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Duclauxin (1) from Talaromyces sp. IQ-313 was reported as a putative allosteric modulator of human recombinant protein tyrosine phosphatase 1B (400 amino acids) (hPTP1B1-400), a validated target for the treatment of type II diabetes. Based on these findings, a one-strain-many-compound (OSMAC) experiment on the IQ-313 strain generated derivatives 5a, 6, and 7. Moreover, a one-/two-step semisynthetic approach guided by docking toward hPTP1B1-400 produced 38 analogs, a series (A) incorporating a lactam functionalization at C-1 (8a-15a, 36a, and 37a) and a series (B) containing a lactam at C-1 and an extra unsaturation between C-7 and C-8 (5b, 11b-37b). In vitro evaluation and structure-activity relationship (SAR) analysis revealed that analogs from the B series are up to 10-fold more active than 1 and derivatives from the A series. Furthermore, duclauxin (1) and 36b were assessed for their potential acute toxicity, estimating their LD50 to be higher than 300 mg/kg. Moreover, 36b significantly reduced glycemia in an insulin tolerance test in mice, suggesting that its mechanism of action is through the PTP1B inhibition.

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In this work, a quantitative sandwich ELISA was optimized, through a full factorial design of experiments (DOE) in successive steps of a preliminary protocol obtained by the method of one factor at a time (OFAT). The specificity of the optimized ELISA, the lower limit of quantification, the quantification range and the analytical sensitivity of the antigen quantification curve were evaluated, in comparison with the curve obtained from the preliminary protocol. The full factorial DOE was linked to a simple statistical processing, which facilitates the interpretation of the results in those laboratories where there is no trained statistician. The step-by-step optimization of the ELISA and the successive incorporation into the protocol of the best combination of factors and levels, allowed obtaining a specific immunoassay, with an analytical sensitivity 20 times greater and with a lower limit of antigen quantification that decreased from 156.25 at 9.766 ng/mL. As far as we know, there are no reports of optimization of an ELISA following the step-by-step scheme used in this work. The optimized ELISA will be used for the quantification of the TT-P0 protein, the active principle of a vaccine candidate against sea lice.

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Introducción: La equinococosis esplénica es una enfermedad zoonótica adquirida de forma accidental por el humano como huésped intermediario. Reporte de caso: paciente mujer de 26 años de edad, con dolor abdominal localizado en hipocondrio izquierdo, moderada intensidad, calmaba con antiespasmódicos endovenosos; antecedente de dolor abdominal de larga data y procedente de región de Huancavelica, Perú hace 6 años. En examen clínico del abdomen: ruidos hidroaéreos; presentes, simétrico, blando, depresible, doloroso a la palpación en hipocondrio izquierdo, impresiona esplenomegalia, timpanismo conservado; en ecografía menciona quiste hidatídico a nivel del bazo Gharbi IV; en tomografía abdominopélvica con contraste muestra bazo con lesión quística heterogénea, de pared parcialmente calcificada y áreas de densidad grasa que se extiende hasta ligamento gastroesplénico, con diámetro de 73 mm x 54 mm; concluyendo equinococosis extrahepática (equinococosis esplénica), realizándose esplenectomía total. Conclusión: enfermedad rara, incluso en áreas endémicas, que plantea desafíos para su diagnóstico y tratamiento.

SUMMARY Introduction: Splenic echinococcosis is a zoonotic disease accidentally acquired by humans as an intermediate host. Case report: a 26-year-old female patient with abdominal pain located in the left hypochondrium, moderate intensity, calmed with intravenous antispasmodics; a history of long-standing abdominal pain and from the Huancavelica region, Peru, 6 years ago. On clinical examination of the abdomen: hydro-air sounds; present, symmetrical, soft, depressible, painful on palpation in the left hypochondrium, impression of splenomegaly, preserved tympany; the ultrasound mentions a hydatid cyst at the level of the spleen Gharbi IV; Contrast-enhanced abdominal and pelvic tomography shows a spleen with a heterogeneous cystic lesion, with a partially calcified wall and areas of fatty density that extend to the gastrosplenic ligament, with a diameter of 73 mm x 54 mm; concluding extrahepatic echinococcosis (splenic echinococcosis), performing total splenectomy. Conclusion: rare disease, even in endemic areas, which poses challenges for its diagnosis and treatment.

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The bean fruit pericarp accumulates a significant amount of starch, which starts to be degraded 20 days after anthesis (DAA) when seed growth becomes exponential. This period is also characterized by the progressive senescence of the fruit pericarp. However, the chloroplasts maintained their integrity, indicating that starch degradation is a compartmentalized process. The process coincided with a transient increase in maltose and sucrose levels, suggesting that ß-amylase is responsible for starch degradation. Starch degradation in the bean fruit pericarp is also characterized by a large increase in starch phosphorylation, as well as in the activities of cytosolic disproportionating enzyme 2 (DPE2, EC 2.4.1.25) and glucan phosphorylase (PHO2, EC 2.4.1.1). This suggests that the rate of starch degradation in the bean fruit pericarp 20 DAA is dependent on the transformation of starch to a better substrate for ß-amylase and the increase in the rate of cytosolic metabolism of maltose.

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OBJECTIVE: We estimated the mortality trends for prostate cancer in Peru and its geographical areas between 2003 and 2017. MATERIAL AND METHODS: We obtained recorded prostate cancer deaths from the Peruvian Ministry of Health Database between 2003 and 2017. Age-adjusted mortality rates per 100,000 men-year were computed with the direct method using the world standard SEGI population. We estimated the annual percent change (APC) using the Joinpoint regression program. RESULTS: A total of 38,617 prostate cancer deaths were reported between 2003 and 2017, with a mortality rate ranging from 18.21 to 19.94 deaths per 100,000 men-year. Since 2006, Peru has experienced a decrease of 2.2 deaths per year, whereas the mortality rate in the coastal region has declined by 2.9% per year.  The highlands and rainforest regions showed stable trends throughout the entire study period. According to provinces, only Moquegua had a significant decrease (APC: -6.0, 95%CI: -11.4, -0.2, p<0.05) from 2003 to 2017. CONCLUSIONS: Although mortality rates are decreasing, there is a high mortality burden by prostate cancer in Peru and by geographical regions, being mostly concentrated in the coastal region. The rainforest provinces deserve the most attention. Our findings suggest wide health care disparities among the different regions of Peru that need greater public health attention to reduce the burden of mortality by prostate cancer.

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Introducción: Los aneurismas intracerebrales son hallazgos incidentales en estudios de imágenes realizado por otros diagnósticos. Reporte de Caso: Paciente femenino de 35 años, que presentó sincope después de cefalea de gran intensidad sin ceder a tratamiento convencional de AINES; con antecedente de cefalea de larga data y tratamiento esporádico. Al examen: neurológico: despierta, asimetría facial, disartria, fuerza muscular disminuida en ambos miembros inferiores, no signos meníngeos; el informe tomográfico cerebral sin contraste indicó: lesiones cerebrales expansivas de etiología a determinar a nivel de ambos lados de diencéfalo: descartar glioma vs aneurismas; Angiotac cerebral con contraste, refleja aneurismas de carótida interna intracraneal bilateral y cerebral media (en espejo). Posteriormente la paciente fue evaluada por neurocirujano de turno, quien indica referir a centro de mayor complejidad, por no contar con instrumental necesario para intervención quirúrgica; paciente fallece camino a centro de referencia. Conclusiones: Al ser una patología poco frecuente, no es considerada como una primera opción de sospecha diagnostica tras un evento de cefalea.

Background: Intracerebral aneurysms are incidental findings in imaging studies performed for other diagnoses. Case Report: 35- year-old female patient, who presented syncope after severe headache without yielding to conventional treatment with NSAIDs; with a history of long-standing headache and sporadic treatment. On examination: neurological: awake, facial asymmetry, dysarthria, decreased muscle strength in both lower limbs, no meningeal signs; the brain tomographic report without contrast indicated: expansive brain lesions of etiology to be determined at both sides of the diencephalon: rule out glioma vs aneurysms; cerebral Angiotac with contrast, reflects bilateral intracranial internal carotid and middle cerebral (mirror) aneurysms. Subsequently the patient was evaluated by the neurosurgeon on duty, who indicated to refer to a center of higher complexity, for not having the necessary instruments for surgery; patient died on the way to the referral center. Conclusions: Being a rare pathology, it is not considered as a first option for diagnostic suspicion after a headache event.

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Cenotes are habitats with unique physical, chemical, and biological features. Unexplored microorganisms from these sinkholes represent a potential source of bioactive molecules. Thus, a series of cultivable fungi (Aspergillus spp. NCA257, NCA264, and NCA276, Stachybotrys sp. NCA252, and Cladosporium sp. NCA273) isolated from the cenote Tza Itzá were subjected to chemical, coculture, and metabolomic analyses. Nineteen compounds were obtained and tested for their antimicrobial potential against ESKAPE pathogens, Mycobacterium tuberculosis, and nontuberculous mycobacteria. In particular, phenylspirodrimanes from Stachybotrys sp. NCA252 showed significant activity against MRSA, MSSA, and mycobacterial strains. On the other hand, the absolute configuration of the new compound 17-deoxy-aspergillin PZ (1) isolated from Aspergillus sp. NCA276 was established via single-crystal X-ray crystallography. Also, the chemical analysis of the cocultures between Aspergillus and Cladosporium strains revealed the production of metabolites that were not present or were barely detected in the monocultures. Finally, molecular networking analysis of the LC-MS-MS/MS data for each fungus was used as a tool for the annotation of additional compounds, increasing the chemical knowledge on the corresponding fungal strains. Overall, this is the first systematic chemical study on fungi isolated from a sinkhole in Mexico.

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Chemical investigation of Punctularia atropurpurascens strain HM1 (Punctulariaceae), a corticioid isolated from a decorticated piece of Quercus bark collected in Bosque de Tlalpan, Mexico City, led to the isolation of a new drimane, 1-α-hydroxy-isodrimenine (1: ) and a new tetrahydroxy kauranol, 16-hydroxy-phlebia-nor-kauranol (2: ), together with the known N-phenylacetamide (3: ). Structures of all compounds were elucidated by spectroscopic and spectrometric methods, and the absolute configuration of 1: and 2: was confirmed via single-crystal X-ray crystallography. The isolated compounds showed modest antimycobacterial activity.

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COVID-19 pandemic poses a serious threat to human health; it has completely disrupted global stability, making vaccine development an important goal to achieve. Monoclonal antibodies play an important role in subunit vaccines strategies. In this work, nine murine MAbs against the RBD of the SARS-CoV-2 spike protein were obtained by hybridoma technology. Characterization of purified antibodies demonstrated that five of them have affinities in the order of 108 L/mol. Six MAbs showed specific recognition of different recombinant RBD-S antigens in solution. Studies of the additivity index of anti-RBD antibodies, by using a novel procedure to determine the additivity cut point, showed recognition of at least five different epitopes. The MAbs CBSSRBD-S.11 and CBSSRBD-S.8 revealed significant neutralizing capacity against SARS-CoV-2 in an ACE2-RBD binding inhibition assay (IC50 = 85.5pM and IC50 = 122.7pM, respectively) and in a virus neutralizing test with intact SARS-CoV-2 (VN50 = 0.552 nM and VN50 = 4.854 nM, respectively) when D614G strain was used to infect Vero cells. Also CBSSRBD-S.11 neutralized the SARS-CoV-2 strains Alpha and Beta: VN50 = 0.707 nM and VN50 = 0.132 nM, respectively. The high affinity CBSSRBD-S.8 and CBSSRBD-S.7 recognized different epitopes, so they are suitable for the development of a sandwich ELISA to quantitate RBD-S recombinant antigens in biomanufacturing processes, as well as in pharmacokinetic studies in clinical and preclinical trials.

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Background: An up-to-date analysis of gastric cancer mortality among Hispanic/Latino populations is required for estimating disease burden and assessing the effectiveness of clinical and preventive strategies. Methods: We retrieved gastric cancer deaths between 1997 and 2017 (as available) from the Surveillance, Epidemiology, and End Results Program (United States Hispanics) and the World Health Organization databases (Puerto Rico, 16 Latin American and Caribbean countries). Joinpoint regression analysis was used to examine trends in age-standardized mortality rates (ASMR; per 100 000 person-years) and calculate average annual percent changes (AAPCs) by country (or territory), age group (25-49 and ≥50 years), and sex. Trends were compared to assess slope parallelism. Findings: In 2017, Chile (31·8), Colombia (24·3) and Costa Rica (24·3) had the highest ASMR of gastric cancer for men, while Guatemala (17·2), Peru (13·5), and Costa Rica (13·3) had the highest ASMR for women. Small-to-moderate mortality declines (AAPCs ranged -4 to -0.5%) were observed between 1997 and 2017. In almost all countries, trends decreased among individuals aged ≥50 years. However, age-specific trends were not parallel (p-values <0.05) in Brazil, Colombia, Mexico, the United States, and Venezuela for both men and women, and in five additional countries for only women; with a few countries showing stable or slightly increasing trends for individuals aged 25-49 years. Interpretation: Overall gastric cancer mortality rates in Hispanics/Latinos declined in the last two decades. However, there was a notable variation in trends by country, sex, and age group. Continued and targeted prevention efforts are needed to reduce the disease burden in these vulnerable populations. Funding: Universidad Cientifica del Sur, Peru, and National Cancer Institute, United States.

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A collection of 29 cultivable fungal strains isolated from deep-sea sediments of the Gulf of Mexico were cultivated under the "one strain, many compounds" approach to explore their chemical diversity and antimicrobial potential. From the 87 extracts tested, over 50% showed antimicrobial activity, and the most active ones were those from cultures grown at 4 °C in darkness for 60 days (resembling deep-sea temperature). PCA analysis of the LC-MS data of all the extracts confirmed that culture temperature is the primary factor in the variation of the 4462 metabolite features, accounting for 21.3% of the variation. The bioactivity-guided and conventional chemical studies of selected fungal strains allowed the identification of several active and specialized metabolites. Finally, metabolomics analysis by GNPS molecular networking and manual dereplication revealed the biosynthetic potential of these species to produce interesting chemistry. This work uncovers the chemical and biological study of marine-derived fungal strains from deep-sea sediments of the Gulf of Mexico.

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The marine-facultative Aspergillus sp. MEXU 27854, isolated from the Caleta Bay in Acapulco, Guerrero, Mexico, has provided an interesting diversity of secondary metabolites, including a series of rare dioxomorpholines, peptides, and butyrolactones. Here, we report on the genomic data, which consists of 11 contigs (N50~3.95 Mb) with a ~30.75 Mb total length of assembly. Genome annotation resulted in the prediction of 10,822 putative genes. Functional annotation was accomplished by BLAST searching protein sequences with different public databases. Of the predicted genes, 75% were assigned gene ontology terms. From the 67 BGCs identified, ~60% belong to the NRPS and NRPS-like classes. Putative BGCs for the dioxomorpholines and other metabolites were predicted by extensive genome mining. In addition, metabolomic molecular networking analysis allowed the annotation of all isolated compounds and revealed the biosynthetic potential of this fungus. This work represents the first report of whole-genome sequencing and annotation from a marine-facultative fungal strain isolated from Mexico.

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Mexico is one of the world's leading mercury producers and exporters. However, mercury mining is carried out using artisanal procedures, which highly impact ecosystems. In the municipality of Pinal de Amoles, Queretaro, Mexico, artisanal mercury mining (AMM) is practiced in a region that has been categorized as a Biosphere Reserve. Therefore, a holistic health risk assessment for mercury was performed in the region, including environmental monitoring (air, water, and soil) and mercury exposure in both humans (children, women, and miners) and biota (plants, rodents, and worms). The atmospheric mercury determination was carried out using the JEROME® J405 analyzer, whereas total mercury in environmental and biological samples was determined by atomic absorption spectrophotometry/cold vapor. Results showed that mercury concentrations in the environmental and biological matrices exceeded their respective reference values. These results demonstrate the direct influence of AMM in the increasing levels of mercury in all the components of the studied ecosystem. Therefore, comprehensive intervention strategies must be implemented to reduce and prevent human health and ecological risks due to the presence of mercury. In this regard, the Minamata Convention for mercury control should include biomonitoring programs not only for humans but also for critical ecological receptors in polluted ecosystems.

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Ovarian cancer is the third most frequent gynaecological malignancy worldwide and in Mexico, with a high mortality rate, due to that in many cases its diagnosis is made in advanced stages. Prognosis is important for determining the subtype and the degree of evolution. During lasts years, the management of ovarian cancer has undergone an important evolution with the incorporation of new therapeutic options, which in turn represent an increase in the survival of these patients. We present recommendations for the management of ovarian cancer developed by an expert panel Mexican based on available evidence so far and the characteristics of health care in the country.

El cáncer de ovario es la tercera neoplasia maligna ginecológica más frecuente globalmente y también en México, con una elevada tasa de mortalidad debido a que en muchos casos su diagnóstico se realiza en etapas avanzadas. Para establecer su pronóstico es importante la determinación del subtipo y del grado de evolución. En los últimos años, el manejo del cáncer de ovario ha sufrido una importante evolución con la incorporación de nuevas opciones terapéuticas, que a su vez representan un incremento en la supervivencia de estas pacientes. Se presentan las recomendaciones para el manejo del cáncer de ovario elaboradas por un panel de expertos mexicanos basadas en la evidencia disponible hasta el momento y en las características de la atención sanitaria del país.

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Resumen El cáncer de ovario es la tercera neoplasia maligna ginecológica más frecuente globalmente y también en México, con una elevada tasa de mortalidad debido a que en muchos casos su diagnóstico se realiza en etapas avanzadas. Para establecer su pronóstico es importante la determinación del subtipo y del grado de evolución. En los últimos años, el manejo del cáncer de ovario ha sufrido una importante evolución con la incorporación de nuevas opciones terapéuticas, que a su vez representan un incremento en la supervivencia de estas pacientes. Se presentan las recomendaciones para el manejo del cáncer de ovario elaboradas por un panel de expertos mexicanos basadas en la evidencia disponible hasta el momento y en las características de la atención sanitaria del país.

Abstract Ovarian cancer is the third most frequent gynaecological malignancy worldwide and in Mexico, with a high mortality rate, due to that in many cases its diagnosis is made in advanced stages. Prognosis is important for determining the subtype and the degree of evolution. During lasts years, the management of ovarian cancer has undergone an important evolution with the incorporation of new therapeutic options, which in turn represent an increase in the survival of these patients. We present recommendations for the management of ovarian cancer developed by an expert panel Mexican based on available evidence so far and the characteristics of health care in the country.

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BACKGROUND: Trend data on hypertension prevalence and attainment indicators at each step of the care cascade (awareness, treatment, control) are required in Chile. This study aims to quantify trends (2003-2017) in prevalence and in the proportion of individuals with hypertension attaining each step of the care cascade among adults aged 17 years or older, and to assess the impact of lowering the blood pressure (BP) thresholds used to define elevated BP on these indicators. METHODS: We used data from 2003, 2010, and 2017 Chilean national health surveys. Each year we assessed levels of (1) mean systolic (SBP) and diastolic (DBP) blood pressure, (2) hypertension prevalence (BP ≥ 140/90 mmHg or use of antihypertensive treatment), and (3) awareness, treatment, and control. Logistic regression on pooled data was used to assess trends in binary outcomes; linear regression was used to assess trends in continuous SBP and DBP. We compared levels of hypertension prevalence using two sources to ascertain antihypertensive treatment (self-reported versus medicine inventory). The 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines were used to re-define hypertension using lower thresholds (BP ≥ 130/80 mmHg). RESULTS: Hypertension prevalence was 34.0, 32.0 and 30.8% in 2003, 2010 and 2017, respectively. Levels of treated- and controlled-hypertension were significantly higher in 2017 than in 2003 (65% versus 41% for treatment, P < 0.001; 34% versus 14% for control, P < 0.001), while levels of awareness were stable (66% versus 59%, P = 0.130). Awareness, treatment, and control levels were higher among females in 2003, 2010, and 2017 (P < 0.001). Mean SBP and DBP decreased over the 15-year period, except for SBP among females on treatment. Adopting the 2017 ACC/AHA guidelines would increase hypertension prevalence by 17 and 55% in absolute and relative terms, respectively. CONCLUSIONS: Chile has experienced a positive population-wide lowering in blood pressure distribution which may be explained partly by a significant rise in levels of treated- and controlled-hypertension since 2003. Lowering the thresholds used to define elevated BP would substantially increase the financial public health challenge of further improving attainment levels at each step of the care cascade. Innovative and collaborative strategies are needed to improve hypertension management, especially among males.

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RESUMEN El 11 de marzo de 2020 la OMS declara el estado de pandemia por COVID-19. Para el 31 de julio de 2020, se han reportado 17 106 007 casos y 668 910 muertes a nivel global. La región de las Américas ha reportado 9 152 173 casos (53%) y 351 121 muertes (52,2%), por lo que resulta de interés el análisis de los datos en países de esta región. Argentina, Chile y Colombia, debido a sus características culturales, políticas y económicas, presentan similitudes que favorecen su estudio y comparación. Objetivo Realizar un análisis exploratorio de variables relacionadas con los sistemas de salud y datos epidemiológicos de COVID-19 en Argentina, Chile y Colombia. Metodología Estudio descriptivo de variables reportadas por los organismos oficiales de cada Estado. Resultados Se presentaron diferencias importantes en los casos activos, el número de pruebas realizadas y la mortalidad entre los tres países. La Ciudad Autónoma de Buenos Aires presenta la mayor tasa de casos activos a julio de 2020. De estos tres países, Colombia presenta las mayores cifras de fallecimientos confirmados por COVID-19 con cierre a 31 de julio de 2020. Se sugiere la unificación de un sistema de información para América Latina que permita hacer un monitoreo integral de variables de interés, que favorezca la calidad de los datos y que unifique el lenguaje técnico.(AU)

ABSTRACT On March 11, 2020 the WHO declared the state of pandemic by COVID-19. As of July 29, 2020, 17 106 007 cases and 668 910 deaths have been reported globally. The region of the Americas has reported 9 152 173 cases (53%) and 351 121 deaths (52,2%), so the aggregate analysis of the data in countries in this region is of interest. Argentina, Chile and Colombia, due to their demographic and economic characteristics, are countries that can be studied. Objetive Analyze variables related to health systems and epidemiological data of SARS-CoV-2 virus disease in Argentina, Chile and Colombia. Methods A descriptive study of variables reported by the official organisms of each state was used. Results There is an important difference in active cases and mortality among the three countries; the Autonomous City of Buenos Aires has the highest number of active cases as of July 2020. Colombia has the highest numbers of deaths confirmed by COVID-19 in the months of February to July 2020. We suggest the unification of an information system for Latin America that allows a comprehensive monitoring of variables, improves the qua-lity of data and unifies the technical language.(AU)

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BACKGROUND: On March 11, 2020 the WHO declared the state of pandemic by COVID-19. As of July 29, 2020, 17 106 007 cases and 668 910 deaths have been reported globally. The region of the Americas has reported 9 152 173 cases (53%) and 351 121 deaths (52,2%), so the aggregate analysis of the data in countries in this region is of interest. Argentina, Chile and Colombia, due to their demographic and economic characteristics, are countries that can be studied. OBJETIVE: Analyze variables related to health systems and epidemiological data of SARS-CoV-2 virus disease in Argentina, Chile and Colombia. METHODS: A descriptive study of variables reported by the official organisms of each state was used. RESULTS: There is an important difference in active cases and mortality among the three countries; the Autonomous City of Buenos Aires has the highest number of active cases as of July 2020. Colombia has the highest numbers of deaths confirmed by COVID-19 in the months of February to July 2020. We suggest the unification of an information system for Latin America that allows a comprehensive monitoring of variables, improves the qua-lity of data and unifies the technical language.

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