Importancia cultural de la flora empleada por la comunidad nativa Asheninka Sheremashe, Ucayali, Perú / Cultural importance of the flora used by the Asheninka Sheremashe native community, Ucayali, Peru

The cultural significance of the flora used by the native Asheninka Sheremashe community in Ucayali, Peru was determined. To do this, a fieldwork of over 4 months was conducted, involving semi-structured interviews with 106 residents through non-probabilistic convenience sampling. The community utilizes 139 plant species in their daily lives, belonging to 120 genera and 52 families, with the most abundant being Fabaceae, Arecaceae, Malvaceae, Solanaceae, Poaceae, and Rutaceae. Furthermore, 25.9% of the species are of significant importance to theinhabitants according to the Cultural Index (CI), such as Manihot esculenta, Theobroma cacao, Bixa orellana, Musa paradisiaca, Ficus insipida, among others. It can be concluded that the flora plays a prominent role in the life of the community, with the categories reporting the highest number of species being: food (29.35%), medicine (28.36%), culture (9.95%), construction (9.45%), lumber (6.97%), commerce (3.48%), craftsmanship (2.49%), toxic (2.49%), and other uses (7.46%)

Se determinó la importancia cultural de la flora empleada por la comunidad nativa Asheninka Sheremashe, en Ucayali, Perú. Para ello, se realizó un trabajo de campo de más de 4 meses, donde se aplicaron entrevistas semiestructuradas a 106 habitantes mediante un muestreo no probabilístico por conveniencia. La comunidad emplea 139 especies vegetales en su día a día, pertenecientes a 120 géneros y 52 familias; siendo las más abundantes las Fabaceae, Arecaceae, Malvaceae, Solanaceae, Poaceae y Rutaceae. Además, el 25.9% de las especies tiene gran importancia para los pobladores según el Índice Cultural (IC): Manihot esculenta, Theobroma cacao, Bixa orellana, Musa paradisiaca, Ficus insipida, entre otras. Se concluye que la flora tiene un rol preponderante en la vida de la comunidad, siendo las categorías que presentaron mayor reporte de especies: alimentación (29.35%), medicina (28.36%), cultura (9.95%), construcción (9.45%), aserrío (6.97%), comercio (3.48%), artesanía (2.49%), tóxico (2.49%) y otros usos (7.46%)

Antimicrobial Activity and Phytochemical Characterization of Baccharis concava Pers., a Native Plant of the Central Chilean Coast.

Few sclerophyllous plants from the central coast of Chile have been systematically studied. This work describes the phytochemical composition and antimicrobial properties of Baccharis concava Pers. (sin. B. macraei), a shrub found in the first line and near the Pacific coast. B. concava has been traditionally used by indigenous inhabitants of today's central Chile for its medicinal properties. Few reports exist regarding the phytochemistry characterization and biological activities of B. concava. A hydroalcoholic extract of B. concava was prepared from leaves and small branches. Qualitative phytochemical characterization indicated the presence of alkaloids, steroids, terpenoids, flavonoids, phenolic, and tannin compounds. The antimicrobial activity of this extract was assessed in a panel of microorganisms including Gram-positive bacteria, Gram-negative bacteria, and pathogenic yeasts. The extract displayed an important antimicrobial effect against Gram-positive bacteria, Candida albicans, and Cryptococcus neoformans but not against Gram-negatives, for which an intact Lipopolysaccharide is apparently the determinant of resistance to B. concava extracts. The hydroalcoholic extract was then fractionated through a Sephadex LH-20/methanol-ethyl acetate column. Afterward, the fractions were pooled according to a similar pattern visualized by TLC/UV analysis. Fractions obtained by this criterion were assessed for their antimicrobial activity against Staphylococcus aureus. The fraction presenting the most antimicrobial activity was HPLC-ESI-MS/MS, obtaining molecules related to caffeoylquinic acid, dicaffeoylquinic acid, and quercetin, among others. In conclusion, the extracts of B. concava showed strong antimicrobial activity, probably due to the presence of metabolites derived from phenolic acids, such as caffeoylquinic acid, and flavonoids, such as quercetin, which in turn could be responsible for helping with wound healing. In addition, the development of antimicrobial therapies based on the molecules found in B. concava could help to combat infection caused by pathogenic yeasts and Gram-positive bacteria, without affecting the Gram-negative microbiota.

M.O.I.S.T. Concept for the Local Therapy of Chronic Wounds: An International Update.

Chronic wounds remain a significant clinical challenge both for those affected and for healthcare systems. The treatment is often comprised and complex. All patients should receive wound care that is integrated into a holistic approach involving local management that addresses the underlying etiology and provides for gold standard therapy to support healing, avoid complications and be more cost effective. There have been significant advances in medicine over the last few decades. The development of new technologies and therapeutics for the local treatment of wounds is also constantly increasing. To help standardize clinical practice with regard to the multitude of wound products, the M.O.I.S.T. concept was developed by a multidisciplinary expert group. The M stands for moisture balance, O for oxygen balance, I for infection control, S for supporting strategies, and T for tissue management. Since the M.O.I.S.T. concept, which originated in the German-speaking countries, is now intended to provide healthcare professionals with an adapted instrument to be used in clinical practice, and a recent update to the concept has been undertaken by a group of interdisciplinary experts to align it with international standards. The M.O.I.S.T. concept can now be used internationally both as an educational tool and for the practical implementation of modern local treatment concepts for patients with chronic wounds and can also be used in routine clinical practice.

"Fibromyalgia - are there any new approaches?"

INTRODUCTION: Approaching patients with fibromyalgia (FM) is challenging due to the limited availability of scientifically proven effective therapies. OBJECTIVE: Review the treatments in use for FM and present new knowledge that could benefit these patients. Non-pharmacological interventions are recommended as the first line of treatment: aerobic exercise, cognitive behavioral therapy and patient education, all aimed at improving pain and other symptoms. Additional approaches have been studied, such as, digital health interventions, combined treatments, noninvasive neuromodulation, and others. Concerning pharmacological therapy, the mechanism of action of the medications currently used is to promote pain modulation. Medications approved by Food and Drug Administration are duloxetine, milnacipran and pregabalin. Amitriptyline, cyclobenzaprine, gabapentin and naltrexone are considered for off-label use. Cannabinoids, vitamin D supplementation are still controversial and further research is needed. CONCLUSION: The combination of therapies, whether old, recent or reformulated, are the most effective strategy for managing symptoms in patients with fibromyalgia. KEY WORDS: fibromyalgia, treatment, nonpharmacological interventions, pharmacological treatment.

The Roles of MicroRNAs in Asthma and Emerging Insights into the Effects of Vitamin D3 Supplementation.

Asthma is one of the most common chronic non-communicable diseases worldwide, characterized by variable airflow limitation secondary to airway narrowing, airway wall thickening, and increased mucus resulting from chronic inflammation and airway remodeling. Current epidemiological studies reported that hypovitaminosis D is frequent in patients with asthma and is associated with worsening the disease and that supplementation with vitamin D3 improves asthma symptoms. However, despite several advances in the field, the molecular mechanisms of asthma have yet to be comprehensively understood. MicroRNAs play an important role in controlling several biological processes and their deregulation is implicated in diverse diseases, including asthma. Evidence supports that the dysregulation of miR-21, miR-27b, miR-145, miR-146a, and miR-155 leads to disbalance of Th1/Th2 cells, inflammation, and airway remodeling, resulting in exacerbation of asthma. This review addresses how these molecular mechanisms explain the development of asthma and its exacerbation and how vitamin D3 may modulate these microRNAs to improve asthma symptoms.

Mechanistic basis for potassium efflux-driven activation of the human NLRP1 inflammasome.

Nigericin, an ionophore derived from Streptomyces hygroscopicus, is arguably the most commonly used tool compound to study the NLRP3 inflammasome. Recent findings, however, showed that nigericin also activates the NLRP1 inflammasome in human keratinocytes. In this study, we resolve the mechanistic basis of nigericin-driven NLRP1 inflammasome activation. In multiple nonhematopoietic cell types, nigericin rapidly and specifically inhibits the elongation stage of the ribosome cycle by depleting cytosolic potassium ions. This activates the ribotoxic stress response (RSR) sensor kinase ZAKα, p38, and JNK, as well as the hyperphosphorylation of the NLRP1 linker domain. As a result, nigericin-induced pyroptosis in human keratinocytes is blocked by extracellular potassium supplementation, ZAKα knockout, or pharmacologic inhibitors of ZAKα and p38 kinase activities. By surveying a panel of ionophores, we show that electroneutrality of ion movement is essential to activate ZAKα-driven RSR and a greater extent of K+ depletion is necessary to activate ZAKα-NLRP1 than NLRP3. These findings resolve the mechanism by which nigericin activates NLRP1 in nonhematopoietic cell types and demonstrate an unexpected connection between RSR, perturbations of potassium ion flux, and innate immunity.

Isolation and Identification of Pigment-Producing Endophytic Fungi from the Amazonian Species Fridericia chica.

Pigments of fungal origin have aroused increasing interest in the food dye and cosmetic industries since the global demand for natural dyes has grown. Endophytic microorganisms are a source of bioactive compounds, and Amazonian plant species can harbor fungi with a wide range of biotechnological applications. Popularly known in Brazil as crajiru, Fridericia chica is a medicinal plant that produces a red pigment. In this study, a total of 121 fungi were isolated in potato dextrose agar from three plants. We identified nine pigment-producing endophytic fungi isolated from branches and leaves of F. chica. The isolates that showed pigment production in solid media were molecularly identified via multilocus analysis as Aspergillus welwitschiae, A. sydowii, Curvularia sp., Diaporthe cerradensis (two strains), Hypoxylon investiens, Neoscytalidium sp. (two strains) and Penicillium rubens. These isolates were subjected to submerged fermentation in two culture media to obtain metabolic extracts. The extracts obtained were analyzed in terms of their absorbance between 400 and 700 nm. The pigmented extract produced by H. investiens in medium containing yeast extract showed maximum absorbance in the red absorption range (UA700 = 0.550) and significant antioxidant and antimicrobial activity. This isolate can thus be considered a new source of extracellular pigment.

Utilizing intramammary Melaleuca alternifolia as an organic internal sealant for dry-off therapy in Murrah buffaloes.

The effects of intramammary dry cow therapy based on the administration of 5% Melaleuca alternifolia tea tree essential oil (TTO) as an internal teat sealant to Murrah cows were evaluated. A longitudinal prospective and retrospective negative control study was performed using 12 buffaloes from a total of 20 Murrah buffaloes on an organic farm, with the cow used as a control for herself. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for treatments with pure oil (TTO) and medication containing 5% TTO (O5) were determined. The buffaloes were clinically examined, and the teats were evaluated using thermography and ultrasound. Udder health was monitored during the first 100 days in milk (DIM) using milk somatic cell count (SCC) and California mastitis test (CMT). Laboratory tests against standard strains Staphylococcus aureus ATCC®25,923™, Escherichia coli ATCC®25,922™, and wild bacterial strains showed maximum MIC values of 50 µL/mL for the TTO and O5 treatments. One wild-type S. aureus strain showed no MBC. No adverse effects were observed after the intramammary application of TTO. The CMT and SCC values were similar (P > 0.05) for all observations. The medication containing 5% TTO was effective in vitro and compatible with the intramammary tissue in vivo of Murrah buffaloes. TTO was safe, not inducing inflammatory processes or other modifications of the teat detectable by thermography or ultrasound. It was able to protect buffaloes during the dry period under field conditions, demonstrating potential use as a teat sealant for organic farms.

Intratumoral injection of melatonin enhances tumor regression in cell line-derived and patient-derived xenografts of head and neck cancer by increasing mitochondrial oxidative stress.

Head and neck squamous cell carcinoma present a high mortality rate. Melatonin has been shown to have oncostatic effects in different types of cancers. However, inconsistent results have been reported for in vivo applications. Consequently, an alternative administration route is needed to improve bioavailability and establish the optimal dosage of melatonin for cancer treatment. On the other hand, the use of patient-derived tumor models has transformed the field of drug research because they reflect the heterogeneity of patient tumor tissues. In the present study, we explore mechanisms for increasing melatonin bioavailability in tumors and investigate its potential as an adjuvant to improve the therapeutic efficacy of cisplatin in the setting of both xenotransplanted cell lines and primary human HNSCC. We analyzed the effect of two different formulations of melatonin administered subcutaneously or intratumorally in Cal-27 and SCC-9 xenografts and in patient-derived xenografts. Melatonin effects on tumor mitochondrial metabolism was also evaluated as well as melatonin actions on tumor cell migration. In contrast to the results obtained with the subcutaneous melatonin, intratumoral injection of melatonin drastically inhibited tumor progression in HNSCC-derived xenografts, as well as in patient-derived xenografts. Interestingly, intratumoral injection of melatonin potentiated CDDP effects, decreasing Cal-27 tumor growth. We demonstrated that melatonin increases ROS production and apoptosis in tumors, targeting mitochondria. Melatonin also reduces migration capacities and metastasis markers. These results illustrate the great clinical potential of intratumoral melatonin treatment and encourage a future clinical trial in cancer patients to establish a proper clinical melatonin treatment.

Omics approaches to investigate the neuroprotective capacity of a Citrus sinensis (sweet orange) extract in a Caenorhabditis elegans Alzheimer's model.

Citrus sinensis by-products are a promising source of neuroprotective molecules. In this study, a pressurized liquid extract of Citrus by-products (PLE100) has been extensively characterized, and its neuroprotective capacity tested in the Caenorhabditis elegans strain CL4176, a validated in vivo model of Alzheimer's disease (AD). More than 450 compounds have been annotated in the extract, being triacylglycerols (TGs), stigmastanes, fatty acids (FAs) and carbohydrates the most abundant. The results demonstrate that worms PLE100-treated are significantly protected in a dose-dependent manner against the Aß-peptide paralysis toxicity. The RNA-Seq data showed an alteration of 294 genes mainly related to the stress response defense along with genes involved in the lipid transport and metabolism. Moreover, the comprehensive metabolomics study allowed the identification of 818 intracellular metabolites, of which 54 were significantly altered (mainly lipids). The integration of these and previous results provides with new evidences of the protection mechanisms of this promising extract.

Cardiac arrest in the perioperative period: a consensus guideline for identification, treatment, and prevention from the European Society of Anaesthesiology and Intensive Care and the European Society for Trauma and Emergency Surgery.

INTRODUCTION: Cardiac arrest in the operating room is a rare but potentially life-threatening event with mortality rates of more than 50%. Contributing factors are often known, and the event is recognised rapidly as patients are usually under full monitoring. This guideline covers the perioperative period and is complementary to the European Resuscitation Council guidelines. MATERIAL AND METHODS: The European Society of Anaesthesiology and Intensive Care and the European Society for Trauma and Emergency Surgery jointly nominated a panel of experts to develop guidelines for the recognition, treatment, and prevention of cardiac arrest in the perioperative period. A literature search was conducted in MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials. All searches were restricted to publications from 1980 to 2019 inclusive and to the English, French, Italian and Spanish languages. The authors also contributed individual, independent literature searches. RESULTS: This guideline contains background information and recommendation for the treatment of cardiac arrest in the operating room environment, and addresses controversial topics such as open chest cardiac massage, resuscitative endovascular balloon occlusion and resuscitative thoracotomy, pericardiocentesis, needle decompression, and thoracostomy. CONCLUSIONS: Successful prevention and management of cardiac arrest during anaesthesia and surgery requires anticipation, early recognition, and a clear treatment plan. The ready availability of expert staff and equipment must also be taken into consideration. Success not only depends on medical knowledge, technical skills and a well-organised team using crew resource management, but also on an institutional safety culture embedded in everyday practice through continuous education, training, and multidisciplinary co-operation.

Cardiac arrest in the perioperative period: a consensus guideline for identification, treatment, and prevention from the European Society of Anaesthesiology and Intensive Care and the European Society for Trauma and Emergency Surgery.

INTRODUCTION: Cardiac arrest in the operating room is a rare but potentially life-threatening event with mortality rates of more than 50%. Contributing factors are often known, and the event is recognised rapidly as patients are usually under full monitoring. This guideline covers the perioperative period and is complementary to the European Resuscitation Council (ERC) guidelines. MATERIAL AND METHODS: The European Society of Anaesthesiology and Intensive Care and the European Society for Trauma and Emergency Surgery jointly nominated a panel of experts to develop guidelines for the recognition, treatment and prevention of cardiac arrest in the perioperative period. A literature search was conducted in MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials. All searches were restricted to publications from 1980 to 2019 inclusive and to the English, French, Italian and Spanish languages. The authors also contributed individual, independent literature searches. RESULTS: This guideline contains background information and recommendation for the treatment of cardiac arrest in the operating room environment, and addresses controversial topics such as open chest cardiac massage (OCCM), resuscitative endovascular balloon occlusion (REBOA) and resuscitative thoracotomy, pericardiocentesis, needle decompression and thoracostomy. CONCLUSION: Successful prevention and management of cardiac arrest during anaesthesia and surgery requires anticipation, early recognition and a clear treatment plan. The ready availability of expert staff and equipment must also be taken into consideration. Success not only depends on medical knowledge, technical skills and a well organised team using crew resource management but also on an institutional safety culture embedded in everyday practice through continuous education, training and multidisciplinary co-operation.

Anti-Inflammatory Chilean Endemic Plants.

Medicinal plants have been used since prehistoric times and continue to treat several diseases as a fundamental part of the healing process. Inflammation is a condition characterized by redness, pain, and swelling. This process is a hard response by living tissue to any injury. Furthermore, inflammation is produced by various diseases such as rheumatic and immune-mediated conditions, cancer, cardiovascular diseases, obesity, and diabetes. Hence, anti-inflammatory-based treatments could emerge as a novel and exciting approach to treating these diseases. Medicinal plants and their secondary metabolites are known for their anti-inflammatory properties, and this review introduces various native Chilean plants whose anti-inflammatory effects have been evaluated in experimental studies. Fragaria chiloensis, Ugni molinae, Buddleja globosa, Aristotelia chilensis, Berberis microphylla, and Quillaja saponaria are some native species analyzed in this review. Since inflammation treatment is not a one-dimensional solution, this review seeks a multidimensional therapeutic approach to inflammation with plant extracts based on scientific and ancestral knowledge.

Long-Term Treatment and Effect of Discontinuation of Calcifediol in Postmenopausal Women with Vitamin D Deficiency: A Randomized Trial.

Vitamin D plays a major role in bone health and probably also in multiple extraskeletal acute and chronic diseases. Although supplementation with calcifediol, a vitamin D metabolite, has demonstrated efficacy and safety in short-term clinical trials, its effects after long-term monthly administration have been studied less extensively. This report describes the results of a 1-year, phase III-IV, double-blind, randomized, controlled, parallel, multicenter superiority clinical trial to assess the efficacy and safety of monthly calcifediol 0.266 mg versus cholecalciferol 25,000 IU (0.625 mg) in postmenopausal women with vitamin D deficiency (25(OH)D < 20 ng/mL). A total of 303 women were randomized and 298 evaluated. Patients were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months (Group A1), calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months (Group A2), and cholecalciferol 25,000 IU/month (0.625 mg/month) for 12 months (Group B). By month 4, stable 25(OH)D levels were documented with both calcifediol and cholecalciferol (intention-to-treat population): 26.8 ± 8.5 ng/mL (Group A1) and 23.1 ± 5.4 ng/mL (Group B). By month 12, 25(OH)D levels were 23.9 ± 8.0 ng/mL (Group A1) and 22.4 ± 5.5 ng/mL (Group B). When calcifediol treatment was withdrawn in Group A2, 25(OH)D levels decreased to baseline levels (28.5 ± 8.7 ng/mL at month 4 versus 14.4 ± 6.0 ng/mL at month 12). No relevant treatment-related safety issues were reported in any of the groups. The results confirm that long-term treatment with monthly calcifediol in vitamin D-deficient patients is effective and safe. The withdrawal of treatment leads to a pronounced decrease of 25(OH)D levels. Calcifediol presented a faster onset of action compared to monthly cholecalciferol. Long-term treatment produces stable and sustained 25(OH)D concentrations with no associated safety concerns. © 2023 Faes Farma SA. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Cantharidin-Podophyllin-Salicylic Acid Formulation as a First-Line Treatment for Plantar Warts? A Case Report with Multiple Plantar Warts of Human Papillomavirus Biotype 27 and Previous Failed Treatments.

BACKGROUND Plantar warts are benign skin tumors caused by the human papillomavirus (HPV). There are multiple treatments, but none ensure absolute success. Successful treatment depends on several factors, such as the location, number of lesions, HPV biotype, and the patient's health condition. This report presents a 53-year-old woman who had multiple recalcitrant plantar warts with HPV biotype 27 that were treated using a cantharidin-podophyllin-salicylic acid (CPS) formulation after 2 failed treatments. CASE REPORT A 53-year-old woman was seen on October 25, 2021. She had 6 plantar warts due to HPV biotype 27, which was confirmed by polymerase chain reaction using a sample of hyperkeratosis scales obtained from the wart after debridement. Five cryotherapy sessions were applied, without clinical improvement. Two sessions of nitric-acid-zinc complex were then applied, from which the patient reported severe pain, without clinical improvement. Finally, 3 sessions of CPS formulation were applied, and the HPV remitted in all warts. CONCLUSIONS Conservative treatments, such as cryotherapy, have not been effective in a case of multiple recalcitrant plantar warts. The combined action of the 3 compounds of CPS formulation was key in the resolution of this case. Plantar wart treatment should be easy to apply, effective, fast, and efficient. In cases of recalcitrant or numerous warts, treatment should be more aggressive from the beginning if the patient's lifestyle allows it. It would be interesting to conduct randomized clinical trials to find out which patients could be indicated for the CPS formulation as a first line of treatment.

Magneto-Fluorescent Mesoporous Nanocarriers for the Dual-Delivery of Ofloxacin and Doxorubicin to Tackle Opportunistic Bacterial Infections in Colorectal Cancer.

Cancer-related opportunistic bacterial infections are one major barrier for successful clinical therapies, often correlated to the production of genotoxic factors and higher cancer incidence. Although dual anticancer and antimicrobial therapies are a growing therapeutic fashion, they still fall short when it comes to specific delivery and local action in in vivo systems. Nanoparticles are seen as potential therapeutic vectors, be it by means of their intrinsic antibacterial properties and effective delivery capacity, or by means of their repeatedly reported modulation and maneuverability. Herein we report on the production of a biocompatible, antimicrobial magneto-fluorescent nanosystem (NANO3) for the delivery of a dual doxorubicin-ofloxacin formulation against cancer-related bacterial infections. The drug delivery capacity, rendered by its mesoporous silica matrix, is confirmed by the high loading capacity and stimuli-driven release of both drugs, with preference for tumor-like acidic media. The pH-dependent emission of its surface fluorescent SiQDs, provides an insight into NANO3 surface behavior and pore availability, with the SiQDs working as pore gates. Hyperthermia induces heat generation to febrile temperatures, doubling drug release. NANO3-loaded systems demonstrate significant antimicrobial activity, specifically after the application of hyperthermia conditions. NANO3 structure and antimicrobial properties confirm their potential use in a future dual anticancer and antimicrobial therapeutical vector, due to their drug loading capacity and their surface availability for further modification with bioactive, targeting species.

Acquisition of resistance to ceftazidime-avibactam during infection treatment in Pseudomonas aeruginosa through D179Y mutation in one of two blaKPC-2 gene copies without losing carbapenem resistance.

Ceftazidime/Avibactam (CAZ/AVI) is frequently used to treat KPC-producing Pseudomonas aeruginosa (KPC-PA) and Enterobacterales. CAZ/AVI resistance is driven by several mechanisms. In P. aeruginosa this mainly occurs through alteration of AmpC, porins, and/or efflux pump overexpression, whereas in Enterobacterales it frequently occurs through D179Y substitution in the active site of KPC enzyme. This aminoacid change abolishes AVI binding to the KPC active site, hence inhibition is impaired. However, this substitution also decreases KPC-mediated resistance to carbapenems ("see-saw" effect). The goal of this work was to characterize the in vivo acquisition of CAZ/AVI resistance through D179Y substitution in a KPC-PA isolated from a hospitalized patient after CAZ/AVI treatment. Two KPC-PA isolates were obtained. The first isolate, PA-1, was obtained before CAZ/AVI treatment and was susceptible to CAZ/AVI. The second isolate, PA-2, was obtained after CAZ/AVI treatment and exhibited high-level CAZ/AVI resistance. Characterization of isolates PA-1 and PA-2 was performed through short and long-read whole genome sequencing analysis. The hybrid assembly showed that PA-1 and PA-2A had a single plasmid of 54,030 bp, named pPA-1 and pPA-2 respectively. Each plasmid harbored two copies of the bla KPC-containing Tn4401b transposon. However, while pPA-1 carried two copies of bla KPC-2, pPA-2 had one copy of bla KPC-2 and one copy of bla KPC-33, the allele with the D179Y substitution. Interestingly, isolate PA-2 did not exhibit the "see-saw" effect. The bla KPC-33 allele was detected only through hybrid assembly using a long-read-first approach. The present work describes a KPC-PA isolate harboring a plasmid-borne CAZ/AVI resistance mechanism based on two copies of bla KPC-2-Tn4401b and D179Y mutation in one of them, that is not associated with loss of resistance to carbapenems. These findings highlight the usefulness of a fine-tuned combined analysis of short and long-read data to detect similar emerging resistance mechanisms.

Efecto de la suplementación del zinc sobre el peso fetal en ratas diabéticas gestadas / Effect of zinc supplementation on fetal weight in pregnant diabetic rats

RESUMEN Introducción: La relación entre la deficiencia de Zn y la elevada incidencia de alteraciones en el crecimiento intrauterino en la diabetes materna aún no se ha dilucidado. En la literatura consultada no existen reportes del efecto de la suplementación con el micronutriente sobre el crecimiento fetal en modelos de diabetes con hiperglucemias moderadas. Objetivo: Determinar el efecto sobre el peso fetal de la suplementación con zinc a ratas con diabetes moderada durante la gestación. Métodos: Se utilizó un modelo de diabetes moderada inducida en ratas Wistar al segundo día de nacidas por inducción subcutánea con estreptozotocina (100mg/kg-pc). En la adultez las ratas sanas y diabéticas fueron apareadas con machos sanos. Según correspondiera recibieron durante 20 días de gestación un suplemento de sulfato de zinc (50mg/kg). Se estudiaron 395 fetos de cuatro grupos: fetos de ratas sanas sin suplemento, de ratas sanas suplementadas, de ratas diabéticas sin suplemento y de ratas diabéticas suplementadas. Los fetos se clasificaron en pequeños (PEG), adecuados (AEG) y grandes (GEG) para la edad gestacional. Resultados: La descendencia de las ratas diabéticas suplementadas mostró valores del peso fetal similares a ambos grupos sanos al término de la gestación, presentando menor porcentaje de fetos PEG y GEG, así como mayor porcentaje de AEG respecto al grupo diabético no suplementado. Conclusiones: La suplementación con Zn durante la gestación a ratas diabéticas con hiperglucemias moderadas causó efectos positivos sobre su descendencia al aumentar el porcentaje de fetos con peso adecuado.

ABSTRACT Introduction: the relationship between Zn deficiency and the high incidence of abnormal intrauterine growth in maternal diabetes has not yet been elucidated. There are no reports in the consulted literature of the effect of micronutrient supplementation on fetal growth in models of diabetes with moderate hyperglycemia. Objective: to determine the effect of zinc supplementation on fetal weight in rats with moderate diabetes during pregnancy. Methods: a model of mild diabetes was used in Wistar rats on the second day of birth by subcutaneous streptozotocin induction (100mg/kg-bw). As adults, healthy and diabetic rats were mated with healthy males. As appropriate, they received a zinc sulfate supplement (50mg/kg) during 20 days of gestation. A number of 395 fetuses from four groups were studied: fetuses from healthy rats without supplementation, from healthy rats supplemented, from diabetic rats without supplementation and from diabetic rats supplemented. Fetuses were classified as small (SGA), adequate (AGA), and large (LGA) for gestational age. Results: the offspring of the supplemented diabetic rats showed similar fetal weight values to both healthy groups at the end of pregnancy, having a lower percentage of SGA and LGA fetuses, as well as a higher percentage of AGA compared to the non-supplemented diabetic group. Conclusions: Zn supplementation during pregnancy in diabetic rats with moderate hyperglycemia had positive effects on their offspring by increasing the percentage of fetuses with adequate weight.

Blood-Brain Barrier Permeability Study of Potential Neuroprotective Compounds Recovered From Plants and Agri-Food by-Products.

Plants and agri-food by-products represent a wide and renewable source of bioactive compounds with neuroprotective properties. In this research, various green extraction techniques were employed to recover bioactive molecules from Kalanchoe daigremontiana (kalanchoe), epicarp of Cyphomandra betacea (tamarillo), and cooperage woods from Robinia pseudoacacia (acacia) and Nothofagus pumilio (lenga), as well as a reference extract (positive control) from Rosmarinus officinalis L. (rosemary). The neuroprotective capacity of these plant extracts was evaluated in a set of in vitro assays, including enzymatic [acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and lipoxygenase (LOX)] and antioxidant [ABTS, and reactive oxygen and nitrogen species (ROS and RNS)] bioactivity tests. Extracts were also submitted to a parallel artificial membrane permeability assay mimicking the blood-brain barrier (PAMPA-BBB) and to two cell viability assays in HK-2 and SH-SY5Y cell lines. Comprehensive phytochemical profiling based on liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (LC-Q-TOF-MS) analysis showed enriched content of phenolic and terpenoid compounds in the target extracts. Moreover, in vitro bioactivity tests showed promising neuroprotective capacity, particularly for supercritical-fluid extraction (SFE) extract from acacia (ABTS IC50 = 0.11 µg ml-1; ROS IC50 = 1.56 µg ml-1; AChE IC50 = 4.23 µg ml-1; BChE IC50 = 1.20 µg ml-1; and LOX IC50 = 4.37 µg ml-1), whereas PAMPA-BBB assays revealed high perfusion capacity of some representative compounds, such as phenolic acids or flavonoids. Regarding cytotoxic assays, tamarillo and rosemary SFE extracts can be considered as non-toxic, acacia SFE extract and lenga pressurized liquid extraction (PLE) extract as mild-cytotoxic, and kalanchoe as highly toxic extracts. The obtained results demonstrate the great potential of the studied biomass extracts to be transformed into valuable food additives, food supplements, or nutraceuticals with promising neuroprotective properties.

Extract of Glycyrrhiza glabra root attenuates nociception in experimental pain models: the role of BKCa channels / Extracto de raíz de Glycyrrhiza glabra atenúa la nocicepción en modelos experimentales de dolor: el rol de los canales BKCa

Abstract: The aim of this study was to evaluate the functional interaction of Glycyrrhiza glabra root extract (GGRE) on the large conductance Ca 2+ - activated K + (BKCa) channels expressed in the peripheral nervo us system by using nociception and inflammation models in rodents in vivo . Besides toxicity studies and open field tests, nociception and inflammation tests were performed on rodents. Different doses of GGRE were given orally to rats and mice. Naloxone, in domethacin, morphine, NS1619 and iberiotoxin (IbTX) were administered. GGRE had both anti - nociceptive and anti - inflammatory activity in rats and mice. GGRE exhibited an analgesic effect by decreasing the time - course of the pain threshold or reaction time i n some nociceptive tests. Furthermore, GGRE reduced level of pro - inflammatory cytokines, including TNF - α and IL - 1ß. As a conclusion, GGRE can alleviate the pain sensation of the afferent nerves and can reduce inflammation and associated pain by activating B KCa channels and reducing the levels of TNF - α, IL1ß

Resumen: El objetivo de este estudio fue evaluar la interacción funcional del extracto de raíz de Glycyrr hiza glabra (GGRE) en los canales de K + (BKCa) activados por Ca 2+ de gran conductancia expresados en el sistema nervioso periférico mediante el uso de modelos de nocicepción e inflamación en roedores in vivo . Además de los estudios de toxicidad y las prueb as de campo abierto, se realizaron pruebas de nocicepción e inflamación en roedores. Se administraron por vía oral diferentes dosis de GGRE a ratas y ratones. Se administraron naloxona, indometacina, morfina, NS1619 e iberiotoxina (IbTX). GGRE tenía activi dad tanto antinociceptiva como antiinflamatoria en ratas y ratones. GGRE mostró un efecto analgésico al disminuir la evolución temporal del umbral del dolor o el tiempo de reacción en algunas pruebas nociceptivas. Además, GGRE redujo el nivel de citocinas proinflamatorias, incluidas TNF - α e IL - 1ß. Como conclusión, GGRE puede aliviar la sensación de dolor de los nervios aferentes y puede reducir la inflamación y el dolor asociado activando los canales BKCa y reduciendo los niveles de TNF - α, IL1ß.