Nitrofuran drugs beyond redox cycling: Evidence of Nitroreduction-independent cytotoxicity mechanism.

Nitrofurans (5-nitro-2-hydrazonylfuran as pharmacophore) are a group of widely used antimicrobial drugs but also associated to a variety of side effects. The molecular mechanisms that underlie the cytotoxic effects of nitrofuran drugs are not yet clearly understood. One-electron reduction of 5-nitro group by host enzymes and ROS production via redox cycling have been attributed as mechanisms of cell toxicity. However, the current evidence suggests that nitrofuran ROS generation by itself is uncapable to explain the whole toxic effects associated to nitrofuran consumption, proposing a nitro-reduction independent mechanism of toxicity. In the present work, a series of nitrated and non-nitrated derivatives of nitrofuran drugs were synthesized and evaluated in vitro for their cytotoxicity, ROS-producing capacity, effect on GSH-S-transferase and antibacterial activity. Our studies showed that in human cells non-nitrated derivatives were less toxic than parental drugs but, unexpectedly preserved the ability to generate intracellular ROS in similar amounts to nitrofurans despite not entering into a redox cycle mechanism. In addition, some non-nitrated derivatives although being uncapable to generate ROS exhibited the highest cell toxicity among all derivatives. Inhibition of cytosolic glutathione-S-transferase activity by some derivatives was also observed. Finally, only nitrofuran derivatives displayed antibacterial effect. Results suggest that the combined 2-hydrazonylfuran moiety, redox cycling of 5-nitrofuran, and inhibitory effects on antioxidant enzymes, would be finally responsible for the toxic effects of the studied nitrofurans on mammalian cells.

Construct validity and responsiveness of the Colombian version of Skindex-29.

BACKGROUND: In recent years, the need for international, objective, patient-reported outcomes measures has grown as international collaboration has increased. As most quality-of-life scales have been developed in English, there is a growing need to adapt them transculturally to obtain equivalence between the original instrument and the adapted scale. OBJECTIVES: To assess the construct and convergent-discriminant validity and responsiveness of the Colombian version of Skindex-29. METHODS: The cross-sectional and longitudinal validity and responsiveness were tested in both healthy and dermatology patients. Construct validity was tested through a confirmatory factor analysis. The convergent-discriminant validity was assessed by examining the Spearman correlation coefficient. Change sensitivity was tested by means of the standardized response mean. The effect size and the minimum detectable change were also assessed. RESULTS: A total of 265 participants were included; 21·1% were healthy individuals, and 78·9% patients had either inflammatory or noninflammatory skin diseases. Confirmatory factor analysis showed an adequate comparative fit index and Tucker-Lewis index adjustment for the root mean square error of approximation. Convergent validity showed moderate correlations between the emotions, functioning and physical function or physical role domains. Discriminant validity showed low correlations between overall domains for both scales. Sensitivity to change at the first and third month showed effect sizes in global Skindex scores of 0·92 and 0·82, respectively. CONCLUSIONS: The Colombian version of Skindex-29 is a valid and clinically sensitive instrument, which can be used for clinical practice and for research to measure the impact of skin diseases on the quality of life of dermatology patients.

Pharmacokinetic Evidence from the HIRIF Trial To Support Increased Doses of Rifampin for Tuberculosis.

Rifamycins exhibit concentration-dependent killing of Mycobacterium tuberculosis; higher exposures potentially induce better outcomes. We randomized 180 tuberculosis patients in Peru to receive rifampin at 10, 15, or 20 mg/kg/day. A total of 168 had noncompartmental pharmacokinetic analyses; 67% were sampled twice, and 33% were sampled six times. The doses administered were well tolerated. The median area under the concentration-time curve from 0 to 6 h (interquartile range) was 24.9 (17.6 to 32.1), 43.1 (30.3 to 57.5), or 55.5 (35.7 to 73.2) h · µg/ml. The median maximum drug concentration in serum in the experimental arms reached the target of 8 µg/ml. Continued investigation of higher rifampin doses is warranted. (This study has been registered at ClinicalTrials.gov under registration no. NCT01408914.).

[CFTR gene sequencing in a group of Chilean patients with cystic fibrosis]. / Secuenciación del gen CFTR en un grupo de pacientes chilenos con fibrosis quística.

INTRODUCTION: Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations of the CFTR gene, in which over 1,900 different mutations have been identified. In Chile, the diagnosis panel with the 36 most common mutations detects approximately 50% of all alleles, while for Caucasians, it is nearly 90%. The objective of this study is to expand the capacity of mutational screening in Chilean patients and look for recurrent mutations at the national level. METHOD: The detection of unknown pathogenic alleles was assessed by CFTR gene sequencing in a selected group of patients from the National Cystic Fibrosis Foundation (NCFF). 39 patients, who met the CF diagnostic criteria and had only one allele identified according to the mutational panel, were studied. Massive sequencing was performed throughout the investigation and the main CFTR databases were used for analysis. RESULTS: The second pathogenic allele was identified in 16 of 39 patients of this study (41%), finding eleven different mutations that had not been reported in our population. We believe that the reason is that one of the variants had not been previously described. CONCLUSIONS: Mutations that had been described mainly in Hispanic and/or Mediterranean populations were identified. We found a variation that had not been previously reported, but not enough recurrent mutations that could explain the low rate of detection were found. Knowledge about mutations can provide appropriate genetic counseling and will be critical to evaluate the potential use of new targeted therapies for treating them.

Development of an Inertial Measurement Unit (IMU) with datalogger and geopositioning for mapping the Earth's magnetic field.

The Earth's magnetic field is used in various navigation systems, but this field has a dynamic behavior that can be affected by different physical factors in local environments. These factors can pose risks to navigation systems and at the same time be a signal of a phenomenon that needs to be investigated, such as mineral concentration or the presence of interference from electrical equipment, among others. For that reason, in this project, this system was designed and integrated using a low-cost, military-grade magnet inductive magnetometer, which is integrated into two Inertial Measurement Units to corroborate the movement data, and at the same time a geopositioning system to georeference the sensor measurements. The information is managed by an MCU, which also stores data on an SD card. The system includes a lithium battery management system to provide more than an hour of autonomy. Wireless communication systems are intentionally avoided to prevent interference, and an infrared transmission LED is included instead, in case the real-time transmission is necessary. The results show that the proposed system allows for obtaining maps of magnetic field intensity in open spaces, and this information can be used to determine regions with anomalies.

Low-cost system for analysis pedestrian flow from an aerial view using Near-Infrared, Microwave, and Temperature sensors.

The use of IoT systems that support the construction of smart cities is a global trend that directly affects the quality of life of citizens. for vehicular and pedestrian traffic, the detection of living beings and especially of humans, is a way of quantifying different variables pertinent to the improvement of roads, traffic flows, frequency of visits, among others. the implementation of low-cost systems that do not involve high-processing systems makes the solutions more scalable at a global level. The data acquired by this type of device offers advantages to the different entities in statistics and public consultations, thus contributing to their growth. In this article, an assistance system for the task of pedestrian flow detection is designed and constructed. It integrates strategically located arrays of sensors to detect the direction and general location, which include microwave sensors to detect motion, and infrared presence sensors. The results demonstrate that the system manages to establish the direction of flow of the individual and laterally of the displacement and differentiation between humans and objects for assistance to other systems of counting or analysis of pedestrian flow.

Preconditioning donor with a combination of tacrolimus and rapamacyn to decrease ischaemia-reperfusion injury in a rat syngenic kidney transplantation model.

Reperfusion injury remains one of the major problems in transplantation. Repair from ischaemic acute renal failure (ARF) involves stimulation of tubular epithelial cell proliferation. The aim of this exploratory study was to evaluate the effects of preconditioning donor animals with rapamycin and tacrolimus to prevent ischaemia-reperfusion (I/R) injury. Twelve hours before nephrectomy, the donor animals received immunosuppressive drugs. The animals were divided into four groups, as follows: group 1 control: no treatment; group 2: rapamycin (2 mg/kg); group 3 FK506 (0, 3 mg/kg); and group 4: FK506 (0, 3 mg/kg) plus rapamycin (2 mg/kg). The left kidney was removed and after 3 h of cold ischaemia, the graft was transplanted. Twenty-four hours after transplant, the kidney was recovered for histological analysis and cytokine expression. Preconditioning treatment with rapamycin or tacrolimus significantly reduced blood urea nitrogen and creatinine compared with control [blood urea nitrogen (BUN): P < 0·001 versus control and creatinine: P < 0·001 versus control]. A further decrease was observed when rapamycin was combined with tacrolimus. Acute tubular necrosis was decreased significantly in donors treated with immunosuppressants compared with the control group (P < 0·001 versus control). Moreover, the number of apoptotic nuclei in the control group was higher compared with the treated groups (P < 0·001 versus control). Surprisingly, only rapamycin preconditioning treatment increased anti-apoptotic Bcl2 levels (P < 0·001). Finally, inflammatory cytokines, such as tumour necrosis factor (TNF)-α and interleukin (IL)-6, showed lower levels in the graft of those animals that had been pretreated with rapamycin or tacrolimus. This exploratory study demonstrates that preconditioning donor animals with rapamycin or tacrolimus improves clinical outcomes and reduce necrosis and apoptosis in kidney I/R injury.

Amelioration of renal damage by administration of anti-thymocyte globulin to potential donors in a brain death rat model.

Brain death (BD), a non-immunological factor of renal injury, triggers an inflammatory process causing pathological signs of cell death in the kidney, such as necrosis and apoptosis. Kidneys from brain dead donors show lower success rates than kidneys from living donors and one strategy to improve transplantation outcome is to precondition the donors. For the first time, anti-rat thymoglobulin (rATG) was administered in an experimental brain death animal model to evaluate if it could ameliorate histopathological damage and improve organ function. Animals were divided into three groups: V (n=5) ventilated for 2h; BD (n=5) brain death and ventilated for 2h; and BD+rATG (n=5) brain death, ventilated for 2h, rATG was administered during brain death (10mg/kg). We observed lower creatinine levels in treatment groups (means): V, 0·88±0·22 mg/dl; BD, 1·37±0·07 mg/dl; and BD+rATG, 0·64±0·02 mg/dl (BD versus BD+rATG, P<0·001). In the BD group there appeared to be a marked increase of ATN, whereas ATN was decreased significantly in the rATG group (V, 2·25±0·5 versus BD, 4·75±0·5, P<0·01; BD+rATG, 2·75±0·5 versus BD 4·75±0·5 P<0·01). Gene expression was evaluated with reverse transcription-polymerase chain reaction; tumour necrosis factor (TNF)-α, interleukin (IL)-6, C3, CD86 showed no significant difference between groups. Increased IL-10 and decreased CCL2 in BD+rATG compared to BD (both cases P<0·01). Myeloperoxidase was increased significantly after the brain death setting (V: 32±7·5 versus BD: 129±18). Findings suggest that rATG administered to potential donors may ameliorate renal damage caused by BD. These findings could contribute in the search for specific cytoprotective interventions to improve the quality and viability of transplanted organs.

Open source and open hardware mobile robot for developing applications in education and research.

Nowadays, additive manufacturing, rapid prototyping and assembly modules represent a market that has invaded the entire world, especially in developing countries where traditional manufacturing is more restricted. In robotics, it is pertinent to think that modular construction is essential, due to the complexity of geometry in each of the pieces and their manufacture. Taking into account the globalization of information and the worldwide reproduction of databases, facilitating access to CAD files to be reproduced in 3D printing promotes the easy construction of archived mechanical designs. A robotic architecture becomes a complex assembly by having multiple operating systems. The sensorics, mechanics, electronics and programming that it requires for navigation, collaboration, development, operation and even industrial manufacturing means that more and more elaborate embedded systems are used. In this work, a mobile robotics architecture was developed with a sensory system that allows free movement and navigation in closed loop inverse kinematics. This kind of robot uses navigation algorithms to take a trajectory in collaborative closed environments, that is, closed industrial environments where obstacles are normally immovable and corridors to move narrow, in addition to having mobile obstacles like humans.

Early and late brain resonance findings of two siblings with Hunter syndrome. / Hallazgos tempranos y tardíos en la resonancia cerebral de dos hermanos con síndrome de Hunter.

INTRODUCTION: Mucopolysaccharidosis type II (MPS II) is a lysosomal disease caused by deficiency of the enzyme iduronate-2-sulfatase (IDS), linked to the X chromosome, producing a wide spectrum of clinical manifestations. CASE REPORT: We present the case of two siblings with MPS II of different paternal origin with the same genetic mutation; the age at the time of diagnosis was 5 years of age (case 1) and 8 months of age (case 2). These brethren present different findings in brain magnetic resonance imaging (MRI) with each other, case 1 presented classic findings for age, case 2 presented multiple early findings, such as dilated perivascular spaces up to 9.5 mm, magna megacisterna, among others; without neurological manifestations. CONCLUSION: This patient's brain compromise was presented before the year of age and prior to hepatosplenomegaly, thus, MRI becomes an early diagnostic tool for MPS II.

TITLE: Hallazgos tempranos y tardíos en la resonancia cerebral de dos hermanos con síndrome de Hunter.Introducción. La mucopolisacaridosis de tipo II (MPS II) es una enfermedad lisosómica causada por deficiencia de la enzima iduronato-2-sulfatasa, ligada al cromosoma X, y produce un gran espectro de manifestaciones clínicas. Caso clínico. Se presenta el caso clínico de dos hermanos con MPS II de diferente origen paterno con la misma mutación genética; la edad en el momento del diagnóstico fue de 5 años (caso 1) y de 8 meses (caso 2). Dichos hermanos presentan hallazgos diferentes en la resonancia magnética cerebral entre sí: el caso 1 presentó hallazgos clásicos para la edad, y el caso 2 presentó múltiples hallazgos tempranos, como espacios perivasculares dilatados de hasta 9,5 mm y megacisterna magna, entre otros, sin presentar manifestaciones neurológicas. Conclusiones. La afectación cerebral del paciente del caso 2 se presentó antes del año de edad y previa a la hepatoesplenomegalia. La resonancia magnética se convierte en una herramienta de diagnóstico temprano para la MPS II.

Nutritional Assessment in Patients with Early-Onset Autosomal Dominant Alzheimer's Disease Due to PSEN1- E280A Genetic Variant: A Cross-Sectional Study.

Background: Weight loss and malnutrition are frequent findings in late-onset and sporadic presentations of Alzheimer's Disease (AD). However, less is known about nutritional status in Early-Onset Autosomal Dominant AD (EO-ADAD). Objective: To analyze the association between nutritional status and other clinical and sociodemographic characteristics in individuals with a genetic form of EO-ADAD. Design settings and participants: Cross-sectional study with 75 non-institutionalized participants from a cohort of Autosomal Dominant AD (13 with mild cognitive impairment and 61 with dementia, ages from 38 to 67 years) underwent a structured clinical assessment with emphasis on nutritional status. Measurements: Primary outcome was nutritional status and it was measured using the Mini Nutritional Assessment (MNA). Patients were categorized according to MNA total score, as undernourished (MNA ≤23.5) and well-nourished (MNA ≥ 24). Sociodemographic and clinical variables identified as potential predictors or confounders of nutritional status were also collected. Results: Undernourishment by MNA was present in 57.3% of the sample. Forty-two percent of participants had abnormal BMI values considered lower than 18.5 or higher than 24.9 kg/m2. Total BMI values were similar in well and undernourished patients (median 24.2 IQR 3.59 and median 23.9 IQR 4.42, respectively, p=0.476). When comparing well and undernourished groups, we found statistically significant differences for variables: severity of dementia (p=0.034), frailty (p=0.001), multimorbidity (p=0.035) and, polymedication (p=0.045). Neither adjusted logistic regression nor the Poisson regression showed that any clinical or sociodemographic variables explained undernourishment. Conclusions: Undernourishment was a frequent finding in our sample of EO-ADAD, especially in later stages of the disease. Patients with polymedication, multimorbidity, frailty and severe dementia show differences in their nutritional status with a tendency to be more frequently undernourished. Further studies with larger sample sizes are needed to establish this association.

Sobredosis de acetaminofén y comportamientos relacionados con suicidio / Acetaminophen overdose and suicide-related behaviors / Overdose de paracetamol e comportamentos suicidas

Objetivo: este trabajo busca caracterizar el comportamiento relacionado con el suicidio en la población admitida al Hospital San Vicente Fundación, Rionegro, con sobredosis de acetaminofén entre enero 2019 y diciembre 2020 y detectar factores asociados con la dosis tóxica. Metodología: análisis descriptivo con información obtenida de historias clínicas. Resultados: 63 individuos presentaron ingestión aguda de dosis tóxica de acetaminofén como comportamiento relacionado con suicidio. Cuarenta y tres eran mujeres, 60% tenía antecedente de enfermedad psiquiátrica, 35% reportó al menos un intento suicida previo y 22% consumieron 25g o más. La lesión hepática aguda se asoció con una dosis tóxica. Conclusiones: evidenciamos una alta prevalencia de antecedente de enfermedad psi­quiátrica y comportamiento relacionado con suicidio y casi un tercio de los pacientes ingirió dosis mayores al umbral de riesgo para falla hepática. Además, la impulsividad e ingesta en casa sugiere que políticas públicas restrictivas pueden no impactar en la reducción de estos eventos en la población.

Objective: this work seeks to characterize the behavior related to suicide in the po­pulation admitted to the Hospital San Vicente Fundación, Rionegro, with an overdose of acetaminophen between January 2019 and December 2020, and to identify factors associated with the toxic dose. Methodology: descriptive analysis with information obtained from medical records. Results: 63 individuals presented acute ingestion of a toxic dose of acetaminophen as behavior related to suicide. Forty-three were women, 60% had a history of psychiatric illness, 35% reported at least one previous suicide attempt, and 22% consumed 25g or more. Acute liver injury was associated with a toxic dose. Conclusions: we evidenced a high prevalence of a history of psychiatric illness and beha­vior related to suicide; almost a third of the patients ingested doses greater than the risk threshold for liver failure. In addition, impulsiveness and eating at home suggests that res­trictive public policies may not have an impact on reducing these events in the population.

Objetivo: Este trabalho busca caracterizar o comportamento relacionado ao suicídio na população internada no Hospital San Vicente Fundación, Rionegro, com overdose de acetaminofeno entre janeiro de 2019 e dezembro de 2020 e detectar fatores associados à dose tóxica. Metodologia: análise descritiva com informações obtidas dos prontuários. Resultados: 63 indivíduos apresentaram ingestão aguda de dose tóxica de paracetamol como comportamento relacionado ao suicídio. Quarenta e três eram mulheres, 60% tinham histórico de doença psiquiátrica, 35% relataram pelo menos uma tentativa de suicídio anterior e 22% consumiram 25g ou mais. A lesão hepática aguda foi associada a uma dose tóxica. Conclusões: evidenciamos alta prevalência de história de doença psiquiátrica e com-portamento relacionado ao suicídio e quase um terço dos pacientes ingeriu doses superiores ao limiar de risco para insuficiência hepática. Além disso, a impulsividade e a alimentação em casa sugerem que políticas públicas restritivas podem não ter impacto na redução desses eventos na população.

Características clínicas de pacientes hospitalizados con infección por Covid-19 en la Clínica SOMA de Medellín, Colombia / Clinical characteristics of hospitalized patients with Covid-19 infection at the SOMA Clinic in Medellín, Colombia / Características clínicas de pacientes hospitalizados com infecção por Covid-19 na Clínica SOMA em Medellín, Colômbia

Objetivo: el virus SARS-COV-2 llegó a Medellín el 9 de marzo del 2020, afectando hasta el 8 de octubre 2021 a 397.395 personas en esta ciudad. Este estudio busca describir el comportamiento clínico de los pacientes hospitalizados en la Clínica SOMA en el periodo entre julio 1 de 2020 y enero 31 de 2021, así como identificar variables clínicas y paraclínicas asociadas a su ingreso a UCI y la mortalidad. Metodología: cohorte retrospectiva con datos de historias clínicas de adultos admitidos en la Clínica SOMA por Covid-19 entre julio 1 de 2020 y enero 31 de 2021. Resultados: se identificaron 849 individuos adultos con Covid-19, de los cuales 326 fueron hospitalizados (38.4%), la mortalidad fue del 13%. Los factores más asociados a severidad fueron la disnea, hipertensión arterial, enfermedad cardiovascular, dímero D elevado, deshidrogenasa láctica, linfopenia y una mayor edad. Conclusiones: nuestro estudio evidenció un comportamiento similar al descrito en otros estudios en el mundo frente a variables al ingreso por Covid-19, que se asocian con peores desenlaces clínicos.

Objective: SARS COV-2 virus arrived in Medellin on March 9, 2020, affecting 397 395 people in Medellin by Oct 8, 2021. This study aims to describe the clinical behavior of patients hospitalized in SOMA Clinic between July 1st, 2020, and January 31st, 2021, and to identify clinical and paraclinical variables associated with ICU entry and mortality. Methodology: retrospective cohort with data from medical records of all patients over 18 years of age admitted to the SOMA Clinic for Covid-19 between July 1st, 2020, and January 31st, 2021. Results: 849 patients with Covid-19 consulted the emergency room of the SOMA Clinic, out of which 326 were hospitalized (38.4%) with a mortality of 13%. Dyspnea, hypertension, cardiovascular disease, elevated D-dimer values, lactic dehydrogenase, and lymphopenia and older age were associated with severity. Conclusions: like other studies worldwide, we evidenced clinical and paraclinical parameters at entry that are associated with worst clinical outcomes in a SARS-COV-2 infection.

Objetivo: o vírus SARS-COV-2 chegou a Medellín em 9 de março de 2020, afetando 397.395 pessoas nesta cidade até 8 de outubro de 2021. Este estudo busca descrever o comportamento clínico dos pacientes internados na Clínica SOMA no período entre 1º de julho de 2020 e 31 de janeiro de 2021, bem como identificar variáveis clínicas e paraclínicas associadas à sua admissão na UTI e mortalidade. Metodologia: coorte retrospectiva com dados de prontuários de adultos internados na Clínica SOMA por Covid-19 entre 1º de julho de 2020 e 31 de janeiro de 2021.Resultados: foram identificados 849 indivíduos adultos com Covid-19, dos quais 326 foram hospitalizados (38,4%), a mortalidade foi de 13%. Os fatores mais associados à gravidade foram dispneia, hipertensão arterial, doença cardiovascular, D-dímero elevado, desidrogenase lática, linfopenia e idade avançada. Conclusões: nosso estudo mostrou um comportamento semelhante ao descrito em outros estudos no mundo frente às variáveis na admissão por Covid-19, que estão associadas a piores desfechos clínicos.

Perfil epidemiológico de pacientes intoxicados con acetaminofén con intenciones suicidas / Epidemiological profile of patients intoxicated with acetaminophen for suicidal purposes / Perfil epidemiológico de pacientes intoxicados com acetaminofen (Paracetamol) com intenções suicidas

Objetivo: este estudio busca describir los individuos evaluados por sobredosis de acetaminofén entre 2019 y 2020 en un centro de referencia de trasplante hepático en Colombia. Metodología: estudio derivado del análisis secundario de historias clínicas entre el 1.º de enero de 2019 y el 31 de diciembre de 2020. Los criterios de inclusión abarcan individuos con ingestión aguda y voluntaria de dosis tóxicas de acetaminofén (>4 g/día). Resultados: sesenta y tres casos, 68% mujeres, 67% menores de 18 años y 54% estudiantes. Reportó historia personal de enfermedad psiquiátrica el 60% y el 35% al menos un intento de suicidio previo. La mediana de dosis de acetaminofén fue 15g, 46% refirieron co-ingesta de otras sustancias y 13% estaba bajo efecto de sustancias psicoactivas. El 57% tenía la intención clara de suicidarse, así como 81% vomitó antes de acudir al servicio de urgencias, 22% recibió medidas de descontaminación y 10% no recibió N - acetilcisteína. Quince individuos desarrollaron lesión hepática aguda, nueve con criterios de severidad. Conclusiones: la población era predominantemente joven, la historia de enfermedad psiquiátrica fue muy prevalente y la mayoría refirieron un evento vital que explicara el comportamiento impulsivo de consumo. Ninguno desarrolló criterios para trasplante hepático, lo cual podría explicarse por la edad de los individuos, los episodios de vómito temprano, y la ausencia de enfermedad hepática crónica o de consumo de sustancias hepatotóxicas.

Objective: this study aims to describe patients with overdose intake of acetaminophen between 2019 and 2020 at a reference center for liver transplantation in Colombia. Methodology: study derived from a secondary analysis of the clinical records between January 1st, 2019, to December 31st, 2020. Inclusion criteria were individuals with voluntary acute ingestion of toxic doses of acetaminophen (>4 g/day). Results: sixty-three cases, 68% women, 67% <18-year-old, and 54% students. 60% had personal history of psychiatric illness and 35% reported at least one previous suicide attempt. The median dose of acetaminophen was 15g, 46% referred to co-ingestion with other substances and 13% were under the effect of any psychoactive substance. 57% had a clear intention of suicide. 81% vomited before the arrival to the emergency room, 22% received decontamination intervention with gastric lavage or activated charcoal, and 10% did not receive any dose of N-Acetylcysteine. Fifteen individuals developed an acute liver injury, nine with severity criteria. Conclusions: the population was predominantly young, the personal history of psychiatric disease was highly prevalent, and most of the cases referred a vital event that explains the impulsive behavior in acetaminophen consumption. None developed criteria for liver transplantation, and this could be explained by the young age of the individuals, the episodes of early vomiting, and the absence of chronic liver disease or hepatotoxic substance consumption.

Objetivo:este estudo busca descrever os indivíduos avaliados por sobredose de acetaminofen entre 2019 e 2020 num centro de referência de transplante hepático na Colômbia. Metodologia: estudo derivado da análise secundário de histórias clínicas entre o dia 1.º de janeiro de 2019 e 31 de dezembro de 2020. Os critérios de inclusão abrangem indivíduos com ingestão aguda e voluntária de dose tóxicas de acetaminofen (>4 g/dia).Resultados:sessenta e três casos, 68% mulheres, 67% menores de 18 anos e 54% estudantes. Reportou história pessoal de doença psiquiátrica, 60% e 35% pelo menos uma tentativa de suicídio prévio. A média de dose de acetaminofen foi de 15g, 46% referiram com ingestão de outras sustâncias e 13% estava sob efeito de sustâncias psicoativas. 57% tinham a intenção clara de suicidar-se, assim como 81% vomitou antes de acudir ao serviço de urgências, 22% receberam medidas de descontaminação e 10% não recebeu N - acetilcisteína. Quinze indivíduos desenvolveram lesão hepática aguda, nove com critérios de severidade. Conclusões: a população era predominantemente jovem, a história de doençapsiquiátrica foi muito prevalente e a maioria referiram um evento vital que explicasse o comportamento impulsivo de consumo. Nenhum desenvolveu critérios para transplantehepático, o qual se poderia explicar pela idade dos indivíduos, os episódios de vómito precoce, e a ausência de doença hepática crónica ou de consumo de sustâncias hepatotóxicas.

In vivo clonogenic tumor cell kinetics following 1,3-bis(2-chloroethyl)-1-nitrosourea brain tumor therapy.

An in vitro colony formation assay was modified to determine the effects of in vivo 1,3-bis(2-chloroethyl)-1-nitrosourea therapy on tumor cell kill and subsequent clonogenic cell kinetics. The measured surviving fraction must be multiplied by the relative total number of tumor cells for each posttreatment interval in order to eliminate inaccuracies caused by dead cell removal in vivo and the lysis of damaged cells by the disaggregation procedure. The assumptions, limitations, and applications of the technique are discussed. 1,3-Bis(2-chloroethyl)-1-nitrosourea doses of 0.25, 0.50, and 1.00 X dose lethal to 10% of animals resulted in approximately at 1-, 2-, and 3-log cell kill, respectively. Significant proliferation of surviving clonogenic cells was observed after a latency period of approximately 2 days, and the rate of tumor regrowth was dose dependent. The cell-doubling times following treatment with 0.25, 0.50, and 1.00 X doses lethal to 10% of animals were 15, 21, and 38 hr, respectively. The interval to complete repopulation of the clonogenic pool corresponds to the observed increase in animal life-span for the 2 larger doses and further validates the assay as a true measure of in vivo chemotherapeutic efficacy.

Hallazgos tempranos y tardíos en la resonancia cerebral de dos hermanos con síndrome de Hunter / Early and late brain resonance findings of two siblings with Hunter syndrome

Introducción: La mucopolisacaridosis de tipo II (MPS II) es una enfermedad lisosómica causada por deficiencia de la enzima iduronato-2-sulfatasa, ligada al cromosoma X, y produce un gran espectro de manifestaciones clínicas. Caso clínico: Se presenta el caso clínico de dos hermanos con MPS II de diferente origen paterno con la misma mutación genética; la edad en el momento del diagnóstico fue de 5 años (caso 1) y de 8 meses (caso 2). Dichos hermanos presentan hallazgos diferentes en la resonancia magnética cerebral entre sí: el caso 1 presentó hallazgos clásicos para la edad, y el caso 2 presentó múltiples hallazgos tempranos, como espacios perivasculares dilatados de hasta 9,5 mm y megacisterna magna, entre otros, sin presentar manifestaciones neurológicas. Conclusiones: La afectación cerebral del paciente del caso 2 se presentó antes del año de edad y previa a la hepatoesplenomegalia. La resonancia magnética se convierte en una herramienta de diagnóstico temprano para la MPS II.(AU)

Introduction: Mucopolysaccharidosis type II (MPS II) is a lysosomal disease caused by deficiency of the enzyme iduronate-2-sulfatase (IDS), linked to the X chromosome, producing a wide spectrum of clinical manifestations. Case report: We present the case of two siblings with MPS II of different paternal origin with the same genetic mutation; the age at the time of diagnosis was 5 years of age (case 1) and 8 months of age (case 2). These brethren present different findings in brain magnetic resonance imaging (MRI) with each other, case 1 presented classic findings for age, case 2 presented multiple early findings, such as dilated perivascular spaces up to 9.5 mm, magna megacisterna, among others; without neurological manifestations. Conclusion: This patient’s brain compromise was presented before the year of age and prior to hepatosplenomegaly, thus, MRI becomes an early diagnostic tool for MPS II.(AU)

A combined CoMFA and CoMSIA 3D-QSAR study of benzamide type antibacterial inhibitors of the FtsZ protein in drug-resistant Staphylococcus aureus.

A major problem today is bacterial resistance to antibiotics and the small number of new therapeutic agents approved in recent years. The development of new antibiotics capable of acting on new targets is urgently required. The filamenting temperature-sensitive Z (FtsZ) bacterial protein is a key biomolecule for bacterial division and survival. This makes FtsZ an attractive new pharmacological target for the development of antibacterial agents. There have been several attempts to develop ligands able to inhibit FtsZ. Despite the large number of synthesized compounds that inhibit the FtsZ protein, there are no quantitative structure-activity relationships (QSAR) that allow for the rational design and synthesis of promising new molecules. We present the first 3D-QSAR study of a large and diverse set of molecules that are able to inhibit the FtsZ bacterial protein. We summarize a set of chemical changes that can be made in the steric, electrostatic, hydrophobic and donor/acceptor hydrogen-bonding properties of the pharmacophore, to generate new bioactive molecules against FtsZ. These results provide a rational guide for the design and synthesis of promising new antibacterial agents, supported by the strong statistical parameters obtained from CoMFA (r(2)(pred) = 0.974) and CoMSIA (r(2)(pred) = 0.980) analyses.

Mechanical ventilation in critically-ill pregnant women: a case series.

BACKGROUND: Approximately 0.1-0.2% of pregnancies are complicated by respiratory failure requiring mechanical ventilatory support, but few data exist to inform clinical management. This study aimed to characterize current practice and the effect of delivery on respiratory function. METHODS: A retrospective review was performed of pregnant women who received mechanical ventilation for more than 24h, from four intensive care units in institutions with large-volume obstetric units. RESULTS: Data were collected from 29 patients with a mean gestation at intensive care unit admission of 25.3 ± 6 weeks. Tidal volumes were 7.7 ± 1.7 mL/kg predicted body weight. Estimated respiratory system compliance was reduced, but was higher in four patients ventilated for neurological conditions without lung disease. Three maternal and three neonatal deaths occurred. Ten patients delivered while on ventilatory support: one spontaneous delivery, four for obstetric indications and five for worsening maternal condition. Following delivery of these 10 patients, three demonstrated a greater than 50% decrease in oxygenation index and five a greater than 50% increase in compliance. No characteristics identified which patients may benefit from delivery. CONCLUSIONS: Review of current practice in four centers suggests that mechanical ventilation in pregnant patients follows usual guidelines applicable to non-pregnant patients. Delivery was associated with modest improvement in maternal respiratory function in some patients. Any potential benefit of delivery in improving maternal physiology must be weighed against the stress of delivery. The risks of premature birth for the fetus must be weighed against continued exposure to maternal hypoxemia and hypotension.