Bacillus subtilis stress-associated mutagenesis and developmental DNA repair.

SUMMARYThe metabolic conditions that prevail during bacterial growth have evolved with the faithful operation of repair systems that recognize and eliminate DNA lesions caused by intracellular and exogenous agents. This idea is supported by the low rate of spontaneous mutations (10-9) that occur in replicating cells, maintaining genome integrity. In contrast, when growth and/or replication cease, bacteria frequently process DNA lesions in an error-prone manner. DNA repairs provide cells with the tools needed for maintaining homeostasis during stressful conditions and depend on the developmental context in which repair events occur. Thus, different physiological scenarios can be anticipated. In nutritionally stressed bacteria, different components of the base excision repair pathway may process damaged DNA in an error-prone approach, promoting genetic variability. Interestingly, suppressing the mismatch repair machinery and activating specific DNA glycosylases promote stationary-phase mutations. Current evidence also suggests that in resting cells, coupling repair processes to actively transcribed genes may promote multiple genetic transactions that are advantageous for stressed cells. DNA repair during sporulation is of interest as a model to understand how transcriptional processes influence the formation of mutations in conditions where replication is halted. Current reports indicate that transcriptional coupling repair-dependent and -independent processes operate in differentiating cells to process spontaneous and induced DNA damage and that error-prone synthesis of DNA is involved in these events. These and other noncanonical ways of DNA repair that contribute to mutagenesis, survival, and evolution are reviewed in this manuscript.

Prebiotics in Global and Mexican Fish Aquaculture: A Review.

Continued human population growth has resulted in increased demand for products, including those derived from aquaculture. The main challenge in aquaculture is producing more every year. In recent years, environmentally friendly supplements that provide the necessary pathways for optimal production have been emphasized. One of them is prebiotics, selectively utilized substrates by host microorganisms conferring a health benefit. Interest in applying prebiotics in global fish farming has increased in recent years as it has been shown to improve growth, boost the immune system, resist stress conditions, and cause the modulation of digestive enzymes. These effects reflect reduced production and disease costs. However, in Latin American countries such as Mexico, large-scale use of these food supplements is needed as a sustainable alternative to improve fish production. This paper gives a review of the current advances obtained with the application of prebiotics in commercially farmed fish worldwide, mentions the prebiotics to use in the aquaculture industry, and updates the status of studies about the used prebiotics in global commercial fish cultivated in Mexico, as well as freshwater and marine endemic fish in this country. Also, the limitations of prebiotics application in terms of their use and legislation are analyzed.

Development of standards for assessing water quality in marine coastal waters of Bahrain.

Marine coastal waters of Bahrain are under pressure due to human activities and climate change. We used marine monitoring data (2005-2020) from 27 sites to establish baseline conditions and develop standards for assessments of water quality. Five hydrodynamic regions were identified: Oyster Beds, North, West, East, East (Coastal). Data from Oyster Beds sites, likely to be less impacted by human activities, were used to determine baseline conditions. For most parameters, candidate thresholds were based on 50 % and 100 % variation from baseline and 95th percentiles. Comparisons of data against different thresholds showed different outcomes. Overall, results indicate good water quality, with potential concerns in East (Coastal). Trend analyses showed some significant trends in all regions: downward (favourable) for some parameters (e.g. turbidity: North) and upward for others (e.g. nitrate: Oyster Beds, East and East (Coastal)). Future work requires greater understanding around optimum guidelines that protect and mitigate any adverse ecological impacts.

Seasonal malaria chemoprevention in a context of high presumed sulfadoxine-pyrimethamine resistance: malaria morbidity and molecular drug resistance profiles in South Sudan.

BACKGROUND: Seasonal malaria chemoprevention (SMC) using sulfadoxine-pyrimethamine plus amodiaquine (SP-AQ), is a community-based malaria preventive strategy commonly used in the Sahel region of sub-Saharan Africa. However, to date it has not been implemented in East Africa due to high SP resistance levels. This paper is a report on the implementation of SMC outside of the Sahel in an environment with a high level of presumed SP-resistance: five cycles of SMC using SPAQ were administered to children 3-59 months during a period of high malaria transmission (July-December 2019) in 21 villages in South Sudan. METHODS: A population-based SMC coverage survey was combined with a longitudinal time series analysis of health facility and community health data measured after each SMC cycle. SMC campaign effectiveness was assessed by Poisson model. SPAQ molecular resistance markers were additionally analysed from dried blood spots from malaria confirmed patients. RESULTS: Incidence of uncomplicated malaria was reduced from 6.6 per 100 to an average of 3.2 per 100 after SMC administration (mean reduction: 53%) and incidence of severe malaria showed a reduction from 21 per 10,000 before SMC campaign to a mean of 3.3 per 10,000 after each cycle (mean reduction: 84%) in the target group when compared to before the SMC campaign. The most prevalent molecular haplotype associated with SP resistance was the IRNGE haplotype (quintuple mutant, with 51I/59R/108N mutation in pfdhfr + 437G/540E in pfdhps). In contrast, there was a low frequency of AQ resistance markers and haplotypes resistant to both drugs combined (< 2%). CONCLUSIONS: The SMC campaign was effective and could be used as an additional preventive tool in seasonal malaria settings outside of the Sahel, especially in areas where access to health care is unstable. Malaria case load reduction was observed despite the high level of resistance to SP.

The safety of BCG revaccination in the context of COVID-19.

The bacille Calmette-Guérin (BCG) vaccine is administered in many countries as part of their vaccination schedules. Epidemiologic studies have suggested a possible benefit of this vaccine in the context of the COVID-19 pandemic and other respiratory infections. We aimed to assess the safety of this intervention in BCG-primed adults. Adult health care workers (n = 451) received a single intradermal application of the BCG vaccine (Tokyo 172 strain) in the deltoid region of the right arm. Follow-up (30 days) calls and clinical inspections were guided using a standardized data sheet to assess local and systemic reactions. Early local reactions were common at 24 h and 7 days, such as erythema (74.9%, 69.2%), induration (55.7%, 59%), a papule (53.4%, 47.7%), and edema (48.3%, 38.1). Local symptoms (pruritus 44.8%, heat 16.2%, and pain 34.8%) were less frequent at day 7. Late expected reactions (14 and 30 days) included the formation of crusts (39.6% and 63.9%), a pustule (36.6% and 17%), or ulcers (28.8% and 17.7%). Severe reactions were limited to subcutaneous abscesses (2%) and lymphadenitis (<1%).

Epidemiology of Eye Cancer in Cali, Colombia: A 55-Year Study.

PURPOSE: To describe the epidemiology, incidence, mortality and survival of ocular cancer in Cali between 1962 and 2019. METHODS: Ecological population-based study analyzing data of incidence, mortality, and 5-years survival of malignant ocular tumors from the Populational Cancer Registry of Cali between 1962 and 2019. RESULTS: Between 1962 and 2019, 586 ocular tumors were found, 50.5% occurred in females, the mean age at diagnosis was 45 years (standard deviation = 25), 70.3% of ocular malignancies occurred in >14 years. The average annual incidence rate was 7.8 per million for male and 6.9 per million for females. Retinoblastoma (21%), squamous cell carcinoma (20%), melanoma (16%) and lymphoma (8%) were the most common neoplasm. In those <15 years, the most frequent malignant tumors were retinoblastomas (85.7%), followed by non-specified malignant neoplasm (NOS, 7.9%), and rhabdomyosarcoma (3.6%). In those >14 years, there were NOS (30%), followed by squamous cell carcinomas (28%), melanomas (23%), and lymphomas (9.7%). Conjunctiva (38.2%), retina (21%) and orbit (10%) constituted the majority of anatomical sites of ocular tumors. The survival rate was about 83.2% and mortality did not show a decreasing trend over time (p > .05). CONCLUSIONS: The incidence of ocular cancer in Cali has a slightly increasing trend, with stable behavior in the last decades. Squamous cell carcinoma, retinoblastoma, melanoma and lymphoma are the most frequent ocular cancers, with being retinoblastoma more frequent than melanoma. In general, ocular cancer had good survival rates in Cali.

Screening for K13-Propeller Mutations Associated with Artemisinin Resistance in Plasmodium falciparum in Yambio County (Western Equatoria State, South Sudan).

Artemisinin-combined treatments are the recommended first-line treatment of Plasmodium falciparum malaria, but they are being threatened by emerging artemisinin resistance. Mutations in pfk13 are the principal molecular marker for artemisinin resistance. This study characterizes the presence of mutations in pfk13 in P. falciparum in Western Equatoria State, South Sudan. We analyzed 468 samples from patients with symptomatic malaria and found 15 mutations (8 nonsynonymous and 7 synonymous). Each mutation appeared only once, and none were validated or candidate markers of artemisinin resistance. However, some mutations were in the same or following position of validated and candidate resistance markers, suggesting instability of the gene that could lead to resistance. The R561L nonsynonymous mutation was found in the same position as the R561H validated mutation. Moreover, the A578S mutation, which is widespread in Africa, was also reported in this study. We found a high diversity of other pfk13 mutations in low frequency. Therefore, routine molecular surveillance of resistance markers is highly recommended to promptly detect the emergence of resistance-related mutations and to limit their spread.

Eutrophication assessment and environmental management perspectives of Tóbari: an arid subtropical coastal lagoon of the Gulf of California.

Coastal lagoons are vulnerable to eutrophication processes. In this study, we evaluate the eutrophication process in the restricted, arid subtropical Tóbari coastal lagoon, located in the eastern coast of the Gulf of California, where the main source of nutrient inputs and other pollutants is agricultural wastewater from the Yaqui Valley. The Assessment of Estuarine Trophic Status (ASSETS) model and the Trophic State Index (TRIX) were used to evaluate eutrophication. Overall, ASSETS showed that the Tóbari lagoon has a moderate eutrophication process, with seasonal symptoms of hypoxia, increased phytoplankton biomass, dominance of macroalgae (indicative of nutrient enrichment), and blooms development of potentially harmful algae species. The TRIX showed that the lagoon is mesotrophic most of the year. Challenges of environmental management detected correspond to reducing the input of nutrients and others contaminants from anthropic sources: agriculture, shrimp farming, livestock, and urban zones.

Spectral flow cytometry identifies distinct nonneoplastic plasma extracellular vesicle phenotype in glioblastoma patients.

Background: Glioblastoma (GBM) is the most common malignant brain tumor and has a poor prognosis. Imaging findings at diagnosis and in response to treatment are nonspecific. Developing noninvasive assays to augment imaging would be helpful. Plasma extracellular vesicles (EVs) are a promising biomarker source for this. Here, we develop spectral flow cytometry techniques that demonstrate differences in bulk plasma EV phenotype between GBM patients and normal donors that could serve as the basis of a liquid biopsy. Methods: Plasma EVs were stained for EV-associated tetraspanins (CD9/CD63/CD81), markers indicating cell of origin (CD11b/CD31/CD41a/CD45), and actin/phalloidin (to exclude cell debris). EVs were analyzed using spectral flow cytometry. Multiparametric analysis using t-distributed stochastic neighbor embedding (t-SNE) and self-organizing maps on flow cytometry data (FlowSOM) was performed comparing GBM and normal donor (ND) plasma EVs. Results: Size exclusion chromatography plus spectral-based flow cytometer threshold settings enriched plasma EVs while minimizing background noise. GBM patients had increased CD9+, CD63+, CD81+, and myeloid-derived (CD11b+) EVs. Multiparametric analysis demonstrated distinct surface marker expression profiles in GBM plasma EVs compared to ND EVs. Fifteen plasma EV sub-populations differing in size and surface marker expression were identified, six enriched in GBM patients and two in normal donors. Conclusions: Multiparametric analysis demonstrates that GBM patients have a distinct nonneoplastic plasma EV phenotype compared to ND. This simple rapid analysis can be performed without purifying tumor EVs and may serve as the basis of a liquid biopsy.

Design of a Whole-Cell Biosensor Based on Bacillus subtilis Spores and the Green Fluorescent Protein To Monitor Arsenic.

A green fluorescent protein (GFP)-based whole-cell biosensor (WCB-GFP) for monitoring arsenic (As) was developed in Bacillus subtilis. To this end, we designed a reporter gene fusion carrying the gfpmut3a gene under the control of the promoter/operator region of the arsenic operon (Pars::gfpmut3a) in the extrachromosomal plasmid pAD123. This construct was transformed into B. subtilis 168, and the resultant strain was used as a whole-cell biosensor (BsWCB-GFP) for the detection of As. The BsWCB-GFP was specifically activated by inorganic As(III) and As(V), but not by dimethylarsinic acid [DMA(V)], and exhibited high tolerance to the noxious effects of arsenic. Accordingly, after 12 h exposure, B. subtilis cells carrying the Pars::gfpmut3a fusion exhibited 50 and 90% lethal doses (LD50 and LD90) to As(III) of 0.89 mM and As 1.71 mM, respectively. Notably, dormant spores from the BsWCB-GFP were able to report the presence of As(III) in a concentration range from 0.1 to 1,000 µM 4 h after the onset of germination. In summary, the specificity and high sensitivity for As, as well as its ability to proliferate under concentrations of the metal that are considered toxic in water and soil, makes the B. subtilis biosensor developed here a potentially important tool for monitoring environmental samples contaminated with this pollutant. IMPORTANCE Arsenic (As) contamination of groundwater is associated with serious worldwide health risks. Detection of this pollutant at concentrations that are established as permissible for water consumption by WHO is a matter of significant interest. Here, we report the generation of a whole-cell biosensor for As detection in the Gram-positive spore former B. subtilis. This biosensor reports the presence of inorganic As, activating the expression of the green fluorescent protein (GFP) under the control of the promoter/operator of the ars operon. The biosensor can proliferate under concentrations of As(III) that are considered toxic in water and soil and detect this ion at concentrations as low as 0.1 µM. Of note, spores of the Pars-GFP biosensor exhibited the ability to detect As(III) following germination and outgrowth. Therefore, this novel tool has the potential to be directly applied to monitor As contamination in environmental samples.

Significados de vivencias en cuidados gestacionales de nacidos con bajo peso

El bajo peso al nacer se considera un problema en salud pública multifactorial, con consecuencias como la morbimortalidad neonatal, deficiencias en el desarrollo cognitivo y el aumento del riesgo de desarrollo de enfermedades crónicas en etapas posteriores de la vida. Objetivo: interpretar los significados de las vivencias en cuidados gestacionales de las mujeres con hijos con bajo peso al nacer a término, que permitan identificar aspectos de salud, socioeconómicos, emocionales, entre otros, que sean relevantes durante la gestación y que puedan ser caracterizados e incluidos en el marco de las políticas públicas vinculantes en Sincelejo, Sucre. Metodología: fenomenología aplicada a ocho mujeres madres de niños/as con bajo peso al nacer a término. La información fue procesada con el método Colaizzi. Resultados: derivaron cinco macro categorías: 1) Cuidado y cuidado de sí en la gestación. 2) La salud en movimiento durante los cuidados de la gestación. 3) El cambio como vivencia permanente en la gestación. 4) Economía y gestación. 5) Las emocionalidades habitan la gestación. Conclusiones: El estudio atiende al nacimiento y a los factores contextuales, sociales y familiares relacionados. Se convirtió en una vía hacia el conocimiento protagonizado por las gestantes de gran utilidad para las políticas públicas.

Low birth weight is considered a multifactorial public health problem with consequences such as neonatal morbidity and mortality, deficiencies in cognitive development and increased risk of developing chronic diseases in later stages of life. Objective: To interpret the meanings of the experiences in pregnancy care of women with low birth weight babies at term, which allow the identification of health, socioeconomic and emotional aspects, among others, that are relevant during pregnancy, and that can be characterized and included in the framework of binding public policies in Sincelejo, Sucre. Method: Phenomenology applied to eight mothers of low-birth-weight babies at term. The information was processed with the Colaizzi method. Results: Five macro-categories were derived: 1) Care and self-care during pregnancy; 2) Health in motion during pregnancy care 3) Change as a permanent experience in pregnancy 4) Economy and gestation 5) Emotionality inhabiting gestation. Conclusions: The study addresses birth, contextual, social and family related factors. This study became a path towards knowledge carried out by pregnant women, which is very useful for public policies.

O baixo peso ao nascer se considera um problema na saúde pública multifatorial, com consequências como a morbimortalidade neonatal, deficiências no desenvolvimento cognitivo e o aumento do risco de desenvolvimento de doenças crônicas em etapas posteriores da vida. Objetivo: interpretar os significados das vivências em cuidados gestacionais das mulheres com filhos com baixo peso ao nascer a termo, identificar aspeitos de saúde, socioeconómicos, emocionais, entre outros, que sejam relevantes durante a gestação e que possam ser caracterizados e incluídos no marco das políticas públicas vinculantes em Sincelejo, Sucre. Metodologia: fenomenologia aplicada a oito mulheres mães de meninos/as com baixo peso ao nascer a termo. A informação foi processada com o método Colaizzi. Resultados: derivaram cinco macro categorias: 1) Cuidado e cuidado de si na gestação. 2) A saúde em movimento durante os cuidados da gestação. 3) O câmbio como vivência permanente na gestação. 4) Economia e gestação. 5) As emocionalidades tem a gestação. Conclusões: O estudo atende ao nascimento e aos fatores contextuais, sociais e familiares relacionados. Tornou-se em uma via para o conhecimento protagonizado pelas gestantes é de grande utilidade para as políticas públicas.

Glycosyltransferases Expression Changes in Leuconostoc mesenteroides subsp. mesenteroides ATCC 8293 Grown on Different Carbon Sources.

Leuconostoc mesenteroides strains are common contributors in fermented foods producing a wide variety of polysaccharides from sucrose through glycosyltransferases (GTFs). These polymers have been proposed as protective barriers against acidity, dehydration, heat, and oxidative stress. Despite its presence in many traditional fermented products and their association with food functional properties, regulation of GTFs expression in Ln. mesenteroides is still poorly understood. The strain Ln. mesenteroides ATCC 8293 contains three glucansucrases genes not found in operons, and three fructansucrases genes arranged in two operons, levLX and levC-scrB, a Glycoside-hydrolase. We described the first differential gene expression analysis of this strain when cultivated in different carbon sources. We observed that while GTFs are expressed in the presence of most sugars, they are down-regulated in xylose. We ruled out the regulatory effect of CcpA over GTFs and did not find regulatory elements with a direct effect on glucansucrases in the condition assayed. Our findings suggest that only operon levLX is repressed in xylose by LexA and that both fructansucrases operons can be regulated by the VicK/VicR system and PerR. It is essential to further explore the effect of environmental conditions in Ln. mesenteroides bacteria to better understand GTFs regulation and polymer function.

The rs7208505 Polymorphism and Differential Expression of the SKA2 Gene in the Prefrontal Cortex of Suicide Victims from the Mexican Population.

OBJECTIVE: The main aim of the current study was to investigate whether SKA2 gene expression in the postmortem brain of rs7208505 genotype are altered in suicide victims from a Mexican population. METHODS: In this study, we report a genetic analysis of expression levels of the SKA2 gene in the prefrontal cortex of the postmortem brain of suicidal subjects (n = 22) compared to subjects who died of causes other than suicide (n = 22) in a Mexican population using RT-qPCR assays. Additionally, we genotyped the rs7208505 polymorphism in suicide victims (n = 98) and controls (n = 88) and we evaluate the association of genotypes for the SNP rs7208505 with expression level of SKA2. RESULTS: The results showed that the expression of the SKA2 gene was significantly higher in suicide victims compared to control subjects (p = 0.044). Interestingly, we observed a greater proportion of allele A of the rs7208505 in suicide victims than controls. Even though there was no association between the SNP with suicide in the study population we found a significative association of the expression level from SKA2 with the allele A of the rs7208505 and suicide. CONCLUSION: The evidence suggests that the expression of SKA2 in the prefrontal cortex may be a critical factor in the etiology of suicidal behavior.

HighlightsSuicide victims have a higher level of SKA2 gene expression in the brain's prefrontal cortex than control subjects.The SKA2 rs7208505 is not associated with suicide in the Mexican population studied.Allele frequencies for G are higher than allele frequencies for A in our study population.The allele A of the rs7208505 affects the expression values of the SKA2 gene.

A Comparative Study Regarding the Impact of Covid-19 on Latin American College Students

COVID-19 has changed educational opportunities for students around the world, and, in the process, affected their lifestyle, happiness, and engagement. The present research is part of a project from six universities in different countries across Latin America to examine the impact of COVID-19 on university students. Objectives: The purpose of this study was to assess and compare the impact of COVID-19 on lifestyle changes, orientations to happiness, and student engagement among a sample of college students in Mexico, El Salvador, Colombia, the Dominican Republic, Peru, and the US. Methods: Participants were 1764 students from the six previously identified countries. Data were collected using the Student Health Behavior Inventory, the Orientations to Happiness Scale, and the University Student Engagement Inventory. Results: Student respondents were mostly female, with a median age of 22. Most reported no changes in academic performance and statistically significant changes in some lifestyle behaviors such as nutrition and physical activity. Conclusions: The global pandemic led to behavioral changes among college students in Latin America, and it affected their orientations to happiness and engagement. Institutions of higher learning are called to create opportunities for their students to reintegrate into an in-person learning environment to facilitate positive lifestyle changes for their students.

El COVID-19 ha cambiado las oportunidades educativas para los estudiantes de todo el mundo y en el proceso afectó su estilo de vida, felicidad y compromiso. La presente investigación es parte de un proyecto de seis universidades en diferentes países de América Latina para determinar el impacto de COVID-19 en estudiantes universitarios. Objetivos: El propósito de este estudio fue evaluar y comparar el impacto del COVID-19 en los cambios de estilo de vida, las orientaciones hacia la felicidad y el compromiso de los estudiantes entre una muestra de estudiantes universitarios en México, El Salvador, Colombia, República Dominicana, Perú y Estados Unidos. Métodos: Los participantes fueron 1764 estudiantes de los seis países previamente identificados. Los datos se recolectaron utilizando el Inventario de Conducta de Salud del Estudiante, la Escala de Orientaciones a la Felicidad y el Inventario de Participación de los Estudiantes Universitarios. Resultados. Los estudiantes encuestados eran en su mayoría mujeres con una edad promedio de 22 años. La mayoría informó que no hubo cambios en el rendimiento académico y cambios estadísticamente significativos en algunos comportamientos de estilo de vida, como la nutrición y la actividad física. Conclusiones: La pandemia global provocó cambios de comportamiento entre los estudiantes universitarios de América Latina y afectó sus orientaciones hacia la felicidad y su compromiso. Las instituciones de educación superior están llamadas a crear oportunidades para que sus estudiantes se reintegren en un entorno de aprendizaje en persona para facilitar cambios positivos en el estilo de vida de sus estudiantes.

Advancements and Technical Considerations for Extracellular Vesicle Isolation and Biomarker Identification in Glioblastoma.

Extracellular vesicles (EVs) are membrane-bound particles released by all cells. Previous research has found that these microscopic vesicles contribute to intercellular signaling and communication. EVs carry a variety of cargo, including nucleic acids, proteins, metabolites, and lipids. The composition of EVs varies based on cell of origin. Therefore, EVs can serve as an important biomarker in the diagnosis and treatment of various cancers. EVs derived from glioblastoma (GBM) cells carry biomarkers, which could serve as the basis for a potential diagnostic strategy known as liquid biopsy. Multiple EV isolation techniques exist, including ultrafiltration, size exclusion chromatography, flow field-flow fractionation, sequential filtration, differential ultracentrifugation, and density-gradient ultracentrifugation. Recent and ongoing work aims to identify cellular markers to distinguish GBM-derived EVs from those released by noncancerous cells. Strategies include proteomic analysis of GBM EVs, identification of GBM-specific metabolites, and use of Food and Drug Administration-approved 5-aminolevulinic acid-an oral agent that causes fluorescence of GBM cells-to recognize GBM EVs in a patient's blood. In addition, accurately and precisely monitoring changes in EV cargo concentrations could help differentiate between pseudoprogression and GBM recurrence, thus preventing unnecessary surgical interventions.

Novel 1,4-Dihydropyridine Derivatives as Mineralocorticoid Receptor Antagonists.

The mineralocorticoid receptor (MR) belongs to the steroid receptor subfamily of nuclear receptors. MR is a transcription factor key in regulating blood pressure and mineral homeostasis. In addition, it plays an important role in a broad range of biological and pathological conditions, greatly expanding its interest as a pharmacological target. Non-steroidal MR antagonists (MRAs) are of particular interest to avoid side effects and achieve tissue-specific modulation of the receptor. The 1,4-dihydropyridine (1,4-DHP) ring has been identified as an appropriate scaffold to develop non-steroidal MRAs. We report the identification of a novel series of 1,4-DHP that has been guided by structure-based drug design, focusing on the less explored DHP position 2. Interestingly, substituents at this position might interfere with MR helix H12 disposition, which is essential for the recruitment of co-regulators. Several of the newly synthesized 1,4-DHPs show interesting properties as MRAs and have a good selectivity profile. These 1,4-DHPs promote MR nuclear translocation with less efficiency than the natural agonist aldosterone, which explains, at least in part, its antagonist character. Molecular dynamic studies are suggestive of several derivatives interfering with the disposition of H12 in the agonist-associated conformation, and thus, they might stabilize an MR conformation unable to recruit co-activators.

High sugar but not high fat diet consumption induces hepatic metabolic disruption and up-regulation of mitochondrial fission-associated protein Drp1 in a model of moderate obesity.

Identification of new modifications and the association with diet patterns are essential for the prevention of non-alcoholic fatty liver disease (NAFLD). To address this problem, we feed rats with high caloric diets based on high sucrose (HSD) and high fat (HFD) and analysed metabolic and mitochondrial alterations. Both diets induce moderated obesity and fat accumulation in the liver after 8, 10 and 12 months of diet. The HSD induces both hyperleptinemia and hyperinsulinemia, as well as up-regulation of transcription factors SRBEP1 and PPARγ along slight increase nitrosylation of proteins and increased mitochondrial fission. In contrast, HFD induced hyperleptinemia without changes in neither insulin levels nor oxidative stress, SREBP1, PPARγ, or mitochondrial dynamics. In conclusion, chronic consumption of high sucrose content diets induces more pathological and metabolic alteration in liver in comparison with consumption of high-fat content diets, although both induces obesity and liver steatosis in these animal models.

Trends in long-term cancer survival in Cali, Colombia: 1998-2017.

Background: Population-based cancer survival is an indicator of the effectiveness of cancer services that reflects the survival of all cancer patients in the population, regardless of socioeconomic status and disease characteristics. Aim: Provision of an up-to-date survival estimate of patients recorded within Cali Population Cancer Registry (RPCC) in 1998-2017. As a second objective, results will be compared with those reported by the CONCORD study for cancers prioritized by the current Ten-Year Cancer Control Plan of Colombia, 2012-2021. Methods: Adult cancer cases (aged 15 to 99 years) for nine cancer types diagnosed between 1998 and 2017, with follow-up to 2018, were obtained from the RPCC. The 5-year age-standardized net survival estimates (NS) were estimated using the Pohar-Perme. The results for the period 1995- 2014 were compared with those reported by the CONCORD study for the following locations: stomach (C16), breast (C50), cervix (C53), prostate (C61), and lung (C33-34). Results: Five-year survival estimates for breast and prostate cancers improved ten percentage points through 2007 (70.8 to 81.1 for breast and 79.9 to 90.2 for prostate) and remained stable during 2008-2017. For cervical cancer, survival estimates has remained stable for the last two decades at 53%. For stomach cancer and lung cancer, five-year NS was lower than 25% over the study period. For colorectal cancer, survival estimates increased from 37.9% in 1998-2002 to 54.8% in 2013-2017. Compared to previous 5-year survival estimates of cases diagnosed in 2010-2014, the estimates in this study are significantly higher than those obtained by CONCORD. Survival estimates of patients diagnosed in 1995-2009 showed no difference to CONCORD study. Conclusions: Periodic update of vital status and date of last contact reduces bias in survival estimates in population-based cancer registries with passive follow-up.

Antecedentes: La supervivencia del cáncer es un indicador de la eficacia de los servicios oncológicos que refleja la supervivencia de todos los pacientes con cáncer de la población, independientemente del nivel socioeconómico y las características de la enfermedad. Objetivo: Realizar una estimación actualizada de la supervivencia de los pacientes registrados en el Registro Poblacional de Cáncer de Cali durante 1998-2017. Como segundo objetivo, los resultados se compararán con los reportados por el estudio CONCORD para los cánceres priorizados por el actual Plan Decenal de Control del Cáncer de Colombia, 2012-2021. Métodos: Los casos de cáncer en adultos (15 a 99 años) para nueve tipos de cáncer diagnosticados entre 1998 y 2017, con seguimiento hasta 2018, se obtuvieron del RPCC. Las estimaciones de supervivencia neta (NS) estandarizada por edad a 5 años se estimaron utilizando el método de Pohar-Perme. Los resultados del periodo 1995-2014 se compararon con los obtenidas por el estudio CONCORD para las siguientes localizaciones: estómago (C16), mama (C50), cuello uterino (C53), próstata (C61) y pulmón (C33-34). Resultados: La SN-5a para los cánceres de mama y próstata mejoró diez puntos porcentuales hasta 2007 (SN=70.8 a 81.1 para mama y NS=79.9 a 90.2 para próstata) y se mantuvo estable durante 2008-2017. Para el cáncer de cuello uterino fue 53% y permaneció estable durante dos décadas. Para el cáncer de estómago y el cáncer de pulmón, la SN-5años fue inferior al 25%. Para cáncer colorrectal las estimaciones de supervivencia aumentaron de 37.9% en 1998-2002 a 54.8% en 2013-2017. En comparación con estimaciones anteriores de supervivencia a 5 años de casos diagnosticados en 2010-2014, las estimaciones de este estudio son significativamente más altas que las obtenidas por CONCORD-3. Para la década 1995-2009 no hubo diferencia. Conclusión: La actualización periódica del estado vital y la fecha de último contacto reduce el sesgo en las estimaciones de supervivencia en los registros de cáncer de base poblacional que hacen seguimiento pasivo.

Survival in stomach cancer: analysis of a national cancer information system and a population-based cancer registry in Colombia

Background: Stomach cancer is among the most frequent, is a leading cause of mortality in low- and middle-income countries. Assessing its survival is important to guide evidence-based health policies. Aims: To estimate stomach cancer survival in Colombia (2014-2019) with data from the National Cancer Information System (NCIS) and in Cali with data from the Cali Population Cancer Registry (RPCC) (1998-2017). Methods: NCIS estimated the overall 3-year net survival for 8,549 people, while RPCC estimated 5-year net survival for 6,776 people. Results: The 3-year net survival was 36.8% (95% CI: 35.5-38.1). Net survival was higher in people with special insurance (61.7%; 95% CI: 44.8-74.8) or third payer (40.5%; 95% CI: 38.7-42.3) than state insurance (30.7%; 95% CI: 28.7-32.8). It was also higher in women and people diagnosed at early stages. Multivariable analysis showed consistency with survival estimations with a higher risk of death in men, people with state insurance, and diagnosed at advanced stages. In Cali, the 5-year net survival remained stable in men during the last 20 years. In women the 5-year net survival in women increased 8.60 percentage points, equivalent to a 50% increase compared to the 1998-2002 period. For 2013-17, it was 19.1% (95%CI: 16.2-22.2) in men, and 24.8% (95% CI: 20.4-29.3) in women. Conclusions: Population survival estimates from the RPCC were lower than those observed in the NCIS. The differences in their methods and scope can explain variability. Nevertheless, our findings could be complementary to improve cancer control planning in the country.

Antecedentes: El cáncer de estómago se encuentra entre los más frecuentes y es una de las principales causas de mortalidad en los países de ingresos bajos y medianos. Evaluar su supervivencia es importante para orientar las políticas de salud basadas en la evidencia. Objetivos: Estimar la supervivencia del cáncer de estómago en Colombia (2014-2019) con datos del Sistema Nacional de Información del Cáncer (NCIS) y en Cali con datos del Registro Poblacional de Cáncer de Cali (RPCC) (1998-2017). Métodos: El NCIS estimó la supervivencia neta a tres años para 8,549 personas y el RPCC la calculó a 5 años para 6,776 personas registradas en sus bases de datos. Resultados: La supervivencia neta a tres años en Colombia fue del 36.8% (IC 95%: 35.5-38.1). La supervivencia neta fue mayor en personas con seguro especial (61.7%; IC 95%: 44.8-74.8) o tercer pagador (40.5%; IC 95%: 38.7-42.3) que el seguro estatal (30.7%; IC 95%: 28.7-32.8). También fue mayor en mujeres y personas diagnosticadas en etapas tempranas. El análisis multivariable mostró consistencia con la estimación de supervivencia con mayor riesgo de muerte en hombres, personas con seguro estatal y diagnosticados en estadios avanzados. En Cali, la supervivencia neta a 5 años se mantuvo estable en los hombres durante los últimos 20 años. En las mujeres aumentó 8.60 puntos porcentuales, equivalente a un aumento del 50% en comparación con el período 1998-2002. Para el período 2013-17 fue 19.1% (IC 95%: 16.2-22.2) en los hombres y 24.8% (IC 95%: 20.4-29.3) en las mujeres. Conclusiones: Las estimaciones de supervivencia del RPCC fueron más bajas que las obtenidas por el NCIS. Las diferencias en sus métodos y alcance pueden explicar la variabilidad. Sin embargo, nuestros hallazgos pueden ser complementarios para mejorar la planificación del control del cáncer en el país..

Cancer epidemiology in Cali, 60 years of experience.

Background: The population-based Cancer Registry of Cali Colombia operates continuously since 1962, disseminating incidence information in the XI volumes of Cancer Incidence in Five Continents. Aim: To describe the incidence and mortality rates for the period 2011-2020 and the changes in the trend of incidence rates (1962-2017) and mortality rates from cancer (1986-2020). Methods: The Joinpoint model and the annual percentage change (APC) were used as summary measures of the changes in the trends of incidence rates (ASR-I) and mortality (ASR-M) standardized by age with the direct method. Results: Trough 1988-2017 the ASR-I for all locations increased 0.4% annually (95% CI: 0.2, 0.6) in men and decreased annually 0.2% (95% CI: -0.3; -0.1) in women. The ASR-Is of cancers related to opportunity screening activities (prostate and breast) increased until the early 21st century and then decreased. The ASR-I of cancers related to infectious agents continue to decrease (cervix, vulva, and stomach). There is evidence of control of cancer related to tobacco consumption (lung, oral cavity, bladder). In both sexes, the ASR-I of thyroid, colorectal and lymphoma cancers increased and those of ovarian cancer decreased. Between 1984-2020 the ASR-M for all locations decreased annually 0.7% (95% CI: -0.9, -0.5) in men and 1.1% (95% CI: -1.3, -0.9) in women. For both sexes, ASR-M decreased for cancers of the esophagus, stomach, lung, bladder, lymphomas, and leukemias; and increased in colorectal cancer. The ASR-M for cervical and prostate cancer decreased annually by 3.5% (95% CI: -3.9, -3.2) and 0.1% (95% CI: -0.5, -0.3), respectively. Comment: This information allows the construction of some indicators to monitor the City Cancer Challenge initiative and the current 10-year plan for cancer control in Colombia, 2011-2021.

Antecedentes: El registro poblacional de Cáncer de Cali-Colombia, opera desde 1962 divulgando continuamente la información de incidencia en los XI volúmenes de Cancer Incidence in Five Continents. Objetivo: Describir las tasas de incidencia y mortalidad del periodo 2011-2020 y los cambios en la tendencia de las tasas de incidencia (1962-2017) y mortalidad por cáncer (1986-2020). Métodos: Se utilizó el modelo de Joinpoint y el cambio porcentual anual (APC) como medidas de resumen de los cambios en las tendencias de las tasas de incidencia (ASR-I) y mortalidad (ASR-M) estandarizadas por edad con el método directo. Resultados: Durante el periodo 1988-2017 las ASR-I para todas las localizaciones aumentaron anualmente 0.4% (IC 95%: 0.2; 0.6) en los hombres y disminuyeron anualmente 0.2% (IC 95%: -0.3; -0.1) en las mujeres. Las ASR-I de los cánceres relacionados con actividades de tamización de oportunidad (próstata y mama) aumentaron hasta principios del siglo XXI y luego descendieron. Las ASR-I de los canceres relacionados con agentes infecciosos continúan disminuyendo (cérvix, vulva y estómago). Hay evidencias de control de los cánceres relacionados al consumo de tabaco (pulmón, cavidad oral, vejiga). En ambos sexos aumentaron las ASR-I de los cánceres de tiroides, colorrectal y linfomas y disminuyeron las de cáncer de ovario. Entre 1984-2020 las ASR-M para todas las localizaciones disminuyeron anualmente 0.7% (IC 95%: -0.9; -0.5) en los hombres y 1.1% (IC 95%: -1.3; -0.9) en las mujeres. Para ambos sexos, disminuyeron las ASR-M para los cánceres de esófago, estómago, pulmón, vejiga, linfomas y leucemias; y aumentaron en cáncer colorrectal. Las ASR-M por cáncer de cérvix y próstata disminuyeron anualmente 3.5% (IC 95%: -3.9; -3.2) y 0.1% (IC 95%: -0.5; -0.3), respectivamente. Comentario: Esta información permite construir algunos indicadores para monitorear la iniciativa City Cancer Challenge y el actual Plan Decenal para el Control del Cáncer en Colombia, 2011-2021.