Mutation profile in liquid biopsy tested by next generation sequencing in Mexican patients with non-small cell lung carcinoma and its impact on survival.

Background: Lung cancer represents a significant global health concern, often diagnosed in its advanced stages. The advent of massive DNA sequencing has revolutionized the landscape of cancer treatment by enabling the identification of target mutations and the development of tailored therapeutic approaches. Unfortunately, access to DNA sequencing technology remains limited in many developing countries. In this context, we emphasize the critical importance of integrating this advanced technology into healthcare systems in developing nations to improve treatment outcomes. Methods: We conducted an analysis of electronic clinical records of patients with confirmed advanced non-small cell lung cancer (NSCLC) and a verified negative status for the epidermal growth factor receptor (EGFR) mutation. These patients underwent next-generation sequencing (NGS) for molecular analysis. We performed descriptive statistical analyses for each variable and conducted both univariate and multivariate statistical analyses to assess their impact on progression-free survival (PFS) and overall survival (OS). Additionally, we classified genetic mutations as actionable or non-actionable based on the European Society for Medical Oncology Scale of Clinical Actionability of Molecular Targets (ESCAT) guidelines. Results: Our study included a total of 127 patients, revealing the presence of twenty-one distinct mutations. The most prevalent mutations were EGFR (18.9%) and Kirsten rat sarcoma viral oncogene homolog (KRAS) (15.7%). Notably, anaplastic lymphoma kinase (ALK) [hazard ratio (HR): 0.258, P<0.001], tumor mutation burden (TMB) (HR: 2.073, P=0.042) and brain magnetic resonance imaging (MRI) (HR: 0.470, P=0.032) demonstrated statistical significance in both the univariate and multivariate analyses with respect to PFS. In terms of OS, ALK (HR: 0.285, P<0.001) and EGFR (HR: 0.482, P=0.024) exhibited statistical significance in both analyses. Applying the ESCAT classification system, we identified actionable genomic variations (ESCAT level-1), including EGFR, ALK, breast cancer (BRAF) gene, c-ros oncogene 1 (ROS1), and rearranged during transfection (RET) gene, in 32.3% of the patients. Conclusions: Our findings from massive DNA sequencing underscore that 32.3% of patients who test negative for the EGFR mutation possess other targetable mutations, enabling them to receive personalized, targeted therapies at an earlier stage of their disease. Implementing massive DNA sequencing in developing countries is crucial to enhance survival rates among NSCLC patients and guide more effective treatment strategies.

Synergistic In Vitro Antiviral Effect of Combinations of Ivermectin, Essential Oils, and 18-(Phthalimid-2-yl)ferruginol against Arboviruses and Herpesvirus.

Combining antiviral drugs with different mechanisms of action can help prevent the development of resistance by attacking the infectious agent through multiple pathways. Additionally, by using faster and more economical screening methods, effective synergistic drug candidates can be rapidly identified, facilitating faster paths to clinical testing. In this work, a rapid method was standardized to identify possible synergisms from drug combinations. We analyzed the possible reduction in the antiviral effective concentration of drugs already approved by the FDA, such as ivermectin (IVM), ribavirin (RIBA), and acyclovir (ACV) against Zika virus (ZIKV), Chikungunya virus (CHIKV), and herpes virus type 2 (HHV-2). Essential oils (EOs) were also included in the study since they have been reported for more than a couple of decades to have broad-spectrum antiviral activity. We also continued studying the antiviral properties of one of our patented molecules with broad-spectrum antiviral activity, the ferruginol analog 18-(phthalimid-2-yl)ferruginol (phthFGL), which presented an IC99 of 25.6 µM for the three types of virus. In general, the combination of IVM, phthFGL, and oregano EO showed the greatest synergism potential against CHIKV, ZIKV, and HHV-2. For instance, this combination achieved reductions in the IC99 value of each component up to ~8-, ~27-, and ~12-fold for CHIKV, respectively. The ternary combination of RIBA, phthFGL, and oregano EO was slightly more efficient than the binary combination RIBA/phthFGL but much less efficient than IVM, phthFGL, and oregano EO, which indicates that IVM could contribute more to the differentiation of cell targets (for example via the inhibition of the host heterodimeric importin IMP α/ß1 complex) than ribavirin. Statistical analysis showed significant differences among the combination groups tested, especially in the HHV-2 and CHIKV models, with p = 0.0098. Additionally, phthFGL showed a good pharmacokinetic profile that should encourage future optimization studies.

Fatty Acids Profile and Healthy Lipids Indices of Native Mexican Guajolote Meat Treated to Two Heat Treatments.

Meat is a complex food with a structured nutritional composition that makes it an essential component of the human diet. In particular, the meat of native guajolote that is traditionally raised in natural conditions is an important dietary source of proteins of high biological value for the rural population of Mexico. The study aimed to evaluate fatty acids (FAs) profile and nutritional indices of breast and leg meat of native guajolote subjected to two heat treatments. For the study, a total of sixty muscle samples (30 breast meat and 30 leg meat) from adult male native guajolotes were used. The FA profile and nutritional indices were evaluated in raw meat (control) and meat subjected to two heat treatments (boiled and baked). The heat treatments, independently of the type of muscle, increased (p ≤ 0.05) the concentration of saturated (SFA) and monounsaturated FA (MUFA); in contrast, polyunsaturated FA (PUFA) decreased. Likewise, the dietary FA index, which has a negative hypercholesterolemic effect, and the atherogenic index increased in guajolote meat from the effect of the heat treatments, while the essential and undesirable hypercholesterolemic FA indices decreased. In conclusion, heat treatments increase the content of SFA and MUFAs in breast and leg meat of native guajolote. Boiling or baking the meat deteriorates PUFAs but increases the nutritional indices. The present investigation would provide valuable information for the guajolote meat product processing.

Screening with Anal Cytology in Colombia: Initial Experience and Need for High-Resolution Anoscopy.

BACKGROUND: Men who have sex with men (MSM) living with human immunodeficiency virus (HIV) are at increased risk of anal cancer. Anal cytology can be used to screen for dysplasia, with high-resolution anoscopy (HRA) required for diagnostic confirmation. We describe the impact lack of HRA had on management of abnormal screening results in Bogotá, Colombia. MATERIAL AND METHODS: This retrospective cohort study includes MSM with HIV who underwent anal cytology screening between January 2019February 2020, with colorectal surgery (CRS) follow-up through July 2020. Cytology results included atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion (HSIL). Categorical and continuous variables were compared via Fisher's exact test and Wilcoxon rank-sum, respectively. RESULTS: Of 211 MSM screened, 68 had abnormal cytology: ASC-US (n = 23), LSIL (n = 41), HSIL (n = 4). Sixty (88.2%) were referred to CRS, and 51 (75.0%) attended ≥ 1 appointment. At initial assessment, 17 were referred for anal exam under anesthesia (EUA) for tissue resection, and 21 for rectosigmoidoscopy. Having perianal condyloma was associated with recommendation for EUA (P < 0.001), while cytology grade of dysplasia was not (P = 0.308). Eleven (16.2%) underwent EUA for condyloma resection. CONCLUSIONS: Few studies have described anal cancer screening in settings without HRA. We found lack of HRA limited management of abnormal cytology in Colombia. Those with condyloma underwent resection, but HRA remains necessary to localize and treat microscopic disease. Next steps include implementation of HRA in order to further develop the anal cancer screening program for MSM with HIV in Bogotá.

Inclusión de compuestos químicos en matrices poliméricas de quitosano y su efecto en las propiedades de película / Chemical compounds inclusion in chitosan polymeric matrices and their effect on film properties

Antecedentes: El quitosano es un polisacárido biodegradable producido a partir de la pesca de quitina derivada de residuos industriales. Hoy en día, los esfuerzos de investigación se centran en la producción de películas de quitosán utilizadas en gran cantidad para aplicaciones industriales con el fin de proporcionar soluciones tecnológicas a los requisitos industriales actuales. Se pueden incluir diferentes compuestos químicos en las matrices de polímeros para la modificación de las propiedades antimicrobianas, físicas y químicas de las películas de quitosán. Los compuestos químicos más comunes incluidos son disolventes, plastificantes, antioxidantes y emulsionantes, así como otras sustancias como carbohidratos, proteínas, lípidos, polímeros, minerales y antibióticos. Objetivos: El propósito de este trabajo es presentar nuevos desarrollos para la inclusión de compuestos químicos en matrices poliméricas de quitosano. Métodos: Esta revisión analiza el trabajo científico sobre el quitosano publicado en los últimos 10 años. Inicialmente, se identificaron y seleccionaron los estudios más representativos relacionados con la inclusión de compuestos químicos en matrices poliméricas de quitosán. Posteriormente, esta información se compiló, organizó y resumió para proporcionar un escrito claro y conciso sobre los desarrollos y los principales hallazgos en el campo. Resultados: Se obtiene un enfoque general de los principales aspectos para el estudio. Esta investigación presenta una descripción general de los aspectos involucrados en la inclusión de compuestos químicos y las interacciones entre la matriz polimérica de quitosán y los químicos incluidos, de acuerdo con su función y composición. Conclusiones: La inclusión de químicos modifica lo físico, Las propiedades químicas y antimicrobianas de las películas de quitosán debido a las interacciones moleculares entre estos compuestos y la matriz polimérica, los cambios estructurales y la modificación de las propiedades físicas, químicas y antimicrobianas de las películas, así como otros factores involucrados. Por esta razón, los desafíos actuales se basan en métodos innovadores para proponer la inclusión de compuestos químicos que mejoren las propiedades de las películas de quitosán.

Preventing mother-to-child HIV transmission in a developing country: the Dominican Republic experience.

Transmission of HIV in the Dominican Republic occurs primarily through heterosexual contact. As part of a continuing strategy to prevent and contain the spread of HIV infection, the Ministry of Health of the Dominican Republic established an integrated package of interventions to reduce HIV mother-to-child transmission that was initiated on May 15, 2000. The program was designed to be implemented in 3 phases. The 1st phase included 4 mother and child hospitals; the 2nd phase included 8 mother and child health institutions in Santo Domingo, the capital of the Dominican Republic, and 7 additional mother and child hospitals. The 3rd phase will include the remaining 12 mother and child health care institutions of the Dominican Republic. Evaluation of the 1st year of this program, involving 8 hospitals and >40000 pregnant women, identified specific benefits and limitations. Low numbers of voluntary counseling sessions (6528/42666 = 28%) and inadequate number of HIV rapid tests (23067/42666 = 54%) were the 2 main obstacles encountered. From the 23067 pregnant women tested, 581 (2.5%) were HIV positive. Advantageous aspects included the successful administration of antiretroviral treatment to 89% (164/185) of the mothers and 98% (183/186) of the children. Cesarean section was performed in 67% (124/185) of the HIV-positive pregnant women, and infant formula was dispensed to 47% (87/186) of all cases. These findings demonstrate the feasibility of implementing a large-scale program to prevent mother-to-child transmission in a developing country.