Safety and oncological effectiveness after desensitization in patients with previous hypersensitivity reactions to chemotherapy.

INTRODUCTION: Taxanes and platinum are first-line treatments in gynecological tumors with high rates of hypersensitivity reactions (HSRs), leading to discontinuation of treatment. Desensitization involves induction of temporary tolerance to previously sensitized medications. The aims of this study are to describe HSRs to paclitaxel and carboplatin and evaluate the safety and effectiveness of desensitization protocols in gynecological cancer patients. METHODS: Original, retrospective, descriptive, analytical study, approved by Bioethics and Research Committee, included >18-year-old patients with gynecological tumors experiencing HSRs to first-line chemotherapy. Patients underwent 3-bag-12-step desensitization. RESULTS: 174 desensitization (95 paclitaxel, 79 carboplatin) in 33 female patients, mean age 45.5 years (18-71y). Cancer diagnosis: breast 8 (24.2%), ovarian 14 (42.2%), endometrial 2 (6.1%) and cervix 9 (27.2%). HSR occurred in paclitaxel during cycles 1-2 and in carboplatin after 6 cycles. The most frequently seen HSR symptom was cardiovascular with paclitaxel (94.7%), and cutaneous (93.3%) with carboplatin. Three-bags 12-steps desensitization protocol (initial dilution 1:100) in 5.67hrs. All patients reached total dose desensitization: 82% with no reaction, 12% mild, 6% moderate and 0% severe reaction. Mean disease-free interval and progression-free interval in months (m): breast cancer 29 m and 14 m, ovarian 22 m and 9 m, endometrial 40 m and cervical cancer: 67.5 m and 27 m. Twenty-five patients (73.5%) are still alive. CONCLUSION: HSRs to paclitaxel manifest in the first 1-2 cycles and to carboplatin after 6 cycles. Symptoms include cardiovascular, atypical neuromuscular and urticaria. Changing treatment lines impacts prognosis. Our study revealed that ovarian cancer patients undergoing desensitization protocols achieved longer progression-free intervals. All patients successfully reached total dose desensitization. This study provides evidence of the effectiveness and safety of desensitization and promising perspective for continuing first-line treatment with HSRs.

Mutation-induced LZTR1 polymerization provokes cardiac pathology in recessive Noonan syndrome.

Noonan syndrome patients harboring causative variants in LZTR1 are particularly at risk to develop severe and early-onset hypertrophic cardiomyopathy. In this study, we investigate the mechanistic consequences of a homozygous variant LZTR1L580P by using patient-specific and CRISPR-Cas9-corrected induced pluripotent stem cell (iPSC) cardiomyocytes. Molecular, cellular, and functional phenotyping in combination with in silico prediction identify an LZTR1L580P-specific disease mechanism provoking cardiac hypertrophy. The variant is predicted to alter the binding affinity of the dimerization domains facilitating the formation of linear LZTR1 polymers. LZTR1 complex dysfunction results in the accumulation of RAS GTPases, thereby provoking global pathological changes of the proteomic landscape ultimately leading to cellular hypertrophy. Furthermore, our data show that cardiomyocyte-specific MRAS degradation is mediated by LZTR1 via non-proteasomal pathways, whereas RIT1 degradation is mediated by both LZTR1-dependent and LZTR1-independent pathways. Uni- or biallelic genetic correction of the LZTR1L580P missense variant rescues the molecular and cellular disease phenotype, providing proof of concept for CRISPR-based therapies.

Enhancing stress measurements accuracy control in the construction of long-span bridges.

This paper introduces new contributions for construction procedures designed to enhance the robustness and precision of stress control in active anchorage and short presetressing units for long-span bridges, particularly addressing potential technical risks. The primary focus is on optimizing stress management for bridge stays, suspension cables, and short prestressing units by emphasizing a unified parameter: stress. The contributions of this research encompass (1) the introduction of advanced load cells for stress control in active anchorages and (2) the implementation of a novel synchronized multi-strain gage load cell network for short prestressing units, crucial in situations where prestressing losses can attain significant magnitudes. To validate these advancements, the authors present (3) a practical experience and results obtained from applying these methodologies in monitoring the structural response during the construction of the Tajo Bridge using the cable-stayed cantilever technique.

Numb positively regulates Hedgehog signaling at the ciliary pocket.

Hedgehog (Hh) signaling relies on the primary cilium, a cell surface organelle that serves as a signaling hub for the cell. Using proximity labeling and quantitative proteomics, we identify Numb as a ciliary protein that positively regulates Hh signaling. Numb localizes to the ciliary pocket and acts as an endocytic adaptor to incorporate Ptch1 into clathrin-coated vesicles, thereby promoting Ptch1 exit from the cilium, a key step in Hh signaling activation. Numb loss impedes Sonic hedgehog (Shh)-induced Ptch1 exit from the cilium, resulting in reduced Hh signaling. Numb loss in spinal neural progenitors reduces Shh-induced differentiation into cell fates reliant on high Hh activity. Genetic ablation of Numb in the developing cerebellum impairs the proliferation of granule cell precursors, a Hh-dependent process, resulting in reduced cerebellar size. This study highlights Numb as a regulator of ciliary Ptch1 levels during Hh signal activation and demonstrates the key role of ciliary pocket-mediated endocytosis in cell signaling.

A detailed study of resampling algorithms for cyberattack classification in engineering applications.

The evolution of engineering applications is highly relevant in the context of protecting industrial systems. As industries are increasingly interconnected, the need for robust cybersecurity measures becomes paramount. Engineering informatics not only provides tools for knowledge representation and extraction but also affords a comprehensive spectrum of developing sophisticated cybersecurity solutions. However, safeguarding industrial systems poses a unique challenge due to the inherent heterogeneity of data within these environments. Together with this problem, it's crucial to acknowledge that datasets that simulate real cyberattacks within these diverse environments exhibit a high imbalance, often skewed towards certain types of traffics. This study proposes a system for addressing class imbalance in cybersecurity. To do this, three oversampling (SMOTE, Borderline1-SMOTE, and ADASYN) and five undersampling (random undersampling, cluster centroids, NearMiss, repeated edited nearest neighbor, and Tomek Links) methods are tested. Particularly, these balancing algorithms are used to generate one-vs-rest binary models and to develop a two-stage classification system. By doing so, this study aims to enhance the efficacy of cybersecurity measures ensuring a more comprehensive understanding and defense against the diverse range of threats encountered in industrial environments. Experimental results demonstrates the effectiveness of proposed system for cyberattack detection and classification among nine widely known cyberattacks.

Hypersensitivity reaction to Abiraterone, successful desensitization protocol in prostate cancer patient.

INTRODUCTION: In prostate cancer, androgens are key in the growth of both normal prostate and cancer cells. Abiraterone acetate inhibits CYP17, an important target in prostate cancer given its central role in the production of adrenal and tumor-derived androgens. Although abiraterone is generally well tolerated, common adverse effects such as hypertension, hypokalemia, and hepatotoxicity have been reported. CLINICAL CASE: We present the case of an 83-year-old Mexican man with high-volume EC IV prostate cancer resistant to castration, orchiectomy, and bone, liver, and lung metastases. First-line treatment with the CHAARTED scheme was indicated, by patient decision refuse chemotherapy treatment. On the fourth day of starting treatment, he developed pruritic erythematous macular skin lesions and urticaria on the posterior chest that resolved spontaneously. A generalized erythematous and pruritic maculopapular rash appeared 12 days after starting abiraterone, for which she was referred to allergies. MANAGEMENT AND RESULTS: An oral provocation test was performed for two days, presenting localized macular lesions eight hours after the administration of abiraterone. An oral desensitization protocol was carried out for ten days in which no hypersensitivity reactions were observed, thus achieving the successful administration of abiraterone.

Efecto hepatoprotector del consumo de Nostoc commune (cushuro) frente al daño inducido por dietas ricas en sacarosa en ratones / Hepatoprotective effect of Nostoc commune (cushuro) consumption against damage induced by sucrose-rich diets in mice

Objetivo: Evaluar el efecto hepatoprotector del consumo de Nostoc commune (cushuro) frente al daño inducido por dietas ricas en sacarosa en ratones. Métodos: El estudio tuvo un enfoque cuantitativo, experimental puro con grupo control y post prueba. Se utilizaron 28 ratones macho con un peso promedio de 30 ± 6,2 g y pulverizado de Nostoc commune. Los animales se dividieron en cuatro grupos y recibieron las siguientes dietas durante 50 días: Grupo I: dieta A (sacarosa 10%), grupo II: dieta B (sacarosa 36,5%), grupo III: dieta C (sacarosa 36,5% + cushuro 1%) y grupo IV: dieta D (sacarosa 36,5% + cushuro 3%). Finalmente se extrajo el hígado y se realizó los análisis bioquímicos e histológicos. El estadístico ANOVA se aplicó para los datos simétricos y para los asimétricos, Kruskall-Wallis. Resultados: En los grupos III y IV se observó que los niveles de triglicéridos (p<0.05) disminuyeron y también se observó una mejor conservación a nivel histológico. Conclusión: El consumo de Nostoc commune (cushuro) presenta efecto hepatoprotector expresado en la disminución de triglicéridos y la conservación a nivel histológico frente al daño inducido por dietas ricas en sacarosa en ratones.(AU)

Objective: To evaluate the hepatoprotective effect of theconsumption of Nostoc commune (cushuro) against the da-mage induced by diets rich in sucrose in mice. Methods: The study had a quantitative, pure experimen-tal approach with control group and post test. Twenty-eightmale mice with an average weight of 30 ± 6.2 g and sprayedwith Nostoc commune were used. The animals were dividedinto four groups and received the following diets for 50 days: Group I: diet A (sucrose 10%), group II: diet B (sucrose36.5%), group III: diet C (sucrose 36.5 % + cushuro 1%)and group IV: diet D (sucrose 36.5% + cushuro 3%). Finally,the liver was extracted and biochemical and histologicalanalyzes were performed. The ANOVA statistic was appliedfor symmetric data and Kruskall-Wallis for asymmetric data. Results: In groups III and IV it was observed that thetriglyceride levels (p<0.05) decreased and a better conserva-tion at the histological level was also observed. Conclusion: The consumption of Nostoc commune (cus-huro) has a hepatoprotective effect expressed in the reduction of triglycerides and conservation at the histological levelagainst the damage induced by diets rich in sucrose in mice.(AU)

Efecto del zumo del fruto Solanum quitoense (lulo) sobre el daño cerebral y cognitivo inducido por cloruro de mercurio en ratones / Effect of Solanum quitoense (lulo) fruit juice on brain and cognitive damageinduced by mercury chloride in mice

Introducción: Las enfermedades neurodegenerativas han ido en aumento durante las últimas décadas, siendo la demencia la principal patología con mayor repercusión a nivel global. Objetivo: Evaluar el efecto neuroprotector del zumo del fruto Solanum quitoense (lulo) frente a la toxicidad del cloruro de mercurio (II) en los ratones. Materiales y métodos: Diseño experimental, con grupo control y posprueba. Se empleó 42 ratones machos. Para inducir a la toxicidad se empleó una solución de HgCl2 (10 mg/kg), vía orogástrica, por un periodo de siete días. Durante ese periodo recibieron los siguientes tratamientos: grupos I y II suero fisiológico; grupos III vitamina E (40UI/kg); grupo IV-V-VI zumo de lulo, 0,5; 2,0 y 8,0 mL/kg, respectivamente. Terminado el tratamiento los animales fueron sacrificados por decapitación, el cerebro y cerebelo fueron extraído de la cavidad craneana. El hemisferio izquierdo fue homogenizado para la determinación de la lipoperoxidación, glutatión (reducido y total), actividad de superóxido dismutasa y catalasa. El hemisferio derecho y cerebelo fueron conservados, para la evaluación histológica. Se evaluó la función cognitiva (aprendizaje y memoria), según protocolo de Deacon y Rawlis. Resultados: La administración del zumo de lulo disminuyeron los índices de cerebro en los grupos V-VI. La lipoperoxidación disminuyó (grupos IV-VI), la relación GSH/GSSG aumentaron (grupos V-VI). La actividad de la catalasa aumentó (grupos IV-VI). La relación SOD/CAT disminuyeron (grupos IV-VI). El tiempo de latencia y número de intentos fueron menores en los grupos IV-VI. Conclusiones: La administración del zumo del fruto Solanum quitoense presenta efecto neuroprotector para el modelo estudiado. Palabras clave: Neuroprotección, Solanum quitoense, cloruro de mercurio, función cognitiva, alimento funcional (Fuente: DeCS BIREME).(AU)

Introduction: Neurodegenerative diseases have beenincreasing in recent decades, with dementia being the mainpathology with the greatest impact globally. Objective: To evaluate the neuroprotective effect ofSolanum quitoense (lulo) fruit juice against the toxicity ofmercury (II) chloride in mice. Materials and methods: Experimental design, withcontrol group and post-test. 42 male mice were used. Toinduce toxicity, a solution of HgCl2 (10 mg/kg) was used viathe orogastric route for a period of seven days. During thisperiod, they received the following treatments: groups I and II physiological saline; groups III vitamin E (40IU/kg); groupIV-V-VI lulo juice, 0.5; 2.0 and 8.0 mL/kg, respectively. Oncethe treatment was completed, the animals were sacrificed bydecapitation, the brain and cerebellum were removed fromthe cranial cavity. The left hemisphere was homogenized forthe determination of lipoperoxidation, glutathione (reducedand total), superoxide dismutase and catalase activity. Theright hemisphere and cerebellum were preserved forhistological evaluation. Cognitive function (learning andmemory) was evaluated according to the Deacon and Rawlisprotocol. Results: The administration of lulo juice decreased brainindices in groups V-VI. Lipoperoxidation decreased (groupsIV-VI), the GSH/GSSG ratio increased (groups V-VI). Catalaseactivity increased (groups IV-VI). The SOD/CAT ratiodecreased (groups IV-VI). The latency time and number ofattempts were lower in groups IV-VI. Conclusions: The administration of Solanum quitoensefruit juice has a neuroprotective effect for the model studied.(AU)

Influence of body mass index on health complains and life satisfaction.

PURPOSE: This research work investigates the influence of children's weight status on well-being and school context in a sample of Spanish adolescences. METHODS: The Spanish records from the 2013-14 Health Behaviour in School-Aged Children Survey are used, which gathers 9,565 adolescences aged 11, 13 and 15. Studies do not usually address the endogeneity of body mass index when analysing their effect on life satisfaction and health complaints, thus resulting in biased estimates. Considering the endogeneity of body mass index, we use the frequency of alcohol consumption as an instrumental variable in order to obtain consistent estimates of its influence. RESULTS: The two-stage least squares estimation shows that children's body mass index has a significant negative influence on health complaints and it conditions the way children relate to each other at school. Likewise, results report significant influence on children's subjective well-being and their self-assessment of general health. CONCLUSIONS: The results of this study provide compelling evidence that BMI plays a crucial role in shaping adolescents' well-being and their interactions with peers at school. These findings underscore the importance of addressing childhood overweight and promoting healthy body mass index levels. Furthermore, the study highlights the need for targeted policy interventions to combat the social stigma associated with being overweight, fostering a more inclusive and supportive school environment for all students.

Effect of Coturnix japonica (quail) egg yolk in ethanol damage-induced mice

Introduction: The high prevalence of neurodegenerativediseases in the older adult population requires research fo-cused on functional foods with regulatory properties on redoxstate and with antioxidant potential. Quail egg yolk is a foodwith a great diversity of antioxidant compounds with neuro-protective activity. Objective: To evaluate the effect of Coturnix japonica eggyolk administration on the nervous tissue of mice againstethanol damage induction. Methodology: 35 mice received the following treatmentvia orogastric for five days: groups I and II water (10 mL/kg),group III egg yolk (5 mL/kg), group IV egg yolk (10 mL/kg)and group V egg yolk (15 mL/kg). On the fifth day, 99%ethanol was administered subcutaneously (5 g/kg) to groupsII-V. After four hours, the mice were decapitated to obtain thebrain and cerebellum and subsequently perform biochemicaltests and histopathological analysis. Results: Group IV presented neuronal proliferation phe-nomenon and Purkinje cells pluristratification in the brain andcerebellum respectively and additionally presented a betterGSH/GSSG ratio (p<0.05) in comparison to group II. Therewas no statistically significant difference between proteinlevels or protein sulfhydryl groups in any of the groups. Conclusions:Coturnix japonica egg yolk administrationresulted in better preservation of the brain and cerebellum’scytoarchitecture and increased GSH profile (AU)

The Future of Patient Education: AI-Driven Guide for Type 2 Diabetes.

Introduction and aim The surging incidence of type 2 diabetes has become a growing concern for the healthcare sector. This chronic ailment, characterized by its complex blend of genetic and lifestyle determinants, has witnessed a notable increase in recent times, exerting substantial pressure on healthcare resources. As more individuals turn to online platforms for health guidance and embrace the utilization of Chat Generative Pre-trained Transformer (ChatGPT; San Francisco, CA: OpenAI), a text-generating AI (TGAI), to get insights into their well-being, evaluating its effectiveness and reliability becomes crucial. This research primarily aimed to evaluate the correctness of TGAI responses to type 2 diabetes (T2DM) inquiries via ChatGPT. Furthermore, this study aimed to examine the consistency of TGAI in addressing common queries on T2DM complications for patient education. Material and methods Questions on T2DM were formulated by experienced physicians and screened by research personnel before querying ChatGPT. Each question was posed thrice, and the collected answers were summarized. Responses were then sorted into three distinct categories as follows: (a) appropriate, (b) inappropriate, and (c) unreliable by two seasoned physicians. In instances of differing opinions, a third physician was consulted to achieve consensus. Results From the initial set of 110 T2DM questions, 40 were dismissed by experts for relevance, resulting in a final count of 70. An overwhelming 98.5% of the AI's answers were judged as appropriate, thus underscoring its reliability over traditional online search engines. Nonetheless, a 1.5% rate of inappropriate responses underlines the importance of ongoing AI improvements and strict adherence to medical protocols. Conclusion TGAI provides medical information of high quality and reliability. This study underscores TGAI's impressive effectiveness in delivering reliable information about T2DM, with 98.5% of responses aligning with the standard of care. These results hold promise for integrating AI platforms as supplementary tools to enhance patient education and outcomes.

In vitro antioxidant capacity of Corryocactus brevistylus (sanky) and its effect on the pancreas morphology of alloxan-induced diabetic rats. / Capacidad antioxidante in vitro del Corryocactus brevistylus (sanky) y su efecto en la morfología del páncreas de ratas diabéticas inducidas con aloxano.

OBJECTIVE.: To determine the in vitro antioxidant capacity of Corryocactus brevistylus and its effect on glycemia and the pancreas of alloxan-induced diabetic rats. MATERIALS AND METHODS.: The antioxidant capacity of the hydroethanolic extract of sanky (HEES) was evaluated by assessing its ability to reduce 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric ion (FRAP). We used thirty adult rats, which were induced to diabetes with two doses of alloxan (80mg/kg). Rats were distributed into 5 groups (n=6), all groups received treatment by orogastric route for eight days. Group I received water, group II received metformin 14mg/kg and groups III, IV and V received sanky juice at 1.0; 4.0 and 16 mL/kg, respectively. Glycemia was evaluated by the rapid method (glucometer) (first and eighth day). After treatment, the animals were sacrificed and the pancreas was removed for histopathological study. RESULTS.: The antioxidant capacity of HEES by DPPH showed an IC50 of 0.77 mg/mL; the FRAP method showed a TEAC-FRAP of 22.31µg/mg. Glycemia decreased on the eighth day of treatment, with respect to the first day; a decrease in glycemia was also found in groups III-V, when compared to group I. Histologically, groups I-II presented severe atrophy and moderate necrosis of the islets of Langerhans; groups IV-V presented hypertrophy and mild multifocal necrosis at the islet level. CONCLUSIONS.: The extract of sanky showed antioxidant capacity in vitro and the juice exerts a hypoglycemic and protective effect on the pancreas.

OBJETIVO.: Determinar la capacidad antioxidante in vitro del Corryocactus brevistylus y su efecto sobre la glicemia y páncreas de ratas diabéticas inducidas con aloxano. MATERIALES Y MÉTODOS.: Se evaluó la capacidad antioxidante del extracto hidroetanólico de sanky (EHES) mediante la capacidad de reducir el 2,2-difenil-1-picrilhidracilo (DPPH) y la capacidad de reducir el ion férrico (FRAP). Se utilizaron 30 ratas adultas inducidas a diabetes con dos dosis de aloxano (80mg/kg), formándose cinco grupos (n=6), recibiendo los tratamientos vía orogástrica durante ocho días, el grupo I (agua), II (metformina 14mg/kg), grupos III-IV-V zumo de sanky a 1,0; 4,0 y 16 mL/kg, respectivamente. La glicemia fue evaluada por el método rápido (glucómetro) (primer y octavo día). Terminado el tratamiento los animales fueron sacrificados y se les extrajo el páncreas, para su estudio histopatológico. RESULTADOS.: La capacidad antioxidante del EHES mediante el DPPH, mostró un IC50 de 0,77 mg/mL, y por el método FRAP se observó el TEAC-FRAP de 22,31µg/mg. La glicemia disminuyó en el octavo día de tratamiento, respecto al primer día; también se observó disminución de la glicemia en los grupos III-V, respecto al grupo I. A nivel histológico los grupos I-II presentaron atrofia severa y necrosis moderada de los islotes de Langerhans; los grupos IV-V presentaron hipertrofia y necrosis leve multifocal a nivel del islote. CONCLUSIONES.: El extracto de sanky presenta capacidad antioxidante in vitro y el zumo ejerce un efecto hipoglicemiante y protector en páncreas.

Interleukin-6 as a biomarker of hypersensitivity reactions in chemotherapeutics and monoclonal antibodies.

BACKGROUND: In recent years, a new type of immediate hypersensitivity reaction known as cytokine release began to emerge, and within this phenotype of reactions, interleukin-6 is the most frequently associated with the presence during drug administration. Chemotherapeutic agents (QT) and monoclonal antibodies. OBJECTIVE: Determine interleukin-6 levels in hypersensitivity reactions to QT and monoclonal antibodies. METHODS: Observational and prospective study that was carried out from March 1, 2021 to March 1, 2022 in a university hospital in northeastern Mexico. Symptoms, severity, interleukin-6 levels, and skin tests of hypersensitivity reaction were evaluated at QT and monoclonal antibodies. RESULTS: A total of 41 patients with oncological disease were included, the most frequent being ovarian cancer. Symptoms as initial hypersensitivity reaction were neuromuscular in taxanes and cutaneous in Platinums.41.5% presented elevation of interleukin-6, and it was found more frequently in presence of metastases. Positive skin tests were found more frequently in the carboplatin and doxorubicin groups. The most frequently presented phenotype was type I in paclitaxel, carboplatin, and doxorubicin, and mixed-reaction (type I and cytokine release) in oxaliplatin. CONCLUSION: With the increasing prevalence of hypersensitivity reactions to biologic and antineoplastic therapies, interleukin-6 should be recognized as a biomarker in immediate hypersensitivity reactions to QT and monoclonal antibodies.

The association of internet searches and actual suicide in Spain.

High suicide rates are a major issue in Spain, to the extent that they are the main non-natural cause of death in this country. The present study analyses the relationship between Internet searches and actual suicide rates in Spain. For this purpose, we employ data from actual suicide rates and Google® searches for Spain, differencing by the means used to commit suicide. Our results show that suicide ("suicidio") search term seems to be positively associated with higher total suicide rates, in addition to suicides using poison, suffocation and jumping. The suicide ("suicidio") topic presents similar results to the suicide search term, and suicide by car crash also seems to be associated with Internet searches of this topic.

Design and Characterization of pMyc/pMax Peptide-Coupled Gold Nanosystems for Targeting Myc in Prostate Cancer Cell Lines.

Myc and Max are essential proteins in the development of prostate cancer. They act by dimerizing and binding to E-box sequences. Disrupting the Myc:Max heterodimer interaction or its binding to E-box sequences to interrupt gene transcription represent promising strategies for treating cancer. We designed novel pMyc and pMax peptides from reference sequences, and we evaluated their ability to bind specifically to E-box sequences using an electrophoretic mobility shift assay (EMSA). Then, we assembled nanosystems (NSs) by coupling pMyc and pMax peptides to AuNPs, and determined peptide conjugation using UV-Vis spectroscopy. After that, we characterized the NS to obtain the nanoparticle's size, hydrodynamic diameter, and zeta potential. Finally, we evaluated hemocompatibility and cytotoxic effects in three different prostate adenocarcinoma cell lines (LNCaP, PC-3, and DU145) and a non-cancerous cell line (Vero CCL-81). EMSA results suggests peptide-nucleic acid interactions between the pMyc:pMax dimer and the E-box. The hemolysis test showed little hemolytic activity for the NS at the concentrations (5, 0.5, and 0.05 ng/µL) we evaluated. Cell viability assays showed NS cytotoxicity. Overall, results suggest that the NS with pMyc and pMax peptides might be suitable for further research regarding Myc-driven prostate adenocarcinomas.

Hypersensitivity Reactions to Taxanes: A Comprehensive and Systematic Review of the Efficacy and Safety of Desensitization.

Taxanes in the treatment of cancer are associated with a significant incidence of hypersensitivity reactions, which may preclude their use in patients in need of first line therapy. Drug desensitization induces transient immunological tolerance and has allowed the reintroduction of taxanes in highly allergic patients. Increase the knowledge of hypersensitivity reactions (HSR) during the administration of taxanes. A systematic review regarding the safety and efficacy of rapid drug desensitization (RDD) for taxanes HSR. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, was registered in PROSPERO(CRD42021242324) and a comprehensive search was conducted in Medline, Embase, Web of Science and Scopus databases. 25 studies encompassing 10 countries were identified and 976 patients with initial HSR to paclitaxel (n = 707) and docetaxel (n = 284), that underwent a total of 2,396 desensitizations. The most common symptoms were cutaneous (74.6%) with paclitaxel and respiratory (72.6%) with docetaxel. Severe initial hypersensitivity reactions including anaphylaxis occurred in 39.6% and 13% of paclitaxel and docetaxel cases respectively and during the first (87.4%) or second exposure (81.5%). Patients tolerated well RDD and breakthrough reactions (BTR) occurred in 32.2% of paclitaxel-treated patients and in 20.6% of docetaxel treated patients. Premedications included corticosteroids, antihistamines and leukotriene receptor antagonists. The most commonly used protocol was the BWH 3 bags 12 steps, all protocols showed a success rate between 95-100%, with no reported deaths. RDD is a safe and effective procedure in patients with HSR to taxanes and protocols should be standardized for wide range implementation.

Hypersensitivity reactions to anticancer chemotherapy and monoclonal antibodies: Safety and efficacy of desensitization.

BACKGROUND: Hypersensitivity reactions to anticancer chemotherapy and monoclonal antibodies may lead to discontinuation of first-line treatment options. Identification of these reactions can provide specific diagnosis and treatment by rapid drug desensitizations. OBJECTIVE: To determine the hypersensitivity reactions involved in anticancer chemotherapy and monoclonal antibodies, and the safety and efficacy of rapid drug desensitization. METHODS: We conducted an observational study of hypersensitivity reaction presented after the administration of anticancer chemotherapy and monoclonal antibodies in Mexico. We documented the symptoms of initial reaction and their severity, and the results of skin tests. We also report our experience of the administration of 12-step (mild-moderate reactions) and 16-step (severe reactions) desensitization protocols in these patients. RESULTS: Overall, 93 patients received 336 rapid drug desensitization; 105 to taxanes, 115 to platinum drugs, 101 to monoclonal antibodies, and 15 other anticancer chemotherapy. Hypersensitivity reaction to taxanes occurred in the first or second administration, platinum drugs after the sixth cycle, and rituximab in the first cycle. The most common symptom in carboplatin was urticaria, paclitaxel back pain, oxaliplatin and docetaxel dyspnea, and in the monoclonal antibodies cardiovascular symptoms. Skin tests were positive in 75% of the carboplatin group, and only 16.7% in docetaxel. There was a rapid drug desensitization success rate of 99.4% and 85.7% did not present any related hypersensitivity reaction. CONCLUSION: The diagnosis of hypersensitivity reaction to anticancer chemotherapy and monoclonal antibodies offers a panorama in the management of oncological diseases. Our standardized desensitization protocol is safe and effective and can be reproduced in other centers to treat patients who need to maintain first-line treatment.

Capacidad antioxidante in vitro del Corryocactus brevistylus (sanky) y su efecto en la morfología del páncreas de ratas diabéticas inducidas con aloxano / In vitro antioxidant capacity of Corryocactus brevistylus (sanky) and its effect on the pancreas morphology of alloxan-induced diabetic rats

Objetivo. Determinar la capacidad antioxidante in vitro del Corryocactus brevistylus y su efecto sobre la glicemia y páncreas de ratas diabéticas inducidas con aloxano. Materiales y métodos. Se evaluó la capacidad antioxidante del extracto hidroetanólico de sanky (EHES) mediante la capacidad de reducir el 2,2-difenil-1-picrilhidracilo (DPPH) y la capacidad de reducir el ion férrico (FRAP). Se utilizaron 30 ratas adultas inducidas a diabetes con dos dosis de aloxano (80mg/kg), formándose cinco grupos (n=6), recibiendo los tratamientos vía orogástrica durante ocho días, el grupo I (agua), II (metformina 14mg/kg), grupos III-IV-V zumo de sanky a 1,0; 4,0 y 16 mL/kg, respectivamente. La glicemia fue evaluada por el método rápido (glucómetro) (primer y octavo día). Terminado el tratamiento los animales fueron sacrificados y se les extrajo el páncreas, para su estudio histopatológico. Resultados. La capacidad antioxidante del EHES mediante el DPPH, mostró un IC50 de 0,77 mg/mL, y por el método FRAP se observó el TEAC-FRAP de 22,31µg/mg. La glicemia disminuyó en el octavo día de tratamiento, respecto al primer día; también se observó disminución de la glicemia en los grupos III-V, respecto al grupo I. A nivel histológico los grupos I-II presentaron atrofia severa y necrosis moderada de los islotes de Langerhans; los grupos IV-V presentaron hipertrofia y necrosis leve multifocal a nivel del islote. Conclusiones. El extracto de sanky presenta capacidad antioxidante in vitro y el zumo ejerce un efecto hipoglicemiante y protector en páncreas.

Objective. To determine the in vitro antioxidant capacity of Corryocactus brevistylus and its effect on glycemia and the pancreas of alloxan-induced diabetic rats. Materials and methods. The antioxidant capacity of the hydroethanolic extract of sanky (HEES) was evaluated by assessing its ability to reduce 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric ion (FRAP). We used thirty adult rats, which were induced to diabetes with two doses of alloxan (80mg/kg). Rats were distributed into 5 groups (n=6), all groups received treatment by orogastric route for eight days. Group I received water, group II received metformin 14mg/kg and groups III, IV and V received sanky juice at 1.0; 4.0 and 16 mL/kg, respectively. Glycemia was evaluated by the rapid method (glucometer) (first and eighth day). After treatment, the animals were sacrificed and the pancreas was removed for histopathological study. Results. The antioxidant capacity of HEES by DPPH showed an IC50 of 0.77 mg/mL; the FRAP method showed a TEAC-FRAP of 22.31µg/mg. Glycemia decreased on the eighth day of treatment, with respect to the first day; a decrease in glycemia was also found in groups III-V, when compared to group I. Histologically, groups I-II presented severe atrophy and moderate necrosis of the islets of Langerhans; groups IV-V presented hypertrophy and mild multifocal necrosis at the islet level. Conclusions. The extract of sanky showed antioxidant capacity in vitro and the juice exerts a hypoglycemic and protective effect on the pancreas.

SARS-CoV-2 Neutralizing Antibodies in Mexican Population: A Five Vaccine Comparison.

Neutralizing antibodies (NAs) are key immunological markers and are part of the humoral response of the adaptive immune system. NA assays determine the presence of functional antibodies to prevent SARS-CoV-2 infection. We performed a real-world evidence study to detect NAs that confer protection against SARS-CoV-2 after the application of five vaccines (Pfizer/BioNTech, AstraZeneca, Sinovac, Moderna, and CanSino) in the Mexican population. Side effects of COVID-19 vaccines and clinical and demographic factors associated with low immunogenicity were also evaluated. A total of 242 SARS-CoV-2-vaccinated subjects were recruited. Pfizer/BioNTech and Moderna proved the highest percentage of inhibition in a mono-vaccine scheme. Muscular pain, headache, and fatigue were the most common adverse events. None of the patients reported severe adverse events. We found an estimated contagion-free time of 207 (IQR: 182-231) and 187 (IQR: 184-189) days for Pfizer/BioNTech and CanSino in 12 cases in each group. On the basis of our results, we consider that the emerging vaccination strategy in Mexico is effective and safe.

Effect of Microwave and Ultrasound during the Killing Stage of the Curing Process of Vanilla (Vanilla planifolia, Andrews) Pods.

The curing process (CP) of Vanilla planifolia pods, which is a long and tedious process, is necessary to obtain the natural vanilla extract. This research evaluated the application of microwave (M) and ultrasound (U) during the "killing" stage of the CP and its effect on vanillin content and ß-glucosidase activity. The pods were immersed in a container with water or with moistened samples for the M treatments. In U treatments, the pods were immersed in an ultrasonic bath. After this stage, the samples were subjected to an additional U treatment. The results show that the application of these technologies significantly improves vanillin yield (p < 0.05) and the curing time is reduced to 20 days. U treatments subjected to additional sonication at 38 °C obtain more than double the yield of vanillin regarding control. The effect of M and U on cell structure damage increases with additional sonication, but at 15 min, ß-glucosidase inactivation decreases the final yield. Disposition of samples in M also affects the final vanillin content. There is no significant correlation between ß-glucosidase and vanillin in the different treatments. The application of M and U with the appropriate parameters reduces the CP time without affecting the compounds of interest.