Rab27a GTPase and its effector Myosin Va are host factors required for efficient Oropouche virus cell egress.

Oropouche fever, a debilitating illness common in South America, is caused by Oropouche virus (OROV), an arbovirus. OROV belongs to the Peribunyaviridae family, a large group of RNA viruses. Little is known about the biology of Peribunyaviridae in host cells, especially assembly and egress processes. Our research reveals that the small GTPase Rab27a mediates intracellular transport of OROV induced compartments and viral release from infected cells. We show that Rab27a interacts with OROV glycoproteins and colocalizes with OROV during late phases of the infection cycle. Moreover, Rab27a activity is required for OROV trafficking to the cell periphery and efficient release of infectious particles. Consistently, depleting Rab27a's downstream effector, Myosin Va, or inhibiting actin polymerization also hinders OROV compartments targeting to the cell periphery and infectious viral particle egress. These data indicate that OROV hijacks Rab27a activity for intracellular transport and cell externalization. Understanding these crucial mechanisms of OROV's replication cycle may offer potential targets for therapeutic interventions and aid in controlling the spread of Oropouche fever.

Improved LINE-1 Detection through Pattern Matching by Increasing Probe Length.

Long Interspersed Element-1 (LINE-1 or L1) is an autonomous transposable element that accounts for 17% of the human genome. Strong correlations between abnormal L1 expression and diseases, particularly cancer, have been documented by numerous studies. L1PD (LINE-1 Pattern Detection) had been previously created to detect L1s by using a fixed pre-determined set of 50-mer probes and a pattern-matching algorithm. L1PD uses a novel seed-and-pattern-match strategy as opposed to the well-known seed-and-extend strategy employed by other tools. This study discusses an improved version of L1PD that shows how increasing the size of the k-mer probes from 50 to 75 or to 100 yields better results, as evidenced by experiments showing higher precision and recall when compared to the 50-mers. The probe-generation process was updated and the corresponding software is now shared so that users may generate probes for other reference genomes (with certain limitations). Additionally, L1PD was applied to other non-human genomes, such as dogs, horses, and cows, to further validate the pattern-matching strategy. The improved version of L1PD proves to be an efficient and promising approach for L1 detection.

Sulfur nanocomposites with insecticidal effect for the control of Bactericera cockerelli.

The purpose of this research was to synthesize nanocomposites consisting of sulfur nanoparticles coated with eucalyptus and rosemary essential oils to determine the insecticidal effect in the control of nymphs of paratrioza (Bactericera cockerelli (Sulc) (Hemiptera: Triozidae)) in potato crops. A solution of thiosulfate was reduced to elemental sulfur, and the sulfur nanoparticles were coated with eucalyptus and rosemary essential oils with the three concentrations of 0.25%, 0.5%, and 0.75%. The samples were characterized by UV-visible spectroscopy, energy-dispersive X-ray spectroscopy, transmission electron microscopy, and scanning electron microscopy. The insecticidal efficacy of the nanocomposites was evaluated in the entomology laboratory 24, 48, and 72 h after application. Furthermore, efficacy was compared to the commercial insecticide thiamethoxam (0.25%) and a control. The results show that eucalyptus nanocomposites with oil concentrations of 0.25%, 0.5%, and 0.75% and rosemary nanocomposites with an oil concentration of 0.5% have an insecticidal efficacy of 100% for the control of insect nymphs 24 h after application. The insecticidal efficacy of rosemary nanocomposites with oil concentrations of 0.25% and 0.75% increases over time and reaches 100% at 24 and 72 h, respectively. The synthesized nanocomposites are more effective in controlling nymphs of paratrioza than the commercial insecticide thiamethoxam; thus, they could be used for the development of new insecticides.

Sistema de gestión de riesgos para reducir el contagio de COVID-19 en el personal de salud

[RESUMEN]. Objetivo. Evaluar los factores laborales asociados con la ocurrencia de COVID-19 en el personal de salud expuesto a distinta magnitud de riesgo con el uso de la política de gestión de crisis de las Naciones Unidas para COVID-19. Métodos. Encuesta transversal realizada entre abril y mayo del 2021. Se consideraron como grupo de riesgo bajo (GRB) quienes tenían contacto mínimo con pacientes; de riesgo medio (GRM) a quienes tenían contacto con pacientes no-COVID-19 y no realizaban intervención instrumental de vías respiratorias; y de riesgo alto (GRA) a quienes atendían pacientes COVID-19 y realizaban intervención instrumental con generación de aerosoles. Se consideró como desenlace el antecedente de enfermedad diagnosticada de COVID-19 y la presencia de anticuerpos IgG positivos contra el SARS-CoV-2 medida con Elecsys® anti-SARS-CoV-2. Resultados. Desenlace en 43,8% en el GRB; 46,7% en el GRM (razón de momios [RM]: 1,125; intervalo de confianza de 95% [IC95%]: 0,896-1,414; p = 0,311); y 48,6% en el GRA (RM: 1,214; IC95%: 0,964-1,530; p = 0,10). Conclusión. Pertenecer al GRM y al GRA por el grado de exposición a pacientes confirmados de COVID-19 en el área de trabajo no se asoció con mayor ocurrencia de enfermedad o de seroconversión.

[ABSTRACT]. Objective. To document trends in inequity in homicide rates in Mexico for the period 2000–2021, at the state and national levels. Methods. An observational, longitudinal ecological study was conducted in which standardized homicide mortality rates were estimated, by municipality and sex. Municipalities were classified in five groups, accor- ding to the Social Lag Index. The absolute inequality gap was obtained, as well as differences between groups with very high and very low social lag, for each year of the study period. Results. In the 32 states, an increase was observed in the rate of death by homicide, with higher rates among men but a greater relative increase among women (+127.86% vs. +110.03%). The absolute gap between municipalities with very high and very low social lag narrowed in the period, due to higher homicide rates in municipalities with low social lag and a modest reduction in municipalities with very high social lag. Conclusions. In Mexico, between 2000 and 2021, the absolute gap in deaths by homicide between municipa- lities with very high and very low social lag declined due to higher homicide rates in municipalities with lower social lag. It is necessary to strengthen policies and actions aimed at addressing the social determinants of interpersonal violence.

[RESUMO]. Objetivo. Avaliar os fatores ocupacionais associados à ocorrência de COVID-19 em profissionais de saúde expostos a diferentes níveis de risco utilizando a política de gestão de crises elaborada pelas Nações Unidas para a COVID-19. Métodos. Pesquisa transversal realizada entre abril e maio de 2021. O grupo de risco baixo (GRB) consistia em profissionais que tinham contato mínimo com os pacientes; o grupo de risco médio (GRM) incluía profis- sionais que tinham contato com pacientes sem COVID-19 e não realizavam intervenções instrumentais nas vias aéreas; e grupo de risco alto (GRA), profissionais que cuidavam de pacientes com COVID-19 e realiza- vam intervenções instrumentais com geração de aerossóis. Para estabelecer o desfecho, considerou-se a história de COVID-19 do profissional de saúde e a detecção de anticorpos IgG anti- SARS-CoV-2 por Elecsys® Anti-SARS-CoV-2. Resultados. A doença foi diagnosticada em 43,8% dos profissionais no GRB, 46,7% no GRM (razão de chan- ces ajustada: 1,125; intervalo de confiança de 95% [IC95%]: 0,896-1,414; p = 0,311) e 48,6% no GRA (razão de chances: 1,214; IC95%: 0,964-1,530; p = 0,10). Conclusões. Pertencer ao GRM e ao GRA em função do nível de exposição a pacientes confirmados com COVID-19 no ambiente de trabalho não foi associado a um aumento da ocorrência da doença ou da soroconversão.

Risk symptoms for progression in Covid-19. Telemedicine cohort study.

Not available.

Oropouche Virus Glycoprotein Topology and Cellular Requirements for Glycoprotein Secretion.

Oropouche virus (OROV; genus Orthobunyavirus) is the etiological agent of Oropouche fever, a debilitating febrile illness common in South America. We used recombinant expression of the OROV M polyprotein, which encodes the surface glycoproteins Gn and Gc plus the nonstructural protein NSm, to probe the cellular determinants for OROV assembly and budding. Gn and Gc self-assemble and are secreted independently of NSm. Mature OROV Gn has two predicted transmembrane domains that are crucial for glycoprotein translocation to the Golgi complex and glycoprotein secretion, and unlike related orthobunyaviruses, both transmembrane domains are retained during Gn maturation. Disruption of Golgi function using the drugs brefeldin A and monensin inhibits glycoprotein secretion. Infection studies have previously shown that the cellular endosomal sorting complexes required for transport (ESCRT) machinery is recruited to Golgi membranes during OROV assembly and that ESCRT activity is required for virus secretion. A dominant-negative form of the ESCRT-associated ATPase VPS4 significantly reduces recombinant OROV glycoprotein secretion and blocks virus release from infected cells, and VPS4 partly colocalizes with OROV glycoproteins and membranes costained with Golgi markers. Furthermore, immunoprecipitation and fluorescence microscopy experiments demonstrate that OROV glycoproteins interact with the ESCRT-III component CHMP6, with overexpression of a dominant-negative form of CHMP6 significantly reducing OROV glycoprotein secretion. Taken together, our data highlight differences in M polyprotein processing across orthobunyaviruses, indicate that Golgi and ESCRT function are required for glycoprotein secretion, and identify CHMP6 as an ESCRT-III component that interacts with OROV glycoproteins. IMPORTANCE Oropouche virus causes Oropouche fever, a debilitating illness common in South America that is characterized by high fever, headache, myalgia, and vomiting. The tripartite genome of this zoonotic virus is capable of reassortment, and there have been multiple epidemics of Oropouche fever in South America over the last 50 years, making Oropouche virus infection a significant threat to public health. However, the molecular characteristics of this arbovirus are poorly understood. We developed a recombinant protein expression system to investigate the cellular determinants of OROV glycoprotein maturation and secretion. We show that the proteolytic processing of the M polypeptide, which encodes the surface glycoproteins (Gn and Gc) plus a nonstructural protein (NSm), differs between OROV and its close relative Bunyamwera virus. Furthermore, we demonstrate that OROV M glycoprotein secretion requires the cellular endosomal sorting complexes required for transport (ESCRT) membrane-remodeling machinery and identify that the OROV glycoproteins interact with the ESCRT protein CHMP6.

Sistema de gestión de riesgos para reducir el contagio de COVID-19 en el personal de salud / Risk management system to reduce COVID-19 infection in health personnel / Sistema de gestão de riscos para reduzir o contágio de COVID-19 em profissionais de saúde

RESUMEN Objetivo. Evaluar los factores laborales asociados con la ocurrencia de COVID-19 en el personal de salud expuesto a distinta magnitud de riesgo con el uso de la política de gestión de crisis de las Naciones Unidas para COVID-19. Métodos. Encuesta transversal realizada entre abril y mayo del 2021. Se consideraron como grupo de riesgo bajo (GRB) quienes tenían contacto mínimo con pacientes; de riesgo medio (GRM) a quienes tenían contacto con pacientes no-COVID-19 y no realizaban intervención instrumental de vías respiratorias; y de riesgo alto (GRA) a quienes atendían pacientes COVID-19 y realizaban intervención instrumental con generación de aerosoles. Se consideró como desenlace el antecedente de enfermedad diagnosticada de COVID-19 y la presencia de anticuerpos IgG positivos contra el SARS-CoV-2 medida con Elecsys® anti-SARS-CoV-2. Resultados. Desenlace en 43,8% en el GRB; 46,7% en el GRM (razón de momios [RM]: 1,125; intervalo de confianza de 95% [IC95%]: 0,896-1,414; p = 0,311); y 48,6% en el GRA (RM: 1,214; IC95%: 0,964-1,530; p = 0,10). Conclusión. Pertenecer al GRM y al GRA por el grado de exposición a pacientes confirmados de COVID-19 en el área de trabajo no se asoció con mayor ocurrencia de enfermedad o de seroconversión.

ABSTRACT Objective. To assess the occupational factors associated with the occurrence of COVID-19 in health personnel who were exposed to different magnitudes of risk and who followed the United Nations crisis management policy for COVID-19. Methods. Cross-sectional survey conducted between April and May 2021. The low-risk group (LRG) were considered to be those who had minimal contact with patients; the medium-risk group (MRG) had contact with non-COVID-19 patients and did not perform instrumental airway intervention; and the high-risk group (HRG) were those who cared for COVID-19 patients and performed instrumental intervention with aerosol generation. Diagnosed COVID-19 disease and the presence of positive IgG antibodies for SARS-CoV-2 measured with Elecsys® anti-SARS-CoV-2 were considered as outcomes. Results. Outcome recorded in 43.8% of the LRG, versus 46.7% in the MRG (odds ratio [OR]: 1.125; 95% confidence interval [CI 95% ]: 0.896-1.414; p = 0.311), and 48.6% in the HRG (OR: 1,214; CI 95%: 0.964-1.530; p= 0.10). Conclusion. Belonging to the high-risk group and the medium-risk group, based on the degree of exposure to confirmed COVID-19 patients in the work area, was not associated with a higher occurrence of disease or seroconversion.

RESUMO Objetivo. Avaliar os fatores ocupacionais associados à ocorrência de COVID-19 em profissionais de saúde expostos a diferentes níveis de risco utilizando a política de gestão de crises elaborada pelas Nações Unidas para a COVID-19. Métodos. Pesquisa transversal realizada entre abril e maio de 2021. O grupo de risco baixo (GRB) consistia em profissionais que tinham contato mínimo com os pacientes; o grupo de risco médio (GRM) incluía profissionais que tinham contato com pacientes sem COVID-19 e não realizavam intervenções instrumentais nas vias aéreas; e grupo de risco alto (GRA), profissionais que cuidavam de pacientes com COVID-19 e realizavam intervenções instrumentais com geração de aerossóis. Para estabelecer o desfecho, considerou-se a história de COVID-19 do profissional de saúde e a detecção de anticorpos IgG anti- SARS-CoV-2 por Elecsys® Anti-SARS-CoV-2. Resultados. A doença foi diagnosticada em 43,8% dos profissionais no GRB, 46,7% no GRM (razão de chances ajustada: 1,125; intervalo de confiança de 95% [IC95%]: 0,896-1,414; p = 0,311) e 48,6% no GRA (razão de chances: 1,214; IC95%: 0,964-1,530; p = 0,10). Conclusões. Pertencer ao GRM e ao GRA em função do nível de exposição a pacientes confirmados com COVID-19 no ambiente de trabalho não foi associado a um aumento da ocorrência da doença ou da soroconversão.

Polyserositis as a Post-Covid-19 Complication.

INTRODUCTION: Polyserositis is described as inflammation with effusion of more than one serous membrane. There is very little published literature linking it to COVID-19 as a late complication. OBJECTIVE: Present and describe a case of post-COVID-19 polyserositis. METHODS: Data were collected from the medical record of a female patient admitted for fainting spells and marked weakness. The patient underwent a clinical evaluation, additional hematology, imaging and histopathology tests, and a surgical procedure. The new index, called the abdominal adipose deposit index, was obtained by multiplying the subcutaneous fat thickness by visceral fat thickness, both measured by ultrasound. A cutoff point was established that facilitated discernment of an unhealthy phenotype: normal weight but metabolically obese, a cardiometabolic risk factor. RESULTS: We present the case of a 57-year-old female patient admitted to hospital for fainting spells and marked weakness, four months after COVID-19 infection. She also had a history of obesity, asthma, type 2 diabetes mellitus and a cholecystectomy in December 1992 for gallstones. Clinical assessment revealed pericardial effusion and bilateral pleural effusion, in addition to a tumor-like lesion outside the pericardium, proximal to the right ventricular wall. A surgical procedure and findings from additional tests led to diagnoses of thymic remnants and polyserositis. CONCLUSIONS: This is a case of polyserositis in a post-COVID-19 patient. After other causes of polyserositis were ruled out, and since there is a likely physiological and pathogenic mechanism operating between the two diseases, the polyserositis was determined to be a late complication of COVID-19. To date, it is the second case reported in the world and the first reported in Cuba.

DIA-Person Integration Model to increase the quality of teaching, research and medical care. A person-oriented strategy.

Current model of medicine has made for medical care, teaching and research to be driven apart, with an impact on the patient: during the process of care, the doctor fails to apply the scientific method, he only treats the ailment without accompanying the patient. The medical researcher looks for answers to questions far removed from patient ailments and, in the best-case scenario, conducts research on patient specimens. In addition, the student-teacher dyad is characterized by the transmission of knowledge and leaves aside understanding of the patient. Patients, doctors, researchers and students are oblivious to decision-making and, without questioning, they merely follow processes. One way to address the problem is to return to the DIA-person Integration Model: "concern and doing for the person, accompanied by the integration of teaching, research and medical care", which would allow the transfer of knowledge, skills and benefits from one activity to others. The model consists of contrasting the patient condition with knowledge, carrying out research during and parallel to the medical care-teaching process, as well as applying the architecture of research model "clinical judgment structured description", as a reference and reflection process that integrates the activities of teaching-research and person-oriented medical care.

El modelo actual de la medicina ha distanciado la atención médica, la docencia y la investigación, con impacto en el paciente: durante la atención, el médico omite aplicar el método científico, solo atiende la dolencia sin acompañar al paciente; el investigador médico busca respuestas a preguntas alejadas de las dolencias del paciente y, en el mejor de los casos, realiza investigación en especímenes provenientes de este; la díada estudiante-profesor se caracteriza por la transmisión de conocimiento y deja de lado la comprensión del paciente. Pacientes, médicos, investigadores y estudiantes son ajenos a la toma de decisiones y sin cuestionamientos solo siguen procesos. Una manera de abordar el problema es regresar al Modelo de Integración DIA-persona: "la preocupación y el hacer por la persona, acompañados por la integración de docencia, investigación y atención médica", lo que permitiría el traslado del conocimiento, destrezas y beneficios de una actividad a otra. El modelo consiste en contrastar la condición del paciente con el conocimiento, realizar investigación durante y en paralelo al proceso de atención-docencia médica, así como aplicar el modelo arquitectónico de la investigación "descripción estructurada del juicio clínico", como proceso de referencia y reflexión que integra las actividades de docencia-investigación y atención médica orientadas a la persona.

Pattern matching for high precision detection of LINE-1s in human genomes.

BACKGROUND: Long interspersed element 1 (LINE-1 or L1) retrotransposons are mobile elements that constitute 17-20% of the human genome. Strong correlations between abnormal L1 expression and several human diseases have been reported. This has motivated increasing interest in accurate quantification of the number of L1 copies present in any given biologic specimen. A main obstacle toward this aim is that L1s are relatively long DNA segments with regions of high variability, or largely present in the human genome as truncated fragments. These particularities render traditional alignment strategies, such as seed-and-extend inefficient, as the number of segments that are similar to L1s explodes exponentially. This study uses the pattern matching methodology for more accurate identification of L1s. We validate experimentally the superiority of pattern matching for L1 detection over alternative methods and discuss some of its potential applications. RESULTS: Pattern matching detected full-length L1 copies with high precision, reasonable computational time, and no prior input information. It also detected truncated and significantly altered copies of L1 with relatively high precision. The method was effectively used to annotate L1s in a target genome and to calculate copy number variation with respect to a reference genome. Crucial to the success of implementation was the selection of a small set of k-mer probes from a set of sequences presenting a stable pattern of distribution in the genome. As in seed-and-extend methods, the pattern matching algorithm sowed these k-mer probes, but instead of using heuristic extensions around the seeds, the analysis was based on distribution patterns within the genome. The desired level of precision could be adjusted, with some loss of recall. CONCLUSION: Pattern matching is more efficient than seed-and-extend methods for the detection of L1 segments whose characterization depends on a finite set of sequences with common areas of low variability. We propose that pattern matching may help establish correlations between L1 copy number and disease states associated with L1 mobilization and evolution.

Modelo de Integración DIA-Persona para incrementar la calidad de la docencia, investigación y atención médica. Estrategia orientada a la persona / DIA-Person Integration Model to increase the quality of teaching, research and medical care. A person-oriented strategy

Resumen El modelo actual de la medicina ha distanciado la atención médica, la docencia y la investigación, con impacto en el paciente: durante la atención, el médico omite aplicar el método científico, solo atiende la dolencia sin acompañar al paciente; el investigador médico busca respuestas a preguntas alejadas de las dolencias del paciente y, en el mejor de los casos, realiza investigación en especímenes provenientes de este; la díada estudiante-profesor se caracteriza por la transmisión de conocimiento y deja de lado la comprensión del paciente. Pacientes, médicos, investigadores y estudiantes son ajenos a la toma de decisiones y sin cuestionamientos solo siguen procesos. Una manera de abordar el problema es regresar al Modelo de Integración DIA-persona: "la preocupación y el hacer por la persona, acompañados por la integración de docencia, investigación y atención médica", lo que permitiría el traslado del conocimiento, destrezas y beneficios de una actividad a otra. El modelo consiste en contrastar la condición del paciente con el conocimiento, realizar investigación durante y en paralelo al proceso de atención-docencia médica, así como aplicar el modelo arquitectónico de la investigación "descripción estructurada del juicio clínico", como proceso de referencia y reflexión que integra las actividades de docencia-investigación y atención médica orientadas a la persona.

Abstract Current model of medicine has made for medical care, teaching and research to be driven apart, with an impact on the patient: during the process of care, the doctor fails to apply the scientific method, he only treats the ailment without accompanying the patient. The medical researcher looks for answers to questions far removed from patient ailments and, in thebest-case scenario, conducts research on patient specimens. In addition, the student-teacher dyad is characterized by thetransmission of knowledge and leaves aside understanding of the patient. Patients, doctors, researchers and students are oblivious to decision-making and, without questioning, they merely follow processes. One way to address the problem is to return to the DIA-person Integration Model "concern and doing for the person, accompanied by the integration of teaching, research and medical care", which would allow the transfer of knowledge, skills and benefits from one activity to others. The model consists of contrasting the patient condition with knowledge, carrying out research during and parallel to the medical care-teaching process, as well as applying the architecture of research model "clinical judgment structured description", as a reference and reflection process that integrates the activities of teaching-research and person-oriented medical care.

Effect of a ready-to-use supplementary food on the recovery of preschool children with malnutrition.

INTRODUCTION: In developing countries, protein-energy malnutrition causes 60% of deaths in children < 5 years of age. OBJECTIVE: To evaluate the effect of a ready-to-use supplementary food (RUSF) on moderate acute malnutrition (MAM) in preschool children. METHOD: Clinical trial that included 155 children with MAM (weight/height Z-score > -3 and ≤ -2). Each child received RUSF in the form of biscuits, four per day (250 kcal), for 12 months. The tutor received education on nutrition, health and hygiene. Recovery (weight/height Z-score > -2) at four, six, and 12 months was assessed using intent-to-treat (ITT) and per protocol (PP) analyses. Changes in chronic malnutrition were also analyzed. RESULTS: In the first semester, adequate RUSF consumption was observed in 61% of the children, and in 42% in the second semester. In the ITT analysis, 78% were identified to have recovered, with 38% reaching normal nutritional values; in the PP analysis, > 90% recovered and > 40% reached normal values. Recovery from chronic malnutrition was also observed. CONCLUSIONS: The consumption of RUSF and an educational program reduced MAM.

INTRODUCCIÓN: En países en desarrollo, la desnutrición proteico-energética causa 60 % de las muertes en los niños menores de cinco años. OBJETIVO: Evaluar el efecto de un suplemento alimenticio listo para consumir (SALC) en la desnutrición aguda moderada (DAM) en niños preescolares. MÉTODO: Ensayo clínico que incluyó 155 niños con DAM (puntuación Z de peso/talla [pZ] mayor de −3 y menor o igual a −2). Cada niño recibió SALC en forma de galletas, cuatro por día (250 kcal), durante 12 meses. El tutor recibió educación sobre nutrición, salud e higiene. La recuperación (pZ peso/talla mayor de −2) a los cuatro, seis y 12 meses se evaluó con un análisis por intención a tratar (AIT) y por protocolo (APP). También se analizaron cambios en la desnutrición crónica. RESULTADOS: En el primer semestre se observó consumo adecuado del SALC en 61 % de los niños y en 42 % en el segundo semestre. Con el AIT se identificó que 78 % se recuperó y 38 % alcanzó valores normales de nutrición; con el APP, > 90 % se recuperó y > 40 % alcanzó valores normales. Se observó recuperación de la desnutrición crónica. CONCLUSIONES: El consumo de SALC y un programa educativo redujeron la DAM.

Back to the clinic. Methods II. The Architecture of Clinical Research. Subject interaction, maneuvers and disease throughout time.

Medicine is characterized by the application of the scientific method through clinical judgment, by correct interpretation and use of the clinical course and/or natural history of the disease; its best description is observed in the architecture of clinical research. Through a temporal sequence, this model explains the phenomenon of causality with three sections: baseline status, maneuver, and outcome. The baseline status assesses who the patient is, where does he come from, his general conditions, the diagnosis, stage and aggressiveness of the pathology, complications, previous therapies, socioeconomic-cultural level, habits, therapeutic indications or contraindications, and the expected evolution is anticipated. In the maneuver, risk or prognostic factors, specific or symptomatic treatment, and general measures can be evaluated. In the outcome, early and late evolution are monitored. The model also allows the causes of follow-up loss to be determined. Anticipating patient evolution by recognizing his condition, disease, and expected effect of medical decisions allows acting in advance, since waiting for the manifestations of the evolutionary process of disease results in detriment to the patient.

La medicina se caracteriza por la aplicación del método científico a través del juicio clínico, por la correcta interpretación y el uso del curso clínico o historia natural de la enfermedad; su descripción más lograda la observamos en la arquitectura de la investigación clínica. A través de una secuencia temporal, este modelo explica el fenómeno de causalidad con tres apartados: estado basal, maniobra y desenlace. En el estado basal se evalúa quién es el paciente, de donde proviene, sus condiciones generales, el diagnóstico, el estadio y la agresividad de la patología, las complicaciones, terapias previas, nivel socioeconómi­co-cultural, hábitos, indicaciones o contraindicaciones terapéuticas y se prevé la evolución esperada. De la maniobra se pueden evaluar los factores de riesgo o pronóstico, tratamiento específico, sintomático y medidas generales. En el desenlace se vigila la evolución temprana y tardía. El modelo también permite determinar las causas de pérdida de seguimiento. Anticipar la evo­lución del paciente al reconocer su condición, enfermedad y efecto esperado de la decisiones médicas permite actuar antici­padamente, ya que esperar las manifestaciones del proceso evolutivo de la enfermedad resulta en detrimento del paciente.

Sensitivity and specificity of increased pulse pressure as a diagnostic test for K/DOQI stage III-b CKD.

BACKGROUND: Increased pulse pressure (IPP) is associated with an estimated glomerular filtration ≤ 60/mL/min/1.73 m2; thus, it can be useful as a diagnostic test to identify people with K/DOQI stage III-b chronic kidney disease (CKD). OBJECTIVE: To determine the usefulness of IPP as a diagnostic test for K/DOQI stage III-b CKD. METHOD: Diagnostic test study that included adult patients without comorbidities, registered in the Health Workers Cohort. The CKD-EPI formula was used to calculate glomerular filtration. Pulse pressure was determined by subtracting diastolic from systolic blood pressure. Sensitivity, specificity, positive predictive value, negative predictive value and prevalence were calculated using standard formulas. A ROC curve was generated to determine the area under the curve. RESULTS: A total of 6,215 patients were included. An IPP ≥ 50 mmHg was observed to have a sensitivity of 74 %, specificity of 70 %, positive predictive value of 1 %, negative predictive value of 100 % and a prevalence of 1 %. The inflection point in the ROC curve to identify K/DOQI III-b CKD was 0.71. CONCLUSION: An IPP ≥ 50 mmHg is useful as a diagnostic test to identify people with K/DOQI stage III-b CKD.

INTRODUCCIÓN: La presión de pulso ampliada (PPA) se asocia a un filtrado glomerular calculado ≤ 60/mL/minuto/1.73 m2, por lo que puede ser útil como prueba diagnóstica para identificar a personas con insuficiencia renal crónica (IRC) estadio K/DOQI III-b. OBJETIVO: Determinar la utilidad de la PPA como prueba diagnóstica de IRC estadio K/DOQI III-b. MÉTODO: Estudio de prueba diagnóstica que incluyó a pacientes adultos sin comorbilidades, registrados en la Cohorte de Trabajadores de la Salud. Se utilizó la fórmula CKD-EPI para calcular la filtración glomerular. Se determinó la presión de pulso restando la presión arterial diastólica a la presión arterial sistólica. Se calculó sensibilidad, especificidad, valor predictivo positivo, valor predictivo negativo y prevalencia. Se elaboró una curva ROC para determinar el área bajo la curva. RESULTADOS: Se incluyeron 6215 pacientes. Se observó que una PPA ≥ 50 mm Hg tuvo sensibilidad de 74 %, especificidad de 70 %, valor predictivo positivo de 1 %, valor predictivo negativo de 100 % y prevalencia de 1 %. El punto de inflexión en la curva ROC para identificar IRC K/DOQI III-b fue de 0.71. CONCLUSIÓN: La PPA ≥ 50 mm Hg es útil como prueba diagnóstica para identificar a personas con IRC estadio K/DOQI III-b.

U-shaped-aggressiveness of SARS-CoV-2: Period between initial symptoms and clinical progression to COVID-19 suspicion. A population-based cohort study.

BACKGROUND: Early identification of different COVID-19 clinical presentations may depict distinct pathophysiological mechanisms and guide management strategies. OBJECTIVE: To determine the aggressiveness of SARS-CoV-2 using symptom progression in COVID-19 patients. DESIGN: Historic cohort study of Mexican patients. Data from January-April 2020 were provided by the Health Ministry. SETTING: Population-based. Patients registered in the Epidemiologic Surveillance System in Mexico. PARTICIPANTS: Subjects who sought medical attention for clinical suspicion of COVID-19. All patients were subjected to RT-PCR testing for SARS-CoV-2. MEASUREMENTS: We measured the Period between initial symptoms and clinical progression to COVID-19 suspicion (PISYCS) and compared it to the primary outcomes (mortality and pneumonia). RESULTS: 65,500 patients were included. Reported fatalities and pneumonia were 2176 (3.32%), and 11568 (17.66%), respectively. According to the PISYCS, patients were distributed as follows: 14.89% in <24 hours, 43.25% between 1-3 days, 31.87% between 4-7 days and 9.97% >7 days. The distribution for mortality and pneumonia was 5.2% and 22.5% in <24 hours, 2.5% and 14% between 1-3 days, 3.6% and 19.5% between 4-7 days, 4.1% and 20.6% >7 days, respectively (p<0.001). Adjusted-risk of mortality was (OR [95% CI], p-value): <24 hours = 1.75 [1.55-1.98], p<0.001; 1-3 days = 1 (reference value); 4-7 days = 1.53 [1.37-1.70], p<0.001; >7 days = 1.67 [1.44-1.94], p<0.001. For pneumonia: <24 hours = 1.49 [1.39-1.58], p<0.001; 1-3 days = 1; 4-7 days = 1.48 [1.41-1.56], p<0.001; >7 days = 1.57 [1.46-1.69], p<0.001. LIMITATIONS: Using a database fed by large numbers of people carries the risk of data inaccuracy. However, this imprecision is expected to be random and data are consistent with previous studies. CONCLUSION: The PISYCS shows a U-shaped SARS-CoV-2 aggressiveness pattern. Further studies are needed to corroborate the time-related pathophysiology behind these findings.

Prevención de desnutrición aguda moderada con un suplemento alimenticio listo para consumir en niños preescolares de comunidades rurales / Moderate acute malnutrition prevention with a ready-to-use therapeutic food in pre-school children from rural communities

Resumen Introducción: La desnutrición infantil en México alcanza prevalencias de 27.5 % en zonas rurales. Objetivo: Evaluar la efectividad de un suplemento alimenticio listo para consumir (SALC) para corregir desnutrición aguda leve y prevenir desnutrición aguda moderada en preescolares de comunidades rurales. Método: Ensayo clínico aleatorizado por grupos: con y sin SALC (g-SALC y g-S/SALC); se incluyeron niños de dos a cinco años, con puntuaciones-Z de peso para la talla (pZ-P/T) mayor de −2 y menor de −1 y nivel socioeconómico bajo. Todos recibieron educación sobre nutrición, salud e higiene dos veces al mes; los niños del g-SALC debieron consumir diariamente una porción del suplemento. Se evaluó pZ-P/T al inicio y a los cuatro, seis y 12 meses. La comparación entre grupos se realizó con el modelo de riesgos proporcionales de Cox. Resultados: Respecto a la recuperación de desnutrición aguda leve, en g-SALC se observó 68.7 versus 52.1% en el grupo control en el análisis de intención para tratar, con una razón de riesgo (HR) = 1.25; en el análisis por protocolo del primer semestre se observó una HR = 1.48 y en el segundo semestre, HR = 1.56. Un paciente progresó a desnutrición aguda moderada. Conclusiones: El g-SALC mostró resolución significativamente mayor de desnutrición aguda leve.

Abstract Introduction: Child malnutrition in Mexico reaches a prevalence as high as 27.5 % in rural areas. Objective: To assess the effectiveness of a ready-to-use supplementary food (RUSF) to correct mild acute malnutrition and prevent moderate acute malnutrition in preschool children from rural communities. Method: Randomized clinical trial, with assignment to two groups: group with RUSF (RUSF-g) or group without it (non-RUSF-g); children aged from two to five years, with weight-for-height Z-scores (WHZ) between -2 and -1 and low socioeconomic status were included. All received education on nutrition, health and hygiene twice monthly; the RUSF-g children had to consume four biscuits of the supplement every day. WHZ was assessed at baseline and at four, six, and 12 months. The comparison between groups was carried out with Cox proportional hazards model. Results: With regard to mild acute malnutrition correction in the RUSF-g, 68.7 versus 52.1 % in the control group was observed in the intent-to-treat analysis, with a hazard ratio (HR) = 1.25; in the per-protocol analysis of first semester, a HR = 1.48 was observed, and in the second semester, HR = 1.56. One patient progressed to moderate acute malnutrition. Conclusions: The RUSF-g showed a significantly higher resolution of mild acute malnutrition.

Sensibilidad y especificidad de la presión de pulso ampliada como prueba diagnóstica de IRC estadio K/DOQI III-b / Sensitivity and specificity of increased pulse pressure as a diagnostic test for K/DOQI III-b

Resumen Introducción: La presión de pulso ampliada (PPA) se asocia a un filtrado glomerular calculado ≤ 60/mL/minuto/1.73 m2, por lo que puede ser útil como prueba diagnóstica para identificar a personas con insuficiencia renal crónica (IRC) estadio K/DOQI III-b. Objetivo: Determinar la utilidad de la PPA como prueba diagnóstica de IRC estadio K/DOQI III-b. Método: Estudio de prueba diagnóstica que incluyó a pacientes adultos sin comorbilidades, registrados en la Cohorte de Trabajadores de la Salud. Se utilizó la fórmula CKD-EPI para calcular la filtración glomerular. Se determinó la presión de pulso restando la presión arterial diastólica a la presión arterial sistólica. Se calculó sensibilidad, especificidad, valor predictivo positivo, valor predictivo negativo y prevalencia. Se elaboró una curva ROC para determinar el área bajo la curva. Resultados: Se incluyeron 6215 pacientes. Se observó que una PPA ≥ 50 mm Hg tuvo sensibilidad de 74 %, especificidad de 70 %, valor predictivo positivo de 1 %, valor predictivo negativo de 100 % y prevalencia de 1 %. El punto de inflexión en la curva ROC para identificar IRC K/DOQI III-b fue de 0.71. Conclusión: La PPA ≥ 50 mm Hg es útil como prueba diagnóstica para identificar a personas con IRC estadio K/DOQI III-b.

Abstract Introduction: Increased pulse pressure (IPP) is associated an estimated glomerular filtration ≤ 60/mL/min/1.73 m2; thus, it can be useful as a diagnostic test to identify people with K/DOQI stage III-b chronic kidney disease (CKD). Objective: To determine the usefulness of IPP as a diagnostic test for K/DOQI stage III-b CKD. Method: Diagnostic test study that included adult patients without comorbidities, registered in the Health Workers Cohort. The CKD-EPI formula was used to calculate glomerular filtration. Pulse pressure was determined by subtracting diastolic from systolic blood pressure. Sensitivity, specificity, positive predictive value, negative predictive value and prevalence were calculated using standard formulas. A ROC curve was generated to determine the area under the curve. Results: A total of 6,215 patients were included. An IPP ≥ 50 mmHg was observed to have a sensitivity of 74 %, specificity of 70 %, positive predictive value of 1 %, negative predictive value of 100 % and a prevalence of 1 %. The inflection point in the ROC curve to identify K/DOQI III-b CKD was 0.71. Conclusion: An IPP ≥ 50 mmHg is useful as a diagnostic test to identify people with K/DOQI stage III-b CKD.

De vuelta a la clínica. Métodos II. Arquitectura de la investigación clínica. Interacción sujeto, maniobras y enfermedad a través del tiempo / Back to the clinic. Methods II. Architecture of clinical research. Subject interaction, maneuvers and disease throughout time

Resumen La medicina se caracteriza por la aplicación del método científico a través del juicio clínico, por la correcta interpretación y el uso del curso clínico o historia natural de la enfermedad; su descripción más lograda la observamos en la arquitectura de la investigación clínica. A través de una secuencia temporal, este modelo explica el fenómeno de causalidad con tres apartados: estado basal, maniobra y desenlace. En el estado basal se evalúa quién es el paciente, de donde proviene, sus condiciones generales, el diagnóstico, el estadio y la agresividad de la patología, las complicaciones, terapias previas, nivel socioeconómico-cultural, hábitos, indicaciones o contraindicaciones terapéuticas y se prevé la evolución esperada. De la maniobra se pueden evaluar los factores de riesgo o pronóstico, tratamiento específico, sintomático y medidas generales. En el desenlace se vigila la evolución temprana y tardía. El modelo también permite determinar las causas de pérdida de seguimiento. Anticipar la evolución del paciente al reconocer su condición, enfermedad y efecto esperado de la decisiones médicas permite actuar anticipadamente, ya que esperar las manifestaciones del proceso evolutivo de la enfermedad resulta en detrimento del paciente.

Abstract Medicine is characterized by the application of the scientific method through clinical judgment, by correct interpretation and use of the clinical course and/or natural history of the disease; its best description is observed in the architecture of clinical research. Through a temporal sequence, this model explains the phenomenon of causality with three sections: baseline status, maneuver, and outcome. The baseline status assesses who the patient is, where does he come from, his general conditions, the diagnosis, stage and aggressiveness of the pathology, complications, previous therapies, socioeconomic-cultural level, habits, therapeutic indications or contraindications and the expected evolution is anticipated. In the maneuver, risk or prognostic factors, specific or symptom treatment, and general measures could be evaluated. In the outcome, early and late evolution are monitored. The model also allows the causes of follow-up loss to be determined. Anticipating patient evolution by recognizing his condition, disease, and expected effect of medical decisions allows acting in advance, since waiting for the manifestations of the evolutionary process of disease results in detriment to the patient.

Surgical and Pharmacological Outcomes in Acromegaly: Real-Life Data From the Mexican Acromegaly Registry.

CONTEXT: Acromegaly registries constitute a valuable source of therapeutic outcome information in real-life. OBJECTIVE: The objective of this work is to analyze surgical and pharmacological outcomes in the Mexican Acromegaly Registry (MAR). DESIGN AND METHODS: Data were extracted from the MAR informatic platform. Surgical remission was defined by a postoperative postglucose (GH) of less than 1 ng/mL and an insulin-like growth factor 1 (IGF-1) of less than 1.2 × upper limit of normal (ULN). Pharmacological remission was defined by a basal GH of less than 1 ng/mL and an IGF-1 of less than 1.2 × ULN. RESULTS: A total of 650 surgical outcomes were analyzed (94.6% transsphenoidal). Surgical remission was achieved in 40.15%, whereas 44.15% remained biochemically active. Persistently active disease after surgery was significantly associated with harboring an invasive macroadenoma, a basal GH of greater than 10 ng/mL, and/or an IGF-1 of greater than 2 × ULN at diagnosis on bivariate and multivariate analysis. The outcome of monotherapy with first-generation somatostatin analogs (SSAs) was evaluated in 267 patients (adjunctive in 65%), of whom 28.4% achieved remission. Persistently active disease was significantly associated with harboring an invasive macroadenoma as well as with pretreatment basal GH and IGF-1 levels of greater than 10 ng/mL and greater than 2 × ULN, respectively, on bivariate and multivariate analysis. Combined therapy with SSA and cabergoline was analyzed in 100 patients, of whom 19% achieved remission and 44% remained active; in this subset of patients, only a pretreatment IGF-1 of greater than 2 × ULN was significantly associated with persistent disease activity. CONCLUSION: Surgical and pharmacological outcomes in acromegaly are highly dependent on tumor size/invasiveness as well as on the degree of hypersomatotropinemia.

A Latin American survey on demographic aspects of hospitalized, decompensated cirrhotic patients and the resources for their management.

INTRODUCTION & OBJECTIVES: Liver cirrhosis is a major cause of mortality worldwide. Adequate diagnosis and treatment of decompensating events requires of both medical skills and updated technical resources. The objectives of this study were to search the demographic profile of hospitalized cirrhotic patients in a group of Latin American hospitals and the availability of expertise/facilities for the diagnosis and therapy of decompensation episodes. METHODS: A cross sectional, multicenter survey of hospitalized cirrhotic patients. RESULTS: 377 patients, (62% males; 58±11 years) (BMI>25, 57%; diabetes 32%) were hospitalized at 65 centers (63 urbans; 57 academically affiliated) in 13 countries on the survey date. Main admission causes were ascites, gastrointestinal bleeding, hepatic encephalopathy and spontaneous bacterial peritonitis/other infections. Most prevalent etiologies were alcohol-related (AR) (40%); non-alcoholic-steatohepatitis (NASH) (23%), hepatitis C virus infection (HCV) (7%) and autoimmune hepatitis (AIH) (6%). The most frequent concurrent etiologies were AR+NASH. Expertise and resources in every analyzed issue were highly available among participating centers, mostly accomplishing valid guidelines. However, availability of these facilities was significantly higher at institutions located in areas with population>500,000 (n=45) and in those having a higher complexity level (Gastrointestinal, Liver and Internal Medicine Departments at the same hospital (n=22). CONCLUSIONS: The epidemiological etiologic profile in hospitalized, decompensated cirrhotic patients in Latin America is similar to main contemporary emergent agents worldwide. Medical and technical resources are highly available, mostly at great population urban areas and high complexity medical centers. Main diagnostic and therapeutic approaches accomplish current guidelines recommendations.