Chemical composition, antioxidant and antimicrobial activities of essential oil from the aerial parts of Chuquiraga arcuataHarling grown in the highlands of Ecuador / Composición química, actividades antioxidantes y antimicrobianas del aceite esencial de las partes aéreas de Chuquiraga arcuataHarling cultivado en las tierras altas del Ecuador

Thechemical composition, antioxidant and antimicrobial activities of the essential oil from aerial parts (leaves and flowers) of Chuquiraga arcuataHarling grown in the Ecuadorian Andes were studied. One hundred and twenty-six compounds were identified in the essential oil. Monoterpene hydrocarbons (45.8%) and oxygenated monoterpenes (44.1%) had the major percentages. The most abundant compounds were camphor (21.6%), myrcene (19.5%), and 1,8-cineole (13.4%). Antioxidant activity was examined using DPPH, ABTS,and FRAP assays. The essential oil had a moderate scavenging effect and reduction of ferric ion capacity through FRAP assay. Antimicrobial activity of the essential oil was observed against four pathogenic bacteria and a fungus. The essential oil exhibited activity against all microorganism strains under test, particularly against Candida albicansand Staphylococcus aureuswith MICs of 2.43-12.10 µg/mL.

Se estudió la composición química, actividades antioxidantes y antimicrobianas del aceite esencial procedente de las partes aérea (hojas y flores) de Chuquiraga arcuataHarling cultivadas en los Andes ecuatorianos. Se identificaron 126 compuestos en el aceite esencial. Los hidrocarburos monoterpénicos (45,8%) y los monoterpenos oxigenados (44,1%) tuvieron el mayor porcentaje. Los compuestos más abundantes fueron alcanfor (21,6%), mirceno (19,5%) y 1,8-cineol (13,4%). La actividadantioxidante se examinó mediante ensayos DPPH, ABTS y FRAP. El aceite esencial tuvo un efecto eliminador moderado y una reducción de la capacidad de iones férricos mediante el ensayo FRAP. Se observó actividad antimicrobiana del aceite esencial contra cuatro bacterias y un hongo patógenos. El aceite esencial mostró actividad contra todas las cepas de microorganismos bajo prueba, particularmente contra Candida albicansy Staphylococcus aureuscon CMI de 2,43-12,10 µg/mL.

Aceite esencial de hojas de Minthostachys mollis [HBK] Griseb. del Ecuador: extracción, composición química, capacidad antioxidante y actividad antimicrobiana / Essential oil of Minthostachys mollis [HBK] Griseb. leaves from Ecuador: extraction, chemical composition, antioxidant capacity and antimicrobial activity

The aim of this study was to optimize by response surface design, the extraction of the leaf essential oil (EO) from Minthostachys mollis [HBK] Griseb., grown in Ecuador, using steam distillation. The factors used were extraction time (XTIE) of 60, 105 and 150 min and plant material/water ratio (XRMA) of 1:3, 1:4 and 1:5. The optimal combination was reached with XRMA 1:5 and XTIE 150 min, obtaining a process yield of 0.67%. The chemical composition of the EO analyzed by GC - MS was determined, where the main compounds were carvacryl acetate (44.01%), carvacrol (16.51%) and menthone (8.20%). The anti oxidant capacity of EO was evaluated using the FRAP and ABTS methodologies, with an IC 50 243.21 µmol Fe 2+ /g and 0.12 mg/mL, respectively. In addition, the antimicrobial activity of EO was found against Pseudomonas aeruginosa , Salmonella enterica , Escherich ia coli and Staphylococcus aureus .

El objetivo del estudio fue optimizar, mediante un diseño de superficie respuesta, la extracción d el aceite esencial (AE) de hojas de Minthostachys mollis [HBK] Griseb. del Ecuador, mediante destilación por arrastre de vapor. Los factores fueron el tiempo de extracción (XTIE) de 60, 105 y 150 min, y relación de material vegetal/ agua destilada (XRMA) d e 1:3, 1:4 y 1:5. La combinación óptima se logró con XTIE 150 min y XRMA 1:5 para un rendimiento de 0,67%. Se determinó la composición química del AE por GC - MS donde los compuestos mayoritarios fueron acetato de carvacrilo (44,01%), carvacrol (16,51%) y me ntona (8,20%). Se evaluó la capacidad antioxidante del AE por las metodologías FRAP y ABTS, con CI 50 de 243,21 µmol Fe 2+ /g y 0,12 mg/mL, respectivamente. Además, se demostró la actividad antimicrobiana contra Pseudomonas aeruginosa , Salmonella enterica , Es cherichia coli y Staphylococcus aureus .

Gold(III) Auracycles featuring C(sp3)-Au-C(sp2) Bonds: Synthesis and Mechanistic Insights into the Cycloauration Step.

The direct auration of arenes is a key step in numerous gold-catalyzed reactions. Although reported more than 100 years ago, understanding of its underlying mechanism has been hampered by the difficulties in the isolation of relevant intermediates given the propensity of gold(III) species to undergo reductive elimination. Here, we report the synthesis and isolation of a new family of intriguing zwitterionic [C(sp3)^C(sp2)]-auracyclopentanes, as well as of their alkyl-gold(III) precursors and demonstrate their value as mechanistic probes to study the Csp2-Au bond-forming event. Experimental investigations employing Kinetic Isotope Effects (KIE), Hammett plot, and Eyring analysis provided important insights into the formation of the auracycle. The data suggest a SEAr mechanism wherein the slowest step might be the p-coordination between the arene and the gold(III) center, en route to the Wheland intermediate. We also show that these auracyclopentanes can work as catalysts in several gold-promoted transformations.

Cytoprotection as an Innovative Therapeutic Strategy to Cardiogenic Shock: Exploring the Potential of Cytidine-5-Diphosphocholine to Mitigate Target Organ Damage.

BACKGROUND: Preservation of organ function and viability is a crucial factor for survival in cardiogenic shock (CS) patients. There is not information enough on cytoprotective substances that may delay organs damage in CS. We hypothesize that cytidine-5-diphosphocholine (CDP-choline) can act as a cytoprotective pharmacological measure that diminishes the target organ damage. So, we aimed to perform a review of works carried out in our institution to evaluate the effect of therapeutic cytoprotection of the CDP-choline. SUMMARY: CDP-choline is an intermediate metabolite in the synthesis of phosphatidylcholine. It is also a useful drug for the treatment of acute ischaemic stroke, traumatic brain injury, and neurodegenerative diseases and has shown an excellent pharmacological safety profile as well. We review our institution's work and described the cytoprotective effects of CDP-choline in experimental models of heart, liver, and kidney acute damage, where this compound was shown to diminish reperfusion-induced ventricular arrhythmias, oxidative stress, apoptotic cell death, inflammation, lactic acid levels and to preserve mitochondrial function. KEY MESSAGES: We propose that additional research is needed to evaluate the impact of cytoprotective therapy adjuvant to mitigate target organ damage in patients with CS.

Simultaneous determination of six catechins and caffeine in tea and wine using salting-out assisted liquid-liquid extraction and high-performance liquid chromatography with ultraviolet detection.

Catechins, renowned for their antioxidant properties and health benefits, are commonly present in beverages, particularly tea and wine. An efficient and cost-effective salting-out assisted liquid-liquid extraction (SALLE) method has been developed and validated for the simultaneous determination of six catechins and caffeine in tea and wine samples using high-performance liquid chromatography-ultraviolet (HPLC-UV). This method demonstrates outstanding performance: linearity (1-120 µg/mL, r2 > 0.999), accuracy (96.5%-103.4% recovery), and precision (≤14.7% relative standard deviation), meeting validation requirements set by the US Food and Drug Administration. The reduced sample size (0.1 g) minimizes matrix interferences and costs without compromising sensitivity. All analytes were detected in Camellia sinensis teas, with green tea displaying the highest total catechin content (47.5-100.1 mg/mL), followed by white and black teas. Analysis of wine samples reveals the presence of catechin in all red and white wines, and epigallocatechin gallate in all red wine samples, highlighting the impact of winemaking processes on catechin content. The SALLE-HPLC-UV approach represents a green alternative by eliminating organic waste, surpassing conventional dilution methods in specificity and sensitivity for catechin determination. AGREEprep assessment emphasizes the strengths of the SALLE procedure, including material reusability, throughput efficiency, minimal sample requirements, low energy consumption, and the absence of organic waste generation.

High-Pressure Processing Effects on Microbiological Stability, Physicochemical Properties, and Volatile Profile of a Fruit Salad.

Nowadays, consumers are more aware of the effects of their diet on their health, and thus demand natural or minimally processed food products. Therefore, research has focused on processes that assure safe products without jeopardizing their nutritional properties. In this context, this work aimed to evaluate the effects of high-pressure processing (550 MPa/3 min/15 °C, HPP) on a fruit salad (composed of melon juice and pieces of Golden apple and Rocha pear) throughout 35 days of storage at 4 °C. For the physicochemical properties analysed (browning degree, polyphenol oxidase activity, antioxidant activity (ABTS assay), and volatile profile), a freshly made fruit salad was used, while for the microbiological tests (total aerobic mesophiles, and yeast and moulds) spoiled melon juice was added to the fruit salad to increase the microbial load and mimic a challenge test with a high initial microbial load. It was determined that processed samples were more microbiologically stable than raw samples, as HPP enabled a reduction of almost 4-log units of both total aerobic mesophiles and yeasts and moulds, as well as an almost 1.5-fold increase in titratable acidity of the unprocessed samples compared to HPP samples. Regarding browning degree, a significant increase (p < 0.05) was observed in processed versus unprocessed samples (roughly/maximum 68%), while the addition of ascorbic acid decreased the browning of the samples by 29%. For antioxidant activity, there were no significant differences between raw and processed samples during the 35 days of storage. An increase in the activity of polyphenol oxidase immediately after processing (about 150%) was confirmed, which was generally similar or higher during storage compared with the raw samples. Regarding the volatile profile of the product, it was seen that the compounds associated with melon represented the biggest relative percentage and processed samples revealed a decrease in the relative quantity of these compounds compared to unprocessed. Broadly speaking, HPP was shown to be efficient in maintaining the stability and overall quality of the product while assuring microbial safety (by inactivating purposely inoculated microorganisms), which allows for longer shelf life (7 versus 28 days for unprocessed and processed fruit salad, respectively).

Factors of poor prognosis in newborns with a prenatal diagnosis of gastroschisis in Bogota, Colombia.

OBJECTIVES: To identify factors associated with poor prognoses in newborns with a prenatal diagnosis of gastroschisis in eight hospitals in Bogota, Colombia, from 2011 to 2022. METHODS: A multi-center retrospective case-control study was conducted on newborns with gastroschisis in eight hospitals in Bogota, Colombia. Poor prognosis was defined as the presence of sepsis, intestinal complications, or death. RESULTS: The study included 101 patients. Preterm newborns under 32 weeks had a poor neonatal prognosis (OR 6.78 95 % CI 0.75-319). Oligohydramnios (OR 4.95 95 % CI 1.15-21.32) and staged closure with silo (OR 3.48; 95 % CI 1.10-10.96) were risk factors for neonatal death, and intra-abdominal bowel dilation of 20-25 mm was a factor for the development of intestinal complications (OR 3.22 95 % CI 1.26-8.23). CONCLUSIONS: Intra-abdominal bowel dilation between 20 and 25 mm was associated with intestinal complications, while oligohydramnios was associated with the risk of perinatal death, requiring increased antenatal surveillance of fetal wellbeing. Management with primary reduction when technically feasible is recommended in these infants, considering that the use of silos was associated with higher mortality.

Locomotion and morphological adaptations in the glass lizard Ophiodes cf. fragilis (Raddi, 1820) (Squamata: Anguidae).

There are few studies related to the biological and ecological aspects of the glass snake, a limbless lizard and with a wide geographic distribution. The aim of this study was to analyze the locomotion mode of specimens of Ophiodes cf. fragilis in different substrates and to investigate the morphological adaptations associated with this type of behavior. We observed that the analyzed specimens presented slide-push locomotion modes and lateral undulation in different substrates, using their hind limbs to aid locomotion in three of the four substrates analyzed. The bones of the hind limbs (proximal - femur - and distal - tibia and fibula) were present and highly reduced and the femur is connected to a thin pelvic girdle. Our data support that hind limbs observed in species of this genus are reduced rather than vestigial. The costocutaneous musculature was macroscopically absent. This is the first study of locomotor behavior and morphology associated with locomotion in Ophiodes, providing important information for studies on morphological evolution in the genus.

Modeling the impact of measured and projected climate and management systems on agricultural fields: Surface runoff, soil moisture, and soil erosion.

As global climate change poses a challenge to crop production, it is imperative to prioritize effective adaptation of agricultural systems based on a scientific understanding of likely impacts. In this study, we applied an integrated watershed modeling framework to examine the impacts of projected climate on runoff, soil moisture, and soil erosion under different management systems in Central Oklahoma. The proposed model uses measured climate data and three downscaled ensembles from the Coupled Model Intercomparison Project Phase 6 (CMIP6) at the water resources and erosion watershed to understand the impact of climate change and various climate conditions under three management systems: (1) continuous winter wheat (Triticum aestivum) under conventional tillage (WW-CT; baseline system), (2) continuous winter wheat under no-till (WW-NT), and (3) cool and warm season forage cover crop mixes under no-till (CC-NT). The study indicates that the occurrence of agricultural drought is projected to increase while erosion rates will remain unchanged under the WW-CT. In contrast, climate simulations imposed on the WW-NT and CC-NT systems significantly reduce runoff and sediment while preserving soil moisture levels. Especially, implementing the CC-NT system can bolster food security and foster sustainable farming practices in Central Oklahoma in the face of a changing climate.

Comprehensive analysis of clinical images contributions for melanoma classification using convolutional neural networks.

BACKGROUND: Timely diagnosis plays a critical role in determining melanoma prognosis, prompting the development of deep learning models to aid clinicians. Questions persist regarding the efficacy of clinical images alone or in conjunction with dermoscopy images for model training. This study aims to compare the classification performance for melanoma of three types of CNN models: those trained on clinical images, dermoscopy images, and a combination of paired clinical and dermoscopy images from the same lesion. MATERIALS AND METHODS: We divided 914 image pairs into training, validation, and test sets. Models were built using pre-trained Inception-ResNetV2 convolutional layers for feature extraction, followed by binary classification. Training comprised 20 models per CNN type using sets of random hyperparameters. Best models were chosen based on validation AUC-ROC. RESULTS: Significant AUC-ROC differences were found between clinical versus dermoscopy models (0.661 vs. 0.869, p < 0.001) and clinical versus clinical + dermoscopy models (0.661 vs. 0.822, p = 0.001). Significant sensitivity differences were found between clinical and dermoscopy models (0.513 vs. 0.799, p = 0.01), dermoscopy versus clinical + dermoscopy models (0.799 vs. 1.000, p = 0.02), and clinical versus clinical + dermoscopy models (0.513 vs. 1.000, p < 0.001). Significant specificity differences were found between dermoscopy versus clinical + dermoscopy models (0.800 vs. 0.288, p < 0.001) and clinical versus clinical + dermoscopy models (0.650 vs. 0.288, p < 0.001). CONCLUSION: CNN models trained on dermoscopy images outperformed those relying solely on clinical images under our study conditions. The potential advantages of incorporating paired clinical and dermoscopy images for CNN-based melanoma classification appear less clear based on our findings.

Loss of anoctamin 1 reveals a subtle role for BK channels in lymphatic muscle action potentials.

Ca2+ signalling plays a crucial role in determining lymphatic muscle cell excitability and contractility through its interaction with the Ca2+-activated Cl- channel anoctamin 1 (ANO1). In contrast, the large-conductance (BK) Ca2+-activated K+ channel (KCa) and other KCa channels have prominent vasodilatory actions by hyperpolarizing vascular smooth muscle cells. Here, we assessed the expression and contribution of the KCa family to mouse and rat lymphatic collecting vessel contractile function. The BK channel was the only KCa channel consistently expressed in fluorescence-activated cell sorting-purified mouse lymphatic muscle cell lymphatic muscle cells. We used a pharmacological inhibitor of BK channels, iberiotoxin, and small-conductance Ca2+-activated K+ channels, apamin, to inhibit KCa channels acutely in ex vivo isobaric myography experiments and intracellular membrane potential recordings. In basal conditions, BK channel inhibition had little to no effect on either mouse inguinal-axillary lymphatic vessel (MIALV) or rat mesenteric lymphatic vessel contractions or action potentials (APs). We also tested BK channel inhibition under loss of ANO1 either by genetic ablation (Myh11CreERT2-Ano1 fl/fl, Ano1ismKO) or by pharmacological inhibition with Ani9. In both Ano1ismKO MIALVs and Ani9-pretreated MIALVs, inhibition of BK channels increased contraction amplitude, increased peak AP and broadened the peak of the AP spike. In rat mesenteric lymphatic vessels, BK channel inhibition also abolished the characteristic post-spike notch, which was exaggerated with ANO1 inhibition, and significantly increased the peak potential and broadened the AP spike. We conclude that BK channels are present and functional on mouse and rat lymphatic muscle cells but are otherwise masked by the dominance of ANO1. KEY POINTS: Mouse and rat lymphatic muscle cells express functional BK channels. BK channels make little contribution to either rat or mouse lymphatic collecting vessel contractile function in basal conditions across a physiological pressure range. ANO1 limits the peak membrane potential achieved in the action potential and sets a plateau potential limiting the voltage-dependent activation of BK. BK channels are activated when ANO1 is absent or blocked and slightly impair contractile strength by reducing the peak membrane potential achieved in the action potential spike and accelerating the post-spike repolarization.

Exploring the relationship between admixture and genetic susceptibility to attention deficit hyperactivity disorder in two Latin American cohorts.

Contemporary research on the genomics of Attention Deficit Hyperactivity Disorder (ADHD) often underrepresents admixed populations of diverse genomic ancestries, such as Latin Americans. This study explores the relationship between admixture and genetic associations for ADHD in Colombian and Mexican cohorts. Some 546 participants in two groups, ADHD and Control, were genotyped with Infinium PsychArray®. Global ancestry levels were estimated using overall admixture proportions and principal component analysis, while local ancestry was determined using a method to estimate ancestral components along the genome. Genome-wide association analysis (GWAS) was conducted to identify significant associations. Differences between Colombia and Mexico were evaluated using appropriate statistical tests. 354 Single-nucleotide polymorphisms (SNPs) and Single-nucleotide variants (SNVs) related to some genes and intergenic regions exhibited suggestive significance (p-value < 5*10e-5) in the GWAS. None of the variants revealed genome-wide significance (p-value < 5*10e-8). The study identified a significant relationship between risk SNPs and the European component of admixture, notably observed in the LOC105379109 gene. Despite differences in risk association loci, such as FOXP2, our findings suggest a possible homogeneity in genetic variation's impact on ADHD between Colombian and Mexican populations. Current reference datasets for ADHD predominantly consist of samples with high European ancestry, underscoring the need for further research to enhance the representation of reference populations and improve the identification of ADHD risk traits in Latin Americans.

Systematic review of recent advancements in antibody-drug and bicycle toxin conjugates for the treatment of urothelial cancer.

Antibody-drug conjugates and bicycle toxin conjugates represent a tremendous advance in drug delivery technology and have shown great promise in the treatment of urothelial cancer. Previously approved systemic therapies, including chemotherapy and immunotherapy, are often impractical due to comorbidities, and outcomes for patients with advanced disease remain poor, even when receiving systemic therapy. In this setting, antibody-drug and bicycle toxin conjugates have emerged as novel treatments, dramatically altering the therapeutic landscape. These drugs harness unique designs consisting of antibody or bicycle peptide, linker, and cytotoxic payload with more targeted delivery than conventional chemotherapy, thus eliminating malignant cells while reducing systemic toxicities. Potential targets investigated in urothelial cancer include Nectin-4, TROP2, HER2, and EphA2. Initial clinical trials demonstrated efficacy in treatment of refractory advanced urothelial cancer, as well as improvement in quality of life. These initial studies led to FDA approval of two antibody-drug conjugates, enfortumab vedotin and sacituzumab govitecan. Moreover, antibody-drug and bicycle toxin conjugates are being studied in ongoing clinical trials in frontline treatment of advanced disease as well as for localized cancer. These studies highlight the potential for additional future therapies with novel targets, novel antibodies, cytotoxic and immunomodulatory payloads, and unique structural designs enhancing efficacy and safety. There is increasing evidence that combinations with other cancer therapies, especially immunotherapy, improve treatment outcomes. The combination of enfortumab vedotin and pembrolizumab was recently approved for first-line treatment of advanced urothelial carcinoma. Despite the great promise of these novel drugs, robust predictive biomarkers are needed to determine the patients who would maximally benefit. This review surveys the rationale and current state of the evidence for these new drugs and describes future directions actively being explored.

Review of recent advances in novel treatments of urothelial cancer Two new types of drugs, called antibody-drug conjugates (ADCs) and bicycle toxin conjugates (BTCs) have shown great promise in treating urothelial cancer. Both types of drugs consist of a structure targeting a specific protein on bladder cancer cells, linked to a drug that can kill cells. This allows for effective treatment of cancer with potentially less toxicity due to the targeted nature of these treatments. We discuss the potential targets in urothelial cancer and the drugs in these classes that could treat each target. Two of these drugs, enfortumab vedotin and sacituzumab govitecan, are in clinical use for cancers that have spread, while the others are in clinical trials. Moreover, the combination of enfortumab vedotin and pembrolizumab, an immunotherapy drug, has excellent results and was recently approved for first-line treatment of urothelial cancer that has spread. Additional studies are looking into these treatments for cancers that have not spread. In the future, management of side effects, determination of which patients benefit, and overcoming when the drugs become no longer effective will be important.

Readability Analysis of Spanish-Language Patient-Reported Outcome Measures in Orthopaedic Surgery.

BACKGROUND: Patient-reported outcome measures (PROMs) are increasingly used to quantify patient symptomatology when assessing intervention effectiveness as well as to guide patient-centered health-care management and research. Previous studies have analyzed the readability of PROMs used in orthopaedics in the English language; however, the readability of PROMs used in orthopaedics in the Spanish language has not been evaluated. Given the increasing number of Spanish-speaking individuals seeking orthopaedic care in the United States, it is imperative that PROMs are at an adequate reading level for patients to answer appropriately in their native language. This study aimed to assess the readability of publicly available Spanish-language PROMs used in orthopaedics. METHODS: Searches of the PubMed, Google Scholar, and Embase databases were conducted to identify publicly available Spanish-language versions of PROMs used in orthopaedics. Additionally, the PROMIS Health Organization was contacted to obtain Spanish-language versions of the PROMIS (Patient-Reported Outcomes Measurement Information System) questionnaires. A total of 42 Spanish-language PROMs were identified and included in this study. The text of each PROM was inserted into multilingual readability software (legible.es), which analyzed the readability of each PROM using the Fernández Huerta and Índice de Legibilidad de Flesch-Szigriszt (INFLESZ) readability formulas. The mean and standard deviation (SD) of the raw readability scores were calculated for the PROMs. The percentage of PROMs at or below the 6th-grade reading level was also calculated. RESULTS: The mean readability of PROMs using the INFLESZ formula was at a 7th to 10th-grade reading level (mean = 63, SD = 16), and the mean readability using the Fernández Huerta formula was 68 (SD = 15). On average, 57% of the PROMs used in orthopaedics were at or below the INFLESZ 6th-grade readability level. CONCLUSIONS: Approximately half of Spanish-language PROMs used in orthopaedics are written at a reading level that does not meet the National Institutes of Health and the American Medical Association recommendations at or below the 6th-grade level. PROM developers and translators should consider the importance of readability when translating PROMs, to maximize their use and efficacy among orthopaedic patients speaking that language.

Rapid Progression of Malignant Peritoneal Mesothelioma Mimicking a Postoperative Complication in a Young Woman: A Case Report.

BACKGROUND Malignant peritoneal mesothelioma is a rare disease with a poor prognosis that often presents with vague symptoms and inconclusive laboratory test results. Causes include industrial pollutants, primarily asbestos, and certain genetic mutations, such as BAP1. Due to the nonspecific symptoms, it is often incidentally diagnosed during or after other surgical procedures. CASE REPORT A 35-year-old healthy woman underwent an uncomplicated laparoscopic left salpingo-oophorectomy for a symptomatic large ovarian mature cystic teratoma. She subsequently presented with late-onset postoperative fever, leukocytosis, and multiple intra-abdominal masses. Following an exploratory laparotomy, extensive infectious disease evaluation, and multiple biopsies requiring interdisciplinary collaboration, malignant peritoneal mesothelioma was diagnosed by positive histologic staining of an omental biopsy for D2-40 and CK5/6. This first specimen was positive for BAP1, with the second, a liver biopsy, testing negative for BAP1. The tumor cell testing was also notable for mutations in NF2, MLL2, and ARID1A, and the hereditary cancer genetic testing was overall unremarkable. Her disease progressed rapidly, and she died 6 months after her initial procedure. CONCLUSIONS This case of rapidly developing malignant peritoneal mesothelioma following surgical management of an ovarian mature teratoma highlights the complexity in diagnosing a rare disease that presents with nonspecific symptoms in an otherwise young and healthy woman. The rapid disease course was likely accelerated by expansive intraperitoneal spread and multiple somatic oncogenic mutations in BAP1, NF2, MLL2, and ARID1A. Gynecologists should keep a broad differential for postoperative complications, as occult malignancies can present with symptoms that mimic postoperative complications.

Extraction of Antioxidants from Brown Macroalgae Fucus spiralis.

In this study, different extraction methods and conditions were used for the extraction of antioxidants from brown macroalgae Fucus spiralis. The extraction methodologies used were ultrasound-assisted extraction (ultrasonic bath and ultrasonic probe), extraction with a vortex, extraction with an Ultra-Turrax® homogenizer, and high-pressure-assisted extraction. The extracts were analyzed for their total phenolic content (TPC) and their antioxidant activity, and evaluated through the 2,2-difenil-1-picrilhidrazil (DPPH) free radical scavenging method and ferric reducing antioxidant power (FRAP) assay. Ultrasonic probe-assisted extraction yielded the highest values of TPC (94.78-474.16 mg gallic acid equivalents/g extract). Regarding the antioxidant activity, vortex-assisted extraction gave the best DPPH results (IC50 1.89-16 µg/mL), while the highest FRAP results were obtained using the Ultra-Turrax® homogenizer (502.16-1188.81 µmol ascorbic acid equivalents/g extract). For each extraction method, response surface methodology was used to analyze the influence of the experimental conditions "extraction time" (t), "biomass/solvent ratio" (R), "solvent" (S, water % in water/ethanol mixture), and "pressure" (P) on TPC, DPPH, and FRAP of the F. spiralis extracts. In general, higher TPC content and higher antioxidant capacity (lower IC50 and higher FRAP) were obtained with higher R, t, and P, and lower S (higher ethanol %). The model regarding the combined effects of independent variables t, R, and S on the FRAP response values for vortex-assisted extractions best fitted the experimental data (R2 0.957), with optimal extraction conditions of t = 300 s, R = 50 g, and S = 25%.

Health economic evaluation of 2-dose and 3-dose rotavirus vaccines in children below 5 years of age in Morocco.

Following the introduction of rotavirus vaccination into the Moroccan National Immunization Program, the prevalence of the disease has decreased by nearly 50%. However, evidence on the economic value of rotavirus vaccinations in Morocco is limited. This health economic analysis evaluated, from both country payer and societal perspectives, the costs and the cost-effectiveness of three rotavirus vaccines using a static, deterministic, population model in children aged < 5 years in Morocco. Included vaccines were HRV (2-dose schedule), HBRV (3-dose schedule) and BRV-PV 1-dose vial (3-dose schedule). One-way and probabilistic sensitivity analyses were conducted to assess the impact of uncertainty in model inputs. The model predicted that vaccination with HRV was estimated to result in fewer rotavirus gastroenteritis events (-194 homecare events, -57 medical visits, -8 hospitalizations) versus the 3-dose vaccines, translating into 7 discounted quality-adjusted life years gained over the model time horizon. HRV was associated with lower costs versus HBRV from both the country payer (-$1.8 M) and societal (-$4.1 M) perspectives, and versus BRV-PV 1-dose vial from the societal perspective (-$187,000), dominating those options in the cost-effectiveness analysis. However, costs of BRV-PV 1-dose vial were lower than HRV from the payer perspective, resulting in an ICER of approximately $328,376 per QALY, above the assumed cost effectiveness threshold of $3,500. Vaccination with a 2-dose schedule of HRV may be a cost-saving option and could lead to better health outcomes for children in Morocco versus 3-dose schedule rotavirus vaccines.

Discovery of BIO-8169─A Highly Potent, Selective, and Brain-Penetrant IRAK4 Inhibitor for the Treatment of Neuroinflammation.

Interleukin receptor associated kinase 4 (IRAK4) plays an important role in innate immune signaling through Toll-like and interleukin-1 receptors and represents an attractive target for the treatment of inflammatory diseases and cancer. We previously reported the development of a potent, selective, and brain-penetrant imidazopyrimidine series of IRAK4 inhibitors. However, lead molecule BIO-7488 (1) suffered from low solubility which led to variable PK, compound accumulation, and poor in vivo tolerability. Herein, we describe the discovery of a series of pyridone analogs with improved solubility which are highly potent, selective and demonstrate desirable PK profiles including good oral bioavailability and excellent brain penetration. BIO-8169 (2) reduced the in vivo production of pro-inflammatory cytokines, was well tolerated in safety studies in rodents and dog at margins well above the predicted efficacious exposure and showed promising results in a mouse model for multiple sclerosis.

Tree demographic strategies largely overlap across succession in Neotropical wet and dry forest communities.

Secondary tropical forests play an increasingly important role in carbon budgets and biodiversity conservation. Understanding successional trajectories is therefore imperative for guiding forest restoration and climate change mitigation efforts. Forest succession is driven by the demographic strategies-combinations of growth, mortality and recruitment rates-of the tree species in the community. However, our understanding of demographic diversity in tropical tree species stems almost exclusively from old-growth forests. Here, we assembled demographic information from repeated forest inventories along chronosequences in two wet (Costa Rica, Panama) and two dry (Mexico) Neotropical forests to assess whether the ranges of demographic strategies present in a community shift across succession. We calculated demographic rates for >500 tree species while controlling for canopy status to compare demographic diversity (i.e., the ranges of demographic strategies) in early successional (0-30 years), late successional (30-120 years) and old-growth forests using two-dimensional hypervolumes of pairs of demographic rates. Ranges of demographic strategies largely overlapped across successional stages, and early successional stages already covered the full spectrum of demographic strategies found in old-growth forests. An exception was a group of species characterized by exceptionally high mortality rates that was confined to early successional stages in the two wet forests. The range of demographic strategies did not expand with succession. Our results suggest that studies of long-term forest monitoring plots in old-growth forests, from which most of our current understanding of demographic strategies of tropical tree species is derived, are surprisingly representative of demographic diversity in general, but do not replace the need for further studies in secondary forests.