Detection of a historic reservoir of bedaquiline/clofazimine resistance-associated variants in Mycobacterium tuberculosis.

BACKGROUND: Drug resistance in tuberculosis (TB) poses a major ongoing challenge to public health. The recent inclusion of bedaquiline into TB drug regimens has improved treatment outcomes, but this advance is threatened by the emergence of strains of Mycobacterium tuberculosis (Mtb) resistant to bedaquiline. Clinical bedaquiline resistance is most frequently conferred by off-target resistance-associated variants (RAVs) in the mmpR5 gene (Rv0678), the regulator of an efflux pump, which can also confer cross-resistance to clofazimine, another TB drug. METHODS: We compiled a dataset of 3682 Mtb genomes, including 180 carrying variants in mmpR5, and its immediate background (i.e. mmpR5 promoter and adjacent mmpL5 gene), that have been associated to borderline (henceforth intermediate) or confirmed resistance to bedaquiline. We characterised the occurrence of all nonsynonymous mutations in mmpR5 in this dataset and estimated, using time-resolved phylogenetic methods, the age of their emergence. RESULTS: We identified eight cases where RAVs were present in the genomes of strains collected prior to the use of bedaquiline in TB treatment regimes. Phylogenetic reconstruction points to multiple emergence events and circulation of RAVs in mmpR5, some estimated to predate the introduction of bedaquiline. However, epistatic interactions can complicate bedaquiline drug-susceptibility prediction from genetic sequence data. Indeed, in one clade, Ile67fs (a RAV when considered in isolation) was estimated to have emerged prior to the antibiotic era, together with a resistance reverting mmpL5 mutation. CONCLUSIONS: The presence of a pre-existing reservoir of Mtb strains carrying bedaquiline RAVs prior to its clinical use augments the need for rapid drug susceptibility testing and individualised regimen selection to safeguard the use of bedaquiline in TB care and control.

Socioeconomic and Demographic Risk Factors for SARS-CoV-2 Seropositivity Among Healthcare Workers in a UK Hospital: A Prospective Cohort Study.

BACKGROUND: To protect healthcare workers (HCWs) from the consequences of disease due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is necessary to understand the risk factors that drive exposure and infection within hospitals. Insufficient consideration of key socioeconomic variables is a limitation of existing studies that can lead to bias and residual confounding of proposed risk factors for infection. METHODS: The Co-STARs study prospectively enrolled 3679 HCWs between April 2020 and September 2020. We used multivariate logistic regression to comprehensively characterize the demographic, occupational, socioeconomic, and environmental risk factors for SARS-CoV-2 seropositivity. RESULTS: After adjusting for key confounders, relative household overcrowding (odds ratio [OR], 1.4 [95% confidence interval {CI}, 1.1-1.9]; P = .006), Black, Black British, Caribbean, or African ethnicity (OR, 1.7 [95% CI, 1.2-2.3]; P = .003), increasing age (ages 50-60 years: OR, 1.8 [95% CI, 1.3-2.4]; P < .001), lack of access to sick pay (OR, 1.8 [95% CI, 1.3-2.4]; P < .001). CONCLUSIONS: Socioeconomic and demographic factors outside the hospital were the main drivers of infection and exposure to SARS-CoV-2 during the first wave of the pandemic in an urban pediatric referral hospital. Overcrowding and out-of-hospital SARS-CoV-2 contact are less amenable to intervention. However, lack of access to sick pay among externally contracted staff is more easily rectifiable. Our findings suggest that providing easier access to sick pay would lead to a decrease in SARS-CoV-2 transmission and potentially that of other infectious diseases in hospital settings. CLINICAL TRIALS REGISTRATION: NCT04380896.

Within-host diversity improves phylogenetic and transmission reconstruction of SARS-CoV-2 outbreaks.

Accurate inference of who infected whom in an infectious disease outbreak is critical for the delivery of effective infection prevention and control. The increased resolution of pathogen whole-genome sequencing has significantly improved our ability to infer transmission events. Despite this, transmission inference often remains limited by the lack of genomic variation between the source case and infected contacts. Although within-host genetic diversity is common among a wide variety of pathogens, conventional whole-genome sequencing phylogenetic approaches exclusively use consensus sequences, which consider only the most prevalent nucleotide at each position and therefore fail to capture low-frequency variation within samples. We hypothesized that including within-sample variation in a phylogenetic model would help to identify who infected whom in instances in which this was previously impossible. Using whole-genome sequences from SARS-CoV-2 multi-institutional outbreaks as an example, we show how within-sample diversity is partially maintained among repeated serial samples from the same host, it can transmitted between those cases with known epidemiological links, and how this improves phylogenetic inference and our understanding of who infected whom. Our technique is applicable to other infectious diseases and has immediate clinical utility in infection prevention and control.

During an infectious disease outbreak, tracing who infected whom allows public health scientists to see how a pathogen is spreading and to establish effective control measures. Traditionally, this involves identifying the individuals an infected person comes into contact with and monitoring whether they also become unwell. However, this information is not always available and can be inaccurate. One alternative is to track the genetic data of pathogens as they spread. Over time, pathogens accumulate mutations in their genes that can be used to distinguish them from one another. Genetically similar pathogens are more likely to have spread during the same outbreak, while genetically dissimilar pathogens may have come from different outbreaks. However, there are limitations to this approach. For example, some pathogens accumulate genetic mutations very slowly and may not change enough during an outbreak to be distinguishable from one another. Additionally, some pathogens can spread rapidly, leaving less time for mutations to occur between transmission events. To overcome these challenges, Torres Ortiz et al. developed a more sensitive approach to pathogen genetic testing that took advantage of the multiple pathogen populations that often coexist in an infected patient. Rather than tracking only the most dominant genetic version of the pathogen, this method also looked at the less dominant ones. Torres Ortiz et al. performed genome sequencing of SARS-CoV-2 (the virus that causes COVID-19) samples from 451 healthcare workers, patients, and patient contacts at participating London hospitals. Analysis showed that it was possible to detect multiple genetic populations of the virus within individual patients. These subpopulations were often more similar in patients that had been in contact with one another than in those that had not. Tracking the genetic data of all viral populations enabled Torres Ortiz et al. to trace transmission more accurately than if only the dominant population was used. More accurate genetic tracing could help public health scientists better track pathogen transmission and control outbreaks. This may be especially beneficial in hospital settings where outbreaks can be smaller, and it is important to understand if transmission is occurring within the hospital or if the pathogen is imported from the community. Further research will help scientists understand how pathogen population genetics evolve during outbreaks and may improve the detection of subpopulations present at very low frequencies.

The influence of time on the sensitivity of SARS-CoV-2 serological testing.

Sensitive serological testing is essential to estimate the proportion of the population exposed or infected with SARS-CoV-2, to guide booster vaccination and to select patients for treatment with anti-SARS-CoV-2 antibodies. The performance of serological tests is usually evaluated at 14-21 days post infection. This approach fails to take account of the important effect of time on test performance after infection or exposure has occurred. We performed parallel serological testing using 4 widely used assays (a multiplexed SARS-CoV-2 Nucleoprotein (N), Spike (S) and Receptor Binding Domain assay from Meso Scale Discovery (MSD), the Roche Elecsys-Nucleoprotein (Roche-N) and Spike (Roche-S) assays and the Abbott Nucleoprotein assay (Abbott-N) on serial positive monthly samples collected as part of the Co-STARs study ( www.clinicaltrials.gov , NCT04380896) up to 200 days following infection. Our findings demonstrate the considerable effect of time since symptom onset on the diagnostic sensitivity of different assays. Using a time-to-event analysis, we demonstrated that 50% of the Abbott nucleoprotein assays will give a negative result after 175 days (median survival time 95% CI 168-185 days), compared to the better performance over time of the Roche Elecsys nucleoprotein assay (93% survival probability at 200 days, 95% CI 88-97%). Assays targeting the spike protein showed a lower decline over the follow-up period, both for the MSD spike assay (97% survival probability at 200 days, 95% CI 95-99%) and the Roche Elecsys spike assay (95% survival probability at 200 days, 95% CI 93-97%). The best performing quantitative Roche Elecsys Spike assay showed no evidence of waning Spike antibody titers over the 200-day time course of the study. We have shown that compared to other assays evaluated, the Abbott-N assay fails to detect SARS-CoV-2 antibodies as time passes since infection. In contrast the Roche Elecsys Spike Assay and the MSD assay maintained a high sensitivity for the 200-day duration of the study. These limitations of the Abbott assay should be considered when quantifying the immune correlates of protection or the need for SARS-CoV-2 antibody therapy. The high levels of maintained detectable neutralizing spike antibody titers identified by the quantitative Roche Elecsys assay is encouraging and provides further evidence in support of long-lasting SARS-CoV-2 protection following natural infection.

Within-host diversity improves phylogenetic and transmission reconstruction of SARS-CoV-2 outbreaks.

Accurate inference of who infected whom in an infectious disease outbreak is critical for the delivery of effective infection prevention and control. The increased resolution of pathogen whole-genome sequencing has significantly improved our ability to infer transmission events. Despite this, transmission inference often remains limited by the lack of genomic variation between the source case and infected contacts. Although within-host genetic diversity is common among a wide variety of pathogens, conventional whole-genome sequencing phylogenetic approaches to reconstruct outbreaks exclusively use consensus sequences, which consider only the most prevalent nucleotide at each position and therefore fail to capture low frequency variation within samples. We hypothesized that including within-sample variation in a phylogenetic model would help to identify who infected whom in instances in which this was previously impossible. Using whole-genome sequences from SARS-CoV-2 multi-institutional outbreaks as an example, we show how within-sample diversity is stable among repeated serial samples from the same host, is transmitted between those cases with known epidemiological links, and how this improves phylogenetic inference and our understanding of who infected whom. Our technique is applicable to other infectious diseases and has immediate clinical utility in infection prevention and control.

The Influence of Time on the Sensitivity of SARS-CoV-2 Serological Testing.

Background: Serological testing is used to quantify SARS-CoV-2 seroprevalence, guide booster vaccination and select patients for anti-SARS-CoV-2 antibodies therapy. However, our understanding of how serological tests perform as time passes after infection is limited. Methods: Four assays were compared in parallel: 1) the multiplexed spike, nucleoprotein and receptor binding domain Meso Scale Discovery (MSD) assay 2) the Roche Elecsys-Nucleoprotein assay (Roche-N) 3) the Roche Spike assay (Roche-S) and 4) the Abbott Nucleoprotein assay (Abbott-N) on serial positive monthly samples from hospital staff up to 200 days following infection as part of the Co-Stars study. Results: We demonstrate that 50% of the Abbott-N assays give a negative result after 175 days (median survival time 95% CI 168-185 days) while the Roche-N assay (93% survival probability at 200 days, 95% CI 88-97%) maintained seropositivity. The MSD spike (97% survival probability at 200 days, 95% CI 95-99%) and the Roche-S assay (95% survival probability at 200 days, 95% CI 93-97%) also remained seropositive. The best performing quantitative Roche-S assay showed no evidence of waning Spike antibody titres over 200-days. Conclusions: The Abbott-N assay fails to detect SARS-CoV-2 antibodies as time passes since infection. In contrast the Roche and the MSD assays maintained high sensitivity. The limitations of the Abbott assay must be considered in clinical decision making. The long duration of detectable neutralizing spike antibody titres by the quantitative Roche-S assay provides further evidence in support of long-lasting SARS-CoV-2 protection to pre-existing strains of SARS-CoV-2 following natural infection. Trial registration : Co-STARs study was registered with ClinicalTrials.gov on May 8th, 2020, with trial number NCT04380896 (www.clinicaltrials.gov, NCT04380896).

Long-Term Persistence of Spike Protein Antibody and Predictive Modeling of Antibody Dynamics After Infection With Severe Acute Respiratory Syndrome Coronavirus 2.

BACKGROUND: Antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been shown to neutralize the virus in vitro and prevent disease in animal challenge models on reexposure. However, the current understanding of SARS-CoV-2 humoral dynamics and longevity is conflicting. METHODS: The COVID-19 Staff Testing of Antibody Responses Study (Co-Stars) prospectively enrolled 3679 healthcare workers to comprehensively characterize the kinetics of SARS-CoV-2 spike protein (S), receptor-binding domain, and nucleoprotein (N) antibodies in parallel. Participants screening seropositive had serial monthly serological testing for a maximum of 7 months with the Meso Scale Discovery Assay. Survival analysis determined the proportion of seroreversion, while 2 hierarchical gamma models predicted the upper and lower bounds of long-term antibody trajectory. RESULTS: A total of 1163 monthly samples were provided from 349 seropositive participants. At 200 days after symptoms, >95% of participants had detectable S antibodies, compared with 75% with detectable N antibodies. S antibody was predicted to remain detectable in 95% of participants until 465 days (95% confidence interval, 370-575 days) using a "continuous-decay" model and indefinitely using a "decay-to-plateau" model to account for antibody secretion by long-lived plasma cells. S-antibody titers were correlated strongly with surrogate neutralization in vitro (R2 = 0.72). N antibodies, however, decayed rapidly with a half-life of 60 days (95% confidence interval, 52-68 days). CONCLUSIONS: The Co-Stars data presented here provide evidence for long-term persistence of neutralizing S antibodies. This has important implications for the duration of functional immunity after SARS-CoV-2 infection. In contrast, the rapid decay of N antibodies must be considered in future seroprevalence studies and public health decision-making. This is the first study to establish a mathematical framework capable of predicting long-term humoral dynamics after SARS-CoV-2 infection. CLINICAL TRIALS REGISTRATION: NCT04380896.

A systematic review of tuberculosis detection and prevention studies in prisons.

Many studies have demonstrated that prisons are hotspots of tuberculosis disease and transmission. Despite this, it remains unclear which interventions are most effective at controlling tuberculosis in prisons. The objective was to determine the study designs used to investigate tuberculosis control in prisons, and the efficacy of interventions undertaken. This systematic review included published studies which had the aim of reducing TB incidence or prevalence, or increasing the number of people screened for active pulmonary tuberculosis in incarcerated populations. 2,429 records were identified, 178 full-text articles were screened, and 17 studies included. The majority of reports were before/after or prospective non-comparative studies. The median study duration was 23 months (range 5-144). The most common intervention was the introduction of active case finding (10/17 studies) but the timing and methods varied. Comparable pre- and post intervention outcome values were infrequently reported; therefore, it was not possible to quantify the efficacy of interventions. Data from studies of tuberculosis control in prisons is limited by a lack of: controlled interventions, reporting of pre-intervention methods, and comparable pre- and post-intervention outcomes. Prospective comparative trials of adequate duration to determine trends in incidence are necessary to understand which interventions are effective in prisons.

Genomic signatures of pre-resistance in Mycobacterium tuberculosis.

Recent advances in bacterial whole-genome sequencing have resulted in a comprehensive catalog of antibiotic resistance genomic signatures in Mycobacterium tuberculosis. With a view to pre-empt the emergence of resistance, we hypothesized that pre-existing polymorphisms in susceptible genotypes (pre-resistance mutations) could increase the risk of becoming resistant in the future. We sequenced whole genomes from 3135 isolates sampled over a 17-year period. After reconstructing ancestral genomes on time-calibrated phylogenetic trees, we developed and applied a genome-wide survival analysis to determine the hazard of resistance acquisition. We demonstrate that M. tuberculosis lineage 2 has a higher risk of acquiring resistance than lineage 4, and estimate a higher hazard of rifampicin resistance evolution following isoniazid mono-resistance. Furthermore, we describe loci and genomic polymorphisms associated with a higher risk of resistance acquisition. Identifying markers of future antibiotic resistance could enable targeted therapy to prevent resistance emergence in M. tuberculosis and other pathogens.

Calidad de vida y estrategias de afrontamiento en pacientes con cáncer ginecológico / Quality of life and coping strategies in patients with gynecological cancer

Resumen Introducción: El cáncer ginecológico impacta psicológicamente a la mujer. En este proceso las Estrategias de Afrontamiento-EA, al parecer, se asocian con la Calidad de Vida relacionada con la Salud-CvRS; sin embargo, se desconoce el valor predictivo de las EA sobre la CvRS. Este artículo tiene como finalidad identificar las diferencias y la naturaleza de la relación entre la CvRS y las EA respecto al apoyo psicológico, así como identificar si las EA predicen la CvRS. Método: Se efectuó un diseño no-experimental con 55 mujeres entre 27 y 69 años, M = 42.3, DE = 10.1, diagnosticadas con cáncer ginecológico. La CvRS se evaluó con el FACT-Cx y el SF-36; las EA, con el CAEPO. Resultados: las mujeres con asistencia psicológica tienen mejor CvRS y EA, igualmente, la CvRS se correlacionó con las EA positivas. La dimensión de salud general también es explicada por las EA positivas e inversamente por las EA negativas. Las EA que mejor predicen las CvRS son: Enfrentamiento y Lucha Activa, y Autocontrol y Control Emocional, mientras que las EA negativas afectan la CvRS. Conclusión: Los resultados resaltan la necesidad de acompañamiento psicológico que promueva EA positivas y beneficien la CvRS en mujeres con cáncer ginecológico.

Abstract Introduction: Gynecological cancer impacts women psychologically. In this process, the Coping Strategies-CS are apparently associated with Health-Related Quality of Life HRQL; however, the predictive value of CS on HRQL is unknown. This article aims to identify the differences and the nature of the relationship of HRQL and CS regarding psychological support, as well as to identify whether CS predict HRQL. Method: A non-experimental design was performed with 55 women between 27 and 69 years old, M = 42.3, DE = 10.1, diagnosed with gynecological cancer. The HRQL was evaluated with the FACT-Cx and the SF-36; and the CS, with CAEPO (Spanish acronym). Results: Women with psychological support have better HRQL and CS, likewise, HRQL was correlated with positive CS. The general health dimension is also explained by positive CS, and inversely by negative CS. The CS that best predict HRQL are: active confrontation and fighting, and self-control and emotional control, while negative CS affect HRQL. Conclusion: The results highlight the need for psychological support that promotes positive CS and benefits HRQL in women with gynecological cancer.

Excerpts from the documents of Mexican positions and recommendations in cardiovascular diseases and COVID-19.

The recommendations in which the Mexican Society of Cardiology (SMC) in conjunction with the National Association of Cardiologists of Mexico (ANCAM) as well as different Mexican medical associations linked to cardiology are presented, after a comprehensive and consensual review and analysis of the topics related to cardiovascular diseases in the COVID-19 pandemic. Scientific positions are analyzed and responsible recommendations on general measures are given to patients, with personal care, healthy eating, regular physical activity, actions in case of cardio-respiratory arrest, protection of the patient and health personnel as well as precise indications in the use of non-invasive cardiovascular imaging, prescription of medications, care in specific topics such as systemic arterial hypertension, heart failure, arrhythmias and acute coronary syndromes, in addition to emphasizing electrophysiology, interventionism, cardiac surgery and in cardiac rehabilitation. The main interest is to provide the medical community with a general orientation on what to do in daily practice and patients with cardiovascular diseases in the setting of this unprecedented epidemiological crisis of COVID-19.

Se presentan las recomendaciones en las cuales la Sociedad Mexicana de Cardiología (SMC) en conjunto con la Asociación Nacional de Cardiólogos de México (ANCAM), así como diferentes asociaciones médicas mexicanas vinculadas con la cardiología, después de una revisión y análisis exhaustivo y consensuado sobre los tópicos relacionados con las enfermedades cardiovasculares en la pandemia de COVID-19, se analizan posturas científicas y se dan recomendaciones responsables sobre medidas generales a los pacientes, con cuidados personales, alimentación saludable, actividad física regular, acciones en caso de paro cardiorrespiratorio, la protección del paciente y del personal de salud así como las indicaciones precisas en el uso de la imagen cardiovascular no invasiva, la prescripción de medicamentos, cuidados en tópicos específicos como en la hipertensión arterial sistémica, insuficiencia cardiaca, arritmias y síndromes coronarios agudos, además de hacer énfasis en los procedimientos de electrofisiología, intervencionismo, cirugía cardiaca y en la rehabilitación cardiaca. El interés principal es brindar a la comunidad médica una orientación general sobre el quehacer en la práctica cotidiana y pacientes con enfermedades cardiovasculares en el escenario esta crisis epidemiológica sin precedentes de COVID-19.

Recommendations for the care of patients with heart failure and COVID-19.

The COVID-19 pandemic decreed by the World Health Organization (WHO) since March 12, 2020 is wreaking havoc globally and it is a true economic, social and health challenge. Although the clinical manifestations of COVID-19 are respiratory symptoms, some patients also have cardiological symptoms. Among patients with cardiological conditions2 they represent a group of higher risk and, in fact, they are a particularly vulnerable group, due to their higher risk of contagion and greater severity in case of acquiring the disease1 those with heart failure (HF), including heart transplant (CT) and ventricular assists, as well as patients with pulmonary arterial hypertension (PAH). HF is the main chronic cardiovascular disease and patients in this group are the most vulnerable for the development of more serious clinical symptoms after suffering the infection, and to a greater extent cases with advanced HF3. In fact, HF is one of the most frequent complications in patients with COVID-194. Likewise, transplant patients who require immunosuppressants to avoid graft rejection, constitute a population especially susceptible to infection and to develop more serious processes. This situation has made the National Association of Cardiologists of Mexico (ANCAM) and the Mexican Society of Cardiology (SMC) together with their respective chapters, have prepared the following recommendations for medical personnel, who participate in the care of this special group of patients in the different clinical settings, who suffer or not, of COVID-19.

La pandemia por COVID-19 decretada por la Organización Mundial de la Salud (OMS) desde el 12 de marzo de 2020 está produciendo estragos a nivel mundial y es un verdadero reto económico, social y sanitario. Aunque las manifestaciones clínicas del COVID-19 son síntomas respiratorios, algunos pacientes también tienen síntomas cardiológicos. Dentro de los pacientes con afecciones cardiológicas2 suponen un grupo de mayor riesgo y que de hecho son un grupo especialmente vulnerable, por su mayor riesgo de contagio y mayor gravedad en caso de adquirir la enfermedad1 aquellos con insuficiencia cardiaca (IC), incluyendo al trasplante cardiaco (TC) y las asistencias ventriculares, así como los pacientes con hipertensión arterial pulmonar (HAP). La IC es la principal patología cardiovascular crónica y los pacientes en este grupo son los más vulnerables para el desarrollo de cuadros clínicos más graves tras sufrir la infección, y en mayor medida los casos con IC avanzada3. De hecho, la IC es unas de las complicaciones más frecuentes en los pacientes con COVID-194. De igual forma, los pacientes trasplantados que requieren de los inmunosupresores para evitar el rechazo del injerto, constituyen una población especialmente susceptible a la infección y a desarrollar procesos más graves. Esta situación ha hecho que la Asociación Nacional de Cardiólogos de México (ANCAM) y la Sociedad Mexicana de Cardiología (SMC) junto con sus respectivos capítulos, hayan elaborado las siguientes recomendaciones para el personal médico, que participa en la atención de este grupo especial de pacientes en los diferentes escenarios clínicos, que padezcan o no, COVID-19.

Emergence of genomic diversity and recurrent mutations in SARS-CoV-2.

SARS-CoV-2 is a SARS-like coronavirus of likely zoonotic origin first identified in December 2019 in Wuhan, the capital of China's Hubei province. The virus has since spread globally, resulting in the currently ongoing COVID-19 pandemic. The first whole genome sequence was published on January 5 2020, and thousands of genomes have been sequenced since this date. This resource allows unprecedented insights into the past demography of SARS-CoV-2 but also monitoring of how the virus is adapting to its novel human host, providing information to direct drug and vaccine design. We curated a dataset of 7666 public genome assemblies and analysed the emergence of genomic diversity over time. Our results are in line with previous estimates and point to all sequences sharing a common ancestor towards the end of 2019, supporting this as the period when SARS-CoV-2 jumped into its human host. Due to extensive transmission, the genetic diversity of the virus in several countries recapitulates a large fraction of its worldwide genetic diversity. We identify regions of the SARS-CoV-2 genome that have remained largely invariant to date, and others that have already accumulated diversity. By focusing on mutations which have emerged independently multiple times (homoplasies), we identify 198 filtered recurrent mutations in the SARS-CoV-2 genome. Nearly 80% of the recurrent mutations produced non-synonymous changes at the protein level, suggesting possible ongoing adaptation of SARS-CoV-2. Three sites in Orf1ab in the regions encoding Nsp6, Nsp11, Nsp13, and one in the Spike protein are characterised by a particularly large number of recurrent mutations (>15 events) which may signpost convergent evolution and are of particular interest in the context of adaptation of SARS-CoV-2 to the human host. We additionally provide an interactive user-friendly web-application to query the alignment of the 7666 SARS-CoV-2 genomes.

Variability in the Massive Open Cluster NGC 1817 from K2: A Rich Population of Asteroseismic Red Clump, Eclipsing Binary, and Main-sequence Pulsating Stars.

We present a survey of variable stars detected in K2 Campaign 13 within the massive intermediate-age (~1 Gyr) open cluster NGC 1817. We identify a complete sample of 44 red clump stars in the cluster, and have measured asteroseismic quantities (ν max and/or Δν) for 29 of them. Five stars showed suppressed dipole modes, and the occurrence rates indicate that mode suppression is unaffected by evolution through core helium burning. A subset of the giants in NGC 1817 (and in the similarly aged cluster NGC 6811) have ν max and Δν values at or near the maximum observed for core helium-burning stars, indicating they have core masses near the minimum for fully nondegenerate helium ignition. Further asteroseismic study of these stars can constrain the minimum helium core mass in red clump stars and the physics that determines this limit. Two giant stars show photometric variations on timescales similar to previously measured spectroscopic orbits. Thirteen systems in the field show eclipses, but only five are probable cluster members. We identify 32 δ Sct pulsators, 27 γ Dor candidates, and 7 hybrids that are probable cluster members, with most being new detections. We used the ensemble properties of the δ Sct stars to identify stars with possible radial pulsation modes. Among the oddities we have uncovered are: an eccentric orbit for a short-period binary containing a δ Sct pulsating star; a rare subgiant within the Hertzsprung gap showing δ Sct pulsations; and two hot γ Dor pulsating star candidates.

Recomendaciones para la atención de pacientes con insuficiencia cardiaca y COVID-19 / Recommendations for the care of patients with heart failure and COVID-19

Resumen La pandemia por COVID-19 decretada por la Organización Mundial de la Salud (OMS) desde el 12 de marzo de 2020 está produciendo estragos a nivel mundial y es un verdadero reto económico, social y sanitario. Aunque las manifestaciones clínicas del COVID-19 son síntomas respiratorios, algunos pacientes también tienen síntomas cardiológicos. Dentro de los pacientes con afecciones cardiológicas2 suponen un grupo de mayor riesgo y que de hecho son un grupo especialmente vulnerable, por su mayor riesgo de contagio y mayor gravedad en caso de adquirir la enfermedad1 aquellos con insuficiencia cardiaca (IC), incluyendo al trasplante cardiaco (TC) y las asistencias ventriculares, así como los pacientes con hipertensión arterial pulmonar (HAP). La IC es la principal patología cardiovascular crónica y los pacientes en este grupo son los más vulnerables para el desarrollo de cuadros clínicos más graves tras sufrir la infección, y en mayor medida los casos con IC avanzada3. De hecho, la IC es unas de las complicaciones más frecuentes en los pacientes con COVID-194. De igual forma, los pacientes trasplantados que requieren de los inmunosupresores para evitar el rechazo del injerto, constituyen una población especialmente susceptible a la infección y a desarrollar procesos más graves. Esta situación ha hecho que la Asociación Nacional de Cardiólogos de México (ANCAM) y la Sociedad Mexicana de Cardiología (SMC) junto con sus respectivos capítulos, hayan elaborado las siguientes recomendaciones para el personal médico, que participa en la atención de este grupo especial de pacientes en los diferentes escenarios clínicos, que padezcan o no, COVID-19.

Abstract The COVID-19 pandemic decreed by the World Health Organization (WHO) since March 12, 2020 is wreaking havoc globally and it is a true economic, social and health challenge. Although the clinical manifestations of COVID-19 are respiratory symptoms, some patients also have cardiological symptoms. Among patients with cardiological conditions2 they represent a group of higher risk and, in fact, they are a particularly vulnerable group, due to their higher risk of contagion and greater severity in case of acquiring the disease1 those with heart failure (HF), including heart transplant (CT) and ventricular assists, as well as patients with pulmonary arterial hypertension (PAH). HF is the main chronic cardiovascular disease and patients in this group are the most vulnerable for the development of more serious clinical symptoms after suffering the infection, and to a greater extent cases with advanced HF3. In fact, HF is one of the most frequent complications in patients with COVID-194. Likewise, transplant patients who require immunosuppressants to avoid graft rejection, constitute a population especially susceptible to infection and to develop more serious processes. This situation has made the National Association of Cardiologists of Mexico (ANCAM) and the Mexican Society of Cardiology (SMC) together with their respective chapters, have prepared the following recommendations for medical personnel, who participate in the care of this special group of patients in the different clinical settings, who suffer or not, of COVID-19.

Extractos de los documentos de posicionamientos y recomendaciones mexicanas en enfermedades cardiovasculares y COVID-19 / Excerpts from the documents of Mexican positions and recommendations in cardiovascular diseases and COVID-19

Resumen Se presentan las recomendaciones en las cuales la Sociedad Mexicana de Cardiología (SMC) en conjunto con la Asociación Nacional de Cardiólogos de México (ANCAM), así como diferentes asociaciones médicas mexicanas vinculadas con la cardiología, después de una revisión y análisis exhaustivo y consensuado sobre los tópicos relacionados con las enfermedades cardiovasculares en la pandemia de COVID-19, se analizan posturas científicas y se dan recomendaciones responsables sobre medidas generales a los pacientes, con cuidados personales, alimentación saludable, actividad física regular, acciones en caso de paro cardiorrespiratorio, la protección del paciente y del personal de salud así como las indicaciones precisas en el uso de la imagen cardiovascular no invasiva, la prescripción de medicamentos, cuidados en tópicos específicos como en la hipertensión arterial sistémica, insuficiencia cardiaca, arritmias y síndromes coronarios agudos, además de hacer énfasis en los procedimientos de electrofisiología, intervencionismo, cirugía cardiaca y en la rehabilitación cardiaca. El interés principal es brindar a la comunidad médica una orientación general sobre el quehacer en la práctica cotidiana y pacientes con enfermedades cardiovasculares en el escenario esta crisis epidemiológica sin precedentes de COVID-19.

Abstract The recommendations in which the Mexican Society of Cardiology (SMC) in conjunction with the National Association of Cardiologists of Mexico (ANCAM) as well as different Mexican medical associations linked to cardiology are presented, after a comprehensive and consensual review and analysis of the topics related to cardiovascular diseases in the COVID-19 pandemic. Scientific positions are analyzed and responsible recommendations on general measures are given to patients, with personal care, healthy eating, regular physical activity, actions in case of cardio-respiratory arrest, protection of the patient and health personnel as well as precise indications in the use of non-invasive cardiovascular imaging, prescription of medications, care in specific topics such as systemic arterial hypertension, heart failure, arrhythmias and acute coronary syndromes, in addition to emphasizing electrophysiology, interventionism, cardiac surgery and in cardiac rehabilitation. The main interest is to provide the medical community with a general orientation on what to do in daily practice and patients with cardiovascular diseases in the setting of this unprecedented epidemiological crisis of COVID-19.

Implementation of Virtual Sensors for Monitoring Temperature in Greenhouses Using CFD and Control.

Virtual sensing is crucial in order to provide feasible and economical alternatives when physical measuring instruments are not available. Developing model-based virtual sensors to calculate real-time information at each targeted location is a complex endeavor in terms of sensing technology. This paper proposes a new approach for model-based virtual sensor development using computational fluid dynamics (CFD) and control. Its main objective is to develop a three-dimensional (3D) real-time simulator using virtual sensors to monitor the temperature in a greenhouse. To conduct this study, a small-scale greenhouse was designed, modeled, and fabricated. The controller was based on the convection heat transfer equation under specific assumptions and conditions. To determine the temperature distribution in the greenhouse, a CFD analysis was conducted. Only one well-calibrated and controlled physical sensor (temperature reference) was enough for the CFD analysis. After processing the result that was obtained from the real sensor output, each virtual sensor had learned the associative transfer function that estimated the output from given input data, resulting in a 3D real-time simulator. This study has demonstrated, for the first time, that CFD analysis and a control strategy can be combined to obtain system models for monitoring the temperature in greenhouses. These findings suggest that, generally, virtual sensing can be applied in large greenhouses for monitoring the temperature using a 3D real-time simulator.

Experiencia en la reparación de hernia incisional por vía laparoscópica en una Unidad de Cirugía Ambulatoria / Experience in the Repair of Incisional Hernia by Laparoscopic Route in an Ambulatory Surgery Unit

Introducción. La hernia Incisional es una complicación frecuente de la cirugía abdominal sobre todo en pacientes que presentan factores de riesgo para desarrollar la misma. El sistema de salud pública no cuenta con suficiente encamamiento para estos pacientes para la realización de una cirugía electiva. La reparación laparoscópica y su aplicación en una unidad de cirugía ambulatoria se ha convertido en una opción para estos pacientes. El presente estudio busca evaluar los resultados de la reparación de la hernia incisional por vía laparoscópica y su aplicación en cirugía ambulatoria. Métodos. Se realizó un estudio retrospectvo de pacientes a quienes se le realizo reparación laparoscópica del año 2010 al año 2016, evaluando los factores de riesgo para la hernia incisional, el tamaño, su localización más frecuente, cierre del defecto, estancia hospitalaria, tiempo quirúrgico, malla utilizada, que tipo de analgésico se utilizaron a su egreso, sus complicaciones, su manejo y el seguimiento a los 8 días, 30 días y cada 2 meses durante un año. Resultados. Se incluyeron un total de 50 pacientes, siendo más frecuente en el sexo femenino. El principal factor de riesgo para el aparecimiento de la hernia incisional fue cirugías múltiples de origen obstétrico. La localización más frecuente fue la línea media infra umbilical. En 80% de los casos se realizó cierre por afrontación del defecto. En 100% de los casos se colocó malla separadora de tejido. El tiempo operatorio promedio fue de 70 minutos. El 75% de los pacientes fueron dados de alta el mismo día de la cirugía, el resto se ingresó al hospital, por condiciones de dolor post operatorio, complicaciones transoperatorias (2 casos) o reparación de un defecto grande (mayor de 15 centímetros). La mayor parte de los pacientes respondieron adecuadamente al uso de analgésicos por vía oral (75%), el resto se utilizó una combinación de dos analgésicos. Conclusiones. La técnica laparoscópica es una técnica adecuada y segura para la reparación de la hernia incisional aplicada en cirugía ambulatoria. Además, permite tratar a los pacientes que la sufren sin recargar la capacidad hospitalaria.

Introduction. Incisional hernia is a common abdominal surgical complication in patents with risk factors. Public hospitals don´t have enough beds to admit patents and perform the repair in an elecitve way, so ambulatory laparoscopic technique became a feasible alternative. The aim of the study is to evaluate our experience with ambulatory laparoscopic incisional hernioplasty. Methods. This retrospective study includes all the patents that presented an incisional hernia and were repaired by ambulatory laparoscopic hernioplasty between 2010 and 2016. We evaluated the presence of risk factors, the size of the hernia defect and location, the type of closure, operative time, type of mesh, length of hospitalization, analgesic treatment and management of complications. Results. We treated 50 patents. The main risk factor for incisional hernia was multiple gynecological surgeries. The most common site was at the infraumbilical medial line. In 80% of the patents we performed a complete defect closure. In all patents we used a two layer mesh. The mean operative time was 70 minutes. 75% of patents were discharged the same day and the rest of the patents were hospitalized because of uncontrolled pain, perioperative complications (2 cases) or extensive defects (above 15 centimeters in diameter). 75% of patents needed one analgesic and the rest a combination of two. Conclusions. Laparoscopic incisional hernioplasty can be safely performed in an ambulatory program and reduce the need of hospitalization.

Algunas consideraciones teóricas sobre la salud reproductiva en mujeres de edad fértil / Some theoretical considerations on the teaching - learning process

A partir de diferentes criterios y de una revisión bibliográfica de los métodos del nivel teórico de la investigación: análisis-síntesis, inducción-deducción, modelación y enfoque sistémico, los autores proponen algunas consideraciones teóricas sobre las habilidades intelectuales y, de esta manera, guiar a profesionales y estudiantes del sector de la salud en cómo enfocar la salud reproductiva en mujeres de edad fértil(AU)

From the opinion of the authors and from bibliographical review taking into account theoretical methods of research: Analysis-Synthesis, Induction, Deduction, Modeling and Systems Approach, the authors propose some theoretical and methodological teaching- learning, on the theoretical basis of Vygotsky fundamentally and so guide professionals and students in the health sector on how should focus the teaching-learning process, from an organization as a process, including stages and essential moments(AU)

Volatile substance misuse in Mexico: correlates and trends.

This paper analyzes volatile substance misuse in Mexico since the 1980s. Data were collected from national household and school surveys, epidemiological surveillance systems, and studies among special populations. Volatile substance misuse begins at 12-14 years. Prevalence is approximately 1% in the general population, 7% among high school students, and higher for street children. Toluene is the main solvent used, but preferences vary within population groups. Volatile substance misuse has increased among youngsters that live in families and attend school. Marijuana and volatile substances are now the drugs of choice among Mexican female high school students. The study's limitations are noted.