Lower Humoral and Cellular Immunity Following Asymptomatic SARS-CoV-2 Infection Compared to Symptomatic Infection in Education (The ACE Cohort).

PURPOSE: Asymptomatic SARS-CoV-2 infections were widely reported during the COVID-19 pandemic, acting as a hidden source of infection. Many existing studies investigating asymptomatic immunity failed to recruit true asymptomatic individuals. Thus, we conducted a longitudinal cohort study to evaluate humoral- and cell-mediated responses to infection and vaccination in well-defined asymptomatic young adults (the Asymptomatic COVID-19 in Education [ACE] cohort). METHODS: Asymptomatic testing services located at three UK universities identified asymptomatic young adults who were subsequently recruited with age- and sex-matched symptomatic and uninfected controls. Blood and saliva samples were collected after SARS-CoV-2 Wuhan infection, and again after vaccination. 51 participant's anti-spike antibody titres, neutralizing antibodies, and spike-specific T-cell responses were measured, against both Wuhan and Omicron B.1.1.529.1. RESULTS: Asymptomatic participants exhibited reduced Wuhan-specific neutralization antibodies pre- and post-vaccination, as well as fewer Omicron-specific neutralization antibodies post-vaccination, compared to symptomatic participants. Lower Wuhan and Omicron-specific IgG titres in asymptomatic individuals were also observed pre- and post-vaccination, compared to symptomatic participants. There were no differences in salivary IgA levels. Conventional flow cytometry analysis and multi-dimensional clustering analysis indicated unvaccinated asymptomatic participants had significantly fewer Wuhan-specific IL-2 secreting CD4+ CD45RA+ T cells and activated CD8+ T cells than symptomatic participants, though these differences dissipated after vaccination. CONCLUSIONS: Asymptomatic infection results in decreased antibody and T cell responses to further exposure to SARS-CoV-2 variants, compared to symptomatic infection. Post-vaccination, antibody responses are still inferior, but T cell immunity increases to match symptomatic subjects, emphasising the importance of vaccination to help protect asymptomatic individuals against future variants.

PBMC-derived extracellular vesicles in a smoking-related inflammatory disease model.

Extracellular vesicles (EVs) function as mediators of intercellular communication and as such influence the recipient cell function. EVs derived from immune cells can carry out many of the same functions as their parental cells, as they carry costimulatory molecules, antigens, and antigen-MHC complexes. As a result, there is a strong interest in understanding the composition and origin of immune cell-derived EVs in order to understand their role in the pathogenesis of diseases. This study aimed to optimize methodologies to study immune cell-derived EVs. Peripheral blood mononuclear cell-derived small EVs were isolated and observed using conventional transmission electron microscopy and sized by nanoparticle tracking analysis. They were then enumerated and profiled using imaging flow cytometry and were further characterized using a flow cytometric multiplex bead assay. These techniques were then applied to our current research, namely smoking-related inflammatory disease. We present here a comprehensive approach to analyze PBMC-derived small EVs in smoking-related inflammatory disease following the Minimal Information for Studies of Extracellular Vesicle 2018 guidelines.

Mendelian Susceptibility to Mycobacterial Disease: Retrospective Clinical and Genetic Study in Mexico.

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare genetic disorder characterized by impaired immunity against intracellular pathogens, such as mycobacteria, attenuated Mycobacterium bovis-Bacillus Calmette-Guérin (BCG) vaccine strains, and environmental mycobacteria in otherwise healthy individuals. Retrospective study reviewed the clinical, immunological, and genetic characteristics of patients with MSMD in Mexico. Overall, 22 patients diagnosed with MSMD from 2006 to 2021 were enrolled: 14 males (64%) and eight females. After BCG vaccination, 12 patients (70%) developed BCG infection. Furthermore, 6 (22%) patients developed bacterial infections mainly caused by Salmonella, as what is described next in the text is fungal infections, particularly Histoplasma. Seven patients died of disseminated BCG disease. Thirteen different pathogenic variants were identified in IL12RB1 (n = 13), IFNGR1 (n = 3), and IFNGR2 (n = 1) genes. Interleukin-12Rß1 deficiency is the leading cause of MSMD in our cohort. Morbidity and mortality were primarily due to BCG infection.

Humoral and cellular immunity in patients with rare autoimmune rheumatic diseases following SARS-CoV-2 vaccination.

OBJECTIVES: Coronavirus 2019 vaccine responses in rare autoimmune rheumatic diseases (RAIRDs) remain poorly understood; in particular there is little known about whether people develop effective T cell responses. We conducted an observational study to evaluate the short-term humoral and cell-mediated T cell response after the second severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in RAIRD patients compared with healthy controls (HCs). METHODS: Blood samples were collected after the second dose and anti-spike, anti-nucleocapsid antibody levels and SARS-CoV-2-specific T cell responses were measured and compared with those of HCs. Activation-induced marker and deep phenotyping assays were used to identify differences in T cells between high and no/low antibody groups, followed by multidimensional clustering. RESULTS: A total of 50 patients with RAIRDs were included (31 with AAV, 4 with other systemic vasculitis, 9 with SLE and 6 with myositis). The median anti-spike levels were significantly lower in RAIRD patients compared with HCs (P < 0.0001). Fifteen (33%) patients had undetectable levels and 26 (57%) had levels lower than the lowest HC. Rituximab in the last 12 months (P = 0.003) was associated with reduced immunogenicity compared with a longer pre-vaccination period. There was a significant difference in B cell percentages (P = 0.03) and spike-specific CD4+ T cells (P = 0.02) between no/low antibody vs high antibody groups. Patients in the no/low antibody group had a higher percentage of terminally differentiated (exhausted) T cells. CONCLUSIONS: Following two doses, most RAIRD patients have lower antibody levels than the lowest HC and lower anti-spike T cells. RAIRD patients with no/low antibodies have diminished numbers and poor quality of memory T cells that lack proliferative and functional capacities.

Extracellular vesicles and chronic obstructive pulmonary disease (COPD): a systematic review.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a common inflammatory disease of the airways characterized by irreversible airflow limitation, ranking the third highest cause of death worldwide. Extracellular vesicles (EVs) are important intercellular communication mediators released by cells into their extracellular environment with the capacity to transfer biological signals. EVs involved in COPD hold great potential to understand disease pathogenesis and identify important biomarkers. This systematic review aims to examine all available research on EVs in the pathogenesis and diagnosis of COPD to identify existing knowledge and support further research within the field. METHODS: Publications were searched using PubMed and EMBASE with the search terms (Exosomes or extracellular vesicles or microvesicles or microparticles or ectosomes) AND (chronic obstructive pulmonary disease or COPD or emphysema or bronchitis). RESULTS: Initial search yielded 512 papers of which 142 were manually selected for review and 43 were eligible for analyses. The studies were divided into groups according to the role of EVs in pathogenesis, EV origin and cargo, their role in COPD exacerbations and their diagnostic utility. EVs were found to be involved in the mechanism of pathogenesis of COPD, derived from various cell types, as well as containing modified levels of miRNAs. EVs also varied according to the pathophysiological status of disease, therefore presenting a possible method for COPD diagnosis and progress monitoring. CONCLUSION: The current findings show the limited but good quality research looking at the role of EVs in COPD, demonstrating the need for more studies to better define and provide further insight into the functional characteristics of EV in COPD pathogenesis.

Audiometric findings of printing press workers exposed to noise and organic solvents.

OBJECTIVE: To determine if exposure to organic solvents and noise is associated with audiometric results among workers from a printing press in Mexico City. DESIGN: Cross-sectional study. STUDY SAMPLE: One hundred and seventy-six male workers at a printing press in Mexico City exposed to noise and organic solvents, including xylene, and 103 non-exposed male workers as reference group. Hearing thresholds were assessed with pure-tone audiometry. RESULTS: Poorer hearing thresholds were observed among printing workers than non-exposed controls, particularly among groups with over 5 years of exposure. Hearing thresholds differences were observed in the frequencies above 500 Hz, especially in 4000 Hz in all exposure groups compared to the reference. Adjusted models for age and previous exposure to noise and organic solvents showed worse hearing thresholds as years of seniority increased -ß coefficients (95% CI): ≤5 years: 3.06 dB (0.01, 6.10); >5-10 years: 4.51 dB (1.13, 7.89); >10 years: 4.58 dB (1.20, 7.96). Further analyses showed no interaction between noise and organic solvents on hearing thresholds, considering both current and previous occupational exposures. CONCLUSION: Exposure to noise levels that were below recommended exposure limits and organic solvents were associated with poorer hearing thresholds than those observed among non-exposed study participants. This suggests that workers exposed to solvents should be included in hearing conservation programmes, even when noise exposures are below 85 dB. If only noise levels were taken into consideration in the risk assessment of this worker population, the risk of hearing effects could have been overlooked.

Clinical and Epidemiological Characteristics of Paediatric Patients Diagnosed with COVID-19 in a Tertiary Hospital in Mexico City.

COVID-19 affects the paediatric population less frequently than adults. A retrospective study was performed in a tertiary paediatric hospital in Mexico City in children <18 years of age who were hospitalized with a positive reverse transcription-polymerase chain reaction for SARS-CoV-2. Included in the study were 86 patients with a median age of 10 years old (IQR 2.6-14.3 years), who were classified in three groups: previously healthy, with chronic disease and immunosuppressed patients. The principal signs and symptoms were fever (81%), cough (51%) and headache (35%). A total of 20 patients (23%) required management in the paediatric intensive care unit (PICU) and 17% needed mechanical ventilation for an average of 12.7 days (IQR 2-29 days). There was no statistically significant difference between the three clinical classification groups in those patients admitted to the PICU, most of which were previously healthy patients. The mortality rate was 5% (four patients). Given that the paediatric population is susceptible to infection, potential transmitters and to clinical presentations with variable degrees of severity, it is important to continue reinforcing social distancing measures.

Dissecting the protein architecture of DNA-binding transcription factors in bacteria and archaea.

Gene regulation at the transcriptional level is a central process in all organisms where DNA-binding transcription factors play a fundamental role. This class of proteins binds specifically at DNA sequences, activating or repressing gene expression as a function of the cell's metabolic status, operator context and ligand-binding status, among other factors, through the DNA-binding domain (DBD). In addition, TFs may contain partner domains (PaDos), which are involved in ligand binding and protein-protein interactions. In this work, we systematically evaluated the distribution, abundance and domain organization of DNA-binding TFs in 799 non-redundant bacterial and archaeal genomes. We found that the distributions of the DBDs and their corresponding PaDos correlated with the size of the genome. We also identified specific combinations between the DBDs and their corresponding PaDos. Within each class of DBDs there are differences in the actual angle formed at the dimerization interface, responding to the presence/absence of ligands and/or crystallization conditions, setting the orientation of the resulting helices and wings facing the DNA. Our results highlight the importance of PaDos as central elements that enhance the diversity of regulatory functions in all bacterial and archaeal organisms, and our results also demonstrate the role of PaDos in sensing diverse signal compounds. The highly specific interactions between DBDs and PaDos observed in this work, together with our structural analysis highlighting the difficulty in predicting both inter-domain geometry and quaternary structure, suggest that these systems appeared once and evolved with diverse duplication events in all the analysed organisms.

A Novel Thermo-Alkaline Stable GDSL/SGNH Esterase with Broad Substrate Specificity from a Deep-Sea Pseudomonas sp.

Marine environments harbor a plethora of microorganisms that represent a valuable source of new biomolecules of biotechnological interest. In particular, enzymes from marine bacteria exhibit unique properties due to their high catalytic activity under various stressful and fluctuating conditions, such as temperature, pH, and salinity, fluctuations which are common during several industrial processes. In this study, we report a new esterase (EstGoM) from a marine Pseudomonas sp. isolated at a depth of 1000 m in the Gulf of Mexico. Bioinformatic analyses revealed that EstGoM is an autotransporter esterase (type Va) and belongs to the lipolytic family II, forming a new subgroup. The purified recombinant EstGoM, with a molecular mass of 67.4 kDa, showed the highest hydrolytic activity with p-nitrophenyl octanoate (p-NP C8), although it was also active against p-NP C4, C5, C10, and C12. The optimum pH and temperature for EstGoM were 9 and 60 °C, respectively, but it retained more than 50% of its activity over the pH range of 7-11 and temperature range of 10-75 °C. In addition, EstGoM was tolerant of up to 1 M NaCl and resistant to the presence of several metal ions, detergents, and chemical reagents, such as EDTA and ß-mercaptoethanol. The enzymatic properties of EstGoM make it a potential candidate for several industrial applications.

The Combination of Citrus Rootstock and Scion Cultivar Influences Trioza erytreae (Hemiptera: Triozidae) Survival, Preference Choice and Oviposition.

Trioza erytreae (Del Guercio, 1918) (Hemiptera: Triozidae) is a citrus pest which produces gall symptoms on leaves and transmits bacteria associated with the citrus disease Huanglongbing, 'Candidatus Liberibacter' spp. In the present work, the biology and behaviour of T. erytreae were studied in different rootstock-cultivar combinations. Six rootstocks were used, Flying dragon (FD), 'Cleopatra' mandarin (CL), Carrizo citrange (CC), Forner-Alcaide no.5 (FA5), Forner-Alcaide no.517 (FA517) and Citrus macrophylla (CM), and six scion cultivars: 'Star Ruby', 'Clemenules', 'Navelina', 'Valencia Late', 'Fino 49' and 'Ortanique'. Survival and oviposition were evaluated in a no-choice trial, and preference in a choice trial, all of them under greenhouse conditions. Trioza erytreae did not show a clear settle preference for any citrus combination. However, it was able to lay more eggs in 'Fino 49' grafted on CC than on FD. In terms of survival, 'Ortanique' grafted onto FA5 was more suitable than when grafted onto FA517, and in the case of 'Valencia Late', when it was grafted onto CM rather than CC. Our results showed that T. erytreae behave differently depending on the citrus combination.

Clinical practice guidelines for diagnostic and treatment of the chronic heart failure.

Chronic heart failure continues to be one of the main causes of impairment in the functioning and quality of life of people who suffer from it, as well as one of the main causes of mortality in our country and around the world. Mexico has a high prevalence of risk factors for developing heart failure, such as high blood pressure, diabetes, and obesity, which makes it essential to have an evidence-based document that provides recommendations to health professionals involved in the diagnosis and treatment of these patients. This document establishes the clinical practice guide (CPG) prepared at the initiative of the Mexican Society of Cardiology (SMC) in collaboration with the Iberic American Agency for the Development and Evaluation of Health Technologies, with the purpose of establishing recommendations based on the best available evidence and agreed upon by an interdisciplinary group of experts. This document complies with international quality standards, such as those described by the US Institute of Medicine (IOM), the National Institute of Clinical Excellence (NICE), the Intercollegiate Network for Scottish Guideline Development (SIGN) and the Guidelines International Network (G-I-N). The Guideline Development Group was integrated in a multi-collaborative and interdisciplinary manner with the support of methodologists with experience in systematic literature reviews and the development of CPG. A modified Delphi panel methodology was developed and conducted to achieve an adequate level of consensus in each of the recommendations contained in this CPG. We hope that this document contributes to better clinical decision making and becomes a reference point for clinicians who manage patients with chronic heart failure in all their clinical stages and in this way, we improve the quality of clinical care, improve their quality of life and reducing its complications.

La insuficiencia cardiaca crónica sigue siendo unas de las principales causas de afectación en el funcionamiento y en la calidad de vida de las personas que la presentan, así como una de las primeras causas de mortalidad en nuestro país y en todo el mundo. México tiene una alta prevalencia de factores de riesgo para desarrollar insuficiencia cardiaca, tales como hipertensión arterial, diabetes y obesidad, lo que hace imprescindible contar con un documento basado en la evidencia que brinde recomendaciones a los profesionales de la salud involucrados en el diagnóstico y el tratamiento de estos pacientes. Este documento establece la guía de práctica clínica (GPC) elaborada por iniciativa de la Sociedad Mexicana de Cardiología (SMC) en colaboración con la Agencia Iberoamericana de Desarrollo y Evaluación de Tecnologías en Salud, con la finalidad de establecer recomendaciones basadas en la mejor evidencia disponible y consensuadas por un grupo interdisciplinario y multicolaborativo de expertos. Cumple con estándares internacionales de calidad, como los descritos por el Institute of Medicine de los Estados Unidos de América (IOM), el National Institute of Clinical Excellence (NICE) del Reino Unido, la Intercollegiate Network for Scottish Guideline Development (SIGN) de Escocia y la Guidelines International Network (G-I-N). El grupo de desarrollo de la guía se integró de manera interdisciplinaria con el apoyo de metodólogos con experiencia en revisiones sistemáticas de la literatura y en el desarrollo de GPC. Se llevó a cabo y se condujo metodología de panel Delphi modificado para lograr un nivel de consenso adecuado en cada una de las recomendaciones contenidas en esta GPC. Esperamos que este documento contribuya para la mejor toma de decisiones clínicas y se convierta en un punto de referencia para los clínicos que manejan pacientes con insuficiencia cardiaca crónica en todas sus etapas clínicas, y de esta manera logremos mejorar la calidad en la atención clínica, aumentar la calidad de vida de los pacientes y disminuir las complicaciones de la enfermedad.

Antibody response to four doses of SARS-CoV-2 vaccine in rare autoimmune rheumatic diseases: an observational study.

Objective: Antibody responses to coronavirus disease 2019 (COVID-19) vaccines are reduced among immunocompromised patients but are not well quantified among people with rare disease. We conducted an observational study to evaluate the antibody responses to the booster SARS-CoV-2 vaccine in people with rare autoimmune rheumatic diseases (RAIRD). Methods: Blood samples were collected after second, before third, after third and after fourth vaccine doses. Anti-spike and anti-nucleocapsid antibody levels were measured using an in-house ELISA. Logistic regression models were built to determine the predictors for non-response. Results were compared with age- and sex-matched healthy controls. Results: Forty-three people with RAIRD were included, with a median age of 56 years. Anti-spike seropositivity increased from 42.9% after second dose to 51.2% after third dose and 65.6% after fourth dose. Median anti-spike antibody levels increased from 33.6 (interquartile range 7.8-724.5) binding antibody units after second dose to 239.4 (interquartile range 35.8-1051.1) binding antibody units after the booster dose (third dose, or fourth dose if eligible). Of the participants who had sufficient antibody levels post-second dose, 22.2% had insufficient levels after the booster, and 34.9% of participants had lower antibodies after the booster than the lowest healthy control had after the second dose. Rituximab in the 6 months prior to booster (P = 0.02) and non-White ethnicity (P = 0.04) were associated with non-response. There was a dose-response relationship between the timing of rituximab and generation of sufficient antibodies (P = 0.03). Conclusion: Although the booster dose increased anti-spike IgG and seropositivity rates, some people with RAIRD, particularly those on rituximab, had insufficient antibody levels despite three or four doses.

Reduced osteoprotegerin expression by osteocytes may contribute to rebound resorption after denosumab discontinuation.

Denosumab is an anti-RANKL Ab that potently suppresses bone resorption, increases bone mass, and reduces fracture risk. Discontinuation of denosumab causes rapid rebound bone resorption and bone loss, but the molecular mechanisms are unclear. We generated humanized RANKL mice and treated them with denosumab to examine the cellular and molecular conditions associated with rebound resorption. Denosumab potently suppressed both osteoclast and osteoblast numbers in cancellous bone in humanized RANKL mice. The decrease in osteoclast number was not associated with changes in osteoclast progenitors in bone marrow. Long-term, but not short-term, denosumab administration reduced osteoprotegerin (OPG) mRNA in bone. Localization of OPG expression revealed that OPG mRNA is produced by a subpopulation of osteocytes. Long-term denosumab administration reduced osteocyte OPG mRNA, suggesting that OPG expression declines as osteocytes age. Consistent with this, osteocyte expression of OPG was more prevalent near the surface of cortical bone in humans and mice. These results suggest that new osteocytes are an important source of OPG in remodeling bone and that suppression of remodeling reduces OPG abundance by reducing new osteocyte formation. The lack of new osteocytes and the OPG they produce may contribute to rebound resorption after denosumab discontinuation.

National Registry of Acute Coronary Syndrome in Paraguay (RENASCA-PY).

OBJECTIVE: To determine the initial management and in-hospital mortality of patients with acute coronary syndrome who attended referral hospitals in Paraguay. METHOD: Observational, multicenter study, in patients over 18 years with a confirmed diagnosis of acute coronary syndrome. RESULTS: 780 patients were included from May 2015 to February 2016; the mean age was 64.1 ± 12.3 years, 64.1% male. The clinical presentation was acute coronary syndrome with ST elevation in 40.1% and without elevation in 59.9%. In patients with ST elevation there is a high percentage of late attendance, more than 12 h of evolution in 49.8%; those with less than 12 h of evolution underwent reperfusion in 52.2% of the cases, received fibrinolytics in 36.3% of the cases, and primary percutaneous coronary intervention 15.9%. In-hospital mortality for acute coronary syndrome was 10.3%, with ST-segment elevation was 12.8%, and without ST-segment elevation was 8.6%. CONCLUSIONS: The management of acute coronary syndrome in Paraguay needs a comprehensive approach, which promotes earlier care, and increases the implementation of reperfusion therapies in the health services network, in order to improve the therapeutic response rates and decrease hospital mortality.

OBJETIVO: Determinar el tratamiento inicial y la mortalidad intrahospitalaria de pacientes con síndrome coronario agudo que acudieron a centros hospitalarios de referencia de Paraguay. MÉTODO: Estudio observacional y multicéntrico en pacientes mayores de 18 años con diagnóstico confirmado de síndrome coronario agudo. RESULTADOS: Se incluyó a 780 pacientes desde mayo de 2015 hasta febrero de 2016; la edad media fue de 64.1 ± 12.3 años y el género masculino representó el 64.1%. La presentación clínica fue la de síndrome coronario agudo con elevación del ST en 40.1% y sin elevación del ST en 59.9%. En pacientes con elevación del ST se observó un alto porcentaje de consultas tardías, mayor de 12 h de evolución en 49.8%; en aquéllos con menos de 12 h de evolución se indicó la reperfusión en 52.2%, el 36.3% recibió fibrinolíticos y 15.9% intervención coronaria percutánea primaria. La mortalidad hospitalaria del síndrome coronario agudo fue de 10.3%, con elevación del segmento ST en 12.8% y sin elevación del segmento ST en 8.6%. CONCLUSIONES: El tratamiento del síndrome coronario agudo en el Paraguay requiere un abordaje integral, que promueva consultas más tempranas y aumente la institución de tratamientos de reperfusión en la red de servicios de salud; el objetivo es mejorar los índices de respuesta terapéutica y disminuir la mortalidad hospitalaria.

Surveillance of osteoarticular infections caused by Staphylococcus aureus in a paediatric hospital in Mexico City.

Staphylococcus aureus is the main aetiologic agent of osteoarticular infections (OAIs) in paediatric patients. The aim of this prospective unicenter study was to describe the phenotypic and genotypic characteristics of S. aureus isolates obtained from OAIs in paediatric patients admitted to tertiary care hospital. Through a surveillance program called OsteoCode, a multidisciplinary team was created and we identified 27 patients with OAIs caused by S. aureus from 2019 to 2021. The susceptibility profile, virulence factors, biofilm formation, pulsed-field gel electrophoresis (PFGE), clonal complex (CC) and sequence type (ST) were determined. In addition, the clinical characteristics and evolution of the patients presented six months after the diagnosis of OAIs were described. Ninety-two percent of the isolates were methicillin-sensitive S. aureus (MSSA). In methicillin-resistant S. aureus (MRSA), SCCmec-II and SCCmec-V were detected. The pvl gene was only observed in MSSA (18.5%) and was associated with highest fever (p=0.015), multiple localization (p=0.017), and soft tissue sites of infection beyond the bone (pyomyositis, pulmonary abscess) (p=0.017). Biofilm formation was detected in 55.6% of isolates. The most common CC were CC5 and CC30 which represent the most common linages for bone and joint infections worldwide. The isolates were distributed in different STs, and ST672 was predominant. MRSA were associated with a longer duration of intravenous treatment and a prolonged hospital stay (p=0.023). Recurrent infection occurred in five children and orthopaedic complications in 33.3% of patients. This is the first study that reflects the epidemiology of S. aureus in OAIs in paediatric patients in Mexico; a clear predominance of MSSA distributed in different STs was observed. Our findings highlight that a multidisciplinary team is required for the diagnosis and treatment of OAIs.

Guía de práctica clínica para el diagnóstico y el tratamiento de la otitis media aguda en niños.

BACKGROUND: Acute otitis media (AOM) is one of the most prevalent acute conditions in the pediatric population worldwide. This work aimed to elaborate a Clinical Practice Guideline with clinical recommendations systematically developed to assist decision-making of specialists, patients, caregivers, and public policymakers involved in managing patients with AOM in children. METHODS: This document was developed by the College of Pediatric Otorhinolaryngology and Head, and Neck Surgery of Mexico (COPEME) in compliance with international standards. The SIGN quality of evidence classification was used. On behalf of the COPEME, the Guideline Development Group (GDG) was integrated, including otolaryngologists, infectologists, pediatricians, general practitioners, and methodologists with experience in systematic literature reviews and the development of clinical practice guidelines. RESULTS: A consensus was reached on 18 clinical questions, covering what was previously established by the GDG in the scope document of the guidelines. Scientific evidence answering each of these clinical questions was identified and critically evaluated. The GDG agreed on the final wording of the clinical recommendations using the modified Delphi panel technique. Specialists and patient representatives conducted an external validation. CONCLUSIONS: This Clinical Practice Guideline presents clinical recommendations for the prevention, diagnosis, and management of AOM to assist shared decision-making among physicians, patients, and caregivers and improve the quality of clinical care.

INTRODUCCIÓN: La otitis media aguda (OMA) es uno de los padecimientos agudos más prevalentes en la población pediátrica a escala global. El objetivo de este trabajo fue elaborar una guía de práctica clínica con recomendaciones para asistir la toma de decisiones de médicos especialistas, pacientes, cuidadores de pacientes y elaboradores de políticas públicas involucrados en el manejo de la OMA en niños. MÉTODOS: El documento ha sido desarrollado por parte del Colegio de Otorrinolaringología y Cirugía de Cabeza y Cuello Pediátricas de México (COPEME) en cumplimiento con los estándares internacionales. Se empleó la clasificación de calidad de la evidencia de SIGN. En representación del COPEME, se integró el Grupo de Desarrollo de la Guía (GDG), que incluyó otorrinolaringólogos, infectólogos, pediatras, médicos generales y metodólogos con experiencia en revisiones sistemáticas de la literatura y el desarrollo de guías de práctica clínica. RESULTADOS: Se consensuaron 18 preguntas clínicas que abarcaron lo establecido previamente por el GDG en el documento de alcances de la Guía. Se identificó la evidencia científica que responde a cada una de estas preguntas clínicas y se evaluó críticamente. El GDG acordó la redacción final de las recomendaciones clínicas mediante la técnica Delphi de panel. Se llevó a cabo una validación externa por colegas especialistas y representantes de pacientes. CONCLUSIONES: En esta Guía de Práctica Clínica se presentan recomendaciones clínicas para la prevención, el diagnóstico y el manejo de la OMA, con el fin de asistir la toma de decisiones compartidas entre médicos, pacientes y cuidadores con la intención de contribuir a mejorar la calidad de la atención clínica.

Diversity and distribution of transcription factors: their partner domains play an important role in regulatory plasticity in bacteria.

The ability of bacteria to deal with diverse environmental changes depends on their repertoire of genes and their ability to regulate their expression. In this process, DNA-binding transcription factors (TFs) have a fundamental role because they affect gene expression positively and/or negatively depending on operator context and ligand-binding status. Here, we show an exhaustive analysis of winged helix-turn-helix domains (wHTHs), a class of DNA-binding TFs. These proteins were identified in high proportions and widely distributed in bacteria, representing around half of the total TFs identified so far. In addition, we evaluated the repertoire of wHTHs in terms of their partner domains (PaDos), identifying a similar trend, as with TFs, i.e. they are abundant and widely distributed in bacteria. Based on the PaDos, we defined three main groups of families: (i) monolithic, those families with little PaDo diversity, such as LysR; (ii) promiscuous, those families with a high PaDo diversity; and (iii) monodomain, with families of small sizes, such as MarR. These findings suggest that PaDos have a very important role in the diversification of regulatory responses in bacteria, probably contributing to their regulatory complexity. Thus, the TFs discriminate over longer regions on the DNA through their diverse DNA-binding domains. On the other hand, the PaDos would allow a great flexibility for transcriptional regulation due to their ability to sense diverse stimuli through a variety of ligand-binding compounds.

[¿Cómo tratar la hipertensión arterial sistémica? Estrategias de tratamiento actuales]. / How to treat hypertension? Current management strategies

Hypertension is a disease that affects almost half of the population. Its complex pathophysiology, mainly affecting the renal, hormonal, cardiovascular and neurological systems, has allowed us to have different pharmacological strategies to treat each of these systems and thus regulate blood pressure. The American Heart Association in 2017, the European Society of Cardiology in 2018, and the American Society of Hypertension in 2020 published their recommendations for the diagnosis, monitoring and treatment of arterial hypertension. The definition of normal blood pressure or hypertension varies according to each guideline. Recommendations on lifestyle and pharmacological therapy are very similar in the guidelines. They recommend blockers of the renin-angiotensin system, calcium antagonists and thiazides, and only in selected cases the use of mineralocorticoid receptor antagonist or beta-blockers.

La hipertensión arterial sistémica es una enfermedad que afecta casi a la mitad de la población. Su compleja fisiopatología, que afecta principalmente a los sistemas renal, hormonal, cardiovascular y neurológico, ha permitido tener diferentes estrategias farmacológicas para tratar cada uno de esos sistemas y así regular la tensión arterial. La American Heart Association en el 2017, la European Society of Cardiology en el 2018 y, por último, la International Society of Hypertension en el 2020, publicaron recomendaciones para el diagnóstico, monitoreo y tratamiento de la hipertensión arterial. La definición de tensión arterial normal o hipertensión varía de acuerdo con cada guía. Las recomendaciones en los cambios del estilo de vida son muy similares, al igual que el tratamiento farmacológico mediante inhibidores del sistema renina-angiotensina, antagonistas de canales de calcio y diuréticos tiazídicos y solo en casos seleccionados el uso de antagonistas de la aldosterona o betabloqueadores.

Comparative genomics of DNA-binding transcription factors in archaeal and bacterial organisms.

Archaea represent a diverse phylogenetic group that includes free-living, extremophile, mesophile, symbiont, and opportunistic organisms. These prokaryotic organisms share a high significant similarity with the basal transcriptional machinery of Eukarya, and they share regulatory mechanisms with Bacteria, such as operonic organization and DNA-binding transcription factors (TFs). In this work, we identified the repertoire of TFs in 415 archaeal genomes and compared them with their counterparts in bacterial genomes. The comparisons of TFs, at a global level and per family, allowed us to identify similarities and differences between the repertoires of regulatory proteins of bacteria and archaea. For example, 11 of 62 families are more highly abundant in archaea than bacteria, and 13 families are abundant in bacteria but not in archaea and 38 families have similar abundances in the two groups. In addition, we found that archaeal TFs have a lower isoelectric point than bacterial proteins, i.e., they contain more acidic amino acids, and are smaller than bacterial TFs. Our findings suggest a divergence occurred for the regulatory proteins, even though they are common to archaea and bacteria. We consider that this analysis contributes to the comprehension of the structure and functionality of regulatory proteins of archaeal organisms.

Characterization of Enterobacter cloacae BAGM01 Producing a Thermostable and Alkaline-Tolerant Rhamnolipid Biosurfactant from the Gulf of Mexico.

The search for novel biosurfactants (Bs) requires the isolation of microorganisms from different environments. The Gulf of Mexico (GoM) is a geographical area active in the exploration and exploitation of hydrocarbons. Recent metagenomic and microbiologic studies in this area suggested a potential richness for novel Bs microbial producers. In this work, nineteen bacterial consortia from the GoM were isolated at different depths of the water column and marine sediments. Bs production from four bacterial consortia was detected by the CTAB test and their capacity to reduce surface tension (ST), emulsion index (EI24), and hemolytic activity. These bacterial consortia produced Bs in media supplemented with kerosene, diesel, or sucrose. Cultivable bacteria from these consortia were isolated and identified by bacterial polyphasic characterization. In some consortia, Enterobacter cloacae was the predominant specie. E. cloacae BAGM01 presented Bs activity in minimal medium and was selected to improve its Bs production using a Taguchi and Box-Behnken experimental design; this strain was able to grow and presented Bs activity at 35 g L-1 of NaCl. This Bs decreased ST to around 34.5 ± 0.56 mNm-1 and presented an EI24 of 71 ± 1.27%. Other properties of this Bs were thermal stability, stability in alkaline conditions, and stability at high salinity, conferring important and desirable characteristics in multiple industries. The analysis of the genome of E. cloacae BAGM01 showed the presence of rhlAB genes that have been reported in the synthesis of rhamnolipids, and alkAB genes that are related to the degradation of alkanes. The bioactive molecule was identified as a rhamnolipid after HPLC derivatization, 1H NMR, and UPLC-QTOF-MS analysis.