Exploring the Phytochemical Composition and the Bioactive Properties of Malbec and Torrontés Wine Pomaces from the Calchaquíes Valleys (Argentina) for Their Sustainable Exploitation.

Hydroalcoholic extracts from Malbec and Torrontés wine pomaces (Vitis vinifera L.) originating from the high-altitude vineyards of Argentina's Calchaquí Valleys were characterized. Total phenolics, hydroxycinnamic acids, orthodiphenols, anthocyanins, non-flavonoid phenolics, total flavonoids, flavones/flavonols, flavanones/dihydroflavonols, and tannins were quantified through spectrophotometric methods, with the Malbec extract exhibiting higher concentrations in most of phytochemical groups when compared to Torrontés. HPLC-DAD identified more than 30 phenolic compounds in both extracts. Malbec displayed superior antiradical activity (ABTS cation, nitric oxide, and superoxide anion radicals), reduction power (iron, copper, and phosphomolybdenum), hypochlorite scavenging, and iron chelating ability compared to Torrontés. The cytotoxicity assessments revealed that Torrontés affected the viability of HT29-MTX and Caco-2 colon cancer cells by 70% and 50%, respectively, at the highest tested concentration (1 mg/mL). At the same time, both extracts did not demonstrate acute toxicity in Artemia salina or in red blood cell assays at 500 µg/mL. Both extracts inhibited the lipoxygenase enzyme (IC50: 154.7 and 784.7 µg/mL for Malbec and Torrontés), with Malbec also reducing the tyrosinase activity (IC50: 89.9 µg/mL), and neither inhibited the xanthine oxidase. The substantial phenolic content and diverse biological activities in the Calchaquí Valleys' pomaces underline their potentialities to be valorized for pharmaceutical, cosmetic, and food industries.

Restraining Staphylococcus aureus Virulence Factors and Quorum Sensing through Lactic Acid Bacteria Supernatant Extracts.

The escalating prevalence of antibiotic-resistant bacteria poses a grave threat to human health, necessitating the exploration of novel alternatives to conventional antibiotics. This study investigated the impact of extracts derived from the supernatant of four lactic acid bacteria strains on factors contributing to the pathogenicity of three Staphylococcus aureus strains. The study evaluated the influence of lactic acid bacteria supernatant extracts on the growth, biofilm biomass formation, biofilm metabolic activity, and biofilm integrity of the S. aureus strains. Additionally, the impact on virulence factors (hemolysin and coagulase) was examined. Gas chromatography coupled with mass spectrometry was used to identify the bioactive compounds in the extracts, while molecular docking analyses explored potential interactions. Predominantly, the extracts contain eight 2,5-diketopiperazines, which are cyclic forms of peptides. The extracts demonstrated inhibitory effects on biofilm formation, the ability to disrupt mature biofilms, and reduce the biofilm cell metabolic activity of the S. aureus strains. Furthermore, they exhibited the ability to inhibit α-hemolysin production and reduce coagulase activity. An in silico docking analysis reveals promising interactions between 2,5-diketopiperazines and key proteins (SarA and AgrA) in S. aureus, confirming their antivirulence and antibiofilm activities. These findings suggest that 2,5-diketopiperazines could serve as a promising lead compound in the fight against antibiotic-resistant S. aureus.

Developmental outcome of electroencephalographic findings in SYNGAP1 encephalopathy.

SYNGAP1 haploinsufficiency results in a developmental and epileptic encephalopathy (DEE) causing generalized epilepsies accompanied by a spectrum of neurodevelopmental symptoms. Concerning interictal epileptiform discharges (IEDs) in electroencephalograms (EEG), potential biomarkers have been postulated, including changes in background activity, fixation-off sensitivity (FOS) or eye closure sensitivity (ECS). In this study we clinically evaluate a new cohort of 36 SYNGAP1-DEE individuals. Standardized questionnaires were employed to collect clinical, electroencephalographic and genetic data. We investigated electroencephalographic findings, focusing on the cortical distribution of interictal abnormalities and their changes with age. Among the 36 SYNGAP1-DEE cases 18 presented variants in the SYNGAP1 gene that had never been previously reported. The mean age of diagnosis was 8 years and 8 months, ranging from 2 to 17 years, with 55.9% being male. All subjects had global neurodevelopmental/language delay and behavioral abnormalities; 83.3% had moderate to profound intellectual disability (ID), 91.7% displayed autistic traits, 73% experienced sleep disorders and 86.1% suffered from epileptic seizures, mainly eyelid myoclonia with absences (55.3%). A total of 63 VEEGs were revised, observing a worsening of certain EEG findings with increasing age. A disorganized background was observed in all age ranges, yet this was more common among older cases. The main IEDs were bilateral synchronous and asynchronous posterior discharges, accounting for ≥50% in all age ranges. Generalized alterations with maximum amplitude in the anterior region showed as the second most frequent IED (≥15% in all age ranges) and were also more common with increasing age. Finally, diffuse fast activity was much more prevalent in cases with 6 years or older. To the best of our knowledge, this is the first study to analyze EEG features across different age groups, revealing an increase in interictal abnormalities over infancy and adolescence. Our findings suggest that SYNGAP1 haploinsufficiency has complex effects in human brain development, some of which might unravel at different developmental stages. Furthermore, they highlight the potential of baseline EEG to identify candidate biomarkers and the importance of natural history studies to develop specialized therapies and clinical trials.

Nutritional composition of quinoa leafy greens: An underutilized plant-based food with the potential of contributing to current dietary trends.

Quinoa (Chenopodium quinoa Willd.) leafy greens (QLGs) are plant-based foods of high nutritional value that have been scarcely studied. In this work, the nutritional and functional composition of three QLGs varieties was evaluated. A protein content higher than 35 g 100 g-1 dw with a well-balanced essential amino acid composition was found making them a good source of vegetable protein. In addition, elevated contents of dietary fibre and minerals, higher than those detected in quinoa seeds and other leafy vegetables, were found. The lipid profile showed higher contents of linoleic (C18:2, ω6) (20.2 %) and linolenic acids (C18:3, ω3) (52.8 %) with low ω6/ ω3 ratios (∼0.4/1). A total sugar content <1 g 100 g-1 dw was found for all varieties tested, lower than that obtained in seeds. The saponin content varied between 0.76 and 0.87 %. Also, high values of total phenolic compounds (969.8-1195.4 mg gallic acid 100 g-1), mainly hydroxycinnamic acids and flavonoids, and great antioxidant activities (7.64-8.90 g Trolox kg-1) were found. Multivariate analysis here used allowed us to classify the samples according to the quinoa variety evaluated, and the sequential stepwise multiple regression applied revealed that the PUFA and sucrose contents negatively influenced the protein content while the palmitic acid content affected positively this parameter. Overall, this study shows that QLGs are promising nutritious and functional plant-based foods supporting the necessity of promoting their cultivation, commercialization, and consumption.

UHPLC-MS/MS and GC-MS Metabolic Profiling of a Medicinal Flourensia Fiebrigii Chemotype.

The comparative metabolic profiling and their biological properties of eight extracts obtained from diverse parts (leaves, flowers, roots) of the medicinal plant Flourensia fiebrigii S.F. Blake, a chemotype growing in highland areas (2750 m a.s.l.) of northwest Argentina, were investigated. The extracts were analysed by GC-MS and UHPLC-MS/MS. GC-MS analysis revealed the presence of encecalin (relative content: 24.86 %) in ethereal flower extract (EF) and this benzopyran (5.93 %) together sitosterol (11.35 %) in the bioactive ethereal leaf exudate (ELE). By UHPLC-MS/MS the main compounds identified in both samples were: limocitrin, (22.31 %), (2Z)-4,6-dihydroxy-2-[(4-hydroxy-3,5-dimethoxyphenyl)methylidene]-1-benzofuran-3-one (21.31 %), isobavachin (14.47 %), naringenin (13.50 %), and sternbin, (12.49 %). Phytocomplexes derived from aerial parts exhibited significant activity against biofilm production of Pseudomonas aeruginosa and Staphylococcus aureus, reaching inhibitions of 74.7-99.9 % with ELE (50 µg/mL). Notably, the extracts did not affect nutraceutical and environmental bacteria, suggesting a selective activity. ELE also showed the highest reactive species scavenging ability. This study provides valuable insights into the potential applications of this chemotype.

Synthesis and Biophysical and Biological Studies of N-Phenylbenzamide Derivatives Targeting Kinetoplastid Parasites.

The AT-rich mitochondrial DNA (kDNA) of trypanosomatid parasites is a target of DNA minor groove binders. We report the synthesis, antiprotozoal screening, and SAR studies of three series of analogues of the known antiprotozoal kDNA binder 2-((4-(4-((4,5-dihydro-1H-imidazol-3-ium-2-yl)amino)benzamido)phenyl)amino)-4,5-dihydro-1H-imidazol-3-ium (1a). Bis(2-aminoimidazolines) (1) and bis(2-aminobenzimidazoles) (2) showed micromolar range activity against Trypanosoma brucei, whereas bisarylimidamides (3) were submicromolar inhibitors of T. brucei, Trypanosoma cruzi, and Leishmania donovani. None of the compounds showed relevant activity against the urogenital, nonkinetoplastid parasite Trichomonas vaginalis. We show that series 1 and 3 bind strongly and selectively to the minor groove of AT DNA, whereas series 2 also binds by intercalation. The measured pKa indicated different ionization states at pH 7.4, which correlated with the DNA binding affinities (ΔTm) for series 2 and 3. Compound 3a, which was active and selective against the three parasites and displayed adequate metabolic stability, is a fine candidate for in vivo studies.

Vertical preparation: a new technique for analogical and digital impressions.

The BOPT technique (Biologically Oriented Preparation Technique) was proposed by Loi et al. (1) and has become a popular form of vertical preparation for complete crowns with promising results. In this procedure, the clinician can operate on the gingival tissue during preparation and modify its structure in thickness and height by adding modifications on the provisional restoration. However, one of the main challenges in this technique is the transference of information about the gingival tissue to the laboratory technician, who will place the margin of the restoration randomly in a space determined by two marks on the working cast. The technique proposed enables the accurate transmission of the exact point where the margin of the restoration needs to be placed. Furthermore, it facilitates the recording of conventional impression materials and intraoral scanners due to the compression of polytetrafluoroethylene (PTFE) tape into the sulcus, which allows to arrest bleeding or intracrevicular liquid and is easily registered irrespective of the method of impression used. Key words:Vertical preparation, BOPT, PTFE, emergence profile, digital impression, conventional impression.

Unique nutritional features that distinguish Amaranthus cruentus L. and Chenopodium quinoa Willd seeds.

Univariate (Analysis of Variance_ANOVA) and multivariate (Principal Component Analysis (PCA) and Canonical Discriminant Analysis (CDA)) analyses were performed in order to classify and authenticate the seeds from different varieties of quinoa (Chenopodium quinoa Will.), and amaranth (Amaranthus cruentus L.). The univariate analysis showed differences between species for sucrose, K, Ca, unsaturated fatty acids, and the ω6/ω3 ratio. Nevertheless, to strengthen this classification, a PCA was applied separating the samples in 2 groups; group 1, formed by quinoa seeds, presented higher contents of margaroleic, eicosadienoic, behenic, erucic, linolenic, linoleic, and gadoleic acids, proteins, sucrose, and total sugars. Group 2, formed by amaranth seeds, showed positive values for Mn, Mg, Fe, P, Zn, Ca, fiber, glucose, and ω6/ω3 ratio. Furthermore, the CDA models developed resulted in a probability of event of 100% when classifying the samples in the groups quinoa or amaranth, highlighting the good sensitivity of the models used.

Chylothorax in newborns after cardiac surgery: a rare complication?

The aim of this study was to analyze patients diagnosed with chylothorax after congenital heart disease surgery among a cohort of neonatal patients, comparing the evolution, complications, and prognosis after surgery of patients who were and were not diagnosed with chylothorax, and to analyze possible risk factors that may predict the appearance of chylothorax in this population. Retrospective and observational study included all neonates (less than 30 days since birth) who underwent congenital heart disease surgery in a level III neonatal intensive care department. We included infants born between January 2014 and December 2019. We excluded those infants who were born before 34 weeks of gestational age or whose birth weight was less than 1800 g. We also excluded catheter lab procedures and patent ductus arteriosus closure surgeries. Included patients were divided into two groups depending on whether they were diagnosed with chylothorax or not after surgery, and both groups were compared in terms of perinatal-obstetrical information, surgical data, and NICU course after surgery. We included 149 neonates with congenital heart disease surgery. Thirty-one patients (20.8%) developed chylothorax, and in ten patients (32.3%), it was considered large volume chylothorax. Regarding the evolution of these patients, 22 infants responded to general dietetic measures, a catheter procedure was performed in 9, and 5 of them finally required pleurodesis. Cardiopulmonary bypass, median sternotomy, and delayed sternal closure were the surgical variables associated with higher risks of chylothorax. Patients with chylothorax had a longer duration of inotropic support and mechanical ventilation and took longer to reach full enteral feeds. As complications, they had higher rates of cholestasis, catheter-related sepsis, and venous thrombosis. Although there were no differences in neonatal mortality, patients with chylothorax had a higher rate of mortality after the neonatal period. In a multiple linear regression model, thrombosis and cardiopulmonary bypass multiplied by 10.0 and 5.1, respectively, the risk of chylothorax and have an umbilical vein catheter decreases risk. CONCLUSION: We have found a high incidence of chylothorax after neonatal cardiac surgery, which prolongs the average stay and causes significant morbidity and mortality. We suggested that chylothorax could be an underestimated complication of congenital heart disease surgery during the neonatal period. WHAT IS KNOWN: • Acquired chylothorax in the neonatal period usually appears as a complication of congenital heart disease surgery, being the incidence quite variable among the different patient series (2.5-16.8%). The appearance of chylothorax as a complication of a cardiac surgery increases both mortality and morbidity in these patients, which makes it a quality improvement target in the postsurgical management of this population. WHAT IS NEW: •Most of the published studies include pediatric patients of all ages, from newborns to teenagers, and there is a lack of studies focusing on neonatal populations. The main strength of our study is that it reports, to the best of our knowledge, one of the largest series of neonatal patients receiving surgery for congenital heart disease in the first 30 days after birth. We have found a high incidence of chylothorax after cardiac surgery during the neonatal period compared to other studies. We suggested that chylothorax could be an underestimated complication of congenital heart disease surgery during this period of life.

Evaluating remission and low disease activity from the perspective of the patient with axial spondyloarthritis: The cross-sectional ConREspAx study.

OBJECTIVES: To evaluate the properties of a single question to determine patient perception of remission and disease activity; to compare this with existing definitions for remission and low disease activity (LDA). METHODS: Single-center, cross-sectional study in a tertiary care hospital. Patients with axSpA (fulfilling ASAS criteria) were consecutively included. Both the patient's perception of remission and LDA and that of the physician were evaluated with a single question. Agreement between the patients' perception and other current definitions was tested using the prevalence-adjusted and bias-adjusted kappa (PABAK). The sensitivity (S) and specificity (Sp) of current definitions of disease states were tested against the patient's perception as the gold standard. RESULTS: The study population included 105 axSpA patients (63.8% males; 67.6% with radiographic sacroiliitis). Patients considered themselves to be in remission in 21% of cases and in LDA in 51.4%; physicians considered patients to be in remission in 45.7% of cases and in LDA in 35.2%. The poorest agreement was recorded for the patient's and the physician's perception of remission. The best agreement for patients' perception of remission was for a BASDAI < 2 and normal C-reactive protein values. This definition was also the most sensitive (S=72.7%) and specific (Sp=83.1%) when the patient's perception was taken as the gold standard. CONCLUSION: In a real-life setting, the evaluation of remission by the patient through a single question was the hardest criterion to achieve, although it did prove to be a feasible, valid, and specific way to assess remission.

Human impact on the recent population history of the elusive European wildcat inferred from whole genome data.

BACKGROUND: The extent and impact of evolutionary change occurring in natural populations in response to rapid anthropogenic impact is still poorly understood on the genome-wide level. Here, we explore the genetic structure, demographic history, population differentiation, and domestic introgression based on whole genome data of the endangered European wildcat in Germany, to assess potential genomic consequences of the species' recent spread across human-dominated cultural landscapes. RESULTS: Reconstruction of demographic history and introgression rates based on 47 wildcat and 37 domestic cat genomes suggested late introgression between wild and domestic cat, coinciding with the introduction of domestic cat during the Roman period, but overall relatively low rates of hybridization and introgression from domestic cats. Main population divergence found between an eastern and central German wildcat clade was found to be of rather recent origin (200 y), and thus the likely consequence of anthropogenic persecution and resulting isolation in population refugia. We found similar effective population sizes and no substantial inbreeding across populations. Interestingly, highly differentiated genes between wild cat populations involved in the tryptophan-kynurenine-serotonin pathway were revealed, which plays a role in behavioral processes such as stress susceptibility and tolerance, suggesting that differential selection acted in the populations. CONCLUSIONS: We found strong evidence for substantial recent anthropogenic impact on the genetic structure of European wildcats, including recent persecution-driven population divergence, as well as potential adaptation to human-dominate environments. In contrast, the relatively low levels of domestic introgression and inbreeding found in this study indicate a substantial level of "resistance" of this elusive species towards major anthropogenic impacts, such as the omnipresence of domestic cats as well as substantial habitat fragmentation. While those findings have strong implications for ongoing conservation strategies, we demand closer inspection of selective pressures acting on this and other wildlife species in anthropogenic environments.

Treatment-related hemophagocytic lymphohistiocytosis due to atezolizumab: a case report and review of the literature.

BACKGROUND: Immune checkpoint inhibitors avoid inhibition of T-cell responses, upregulating antitumor immune response. Moreover, a dysregulation with hyperactive immune response can be caused, some of them underdiagnosed. Hemophagocytic lymphohistiocytosis is a rare and often fatal syndrome of uncontrolled and ineffective hyperinflammatory response that triggers an inflammatory cascade that can lead in many cases to death. CASE PRESENTATION: We report the case of a 67-year-old Caucasian man with stage IV lung adenocarcinoma who developed hemophagocytic lymphohistiocytosis after initiation of atezolizumab, an antagonist of programmed death-ligand 1. Even with early diagnosis and proper treatment, death occurs in approximately half of all cases reported. CONCLUSION: Key markers are needed to better identify patients at risk of developing severe immune-related adverse events. In addition to key markers, a higher degree of suspicion and early intervention are needed to improve outcomes in acquired hemophagocytic lymphohistiocytosis, especially with the increasingly and expanding use of immune activation.

Comprehensive Approach to Genomic and Immune Profiling: Insights of a Real-World Experience in Gynecological Tumors.

Gynecological cancer accounts for an elevated incidence worldwide requiring responsiveness regarding its care. The comprehensive genomic approach agrees with the classification of certain tumor types. We evaluated 49 patients with gynecological tumors undergoing high-throughput sequencing to explore whether identifying alterations in cancer-associated genes could characterize concrete histological subtypes. We performed immune examination and analyzed subsequent clinical impact. We found 220 genomic aberrations mostly distributed as single nucleotide variants (SNV, 77%). Only 3% were classified as variants of strong clinical significance in BRCA1 and BRCA2 of ovarian high-grade serous (HGSC) and uterine endometrioid carcinoma. TP53 and BRCA1 occurred in 72% and 28% of HGSC. Cervical squamous cell carcinoma was entirely HPV-associated and mutations occurred in PIK3CA (60%), as well as in uterine serous carcinoma (80%). Alterations were seen in PTEN (71%) and PIK3CA (60%) of uterine endometrioid carcinoma. Elevated programmed death-ligand 1 (PD-L1) was associated with high TILs. Either PD-L1 augmented in deficient mis-matched repair (MMR) proteins or POLE mutated cases when compared to a proficient MMR state. An 18% received genotype-guided therapy and a 4% immunotherapy. The description of tumor subtypes is plausible through high-throughput sequencing by recognizing clinically relevant alterations. Additional concomitant assessment of immune biomarkers identifies candidates for immunotherapy.

Usefulness of implementing the OHIP-14 questionnaire to assess the impact of xerostomia and hyposalivation on quality of life in patients with primary Sjögren's syndrome.

BACKGROUND: The aim of this study is to analyze if the results of the Oral Health Impact Profile-14 questionnaire (OHIP-14) in patients with primary Sjögren's syndrome (pSS) are correlated with salivary flow and level of xerostomia. METHODS: This observational cross-sectional study was conducted in 61 patients (60 women, one man, mean age 57.64 [13.52]) diagnosed of pSS according to the American-European Criteria (2002). After recording demographic, medical and dental data (decayed-missing-filled teeth index [DMFT]), unstimulated (UWS) and stimulated (SWS) salivary flows were collected. Subsequently, UWS flow was categorized into two groups (<0.1 ml/min and ≥0.1 ml/min) and SWS into three groups (<0.1 ml/min, 0.1-0.7 ml/min and >0.7 ml/min). Patients also filled out a visual analog scale (VAS) for xerostomia and OHIP-14 for self-reported quality of life (QoL). RESULTS: Data showed positive and significant correlation between OHIP-14 and xerostomia, based on VAS results (r = 0.52; p = 0.001). Furthermore, there was a negative correlation between UWS and OHIP-14 scores (r = -0.34; p = 0.006) and VAS for xerostomia (r = -0.22; p = 0.09). No significant correlation was found between SWS and OHIP-14 or VAS neither between DMFT and OHIP-14. When assessing the level of QoL by the UWS and SWS flow categories a significant association was found for UWS (p = 0.001) but not for SWS (p = 0.11). The OHIP-14 values were higher in the groups with lower salivary flow. The multiple linear regression to predict OHIP-14 only selected VAS for xerostomia as a statistically significant predictor. CONCLUSIONS: Increased level of xerostomia and reduced UWS flow decrease oral health-related QoL in patients with pSS.

Contamination in Urine Samples Collected Using Bladder Stimulation and Clean Catch Versus Urinary Catheterization in Infants Younger Than 90 Days.

OBJECTIVES: The objective of this study was to compare the risk of contamination for urine samples collected from patients younger than 90 days using 2 different techniques: bladder stimulation and "clean catch" (CC) and urinary catheterization (CATH). METHODS: A case-control study was carried out in the pediatric emergency room of a tertiary hospital between January 2016 and September 2017. All urine samples collected from patients younger than 90 days by CC or CATH were included. The incidence of contaminated urine samples was compared for both methods, and the risk of contamination was estimated using univariate and multivariate analyses. RESULTS: A total of 473 urine samples were collected, 310 via CATH (65.5%) and 163 via CC (34.5%). The median age was 1.4 months (interquartile range, 0.8-2.1 months), and 54.1% were males. Seventeen patients had a history of urinary tract infection (3.6%), and 16 were diagnosed with a congenital urorenal anomaly (3.4%). Sixteen urine samples were found to be contaminated (3.4%): 5 collected via CATH (1.6%) and 11 via CC (6.8%). The univariate analysis revealed a greater risk of contamination in specimens obtained using CC versus CATH (odds ratio, 4.41; 95% confidence interval, 1.51-12.93), and the multivariate analysis confirmed CC collection as an independent risk factor for contamination (odds ratio, 5.61; 95% confidence interval, 1.83-17.19). CONCLUSIONS: The number of contaminated urine samples in infants younger than 90 days in our pediatric emergency department is low. However, using the CC urine collection technique seems to be an independent risk factor for sample contamination.

Fatal Staphylococcus Aureus Endocarditis Misdiagnosed as Multisystem Inflammatory Syndrome in Children.

We present a case of a 10-year-old male with Staphylococcus aureus mitral endocarditis who was initially misdiagnosed with multisystem inflammatory syndrome associated with coronavirus disease 2019, with eventual fatal outcome due to brain hemorrhage after cardiac intervention. Our case differs from recent studies, in which microbleeds did not increase the risk of hemorrhagic stroke or global mortality risk.

Healthy Zerumbone: From Natural Sources to Strategies to Improve Its Bioavailability and Oral Administration.

Zerumbone is a multifunctional compound with antimicrobial, antitumor, hyperalgesic, antioxidant and anti-inflammatory applications, and constitutes a point molecule for the future synthesis of derivatives with improved efficiency. This monocyclic sesquiterpenoid is found in high content in wild ginger (Zingiber zerumbet Smith), a perennial herb with economic importance as an ornamental as well as a medicinal plant. The presence of zerumbone is a distinctive feature that allows identification and differentiation from other species, not only in Zingiber, but also in Curcuma, Alpinia, Boesenbergia, Ethlingera and Ammomum spp., as well as related families (Costaceaee). To successfully use zerumbone in areas such as medicine, food and agriculture, further research on improving its low solubility and bioavailability, as well as its preservation, is a major current priority. In addition, despite its promising pharmacological activities, preclinical and clinical studies are required to demonstrate and evaluate the in vivo efficacy of zerumbone.