Tumor Subtype Classification Tool for HPV-associated Head and Neck Cancers.

Importance: Molecular subtypes of HPV-associated Head and Neck Squamous Cell Carcinoma (HNSCC), named IMU (immune strong) and KRT (highly keratinized), are well-recognized and have been shown to have distinct mechanisms of carcinogenesis, clinical outcomes, and potentially differing optimal treatment strategies. Currently, no standardized method exists to subtype a new HPV+ HNSCC tumor. Our paper introduces a machine learning-based classifier and webtool to reliably subtype HPV+ HNSCC tumors using the IMU/KRT paradigm and highlights the importance of subtype in HPV+ HNSCC. Objective: To develop a robust, accurate machine learning-based classification tool that standardizes the process of subtyping HPV+ HNSCC, and to investigate the clinical, demographic, and molecular features associated with subtype in a meta-analysis of four patient cohorts. Data Sources: We conducted RNA-seq on 67 HNSCC FFPE blocks from University of Michigan hospital. Combining this with three publicly available datasets, we utilized a total of 229 HPV+ HNSCC RNA-seq samples. All participants were HPV+ according to RNA expression. An ensemble machine learning approach with five algorithms and three different input training gene sets were developed, with final subtype determined by majority vote. Several additional steps were taken to ensure rigor and reproducibility throughout. Study Selection: The classifier was trained and tested using 84 subtype-labeled HPV+ RNA-seq samples from two cohorts: University of Michigan (UM; n=18) and TCGA-HNC (n=66). The classifier robustness was validated with two independent cohorts: 83 samples from the HPV Virome Consortium and 62 additional samples from UM. We revealed 24 of 39 tested clinicodemographic and molecular variables significantly associated with subtype. Results: The classifier achieved 100% accuracy in the test set. Validation on two additional cohorts demonstrated successful separation by known features of the subtypes. Investigating the relationship between subtype and 39 molecular and clinicodemographic variables revealed IMU is associated with epithelial-mesenchymal transition (p=2.25×10-4), various immune cell types, and lower radiation resistance (p=0.0050), while KRT is more highly keratinized (p=2.53×10-8), and more likely female than IMU (p=0.0082). Conclusions and Relevance: This study provides a reliable classifier for subtyping HPV+ HNSCC tumors as either IMU or KRT based on bulk RNA-seq data, and additionally, improves our understanding of the HPV+ HNSCC subtypes.

Diet specialization mediates drivers of Cucurbita herbivory in a semi-arid agroecosystem.

Herbivory is a major fitness pressure for plants and a key driver of crop losses in agroecosystems. Dense monocultures are expected to favor specialist herbivorous insects, particularly those who primarily consume crop species; yet, levels and types of herbivory are not uniform within regional cropping systems. It is essential to determine which local and regional ecological factors drive variation in herbivory in order to support functional agroecosystems that rely less on chemical inputs. Crops in the genus Cucurbita host a suite of both generalist and specialist herbivores that inflict significant damage, yet little is known about the relative contribution of these herbivores to variation in herbivory and how local- and landscape-scale Cucurbita resource concentrations, management practices, and natural enemies mediate this relationship. In this study, we tested whether three foundational ecological hypotheses influenced Cucurbita herbivory across 20 pumpkin fields in the semi-arid Southern High Plains Region of Texas. We used generalized linear mixed models and confirmatory path analysis to assess whether the Density-dependent Herbivory Hypothesis, Resource Concentration Hypothesis, or the Natural Enemies Hypothesis, could explain variation in Cucurbita herbivory and insect dynamics in the context of conventional agronomic practices. We found that herbivory increased over time, indicating that herbivores were causing sustained damage throughout the growing season. We also found that fields with higher local Cucurbita resources had lower herbivory, suggesting a resource dilution effect. Natural enemy communities were more abundant and taxonomically rich in sites with greater generalist herbivore abundance, though predator abundance declined over time, indicating that late-season crop fields are most at risk given high herbivory and low natural enemy-based control. Our findings also suggest that while local resource availability may drive the abundance and richness of arthropod communities, additional agronomic and phenological information is needed to anticipate herbivory risk in an agriculturally dominated landscape.

Development, Application and Utility of a Machine Learning Approach for Melanoma and Non-Melanoma Lesion Classification Using Counting Box Fractal Dimension.

The diagnosis and identification of melanoma are not always accurate, even for experienced dermatologists. Histopathology continues to be the gold standard, assessing specific parameters such as the Breslow index. However, it remains invasive and may lack effectiveness. Therefore, leveraging mathematical modeling and informatics has been a pursuit of diagnostic methods favoring early detection. Fractality, a mathematical parameter quantifying complexity and irregularity, has proven useful in melanoma diagnosis. Nonetheless, no studies have implemented this metric to feed artificial intelligence algorithms for the automatic classification of dermatological lesions, including melanoma. Hence, this study aimed to determine the combined utility of fractal dimension and unsupervised low-computational-requirements machine learning models in classifying melanoma and non-melanoma lesions. We analyzed 39,270 dermatological lesions obtained from the International Skin Imaging Collaboration. Box-counting fractal dimensions were calculated for these lesions. Fractal values were used to implement classification methods by unsupervised machine learning based on principal component analysis and iterated K-means (100 iterations). A clear separation was observed, using only fractal dimension values, between benign or malignant lesions (sensibility 72.4% and specificity 50.1%) and melanoma or non-melanoma lesions (sensibility 72.8% and specificity 50%) and subsequently, the classification quality based on the machine learning model was ≈80% for both benign and malignant or melanoma and non-melanoma lesions. However, the grouping of metastatic melanoma versus non-metastatic melanoma was less effective, probably due to the small sample size included in MM lesions. Nevertheless, we could suggest a decision algorithm based on fractal dimension for dermatological lesion discrimination. On the other hand, it was also determined that the fractal dimension is sufficient to generate unsupervised artificial intelligence models that allow for a more efficient classification of dermatological lesions.

Arabinoxylans matrixes as a potential material for drug delivery systems development - A bibliometric analysis and literature review.

Arabinoxylans (AX) have become a focal point in the pharmaceutical sector owing to their physicochemical, biological, and functional properties. The purpose of this paper was to present a summary of the utilization of AX as drug release matrices through a bibliometric analysis (BA) and a literature review to spotlight the AX functional characteristics and their technological applications to promote this line of research. The BA was carried out using data from a Web of Science database research, specifically emphasizing the analysis of authors' keywords. This approach was chosen due to its significance in comprehensively understanding a particular research field and its relevance for in-depth knowledge of a research field. The BA outcomes revealed limited information concerning the AX applications in both release matrices and as excipients in the formulation and development of drug delivery systems (DDS), so there is a need for additional scientific and technological research in these areas to address the existing information gaps. However, the literature review shows that the native and modified AX from different delivery release systems, such as macrogels (including films, tablets, and hard gelatin capsules) and multi-particulate systems (including micro and nanogels), present an excellent potential as release matrices of biomolecules and drugs, such as doxorubicin, diclofenac sodium, caffeine, gentamicin, tizanidine hydrochloride, and insulin. In conclusion, AX have a wide potential for application in the pharmaceutical industry, so this work is expected to be a reference point for future research by scientists, technologists, and entrepreneurs who cope with the subject.

Development and application of novel ELISA-based analytical tools for assessing nitroxidative distress biomarkers in ischemic stroke: implications for improved diagnosis and clinical management.

Ischemic cerebrovascular accident (iCVA) is a public health issue, whose subjacent events involve the development of nitroxidative distress. Identifying biomarkers that assist in the diagnosis of this disease has clinically relevant implications. The aim of this study was to develop an analytic tool for measuring nitroxidative distress biomarkers, intended for application in clinical practice to enhance patient healthcare. Three enzyme linked immunosorbent assays (ELISA) were developed, with different detection objectives. One of them, in a sandwich format, quantifies the amount of fibrinogen in human plasma, an important glycoprotein involved in the blood coagulation process, contributing to thrombus formation and thereby participating in the mechanism of ischemic stroke. Another ELISA, also in a sandwich format, detects the presence of nitrotyrosine residues in fibrinogen from human plasma, a nitroxidative posttranslational modification resulting from the attack of peroxynitrite by-products on tyrosine residues present in proteins. The third one, in inhibition format, determines human plasma nitrotyrosine total content and was used to analyze human plasma samples from control and iCVA patients. Those two groups of plasma samples were analyzed using inhibition ELISA, revealing statistically significant differences in their nitrotyrosine content and molar ratios of nitrotyrosine to fibrinogen, which were higher in the iCVA group. This study provides evidence that nitroxidative distress occurs in ischemic stroke, as indicated by the detection of the biomarker nitrotyrosine. This finding supports other studies that also identified nitrotyrosine in ischemic stroke, through several different methods. This specific ELISA method is applicable for the rapid analysis of clinical samples, making it a potential clinical tool for assessing iCVA patients.

Evaluating the application of an arabinoxylan-rich fraction from brewers' spent grain as a release modifier of drugs.

This study evaluated the possible use of a fraction of brewers' spent grain rich in arabinoxylans (BSG-AX) as an excipient that modifies the release of class III drugs (Biopharmaceutics Classification System), by determining the release profile of metformin hydrochloride (MH), in a water medium. The cumulative percentage of MH release showed the best linear fit when modeled with the cumulative distribution function (CDF) of the Weibull distribution (R2 = 0.993 ± 0.001). According to the Korsmeyer-Peppas model, the first stage of MH release is regulated by a super case-II transport mechanism controlled by the expansion and relaxation of BSG-AX. Finally, with the Hixson-Crowell model, a release rate (kHC) of 0.350 ± 0.026 h-13 was obtained (R2 = 0.996 ± 0.007). BSG-AX constitutes a suitable material for producing prolonged drug release vehicles; however, additional research is required to provide a better encapsulation of the active ingredients to ensure their optimal applicability and performance.

Evaluación de parámetros inflamatorios, trombóticos y variantes genéticas en pacientes con ataque cerebrovascular isquémico que se asisten en un hospital de Uruguay

Introducción: El ataque cerebrovascular es la segunda causa de muerte en adultos en el mundo occidental y una de las principales causas de discapacidad permanente, aumentando su frecuencia con la edad, el 85 % es de tipo isquémico. Objetivos: Analizar parámetros trombofílicos, hipofibrinolíticos y genéticos en pacientes con ataque cerebrovascular isquémico y evaluar la posible asociación de estos con factores de riesgo cardiovascular. Metodología: Se utilizó un cuestionario para evaluar la presencia de factores de riesgo cardiovascular en 114 pacientes incluidos en el estudio con diagnóstico de ataque cerebrovascular isquémico. Proteína C y antitrombina fueron determinados mediante métodos cromogénicos, resistencia a la proteína C activada e inhibidor lúpico mediante métodos coagulométricos y proteína S libre, inhibidor del activador del plasminógeno-1, homocisteína y lipoproteína (a) por métodos inmunoquímicos. Fibrinógeno fue determinado por coagulometría y proteína C reactiva por inmunoturbidimetría, ambos contra un grupo control. Las variantes genéticas factor V Leiden, protrombina G20210A, rs1205 (gen PCR), rs1800779 (gen NOS3) y rs2257073 (gen ASB10) fueron analizadas mediante real-time PCR, comparando los últimos tres con una población de referencia. La alteración de las frecuencias de las variables fue determinada por análisis estadístico chi-cuadrado. Resultados: Tres de los cuatro pacientes jóvenes estudiados presentaron indicadores de trombofilia. El resto de los parámetros alterados fueron homocisteína 30.1% (22.4-39.1), lipoproteína (a) 32.1% (24.1-41.4), inhibidor del activador del plasminógeno-1 36.0% (27.8-45.1), fibrinógeno 12.3% (7.5-19.6) y proteína C reactiva 78.1% (69.6-84.7). Se encontró asociación (p < 0.05) entre ciertos factores de riesgo cardiovascular y los parámetros evaluados como hipertensión/proteína C reactiva, dislipemia/lipoproteína (a), arritmia/lipoproteína (a) y arritmia/fibrinógeno. Para pacientes con ataque cerebrovascular isquémico solo la variante rs1205 mostró una frecuencia más alta del alelo T. Conclusiones: Este estudio revela la importancia de analizar la trombofilia en pacientes jóvenes, especialmente en aquellos sin factores de riesgo cardiovascular, así como el rol de la hipofibrinolisis, inflamación y algunas variantes genéticas en el desarrollo de ataque cerebro vascular isquémico.

Introduction: Stroke is the second cause of death in adults in the Western world and one of the main causes of permanent disability, increasing in frequency with age; 85% are ischemic. Objectives: To analyze thrombophilic, hypofibrinolytic, inflammatory, and genetic parameters in patients with ischemic stroke and evaluate possible associations with vascular risk factors. Methodology: Questionnaires were used to evaluate vascular risk factors in 114 patients included in the study with ischemic stroke diagnosis. Protein C and Antithrombin were determined by chromogenic assays, Activated Protein C Resistance and Lupus Anticoagulant were determined with by coagulometry and Free Protein S, Plasminogen activator inhibitor-1, Homocysteine and Lipoprotein (a) by immunochemistry. Fibrinogen was assayed by coagulometry and C-reactive protein by immunoturbidimetry, both against a control group. Factor V Leiden, Prothrombin G20210A, rs1205 (CRP gene), rs1800779 (NOS3 gene) and rs2257073 (ASB10 gene) genetic variants were analyzed by Real-Time PCR, comparing the last three with a reference population. Alteration frequencies of the variables were determined by chi-square statistical analysis. Results: Three out of four of the young patients studied presented indicators of thrombophilia. The rest of the altered parameters were Homocysteine 30.1% (22.4-39.1), Lipoprotein (a) 32.1% (24.1-41.4), Plasminogen activator inhibitor-1 36.0% (27.8-45.1), Fibrinogen 12.3% (7.5-19.6) and C-reactive protein 78.1% (69.6-84.7). Associations were found (p<0.05) between certain vascular risk factors and parameters evaluated, namely hypertension/C-reactive protein, dyslipidemia/lipoprotein (a), arrhythmia/lipoprotein (a) and arrhythmia/fibrinogen. For ischemic stroke patients only the genetic variant rs1205 showed higher frequency of the T allele. Conclusions: This study reveals the importance of analyzing thrombophilia in young patients, especially those without vascular risk factors, as well as the role of hypofibrinolysis, inflammation and some genetic variants in the development of ischemic stroke.

Introdução: O AVC é a segunda causa de morte em adultos no mundo ocidental e uma das principais causas de incapacidade permanente, aumentando de frequência com a idade; 85% são isquémicos. Metas: Analisar os parâmetros trombofílicos, hipofibrinolíticos e genéticos em pacientes com acidente vascular cerebral isquêmico e avaliar a possível associação com fatores de risco cardiovascular. Metodologia: Um questionário foi utilizado para avaliar a presença de fatores de risco cardiovascular em 114 pacientes incluídos no estudo com diagnóstico de acidente vascular cerebral isquêmico. Proteína C e antitrombina foram determinadas por métodos cromogênicos, resistência à proteína C ativada e inibidor de lúpus por métodos coagulométricos e proteína S livre, inibidor do ativador do plasminogênio-1, homocisteína e lipoproteína (a) por métodos imunoquímicos. O fibrinogênio foi determinado por coagulometria e a proteína C-reativa por imunoturbidimetria, ambos contra um grupo controle. As variantes genéticas fator V Leiden, protrombina G20210A, rs1205 (gene PCR), rs1800779 (gene NOS3) e rs2257073 (gene ASB10) foram analisadas por PCR em tempo real, comparando as três últimas com uma população de referência. As frequências de alteração das variáveis ​​foram determinadas pela análise estatística qui-quadrado. Resultados: Três dos quatro pacientes jovens estudados apresentaram indicadores de trombofilia. O resto dos parâmetros alterados foram homocisteína 30,1% (22,4-39,1), lipoproteína (a) 32,1% (24,1-41,4), inibidor do ativador de plasminogênio-1 36,0% (27,8-45,1), fibrinogênio 12,3% (7,5-19,6) e proteína C reativa 78,1% (69,6-84,7). Foi encontrada associação (p<0,05) entre alguns fatores de risco cardiovascular e os parâmetros avaliados como hipertensão/proteína C reativa, dislipidemia/lipoproteína (a), arritmia/lipoproteína (a) e arritmia/fibrinogênio. Para pacientes com acidente vascular cerebral isquêmico apenas a variante rs1205 apresentou maior frequência do alelo T. Conclusões: Este estudo revela a importância de analisar a trombofilia em pacientes jovens, especialmente aqueles sem fatores de risco cardiovascular, bem como o papel da hipofibrinólise, inflamação e algumas variantes genéticas no desenvolvimento do acidente vascular cerebral isquêmico.

ACE-Inhibitory Activity of Whey Proteins Fractions Derived of Fermentation by Lacticaseibacillus rhamnosus GG and Streptococcus thermophilus SY-102.

Many studies have reported the benefits of probiotic microorganisms and the production of angiotensin-converting enzyme (ACE) inhibitors. Determining the proteolytic and ACE inhibition capacities during whey fermentation was the goal of the study. Lacticaseibacillus rhamnosus GG, Streptococcus thermophilus SY-102, and both bacteria together were initially inoculated into whey, reaching an initial concentration of 108 CFU per milliliter in each fermentation system. Through the use of TNBS, SDS-PAGE, and SEC-HPLC methods, the proteolytic profile was examined. An in vitro investigation was performed to test the ACE inhibition capacity. With S. thermophilus, the logarithmic phase of microbial development was shorter than with L. rhamnosus (6 and 12 h, respectively). The logarithmic phase in the co-culture fermentation, however, was extended to 24 h. There were no significant differences in pH between the fermentations. However, the co-culture had a greater concentration of protein hydrolysis (453 ± 0.06 µg/mL), as indicated by the amount of free amino groups. Similarly, this fermentation produced more low molecular weight peptides. The higher inhibition activity, which increased at the conclusion of the fermentation with the co-culture and reached 53.42%, was influenced by the higher peptide synthesis. These findings highlighted the significance of creating useful co-culture products.

Sífilis: las sombras en el diagnóstico. A propósito de un caso clínico

La sífilis es una infección de transmisión sexual, potencialmente grave. La presentación clínica es muy variada, desde manifestaciones cutáneo-mucosas hasta neurológicas. Para el diagnóstico se emplean estudios de laboratorio, treponémicos y no treponémicos, con los que se realizan diferentes algoritmos para disminuir las limitaciones de cada prueba por separado. Se discute el caso de un joven que se presenta con fiebre y lesiones en piel sugestivas de sífilis secundaria, con un test VDRL falso negativo por efecto prozona. Este fenómeno, infrecuente, se debe a la concentración desproporcionadamente alta de anticuerpos. Conocer las herramientas diagnósticas y trabajar en conjunto con el equipo de laboratorio, puede facilitar el acercamiento a la enfermedad y a un tratamiento oportuno disminuyendo así la morbimortalidad de los pacientes.

Syphilis is a potentially serious sexually transmitted infection. The clinical presentation is very varied, from cutaneous-mucosal to neurological manifestations. For the diagnosis, treponemal and non-treponemal laboratory studies are used, with which different algorithms are performed to reduce the limitations of each test separately. We discuss the case of a young man who presented with fever and skin lesions suggestive of secondary syphilis, with a false negative VDRL test due to prozone effect. This rare phenomenon is due to a disproportionately high concentration of antibodies. Knowing the diagnostic tools and working together with the laboratory team can facilitate the approach to the disease and timely treatment, thus reducing the mor bidity and mortality of patients.

A sífilis é uma infecção sexualmente transmissível potencialmente grave. A apresentação clínica é muito variada, desde manifestações cutâneo-mucosas a neurológicas. Para o diagnóstico, são utilizados estudos laboratoriais, treponêmicos e não treponêmicos, com os quais são realizados diferentes algoritmos para reduzir as limitações de cada teste separadamente. Discutimos o caso de um jovem que apresentou febre e lesões cutâneas sugestivas de sífilis secundária, com teste VDRL falso negativo devido ao efeito prozona. Esse fenômeno raro se deve à concentração desproporcionalmente alta de anticorpos. Conhecer as ferramentas diagnósticas e trabalhar em conjunto com a equipe do laboratório pode facilitar a abordagem da doença e o tratamento oportuno, reduzindo assim a morbimortalidade dos pacientes.

Characterizing the impact of verbal communication and health literacy in the patient-surgeon encounter.

BACKGROUND: Patients with limited health literacy (HL) have difficulty understanding written/verbal information. The quality of verbal communication is not well understood. Therefore, our aim was to characterize patient-surgeon conversations and identify opportunities for improvement. METHODS: New colorectal patient-surgeon encounters were audio-recorded and transcribed. HL was measured. Primary outcomes were rates-of-speech, understandability of words, patient-reported understanding, and usage of medical jargon/statistics. Secondary outcomes included length-of-visit (LOV), conversation possession time, patient-surgeon exchanges, and speech interruptions. RESULTS: Significant variations existed between surgeons in rates-of-speech and understandability of words (p < 0.05). Faster rates-of-speech were associated with significantly less understandable words (p < 0.05). Patient-reported understanding varied by HL and by surgeon. Conversation possession time and usage of medical jargon/statistics varied significantly by surgeon (p < 0.05) in addition to patient-surgeon exchanges and interruptions. Patients with limited HL had shorter LOV. CONCLUSIONS: Significant variations exist in how surgeons talk to patients. Opportunities to improve verbal communication include slowing speech and using more understandable words.

Crystal structures of cocrystals of 2,7-dihydroxynaphthalene with isoniazid and piracetam.

Cocrystals of 2,7-dihydroxynaphthalene (DHN, or naphthalene-2,7-diol) with isoniazid (pyridine-4-carbohydrazide) (INH), denoted DHN-INH [C10H8O2·C6H7N3O, (I)], and piracetam [2-(2-oxopyrrolidin-1-yl)acetamide] (PIR), denoted DHN-PIR [C10H8O2·C6H10N2O2, (II)], were obtained by the solvent-assisted grinding method and characterized by IR spectroscopy, powder X-ray diffraction and single-crystal X-ray diffraction. Cocrystal (I) crystallized in the triclinic space group P-1 and showed a 2:2 stoichiometry. DHN and INH molecules are connected by O-H...N(pyridine) and O-H...N(hydrazide) hydrogen bonds. Cocrystal (II) crystallized in the space group Pca21 with a 1:1 stoichiometry. DHN and PIR molecules are connected by O-H...O=C hydrogen bonds. The supramolecular architecture of cocrystal (I) showed interlinked supramolecular tapes; meanwhile, in cocrystal (II), interlinked supramolecular sheets were observed.

Stem Cell Therapy in the Treatment of Patients With Autism Spectrum Disorder: a Systematic Review and Meta-analysis.

OBJECTIVE: Assess the safety and efficacy of upcoming stem cell treatments and analyze their effects on the cognitive and behavioral impairments in patients diagnosed with autism. METHODS: We included controlled and noncontrolled, randomized and non-randomized trials evaluating stem cell therapy as a treatment in patients with autism spectrum disorder compared to placebo or without comparator. DATA SOURCES: Scopus, Web of Science, MEDLINE and EMBASE. Risk of bias was assessed using Cochrane's Risk of Bias tool and the NIH's Quality Assessment Tool for Studies With No Control Group. RESULTS: Eleven trials including 461 patients proved eligible. ABC scale meta-analysis showed a mean raw of -11.97 in the intervention groups (95 % CI -91.45 to 67.52, p < 0.01). CARS scale reported a mean raw of -9.08 (95 % CI -15.43 to -2.73, p < 0.01). VABS scale was reported by their domains: communication domain reported a mean raw of 2.69 (95 % CI 1.30 to 4.08, p = 0.92); daily living domain, 1.99 (95 % CI 0.83 to 3.15, p = 0.51); motor domain, 1.06 (95 % CI -0.37 to 2.48, p = 0.20); socialization domain, 3.09 (95 % CI 1.71 to 4.48, p = 0.61); adaptive behavior domain, 2.10 (95 % CI 1.04 to 3.16, p = 0.36). Furthermore, the most common side effects reported included fever, hyperactivity, vomit, headache, and aggressiveness; no serious adverse events were reported. CONCLUSIONS: The body of evidence suggests that stem cell therapy significantly improves scales in patients with autism spectrum disorder, hence, future studies should help us have more confidence in the results. We found no serious adverse events related to the stem cell therapy.

The association of health literacy and postoperative complications after colorectal surgery: A cohort study.

BACKGROUND: Health literacy is a determinant of health. Few studies characterize its association with surgical outcomes. METHODS: Retrospective cohort study of patients undergoing elective colorectal surgery 2015-2020. Health literacy assessed using Brief Health Literacy Screening Tool. Outcomes were postoperative complications, LOS, readmissions, mortality. RESULTS: Of 552 patients, 46 (8.3%) had limited health literacy, 506 (91.7%) non-limited. Median age 57.7 years, 305 (55.1%) patients were female, 148 (26.8%) were Black. Limited patients had higher rates of overall complications (43.5% vs. 24.3%, p = 0.004), especially surgical site infections (21.7% vs. 11.3%, p = 0.04). Limited patients had longer LOS (5 vs 3.5 days, p = 0.006). Readmissions and mortality did not differ. On multivariable analysis, limited health literacy was independently associated with increased risk of complications (OR 2.03, p = 0.046), not LOS (IRR 1.05, p = 0.67). CONCLUSION: Limited health literacy is associated with increased likelihood of complications after colorectal surgery. Opportunities exist for health literate surgical care to improve outcomes for limited health literacy patients.

Impact of the Gut Microbiota Balance on the Health-Disease Relationship: The Importance of Consuming Probiotics and Prebiotics.

Gut microbiota is a group of microorganisms that are deposited throughout the entire gastrointestinal tract. Currently, thanks to genomic tools, studies of gut microbiota have pointed towards the understanding of the metabolism of important bacteria that are not cultivable and their relationship with human homeostasis. Alterations in the composition of gut microbiota could explain, at least in part, some epidemics, such as diabetes and obesity. Likewise, dysbiosis has been associated with gastrointestinal disorders, neurodegenerative diseases, and even cancer. That is why several studies have recently been focused on the direct relationship that these types of conditions have with the specific composition of gut microbiota, as in the case of the microbiota-intestine-brain axis. In the same way, the control of microbiota is related to the diet. Therefore, this review highlights the importance of gut microbiota, from its composition to its relationship with the human health-disease condition, as well as emphasizes the effect of probiotic and prebiotic consumption on the balance of its composition.

Characterization of Neonatal Infections by Gram-Negative Bacilli and Associated Risk Factors, Havana, Cuba.

Infections represent an important problem in neonates because of the high mortality. An increase in neonatal infections has been found in Cuban hospitals in recent years. The aim of this study was to provide evidence on the clinical and microbiological behavior of Gram-negative bacilli that cause neonatal infections in hospitals of Havana, Cuba. It was carried out as a descriptive cross-sectional investigation from September 2017 to July 2018 in The Tropical Medicine Institute "Pedro Kouri" (IPK). Sixty-one Gram-negative bacilli isolated from neonates with infections in six Gyneco-Obstetric and Pediatric Hospitals of Havana were analyzed for their species and antimicrobial susceptibility. Late-onset infections were more common than early-onset ones and included urinary tract infection in the community (87%) and sepsis in hospitals (63.3%). Catheter use (47%) and prolonged stay (38%) were the most frequent risk factors. Species of major pathogens were Escherichia coli (47%) and Klebsiella spp. (26%). The isolated Gram-negative bacilli showed high resistance rates to third-generation cephalosporins, ciprofloxacin and gentamicin, while being more susceptible to carbapenems, fosfomycin, colistin and amikacin. The present study revealed the clinical impact of Gram-negative bacilli in neonatology units in hospitals of Havana. Evaluation of antimicrobial susceptibilities to the isolates from neonates is necessary for selection of appropriate empirical therapy and promotion of the rational antibiotic use.

Comparative Evaluation of Four Extraction Methods of Antioxidant Compounds from Decatropis bicolor in Aqueous Medium Applying Response Surface Design.

The objective of this paper is to compare conventional, ultrasound, microwave, and French press methods for the extraction of antioxidant compounds from Decatropis bicolor in an aqueous medium. This plant is widely used in Mexican traditional medicine for breast cancer treatment. Despite that, there are few studies on D. bicolor. Two response surface designs were applied to establish the best conditions of the liberation of antioxidants from D. bicolor, which were determined by DPPH• and Ferric Reducing Antioxidant Power (FRAP) techniques. The total phenolic content was evaluated by the Folin-Ciocalteu method. The results showed that D. bicolor is a source of antioxidants (669-2128 mg ET/100 g and 553-1920 mg EFe2+/100 g, respectively) and phenolic compounds (2232-9929 mg EGA/100 g). Among the physical factors that were analyzed, the temperature was the determinant factor to liberate the compounds of interest by using low concentrations of the sample and short times of extraction. The French press was the most efficient method, obtaining values of antioxidant activity and phenolic compounds even higher than those reported by using extraction methods with solvents such as methanol.

Identification and relative quantification of 3-nitrotyrosine residues in fibrinogen nitrated in vitro and fibrinogen from ischemic stroke patient plasma using LC-MS/MS.

Ischemic stroke is one of the leading causes of death and disability worldwide. This acute vascular event interferes with blood supply to the brain and induces a burst of free radicals such as nitric oxide and superoxide, producing peroxynitrite, a precursor of strong nitrating agents. Fibrinogen is one of the most abundant plasma proteins; it plays a role in the hemostatic system, mediating clot formation, which can be affected by nitrotyrosine formation. We hypothesized that nitration of fibrinogen by ONOOH and ONOOCO2- radical products could be one of the early events of the ischemic stroke, and protein-bound 3-nitrotyrosine could be a potential biomarker for diagnosis and/or prognosis of this condition. A targeted mass spectrometry approach was developed to analyze the nitration of fibrinogen and its association with ischemic stroke. First, a comprehensive mapping of 3-nitrotyrosine locations and their relative quantification was performed by LC-MS/MS, using in vitro nitrated fibrinogen samples. Twenty different 3-nitrotyrosine residues were identified on fibrinogen nitrated in vitro, varying with the peroxynitrite tofibrinogen molar ratio used. Nine tyrosine residues that were consistently modified at different treatment ratios were chosen to perform a targeted LC-MS/MS analysis in clinical samples. Enriched fibrinogen fractions from clinical samples from 24 ischemic stroke and 12 patients with non-inflammatory conditions were analysed with this method. Three of the nine tyrosine residues analysed (ßY452, ßY475 and γY380) showed a significant difference between the ischemic stroke and non-inflammatory disease groups. ROC curve analysis suggested an association of these residues either individually or in combination with ischemic stroke. Different tyrosine nitration patterns were also observed in fibrinogen modified in vitro and in vivo, suggesting differences in the nitration process in these situations. This is the first study showing a putative association between the nitration profile of specific tyrosine residues in human fibrinogen and ischemic stroke.

What the Pandemic Experience Taught Us About STEM Higher Education-School Partnerships.

The move to virtual schooling and other measures to reduce the spread of SARS-CoV-2 infection dramatically changed the educational experience for grades K-12 populations during the years 2020 and 2021. STEM teaching and learning, and community partnerships focused on STEM education, were not exempt from the changes. Universities and other community partners had to adapt their STEM partnership programming to address new needs and assist students, teachers, families, and schools throughout periods of at-home learning and the re-reintroduction of in-person classes. Some of the changes included developing new programs, providing health-related guidance to school leaders, and converting student-focused programs to virtual formats. Through these experiences, new approaches emerged and lessons were learned that can be applied to partnership activities during normal times. These lessons included recognizing the importance of addressing inequities in students' access to technology; development of strategies to redesign enrichment programs and classroom instruction for effective online delivery; and identifying and adapting to the range of technologies available to support virtual teaching in differing schools. The increased familiarity by all partners with virtual formats has opened the door to greater participation by students in STEM enrichment programs, online partnerships with STEM professionals and mentoring opportunities.

Lactobacillus pentosus ABHEAU-05: An in vitro digestión resistant lactic acid bacterium isolated from a traditional fermented Mexican beverage / Lactobacillus pentosus ABHEAU-05: una bacteria ácido láctica resistente a la digestión in vitro aislada de una bebida fermentada tradicional mexicana

Abstract The health benefits attributed to probiotics generate interest in the search of competent strains adapted to several ecological niches, especially those related to traditional beverages and foods of each country. Pineapple tepache, a traditional Mexican fermented beverage, was used for the isolation of lactic acid bacteria with probiotic potential, one of which withstood the in vitro tests. The isolated strain AB-05, which exhibited the tested probiotic functional properties, was designated as Lactobacillus pentosus ABHEAU-05. The sequence was registered in GenBank under access code MK587617. This study is the first report of a lactic acid bacterium with in vitro digestion resistance isolated from pineapple tepache. The survival of L. pentosus ABHEAU-05 in a symbiotic medium was proven using fermented milk enriched with inulin. The in vitro digestion-resistant probiotic activity of lactobacilli was measured through analysis of pH and proteolysis. Results showed that L. pentosus grew properly in fermented milk; therefore, this microorganism could be used in the manufacture of this kind of products. The concentration of L. pentosus reached up to 8.5 logCFU/ml after 40 h of fermentation. In addition, the production of peptides and the decrease in pH indicated the vigorous and active metabolic state of the lactic acid bacterium tested. The activity and the concentration of this microorganism were maintained during refrigeration. The results of this research conclude that L. plantarum ABHEAU-05 is an in vitro digestion-resistant microorganism that can be used as a starter culture for the production of functional foods of dairy origin.

Resumen Los beneficios a la salud atribuidos a los probióticos generan interés en la búsqueda de cepas competentes adaptadas a varios nichos ecológicos, especialmente los relacionados con bebidas y alimentos tradicionales de cada país. En este estudio, se aisló del tepache de pina, una bebida fermentada tradicional mexicana, una bacteria láctica resistente a la digestión in vitro. Entre 5 bacterias aisladas, una de ellas soportó las pruebas simuladas de digestión gastrointestinal. Se analizó la resistencia a sales biliares, a condiciones ácidas y al ataque enz-imático con pepsina. La bacteria aislada, que exhibió las propiedades funcionales probióticas referidas, fue identificada como Lactobacillus pentosus y designada como L. pentosus ABHEAU-05. La secuencia fue depositada en GenBank (acceso MK587617). Se comprobó la supervivencia de L. pentosus ABHEAU-05 en una leche fermentada adicionada con inulina y su resistencia a la digestión in vitro mediante el análisis del pH y la proteólisis. Los resultados muestran que la leche fermentada es una matriz adecuada, donde L. pentosus ABHEAU-05 se desarrolla sin inconvenientes, alcanzando un título de 8,5 logufc/ml después de 40 h de fermentación. Además, la producción de péptidos y el descenso del pH indicaron el estado metabólico vigoroso y activo del microorganismo probiótico. Se concluye que L. pentosus ABHEAU-05 es un microorganismo resistente a la digestión in vitro, que puede servir como cultivo iniciador para la producción de alimentos de origen lácteo. Este es el primer informe acerca del aislamiento de una bacteria ácido láctica resistente a la digestión in vitro a partir del tepache de piña.