Design of Liquid Formulation Based on F127-Loaded Natural Dimeric Flavonoids as a New Perspective Treatment for Leishmaniasis.

Infectious and Parasitic Diseases (IPD) remain a challenge for medicine due to several interconnected reasons, such as antimicrobial resistance (AMR). American tegumentary leishmaniasis (ATL) is an overlooked IPD causing persistent skin ulcers that are challenging to heal, resulting in disfiguring scars. Moreover, it has the potential to extend from the skin to the mucous membranes of the nose, mouth, and throat in both humans and various animals. Given the limited effectiveness and AMR of current drugs, the exploration of new substances has emerged as a promising alternative for ATL treatment. Arrabidaea brachypoda (DC). Bureau is a native Brazilian plant rich in dimeric flavonoids, including Brachydin (BRA), which displays antimicrobial activity, but still little has been explored regarding the development of therapeutic formulations. In this work, we present the design of a low-cost liquid formulation based on the use of Pluronic F127 for encapsulation of high BRA concentration (LF-B500). The characterization techniques revealed that BRA-loaded F127 micelles are well-stabilized in an unusual worm-like form. The in vitro cytotoxicity assay demonstrated that LF-B500 was non-toxic to macrophages but efficient in the inactivation of forms of Leishmania amazonensis promastigotes with IC50 of 16.06 µg/mL. The results demonstrated that LF-B500 opened a new perspective on the use of liquid formulation-based natural products for ATL treatment.

HPV Prevalence and Predictive Biomarkers for Oropharyngeal Squamous Cell Carcinoma in Mexican Patients.

BACKGROUND: Worldwide prevalence of Oropharyngeal Squamous Cell Carcinoma (OPSCC) has increased, affecting mostly young males. OPSCC associated with Human Papillomavirus (HPV) infection exhibits particular characteristics in terms of response to treatment, hence HPV has been proposed as a prognostic factor. The impact of HPV positivity and associated biomarkers on OPSCC in the Mexican population has not been addressed. Therefore, the analysis of OPSCC prognostic markers in the Mexican population is necessary. METHODS: Retrolective study in Mexican OPSCC patients, where HPV prevalence, p16 and EGFR levels were assessed using INNO-LiPA and immunohistochemistry. RESULTS: We found an HPV prevalence of 57.6% in OPSCC cases treated at a reference center in Mexico. HPV and p16 positivity, as well as EGFR, associate with better outcomes in OPSCC patients, and they also promote reduced death risk. Notably, HPV presence and p16 positivity showed a significant association with disease-free survival (DFS), with a HR of 0.15 (p = 0.006) and a HR of 0.17 (p = 0.012), respectively, indicating a possible role as predictive biomarkers in Mexican OPSCC patients. CONCLUSIONS: Our results reflect the clinical utility of p16 analysis to improve overall survival (OS) and to predict recurrence in oropharyngeal cancer. These results position p16 and HPV as predictive biomarkers for OPSCC.

MnO2-Ir Nanowires: Combining Ultrasmall Nanoparticle Sizes, O-Vacancies, and Low Noble-Metal Loading with Improved Activities towards the Oxygen Reduction Reaction.

Although clean energy generation utilizing the Oxygen Reduction Reaction (ORR) can be considered a promising strategy, this approach remains challenging by the dependence on high loadings of noble metals, mainly Platinum (Pt). Therefore, efforts have been directed to develop new and efficient electrocatalysts that could decrease the Pt content (e.g., by nanotechnology tools or alloying) or replace them completely in these systems. The present investigation shows that high catalytic activity can be reached towards the ORR by employing 1.8 ± 0.7 nm Ir nanoparticles (NPs) deposited onto MnO2 nanowires surface under low Ir loadings (1.2 wt.%). Interestingly, we observed that the MnO2-Ir nanohybrid presented high catalytic activity for the ORR close to commercial Pt/C (20.0 wt.% of Pt), indicating that it could obtain efficient performance using a simple synthetic procedure. The MnO2-Ir electrocatalyst also showed improved stability relative to commercial Pt/C, in which only a slight activity loss was observed after 50 reaction cycles. Considering our findings, the superior performance delivered by the MnO2-Ir nanohybrid may be related to (i) the significant concentration of reduced Mn3+ species, leading to increased concentration of oxygen vacancies at its surface; (ii) the presence of strong metal-support interactions (SMSI), in which the electronic effect between MnOx and Ir may enhance the ORR process; and (iii) the unique structure comprised by Ir ultrasmall sizes at the nanowire surface that enable the exposure of high energy surface/facets, high surface-to-volume ratios, and their uniform dispersion.

Pega na mentira: notas antropológicas sobre tempos inquietantes / Catch the lie: anthropological notes on unsettling times / Atrapa la mentira: apuntes antropológicos sobre tiempos inquietantes

O artigo emprega o método etnográfico e comparativo por contraste, fundado em observação direta, participante e entrevistas no campo no Brasil, na França e nos EUA. O objetivo do mesmo consiste em analisar a produção de narrativas contraditórias no mundo contemporâneo que se arrogam a qualidade de verdades legítimas para aqueles que acreditam nelas. Como resultado demonstramos como tais narrativas se articulam a uma generalizada quebra de 'confiança' (trust), característica presumida nas interações das sociedades de mercado, por uma desconfiança generalizada, mais especificamente caracterizada na língua portuguesa como 'a cisma'. O principal problema é o renascimento do ethos inquisitorial na sociedade contemporânea e suas implicações nas formas de produção da verdade. A intersecção entre a cisma e o ethos inquisitorial de suspeição sistemática sobre todas as interações sociais na sociedade contemporânea parece estar intimamente relacionada com os efeitos das redes sociais nas práticas e dinâmicas sociais, em particular no que diz respeito à rachadura produzida por estes instrumentos na construção de consensos, das concepções do "comum" da ideia da verdade, da inclinação ao debate e à crítica, etc.

The article employs the ethnographic and comparative method by contrast, based on direct and participant observation, and field interviews in Brazil, France and the USA. Its purpose is to analyze the production of contradictory narratives in the contemporary world that claim to be legitimate truths for those who believe them. As a result, we show how such narratives are articulated to a generalized breakdown of 'trust', a presumed characteristic in the interactions of market societies, by a generalized distrust, more specifically characterized in Portuguese as 'a cisma'. The main problem is the revival of the inquisitorial ethos in contemporary society and its implications for the forms of truth production. The intersection between schism and the inquisitorial ethos of systematic suspicion about all social interactions in contemporary society seems to be closely related to the effects of social networks on social practices and dynamics, in particular with regard to the cracking produced by these instruments in the construction of consensus, of the conceptions of the 'common' idea of truth, of the inclination to debate and criticism, etc.

El artículo utiliza el método etnográfico y comparativo por contraste, basándose en la observación directa y participante y en entrevistas sobre el terreno en Brasil, Francia y Estados Unidos. Su objetivo es analizar la producción de narrativas contradictorias en el mundo contemporáneo que pretenden ser verdades legítimas para quienes las creen. Como resultado, demostramos cómo tales narrativas se articulan a una ruptura generalizada de la 'confianza', una presunta característica en las interacciones de las sociedades de mercado, por una desconfianza generalizada, más específicamente caracterizada en el idioma portugués como 'a cisma'. El problema principal es el resurgimiento del ethos inquisitorial en la sociedad contemporánea y sus implicaciones para las formas de producción de la verdad. La intersección entre el cisma y el ethos inquisitorial de sospecha sistemática sobre todas las interacciones sociales en la sociedad contemporánea parece estar estrechamente relacionada con los efectos de las redes sociales en las prácticas y dinámicas sociales, en particular en lo que se refiere a la fisura producida por estos instrumentos en la construcción del consenso, de las concepciones de lo 'común' de la idea de verdad, de la inclinación al debate y la crítica, etc.

Blanching Effect on the Quality and Shelf-Life Characteristics of Fresh Cowpea Grains [Vigna unguiculata (L.) Walp.].

The high perishability of fresh cowpeas impairs its commercialization. Thus, this study aims to determine the temperature-time binomial for blanching fresh cowpea [Vigna unguiculata (L.) Walp] by evaluating the effects of heat treatment and kinetic behavior on the peroxidase (POD) activity and on the physical characteristics (firmness, color, mass gain). A factorial design (3 × 6) with temperature (70, 80, and 90 °C) and time (1, 2, 4, 6, 8, and 10 min) was implemented. Physicochemical, microbiological, and enzymatic (POD) changes, in addition to photographic monitoring, were evaluated throughout the storage period (4.90 °C). With regard to the effects of the independent variables and the first-order kinetic model, it was determined that 70 °C for 4 min of blanching maintained and/or improved the physical characteristics of the raw material. The pH and the acidity of the blanched fresh cowpea changed little during the storage period; the microbiological load and POD activity reduced with blanching and remained stable until the eighth day of storage, and provided an increase of 5 days in shelf-life under refrigeration when compared to non-blanched. Blanching is shown as an alternative for improving fresh cowpeas, favoring an economic increase in production with guaranteed quality and safety attributes.

Effectiveness of Concomitant Chemoradiotherapy with Gemcitabine in Locally Advanced Cervical Cancer Patients with Comorbidities.

PURPOSE: The standard treatment for locally advanced cervical cancer (LACC) is concomitant chemoradiotherapy with cisplatin (CDDP) followed by brachytherapy. The presence of comorbidities are risk factors for nephrotoxicity and are associated with lower survival. Gemcitabine is a radiosensitizing drug that has shown efficacy and safety in this context. The effectiveness of concomitant chemoradiotherapy with gemcitabine was evaluated versus cisplatin in LACC patients with comorbidities and preserved renal function. MATERIALS AND METHODS: An observational, longitudinal and paired study was carried out that included patients treated between February 2003 and December 2015. The primary objectives were to evaluate response rates, progression-free survival, and overall survival; the secondary objectives were to evaluate toxicity and renal function. RESULTS: Sixty-three patients treated with gemcitabine at 300 mg/m2 weekly and 126 patients treated with CDDP 40 mg/m2 weekly were included. There were no significant differences in response rates and survival rates. Treatment with cisplatin presented a higher frequency of hematological toxicities, while gemcitabine presented a higher frequency of gastrointestinal toxicities. A decrease in glomerular filtration rate (GFR; baseline vs. 1-year post-treatment) was observed in the cisplatin group (p=0.002), while not in the gemcitabine group (p=0.667). In a multivariate analysis, it is observed that only CDDP correlates with the decrease in GFR (hazard ratio, 2.42; p=0.012). CONCLUSION: In LACC patients with comorbidities, gemcitabine and CDDP show the same efficacy, with different toxicity profiles. Treatment with cisplatin is associated with a significant decrease in GFR during follow-up, compared to treatment with gemcitabine that does not decrease it.

HPV oral and oropharynx infection dynamics in young population.

The incidence of human papillomavirus (HPV)-associated cancers, especially those from the head and neck region, has increased. The relatively early age of presentation of HPV-positive head and neck cancer (HNC) indicates that viral infection might be acquired early in life. Persistent HPV infection has been recognized as the main risk factor for cancer development, but most studies have focused on evaluating HPV persistence in the genital region. Thus, in this work, we aimed to evaluate the prevalence of HPV in oral cavity and oropharynx in a young population, as well as the possible persistence of the infection after 12 months. Our results indicate that almost half (46.8%) of the analyzed population harbors an HPV infection either in the oral cavity or in the oropharynx. Furthermore, after 1 year of initial identification, half of them eliminated the infection, and only one person (5.26%) exhibited persistence. Interestingly, 50% of the individuals who successfully eliminated the infection acquired a new viral type, indicating that even when the primary infection is effectively eliminated by the immune system, there is a dynamic circulation of HR-HPV types that produce reinfection. This dynamic HPV infection among young individuals could influence the future establishment of cancer in some proportion of the cases.

Validation of the QLQ-CX24 questionnaire for the assessment of quality of life in Mexican women with cervical cancer.

OBJECTIVE: Cervical cancer is the fourth most frequent neoplasm among women in terms of incidence and mortality. Health-related quality of life (HRQL) is an important outcome in oncology. The QLQ-CX24 instrument was developed to measure HRQL in patients with cervical cancer, and its Mexican-Spanish version had not been validated. METHODS: Between March 2018 and May 2019, Mexican women older than 18, with any-stage cervical cancer were invited to participate in the study. Patients answered the QLQ-C30 and QLQ-CX24 questionnaires. Current tests for psychometric and clinical validation were performed. RESULTS: Three hundred and thirty patients with cervical cancer were included in this study. All women invited to participate accepted and were included. The QLQ-CX24 internal consistency test demonstrated adequate convergent (Spearman correlation coefficient 0.001-0.847) and divergent validity (Spearman correlation coefficient <0.0001-0.45). Cronbach's alpha coefficients of the three multi-item scales were >0.7 (minimum 0.76, maximum 0.89). Four scales of the QLQ-CX24 distinguished patients in different clinical stages. The evaluation of responsiveness demonstrated that the peripheral neuropathy scale was sensitive to change over time during chemo-radiation therapy. Six scales of the QLQ-CX24 instrument were associated with survival. CONCLUSION: The Mexican-Spanish version of the QLQ-CX24 questionnaire is reliable and valid for the assessment of HRQL in patients with cervical cancer.

Antimicrobial resistance of bacterial strains in patients undergoing orthodontic treatment with and without fixed appliances.

OBJECTIVES: To identify microorganisms isolated from patients wearing fixed orthodontic appliances and to evaluate the resistance of isolated bacterial strains to different antimicrobials. MATERIALS AND METHODS: Seventeen healthy patients wearing a fixed orthodontic appliance (group 1) and six nonwearers (group 2, control group) were evaluated. The biofilm that formed around the orthodontic brackets was collected, and the samples were then plated in a chromogenic medium (chromIDT, bioMérieux). Colony-forming units (CFUs) were isolated and inoculated in blood-agar medium. Automated biochemical tests (VITEK 2, bioMérieux) were carried out to identify the genus and species of the microorganisms and the resistance provided by 43 drugs (37 antibacterial and 6 antifungal). RESULTS: The most prevalent microbial genera identified in group 1 were Streptococcus (24.0%), Staphylococcus (20.0%), Enterobacter (12.0%), Geobacillus (12.0%), and Candida (12.0%), and the most frequent species were Enterobacter cloacae complex (13.6%) and Staphylococcus hominis (13.6%). In group 2, the most prevalent genera were Streptococcus (57.1%), Staphylococcus (14.2%), Sphingomonas (14.2%), and Enterobacter (14.2%). With regard to antimicrobial resistance, 14 of 19 (74%) isolated bacterial strains were found to be resistant to at least 1 of the tested antimicrobials. CONCLUSIONS: The findings of the present study suggest that patients undergoing orthodontic treatment with fixed appliances have a more complex biofilm with a higher level of bacterial resistance.

Body composition and nutritional status according to clinical stage in patients with locally advanced cervical cancer.

The objective was to evaluate body composition and nutritional status in women with locally advanced cervical cancer (LACC) before receiving oncologic treatment. Women with cervical cancer diagnoses in clinical stage IB2 to IIIB were studied. Body composition was measured with bioimpedance, sarcopenia determined according to the European Consensus, and nutritional status according to the Patient-Generated Subjective Global Assessment. A total of 155 women with age 50.4 ± 13.7, 29 clinical stage I, 82 II, and 44 III, were studied. Patients in advanced clinical stage III, compared with patients in stage II and stage I, lower phase angle (III: 5.2 ± 0.98 vs. II: 5.7 ± 1.9 and I: 5.8 ± 0.69, p = 0.007). Impedance vector distribution was different in patients in clinical stage III vs. those in clinical stage II (p = 0.014) and I (p = 0.039). LACC patients in advanced stages had worse body composition and nutritional status before treatment.

The direct correlation between oxidative stress and LDL-C levels in adults is maintained by the Friedewald and Martin equations, but the methylation levels in the MTHFR and ADRB3 genes differ.

Low-density lipoprotein (LDL-C) concentrations are a standard of care in the prevention of cardiovascular disease and are influenced by different factors. This study compared the LDL-C concentrations estimated by two different equations and determined their associations with inflammatory status, oxidative stress, anthropometric variables, food intake and DNA methylation levels in the LPL, ADRB3 and MTHFR genes. A cross-sectional population-based study was conducted with 236 adults (median age 37.5 years) of both sexes from the municipality of João Pessoa, Paraíba, Brazil. The LDL-C concentrations were estimated according to the Friedewald and Martin equations. LPL, ADRB3 and MTHFR gene methylation levels; malondialdehyde levels; total antioxidant capacity; ultra-sensitive C-reactive protein, alpha-1-acid glycoprotein, homocysteine, cobalamin, and folic acid levels; usual dietary intake; and epidemiological variables were also determined. For each unit increase in malondialdehyde concentration there was an increase in the LDL-C concentration from 6.25 to 10.29 mg/dL (p <0.000). Based on the Martin equation (≥70 mg/dL), there was a decrease in the DNA methylation levels in the ADRB3 gene and an increase in the DNA methylation levels in the MTHFR gene (p <0.05). There was a positive relation of homocysteine and cholesterol intake on LDL-C concentrations estimated according to the Friedewald equation and of waist circumference and age based on the two estimates. It is concluded the LDL-C concentrations estimated by the Friedewald and Martin equations were different, and the Friedewald equation values were significantly lower than those obtained by the Martin equation. MDA was the variable that was most positively associated with the estimated LDL-C levels in all multivariate models. Significant relationships were observed based on the two estimates and occurred for most variables. The methylation levels of the ADRB3 and MTHFR genes were different according to the Martin equation at low LDL-C concentrations (70 mg/dL).

IMMUNOLOGY OF CERVICAL CANCER.

Optimal function of the immune system allows the recognition and elimination of infected and tumor cells. However, these cells can develop mechanisms to evade the cellular immune response. In human papillomavirus (HPV) infection, dysregulation of major histocompatibility complex Class I molecules and other components of the innate immune system promote the survival of infected cells by allowing the infection to persist which, in turn, favors the development of cancer. Further, tumor cells possess inherent mechanisms designed to block the recognition and activation of cytotoxic lymphocytes: particularly, HPV proteins such as E1 and E2 and oncoproteins E5, E6, and E7 that inhibit immune mechanisms and/or stimulate the expression of immunosuppressive cytokines. These mechanisms include a decrease in receptor activation and costimulating molecules on the surface of immune cells, as well as the constitutive expression of molecules that inhibit their function, which allow HPV persistence and tumor progression. Immunotherapy-based therapeutic options are positioned as excellent candidates for the treatment of cervical cancer.

IMMUNOTHERAPY TREATMENT AGAINST CERVICAL CANCER.

Cervical cancer (CC) is one of the most common gynecological tumors and an important health problem, especially in developing countries. The vast majority of patients in early stages are cured of the disease with surgical treatment and with concomitant chemoradiotherapy in locally advanced stages. However, in patients with recurrent, persistent, or metastatic cervical CC, the effectiveness of treatment is limited, except for the combination of chemotherapy based on platinum doublets plus bevacizumab, the treatment that has achieved the best results to date. Programmed cell death-1/PD ligand-1 (PD-1/PD-L1) inhibitors could be a novel and cutting-edge therapeutic option to improve clinical outcomes in this group of patients. Thus far, there are a few Phase I/II clinical trials that have assessed the usefulness of pembrolizumab and nivolumab in this group of patients; these include the KEYNOTE 028, KEYNOTE 158, and CHECKMATE 358 trials, in which clinical benefit has been proven with PD-1/PD-L1 inhibitors in recurrent, persistent, or metastatic CC, as second-line treatment. There are also some ongoing trials that could provide further evidence on the PD-1/PD-L1 pathway as a therapeutic target in CC. In this review, we will focus on the usefulness of these PD-1/PDL1 inhibitors in CC, as well as on trials that are still in the recruitment phase, to confirm their effectiveness in this clinical setting.

Immunology of cervical cancer

ABSTRACT Optimal function of the immune system allows the recognition and elimination of infected and tumor cells. However, these cells can develop mechanisms to evade the cellular immune response. In human papillomavirus (HPV) infection, dysregulation of major histocompatibility complex Class I molecules and other components of the innate immune system promote the survival of infected cells by allowing the infection to persist which, in turn, favors the development of cancer. Further, tumor cells possess inherent mechanisms designed to block the recognition and activation of cytotoxic lymphocytes: particularly, HPV proteins such as E1 and E2 and oncoproteins E5, E6, and E7 that inhibit immune mechanisms and/or stimulate the expression of immunosuppressive cytokines. These mechanisms include a decrease in receptor activation and costimulating molecules on the surface of immune cells, as well as the constitutive expression of molecules that inhibit their function, which allow HPV persistence and tumor progression. Immunotherapy-based therapeutic options are positioned as excellent candidates for the treatment of cervical cancer.

Immunotherapy treatment against cervical cancer

ABSTRACT Cervical cancer (CC) is one of the most common gynecological tumors and an important health problem, especially in developing countries. The vast majority of patients in early stages are cured of the disease with surgical treatment and with concomitant chemoradiotherapy in locally advanced stages. However, in patients with recurrent, persistent, or metastatic cervical CC, the effectiveness of treatment is limited, except for the combination of chemotherapy based on platinum doublets plus bevacizumab, the treatment that has achieved the best results to date. Programmed cell death-1/PD ligand-1 (PD-1/PD-L1) inhibitors could be a novel and cutting-edge therapeutic option to improve clinical outcomes in this group of patients. Thus far, there are a few Phase I/II clinical trials that have assessed the usefulness of pembrolizumab and nivolumab in this group of patients; these include the KEYNOTE 028, KEYNOTE 158, and CHECKMATE 358 trials, in which clinical benefit has been proven with PD-1/PD-L1 inhibitors in recurrent, persistent, or metastatic CC, as second-line treatment. There are also some ongoing trials that could provide further evidence on the PD-1/PD-L1 pathway as a therapeutic target in CC. In this review, we will focus on the usefulness of these PD-1/PDL1 inhibitors in CC, as well as on trials that are still in the recruitment phase, to confirm their effectiveness in this clinical setting.

Habilidades informacionales: un requisito de alta demanda en la formación doctoral / Information skills: a crucial requirement in doctoral training

El imponente uso de las tecnologías de la información y la comunicación en el entorno investigativo trae consigo un constante crecimiento y divulgación de la información, lo que demanda la necesidad del dominio de las habilidades para el acceso y el uso adecuado de este recurso. El objetivo de este artículo fue identificar las habilidades informacionales que los doctorandos necesitan desarrollar, basándose en el uso de la información científica para la solución de las tareas de investigación en el proceso de formación doctoral. Para el desarrollo de este trabajo se realizó la revisión bibliográfica, el análisis de la información y del modelado, y se utilizó el software EndNote y Bizagi para el análisis y la discusión de los resultados. El trabajo de investigación se centró en las particularidades del sistema de Educación Superior en Cuba, específicamente en la educación doctoral de posgrado. Se examinaron las etapas de la formación doctoral, con mayor énfasis en las actividades relacionadas con el uso de la información científica. Finalmente se describen las habilidades informacionales que los doctorandos deben dominar para el uso de la información científica, teniendo en cuenta la proyección internacional de la comunidad científica que trabaja la alfabetización informacional(AU)

The impressive use of information and communications technologies in the field of research has resulted in permanent growth and dissemination of information, leading to the need to master the skills involved in the access and adequate use of this resource. The purpose of the study was to identify the information skills that aspiring PhDs need to develop in terms of the use of scientific information to solve research tasks throughout the process of doctoral training. The study was based on a bibliographic review as well as analysis and modeling of the information. EndNote and Bizagi software was used for the analysis and discussion of results. The research focused on the specific features of the Higher Education System in Cuba, particularly as concerns graduate doctoral education. Examination was performed of the doctoral training stages, with greater emphasis on activities related to the use of scientific information. A description is provided of the information skills that aspiring PhDs should master to use scientific information, bearing in mind the international projection of the scientific community involved in information literacy(AU)