility, and therefore the basal tone and blood pressure. Based on the functional nature of the model, we focused on studies that determined the endothelium-dependent and -independent vasodilatory activity of phytochemicals. We describe the mechanisms that account for aorta contraction and relaxation, and subsequently show the vasoactive effect of a series of phytochemicals acting as vasodilators and its endothelium dependence. We highlight information regarding the cardiovascular benefits of phytochemicals, especially their potential antihypertensive effect. On this basis, we discuss the advantages of the IRA as a predictive model to support the research and development of new drugs that may be of help in the prevention and treatment of cardiovascular diseases, the number one cause of death worldwide.

Vascular endothelium plays a key role in regulating cardiovascular homeostasis by controlling the vascular tone. Variations in sex hormones during the reproductive cycle of females affect the homeostasis of the cardiovascular system. Also, the evidence shows that estrogens show a cardioprotective effect. On this basis, this study describes some vascular responses induced by vasoactive substances during the estrous cycle in rats. We obtained the information available on this topic from the online databases that included scientific articles published in the Web of Science, PubMed, and Scielo. Many investigations have evaluated the vasoactive response of substances such as acetylcholine and norepinephrine during the estrous cycle. In this review, we specifically described the vascular response to vasoactive substances in rats during the estrous cycle, pregnancy, and in ovariectomized rats. In addition, we discussed the existence of different signaling pathways that modulate vascular function. The knowledge of these effects is relevant for the optimization and development of new treatments for some vascular pathologies.

The United States Pharmacopeial Convention (USP) is a nonprofit, scientific, standard-setting organization, and world leader in establishing quality, purity, and testing standards for medicines, foods, and dietary supplements. USP quality standards are used in more than 140 countries and are legally recognized by more than 40 countries. Currently, there is renewed interest in herbal medicines globally, and health policies are being implemented worldwide for the use of complementary and traditional medicine. In response, USP has developed a robust body of monographs that can be used to guide industry and regulators in ensuring the quality and safety of botanical ingredients used in dietary supplements and herbal medicines. Throughout the Pan American regions, there is a strong tradition of using botanicals as herbal medicines and, as in other regions, a growing desire for botanical dietary supplements. This underscores the need for public quality standards to ensure quality, reduce the flow of substandard and adulterated products, and ensure public health and safety. In April 2022, USP launched the Pan America Botanical Dietary Supplements and Herbal Medicines Expert Panel, with experts representing 12 different countries. The Expert Panel’s work focuses on developing quality control standards for the most important botanical ingredients used in the respective countries, ingredients that are also of global importance. This article provides an overview of the state of botanical dietary supplements and herbal medicines in different Pan American regions with a focus on the regulatory status of herbal products, the development of national quality and research initiatives, and policies related to agriculture conservation and sustainability, among other topics.

Detecting antibiotic residues is vital to minimize their impact. Yet, existing methods are complex and costly. Biosensors offer an alternative. While many biosensors detect various antibiotics, specific ones for beta-lactams are lacking. To address this gap, a biosensor based on the AmpC beta-lactamase regulation system (ampR–ampC) from Pseudomonas sp. IB20, an Antarctic isolate, was developed in this study. The AmpR–AmpC system is well-conserved in the genus Pseudomonas and has been extensively studied for its involvement in peptidoglycan recycling and beta-lactam resistance. To create the biosensor, the ampC coding sequence was replaced with the mCherry fluorescent protein as a reporter, resulting in a transcriptional fusion. This construct was then inserted into Escherichia coli SN0301, a beta-lactam hypersensitive strain, generating a whole-cell biosensor. The biosensor demonstrated dose-dependent detection of penicillins, cephalosporins and carbapenems. However, the most interesting aspect of this work is the high sensitivity presented by the biosensor in the detection of carbapenems, as it was able to detect 8 pg/mL of meropenem and 40 pg/mL of imipenem and reach levels of 1–10 ng/mL for penicillins and cephalosporins. This makes the biosensor a powerful tool for the detection of beta-lactam antibiotics, specifically carbapenems, in different matrices.

A novel acidophilic member of the phylum Actinobacteria was isolated from an acidic, metal-contaminated stream draining from an abandoned underground coal mine (Trongol mine), situated close to Curanilahue, Biobío Region, Chile. The isolate (USS-CCA1T) was demonstrated to be a heterotroph that catalysed under aerobic conditions the oxidation of ferrous iron and the reduction of ferric iron under anaerobic conditions, but not the oxidation of sulfur nor hydrogen. USS-CCA1T is a Gram-positive, motile, short rod-shaped, mesophilic bacterium with a temperature growth optimum at 30 °C (range 20–39 °C). It was categorized as an extreme acidophile growing between 1.7 and 4.5 and optimally at pH 3.0. The G+C content of the chromosomal DNA of the isolate was 74.1 mol%, which is highly related to Aciditerrimonas ferrireducens IC-180T , (the most closely related genus; 94.4 % 16S rRNA gene identity), and higher than other acidophilic actinobacteria. The isolate (USS-CCA1T) was shown to form a distinct 16S rRNA clade from characterized acidophilic actinobacteria, well separated from the genera Acidimicrobium , Ferrimicrobium , Ferrithrix , ‘Acidithrix’ and Aciditerrimonas . Genomic indexes (ANIb, DDH, AAI, POCP) derived from the USS-CCA1T draft genome sequence (deposited at DDBJ/ENA/GenBank under the accession WJHE00000000) support assignment of the isolate to a new species and a new genus within the Acidimicrobiaceae family. Isolate USS-CCA1T is the designated type strain of the novel species Acidiferrimicrobium australe (=DSM 106828T,=RGM 2506T).

Background: Blueberries are polyphenol-rich fruits with antioxidant and anti-inflammatory properties. Polyphenols from berries act by blocking digestive enzymes, reshaping gastrointestinal microbiota, and affecting the release of gastrointestinal hormones to regulate insulin dynamics and glucose management. However, most studies use fruit extracts instead of fresh fruit. We aimed to evaluate postprandial glucose management and antioxidant capacity of fresh blueberries consumed acutely or as a six-day supplementation in 10 sedentary subjects. Methods: To evaluate the effect of acute blueberry intake, 150 g of blueberries were consumed together with 150 g of white bread by the subject and blood samples were collected at 0, 30, 60, 90 and 120 min to measure glucose, insulin, and plasma antioxidant capacity. To evaluate supplementation, 150 g of blueberries were provided daily for six days and sample collection was performed at day 7. Results: Acute consumption of blueberries decreased postprandial glucose area under the curve (AUC) and increased insulin levels at 15 min timepoint. Supplementation did not affect glucose levels but decreased insulin levels at 120 min. No changes in antioxidant capacity were observed. Conclusions: Consumption of fresh blueberries improves postprandial glucose management presumably due to actions on the gastrointestinal tract, while supplementation improves insulin sensitivity, probably due antioxidant and anti-inflammatory effects.

Objective To examine the effects of d -tagatose or stevia preloads on carbohydrate metabolism markers after an oral glucose load, as well as subjective and objective appetite in women with insulin resistance (IR). Research design and methods Randomized controlled crossover study. Women with IR without T2DM (n = 33; aged 23.4 ± 3.8; BMI 28.1 ± 3.4 kg × m −2 ) underwent three oral glucose loads (3 h each) on three different days. Ten min before oral glucose load, volunteers consumed a preload of 60 mL water (control), 60 mL water with stevia (15.3 mg), or d -tagatose (5000 mg). Serum glucose and C-peptide were evaluated at −10, 30-, 60-, 90-, 120-, and 180-min. Subjective appetite was determined with a visual analog scale. Food intake was measured at ad libitum buffet after 180 min. Results C-peptide iAUC was significantly higher for stevia (median (IQR): 1033 (711–1293) ng × min × L −1 ) vs. d -tagatose (794 (366–1134) ng × min × L −1 ; P = 0.001) or control (730 (516–1078) ng × min × L −1 ; P = 0.012). At 30- and 60-min serum glucose was higher for stevia vs other conditions ( P < 0.01). Volunteers reported greater satiety for stevia and d -tagatose vs. control at 60 min and greater desire to eat for stevia vs. control at 120- min (all P < 0.05). Objective appetite did not vary by condition ( P = 0.06). Conclusions Our findings suggest that these NNS are not inert. Stevia intake produced an acute response on C-peptide release while increased serum glucose at earlier times. It is possible that NNS affects subjective but not objective appetite. This trial is registered at clinicaltrials.gov as NCT04327245. Clinical trial registry NCT04327245.

Introduction: The hippocampus is especially susceptible to age-associated neuronal pathologies, and there is concern that the age-associated rise in cortisol secretion from the adrenal gland may contribute to their etiology. Furthermore, because 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1) catalyzes the reduction of cortisone to the active hormone cortisol, it is plausible that an increase in the expression of this enzyme enhances the deleterious impact of cortisol in the hippocampus and contributes to the neuronal pathologies that underlie cognitive decline in the elderly. Methods: Rhesus macaques were used as a translational animal model of human aging, to examine age-related changes in gene and protein expressions of (HSD11B1/HSD11B1) in the hippocampus, a region of the brain that plays a crucial role in learning and memory. Results: Older animals showed significantly (p < 0.01) higher base-line cortisol levels in the circulation. In addition, they showed significantly (p < 0.05) higher hippocampal expression of HSD11B1 but not NR3C1 and NR3C2 (i.e., two receptor-encoding genes through which cortisol exerts its physiological actions). A similar age-related significant (p < 0.05) increase in the expression of the HSD11B1 was revealed at the protein level by western blot analysis. Discussion: The data suggest that an age-related increase in the expression of hippocampal HSD11B1 is likely to raise cortisol concentrations in this cognitive brain area, and thereby contribute to the etiology of neuropathologies that ultimately lead to neuronal loss and dementia. Targeting this enzyme pharmacologically may help to reduce the negative impact of elevated cortisol concentrations within glucocorticoid-sensitive brain areas and thereby afford neuronal protection.