Transcriptional study of genes involved in the passage from teliospore to hyphae stage in the fungus Thecaphora frezii, the causal agent of peanut smut.

Peanuts (Arachis hypogaea L.) are among the most important leguminous crops in Argentina. During the growing season, they are frequently attacked by fungal diseases, including Thecaphora frezii. The spores of T. frezii are structures that confer resistance to this phytopathogen. The transition from teliospore to hypha is a characteristic process of some fungi, which is essential for completing their life cycle. Using the transcriptomes of teliospores and hyphae of T. frezii, we aimed to identify genes that were differentially expressed during this transition, and we found 134 up-regulated and 66 down-regulated genes, which would participate in different cellular processes such as: (a) cell cycle and DNA processing; (b) cell fate; (c) rescue, defense and cellular virulence; (d) detoxification by CYP450; (e) energy; (f) nutrient interaction and nutritional adaptation; (g) metabolism; (g) proteins with binding functions or cofactor requirements; (h) stress, cell differentiation and biogenesis of cell components; and (i) transport, cell communication and transcription. The identification of genes in T. frezii and their expression levels during different stages of differentiation could contribute to our understanding of the biological mechanisms in this fungus.

Tibiotalocalcaneal nailing for osteoporotic ankle fractures in the frail patient: a narrative review with a clinical score proposal for the decision-making process.

Osteoporotic ankle fractures result from mechanical forces that would not ordinarily result in fracture, known as 'low-energy' trauma, such as those equivalent to a fall from a standing height or less. Osteoporotic ankle fractures in frail patients are becoming more and more frequent in daily practice and represent a therapeutic challenge for orthopaedic surgeons. The main problems with frail patients are the poor condition of the soft tissues around the ankle, dependence for activities of daily living and high comorbidity. The decision to operate on these patients is complex because conservative treatment is poorly tolerated in unstable fractures and conventional open reduction and internal fixation is associated with a high rate of complications. The authors conducted a narrative review of the literature on primary tibiotalocalcaneal nailing of ankle fractures in frail patients and categorized the different factors to consider when treatment is indicated for this conditon. Difficulty of ambulation, age over 65 years old, deteriorated baseline state and instability of the fracture were the most frequently considered factors. Finally, the authors propose an easy and quick clinical scoring system to help in the decision-making process, although further comparative studies are required to explore its validity.

SARS-CoV-2 detection in multi-sample pools in a real pandemic scenario: A screening strategy of choice for active surveillance.

BACKGROUND: The current COVID-19 pandemic has overloaded the diagnostic capacity of laboratories by the gold standard method rRT-PCR. This disease has a high spread rate and almost a quarter of infected individuals never develop symptoms. In this scenario, active surveillance is crucial to stop the virus propagation. METHODS: Between July 2020 and April 2021, 11,580 oropharyngeal swab samples collected in closed and semi-closed institutions were processed for SARS-CoV-2 detection in pools, implementing this strategy for the first time in Córdoba, Argentina. Five-sample pools were constituted before nucleic acid extraction and amplification by rRT-PCR. Comparative analysis of cycle threshold (Ct) values from positive pools and individual samples along with a cost-benefit report of the whole performance of the results was performed. RESULTS: From 2,314 5-sample pools tested, 158 were classified as positive (6.8%), 2,024 as negative (87.5%), and 132 were categorized as indeterminate (5.7%). The Ct value shift due to sample dilution showed an increase in Ct of 2.6±1.53 cycles for N gene and 2.6±1.78 for ORF1ab gene. Overall, 290 pools were disassembled and 1,450 swabs were analyzed individually. This strategy allowed correctly identifying 99.8% of the samples as positive (7.6%) or negative (92.2%), avoiding the execution of 7,806 rRT-PCR reactions which represents a cost saving of 67.5%. CONCLUSION: This study demonstrates the feasibility of pooling samples to increase the number of tests performed, helping to maximize molecular diagnostic resources and reducing the work overload of specialized personnel during active surveillance of the COVID-19 pandemic.

Microbiota y sepsis

La sepsis es la respuesta desordenada del organismo a la infección y se caracteriza por un daño a los órganos que puede ser irreversible y mortal. El microbioma intestinal regula a un grupo de mecanismos homeostáticos en el huésped, como la función inmunológica y la protección de la barrera intestinal, la pérdida de la estructura y la función microbiana intestinal normal; además, se ha asociado con el inicio de enfermedades de características diversas. La evidencia reciente ha demostrado un nexo entre el microbioma intestinal y la sepsis: la alteración del microbioma intestinal aumenta la susceptibilidad a la sepsis a través de varios mecanismos como la expansión de bacterias intestinales patógenas, la respuesta proinflamatoria marcada y la disminución de la formación de productos microbianos beneficiosos como los ácidos grasos de cadena corta. Una vez establecida la sepsis, la alteración del microbioma intestinal empeora y aumenta la susceptibilidad a la disfunción del órgano terminal. Existen pruebas limitadas de que las terapias basadas en microbiomas (que incluyen a probióticos y a la descontaminación digestiva selectiva) pueden disminuir el riesgo de sepsis y mejorar sus resultados en poblaciones de pacientes seleccionadas, pero las preocupaciones sobre la seguridad causan una aceptación limitada. Si bien gran parte de la evidencia que vincula el microbioma intestinal y la sepsis se ha establecido en estudios preclínicos, aún es necesaria la evidencia clínica en distintas áreas.

Sepsis is the body's overwhelming response to an infection. It is characterized by damage to the organs that may be irreversible and life-threatening. The gastrointestinal microbiome regulates a series of homeostatic mechanisms in the host, such as the immune function and the protection of the intestinal barrier, and the loss of normal intestinal microbial structure and function. Moreover, it has been associated with the onset of diseases of diverse characteristics. Recent evidence has shown a link between the gastrointestinal microbiome and sepsis: the alteration of the gastrointestinal microbiome increases the susceptibility to sepsis through various mechanisms, including the expansion of pathogenic intestinal bacteria, marked pro-inflammatory response and decreased production of beneficial microbial products such as short-chain fatty acids. Once sepsis is established, the alteration of the gastrointestinal microbiome worsens and the susceptibility to end-organ dysfunction increases. There is limited evidence that microbiome-based therapies, which include probiotics and selective digestive decontamination, can decrease the risk of sepsis and improve its outcomes in selected patient populations. However, safety concerns generate limited acceptance. While much of the evidence linking the gastrointestinal microbiome and sepsis has been established in preclinical studies, clinical evidence is still necessary in many areas.

Periprosthetic Hip Fractures With a Loose Stem: Open Reduction and Internal Fixation Versus Stem Revision.

BACKGROUND: It is recommended revision for periprosthetic hip fractures (PPHF) with a loose stem. However, several authors have argued that under certain conditions, this fracture could be treated using osteosynthesis. The aim is to compare stem revision versus internal fixation in the treatment of PPHF with a loose stem. METHODS: All patients with PPHF with a loose stem treated by osteosynthesis and stem revision between January 2009 and January 2019 were included. We assessed hospital stay, American Society of Anesthesiologists, Charlson comorbidity index, surgery time, blood transfusion, complications, reoperation rate, first-year mortality, radiological, and functional results. RESULTS: A total of 57 patients were included (40 osteosyntheses and 17 stem revision), with an average follow-up time of 3.1 years. Their mean age was 78.47 years (R 45-92). In the osteosynthesis group, fewer patients required blood transfusion (32.5% vs. 70.6%), surgical times were shorter (108 minutes vs. 169 minutes), and the cost was lower, both in terms of total cost (€14,239.07 vs. €21,498.45 and operating room cost (€5014.63 vs. €8203.34). No significant differences were found between the groups in terms of complications, reoperation rate, or functional outcomes. CONCLUSION: Compared with stem revision, osteosynthesis requires less surgery time, has a lower need for blood transfusions, and a reduced hospital cost. Stem revision remains the treatment of choice in PPHF with a loose stem, but in V-B2 fractures in elderly patients with low functional demand, high anesthetic risk (American Society of Anesthesiologists ≥3), and many comorbidities (Charlson comorbidity index ≥5) in whom anatomic reconstruction is possible, osteosynthesis can be a viable option. EVIDENCE LEVEL: Historical cohorts. Level III.

The diversity and coexistence of extracellular mitochondria in circulation: A friend or foe of the immune system.

The diversity and coexistence of extracellular mitochondria may have a key role in the maintenance of health and progression of disease. Studies report that active mitochondria can be found physiologically outside of cells and circulating in the blood without inducing an inflammatory response. In addition, inactive or harmed mitochondria have been recognized as activators of immune cells, as they play an essential role in diseases characterized by the metabolic deregulation of these cells, such as sepsis. In this review we analyze key aspects regarding the existence of a diversity of extracellular mitochondria, their coexistence in body fluids and their effects on various immune cells. Additionally, we introduce models of how extracellular mitochondria could be interacting to maintain health and affect disease prognosis. Unwrapped mitochondria (freeMitos) can exist as viable, active, inactive or harmed organelles. Mitochondria can also be found wrapped in a membrane (wrappedMitos) that may differ depending on the cell of origin. Mitochondrial fragments can also be present in various body fluids as DAMPs, as mtDNA enclosed in vesicles or as circulating-cell-free mtDNA (ccf-mtDNA). Interestingly, the great quantity of evidence regarding the levels of ccf-mtDNA and their correlation with aging and disease allows for the identification of the diversity, but not type, of extracellular mitochondria. The existence of a diversity of mitochondria and their effects on immune cells opens a new concept in the biomedical field towards the understanding of health, the progression of disease and the development of mitochondria as therapeutic agents.

Glicocálix endotelial: relevancia clínica y enfoque traslacional / Endothelial glycocalyx: clinical relevance and translational approach

El glicocálix endotelial es una estructura sin forma definida que recubre la capa luminal del endotelio vascular y que está constituido, principalmente, por tres elementos: proteoglicanos, glucosaminoglicanos y glicoproteínas. Cumple distintas funciones, como regular la permeabilidad vascular a las moléculas y líquidos, la transducción de las fuerzas mecánicas de tensión y las cascadas de fibrinólisis y coagulación vascular; además, protege de la adhesión leucocitaria, plaquetaria y de patógenos. Los determinantes de lesión del glicocálix pueden ser de varios tipos, por ejemplo, incremento las fuerzas de tensión, especies reactivas de oxígeno (O2), aumento, a nivel plasmático, de sustancias como el sodio (hipernatremia), glucosa (hiperglicemia) y colesterol (hipercolesterolemia), y las moléculas proinflamatorias. Cualquiera de las noxas citadas, individualmente o combinadas, lesionan el glicocálix y la disfunción resultante se expresará clínicamente como disfunción endotelial, aumento de la permeabilidad vascular, paso de lipoproteínas al subendotelio, activación de la coagulación o aumento de la adhesión de plaquetas y leucocitos al endotelio.

Endothelial glycocalyx is an undefined structure covering the luminal layer of the vascular endothelium and consisting mainly of three elements: proteoglycans, glycosaminoglycans and glycoproteins. It has different functions, such as the regulation of vascular permeability to liquids and molecules; transduction of the mechanical forces of vascular tension; regulation of coagulation and fibrinolysis cascades; and protection of leukocyte, platelet and pathogen adhesion. The determinants of a glycocalyx lesion can be of several types­e.g., increased tensile forces; reactive oxygen (O2) species; increased plasma level of substances such as sodium (hypernatremia), glucose (hyperglycemia) and cholesterol (hypercholesterolemia); and pro-inflammatory molecules. Any of the above-mentioned noxas, alone or combined, injure the glycocalyx. Its dysfunction will be clinically expressed as endothelial dysfunction, increased vascular permeability, filtration of lipoproteins to the subendothelium, activation of coagulation, or increased adhesion of leukocytes and platelets to the endothelium.

Prevalence of bone marrow edema in a study population with foot and/or ankle pain.

Bone marrow edema (BME) is an imaging diagnosis defined by an abnormal accumulation of intraosseous interstitial fluid within a bone on magnetic resonance imaging (MRI) investigation. The aim of this study was to determine the prevalence of BME in patients with foot and/or ankle pain studied using MRI. This was a retrospective observational work on patient cases and controls studied through MRI of the foot and/or ankle at our Foot and Ankle Unit (FAU). An analytical statistical analysis and a multivariate analysis were performed to eliminate possible confounding factors. 1950 foot and/or ankle MRI cases were reviewed, of which 451 presented bone edema (23% prevalence). The average patient age was 51.8 (range, 7-87); the talus bone was most frequently affected: post-traumatic in 43.5% of cases, degenerative in 34.7% and there was no specific cause identified in 6.3% (these cases were termed 'idiopathic'). With regards to risk factors, in the case of gender, the odds ratio (OR) of men suffering bone oedema was 1.5 times higher than that of women (P = 0.003); for immunosuppression the OR was 3.4 times higher (P = 0.001); while among those with a smoking habit it was 0.59 (P = 0.001), meaning that after ruling smoking out as a possible confounding factor, it was, in fact, revealed to be a protective factor. The prevalence of bone edema in MRI in patients with foot and/or ankle pain was 23%. The average patient was male, aged approximately 50, with traumatic or degenerative origin talus bone oedema. Level of Evidence: Level IV, revision observational study.

Aclaramiento del lactato: revisión de la literatura / Lactate clearance: review of the literature

Cuando hablamos del aclaramiento de lactato debemos conocer con claridad la complejidad del proceso, pues abarca todo el metabolismo del lactato desde su producción hasta su remoción: a este proceso se ha denominado equilibrio reversible de lactato. Este concepto que permitirá entender mejor los procesos dinámicos de su metabolismo no como producto final o de desecho (según, tradicionalmente, se nos ha hecho creer) sino, más bien, como un producto intermedio que ejerce funciones específicas y bien definidas que lo convierten no sólo en indicador de perfusión tisular sino en un indicador global del metabolismo celular.

When we talk about lactate clearance we have to be clear about the complexity of the process, since it involves the metabolism of lactate from its production to its removal what has been called reversible lactate equilibrium, this concept that will allow us to better understand the dynamic processes of its metabolism not as a final product or waste, as we have traditionally been led to believe, but rather as an intermediate product with specific and welldefined functions that make it not only an indicator of tissue perfusion, but a global indicator of metabolism cell

¿Es el volumen medio plaquetario un predictor de mortalidad en sepsis? / Is mean platelet volume a predictor of mortality in sepsis?

Introducción: la sepsis es la respuesta del huésped a una infección sistémica; sus formas severas (sepsis grave y choque séptico) afectan a millones de personas en el mundo, provocando la muerte a uno de cada cuatro pacientes (campaña de sobrevida a la sepsis). Pese a los avances tecnológicos que implican nuevos fármacos, investigación molecular, biomarcadores y estrategias terapéuticas, los logros alcanzados no permiten predecir la severidad del cuadro y anticipar la mortalidad. Objetivo: validar al volumen medio plaquetario (VMP), un valor reportado rutinariamente en el hemograma como predicitor de mortalidad en pacientes sépticos. Material y métodos: se realizó un estudio prospectivo no experimental, en la unidad de terapia intensiva del hospital Pablo Arturo Suárez de Quito en el periodo julio de 2012 hasta octubre de 2014; el universo lo conforman todos los pacientes ingresados con diagnóstico de sepsis que cumplieron los criterios de inclusión. Se consideraron las variables: VMP, contaje leucocitario, sitio de la infección, edad, género y condición al egreso. Resultados: el grupo de estudio se conformó con 87 pacientes; el sitio de infección más frecuente fue a nivel abdominal, seguido de pulmón y vías urinarias. El porcentaje de supervivencia fue 63,2%, dato que coincide con la mortalidad promedio a nivel mundial. Las curva ROC (AUC: 85,4) y la correlación lineal de Pearson (contaje leucocitario­VMP) (r: 0,94), confirman la utilidad del VMP como predictor de mortalidad en casos de sepsis. Conclusión: el volumen medio plaquetario igual o mayor a 8.5 fl predice adecuadamente la mortalidad en pacientes con sepsis. (AU)

Context: Sepsis is the host's response to a systemic infection. Its severe forms (severe sepsis and septic shock) affect millions of people worldwide, leading to death in one in four patients (sepsis survival campaign). Despite technological advances involving new drugs, molecular research, biomarkers and therapeutic strategies, achievements do not allow predicting the severity of the condition and anticipate mortality. Objective: to validate the mean platelet volume (VMP), a value routinely reported in the blood count as a predictor of mortality in septic patients. Materials and methods: a non-experimental prospective study was conducted at the intensive care unit of the Pablo Arturo Suárez Hospital in Quito from July 2012 to October 2014. Universe is made up of all patients admitted with a diagnosis of sepsis who met the inclusion criteria. The following variables were considered: VMP, leukocyte count, site of infection, age, gender and condition at discharge. Results: the study group consisted of 87 patients. The most frequent site of infection was at the abdominal level, followed by lung and urinary tract. The survival rate was 63.2%, which coincides with the average mortality worldwide. The ROC curve (AUC: 85.4) and the linear correlation of Pearson (WBC count-VMP) (r: 0.94) confirm the utility of VMP as a predictor of mortality in sepsis cases. Conclusion: mean platelet volume equal to or greater than 8.5 fl adequately predicts mortality in patients with sepsis. (AU)

Fisiología, bioquímica y metabolismo del ácido láctico: revisión de la literatura / Physiology, biochemistry and metabolism of lactic acid: review of the literature

El ácido láctico o lactato es un marcador bioquímico cuyo rol biológico ha ido adquiriendo mayor importancia a medida que entendemos su comportamiento bioquímico, fisiológico, metabólico y fisiopatológico. Inicialmente fue visto como un sustrato nocivo y luego, paulatinamente entendido como una vía vital de supervivencia celular y sustrato energético en condiciones extremas y aún normales (sistema nervioso central). Actualmente es un objetivo de resucitación hemodinámica, tan importante, que su descenso o ascenso luego de reanimación hemodinámica predice alta morbilidad y mortalidad. En esta revisión tenemos el propósito de facilitar el entendimiento del metabolismo del lactato y, por tanto, de la glucosa (ambas sustancias comparten paralelismos bioquímicos y metabólicos), recalcar la importancia del hígado y del músculo esquelético y alcanzar enfoques traslacionales sobre el tema.(AU)

Lactic acid or lactate is a biochemical marker whose biological role has become more important as we understand its biochemical, physiological, metabolic and pathophysiological behavior. Initially it was seen as a harmful substrate and then, gradually understood as a vital way of cell survival and energy substrate in extreme and still normal conditions (central nervous system). Currently, it is an important hemodynamic resuscitation objective, that its descent or rise after hemodynamic resuscitation predicts high morbidity and mortality. In this review we will try to facilitate the understanding of lactate metabolism and, therefore, of glucose (both substances share biochemical and metabolic parallelisms), emphasize the importance of the liver and skeletal muscle and achieve translational approaches on the subject.(AU)

Evaluación del índice leuco-glicémico como predictor de mortalidad en pacientes sépticos clínico-quirúrgicosy críticos / Evaluation of leuco-glycemic index as mortality predictor in critically ill and clinical-surgical patients

Contexto La glucemia y el leucograma al ingreso han demostrado importancia pronóstica en pacientes con estados inflamatorios/isquémicos. El índice leuco-glucémico, un marcador recientemente propuesto, aún carece de suficiente validación como predictor de mortalidad y otros desenlaces. Su utilidad en procesos infecciosos ha sido poco estudiada. Objetivo Evaluar el índice leuco-glucémico como marcador pronóstico de mortalidad en pacientes críticos y clínico-quirúrgicos no diabéticos con sepsis. Métodos Se analizó retrospectivamente 100 pacientes clínico-quirúrgicos (no críticos) y 100 pacientes de terapia intensiva (críticos), del Hospital General Docente Pablo Arturo Suárez, atendidos entre agosto-2014 y agosto-2015, con diagnóstico de sepsis de cualquier origen y etiología. Se recogieron los datos clínicos, scores (APACHE II-SOFA) y de laboratorio, incluyendo glucemia y leucograma al ingreso, a partir de los cuales se calculó el índice leuco-glucémico y se evaluó su valor pronóstico. Resultados No se encontró correlación positiva entre el valor del índice leuco- glicémico y la mortalidad. Este hallazgo no fue diferente en los pacientes severamente enfermos (críticos) vs los pacientes clínico-quirúrgicos (no críticos). Conclusiones Un valor elevado de índice leuco-glicémico no se correlacionó con probabilidad de muerte en nuestra serie de pacientes no diabéticos con sepsis y la ausencia de predicción es similar en pacientes críticos y no críticos.

Context Leukogram and blood sugar have shown prognostic significance in patients with inflammatory/ischemic conditions. A recently proposed marker is the leuco-glycemic index, but it still lacks of sufficient validation as a mortality predictor mortality and other outcomes. Objective To evaluate the leuco-glycemic index as a prognostic marker of mortality in critical ill and clinical and surgical patients with sepsis and without diabetes. Methods A retrospective analysis of 100 clinical-surgical patients (non-critical) and 100 patients from intensive care unit (critically ill) diagnosed with sepsis from any source and etiology who were hospitalized at the General Teaching Hospital Pablo Arturo Suarez during the period August 2014 to August 2015. Clinical data, scores (APACHE II-SOFA) and laboratory data were collected. Blood sugar and white blood cell count on admission were used to calculate the leuco-glycemic index and its prognostic value was estimated. Results We did not find a positive correlation between the value of leuco- glycemic index and mortality. This finding was not different in the severely ill (critical) vs clinical-surgical (non-critical) patients. Conclusion A high value of leuco-glycemic index was not correlated with probability of death in our non-diabetic septic patients. The absence of prediction was similar in critical and non-critical patients.

Efectividad de la metformina en pacientes con diabetes tipo II según variantes en el gen SLC22A1 / Effectiveness of Metformin in patients with type II diabetes related to variants in the SLC22A1 gene / Eficácia de Metformina em doentes com diabetes tipo II, relacionado com variantes do gene SLC22A1

La diabetes mellitus tipo II (DM II) es una enfermedad que afecta una gran cantidad de individuos. Un medicamento empleado en el tratamiento de los pacientes es la metformina. Este medicamento es transportado al interior de los hepatocitos por un transportador codificado por el gen SLC22A1. Variantes en el gen con actividad reducida pueden disminuir la cantidad de metformina disponible en el hígado y reducir la respuesta terapéutica. Se propuso evaluar diferentes parámetros bioquímicos en relación a la dosis de metformina y la presencia de variantes en el transportador. Se estudiaron 103 pacientes mayores de 18 años con diagnóstico de DM II, tratados con 1700 mg/día de metformina por más de 6 meses. Se analizaron 5 polimorfismos en el gen SLC22A1, glucemia, HbA1c, función hepática, perfil lipídico y renal. Los niveles de HbA1c y de glucemia fueron más elevados en los pacientes que presentaban los polimorfismos R61C, G401S, M420del y G465R aunque la diferencia fue estadísticamente significativa sólo para la HbA1c en los pacientes que presentaban las variantes M420del y G465R (p=0,0273 y 0,0018, respectivamente). La presencia de polimorfismos con actividad reducida en el gen SLC22A1 afecta los niveles de glucemia y de HbA1c en pacientes con DM II cuando son tratados con metformina.(AU)

Diabetes mellitus type II (DM II) is a disease that affects a large number of individuals. One of the drugs used for the treatment is metformin. Metformin is delivered into hepatocytes by a transporter encoded by the SLC22A1 gene. Gene variants with reduced activity may decrease the amount of metformin available in the liver and reduce the therapeutic response. Various biochemical parameters were evaluated in relation to the metformin dose and the presence of transporter variants. A total of 103 patients older than 18 diagnosed with DM II who were treated with 1700 mg/day of metformin for more than six months were studied. Five polymorphisms in the SLC22A1 gene were analyzed as well as glycemia, HbA1c level, liver function, and lipid and kidney profiles. HbA1c and glycemia levels were higher in patients with the R61C, G401S, M420del and G465R polymorphisms; although the difference was statistically significant only for HbA1c in patients with the M420del and G465R variants (p=0.0273 and 0.0018, respectively). Polymorphisms with reduced activity in the SLC22A1 gene affect blood glucose levels and HbA1c in patients with DM II when they are treated with metformin.(AU)

O diabetes mellitus tipo II (DM II) é uma doenþa que afeta uma grande quantidade de indivíduos. Um medicamento utilizado no tratamento dos doentes é a metformina. Esse medicamento é transportado no interior dos hepatócitos por um transportador codificado pelo gene SLC22A1. Variantes no gene com atividade reduzida podem diminuir a quantidade de Metformina disponível no fígado e reduzir a resposta terapÛutica. Prop¶s-se avaliar diferentes parÔmetros bioquímicos em relaþÒo O dose da metformina e O presenþa de variantes no transportador. Foram estudados 103 pacientes maiores de 18 anos com diagnóstico de DM II tratados com 1700 mg/dia de metformina por mais de 6 meses. Foram analisados 5 polimorfismos no gene SLC22A1; glicemia, HbA1c, funþÒo hepática, perfil lipídico e renal. Os níveis de HbA1c e de glicemia foram superiores em doentes que apresentavam os polimorfismos R61C, G401S, M420del e G465R; embora a diferenþa seja estatisticamente significativa apenas para o HbA1c nos doentes que apresentavam as variantes M420del e G465R (p=0,0273 e 0,0018; respectivamente). A presenþa de polimorfismos com atividade reduzida no gene SLC22A1 afeta os níveis da glicemia e do HbA1c em doentes com DM II quando sÒo tratados com metformina.(AU)

Efectividad de la metformina en pacientes con diabetes tipo II según variantes en el gen SLC22A1 / Effectiveness of Metformin in patients with type II diabetes related to variants in the SLC22A1 gene / Eficácia de Metformina em doentes com diabetes tipo II, relacionado com variantes do gene SLC22A1

La diabetes mellitus tipo II (DM II) es una enfermedad que afecta una gran cantidad de individuos. Un medicamento empleado en el tratamiento de los pacientes es la metformina. Este medicamento es transportado al interior de los hepatocitos por un transportador codificado por el gen SLC22A1. Variantes en el gen con actividad reducida pueden disminuir la cantidad de metformina disponible en el hígado y reducir la respuesta terapéutica. Se propuso evaluar diferentes parámetros bioquímicos en relación a la dosis de metformina y la presencia de variantes en el transportador. Se estudiaron 103 pacientes mayores de 18 años con diagnóstico de DM II, tratados con 1700 mg/día de metformina por más de 6 meses. Se analizaron 5 polimorfismos en el gen SLC22A1, glucemia, HbA1c, función hepática, perfil lipídico y renal. Los niveles de HbA1c y de glucemia fueron más elevados en los pacientes que presentaban los polimorfismos R61C, G401S, M420del y G465R aunque la diferencia fue estadísticamente significativa sólo para la HbA1c en los pacientes que presentaban las variantes M420del y G465R (p=0,0273 y 0,0018, respectivamente). La presencia de polimorfismos con actividad reducida en el gen SLC22A1 afecta los niveles de glucemia y de HbA1c en pacientes con DM II cuando son tratados con metformina.

Diabetes mellitus type II (DM II) is a disease that affects a large number of individuals. One of the drugs used for the treatment is metformin. Metformin is delivered into hepatocytes by a transporter encoded by the SLC22A1 gene. Gene variants with reduced activity may decrease the amount of metformin available in the liver and reduce the therapeutic response. Various biochemical parameters were evaluated in relation to the metformin dose and the presence of transporter variants. A total of 103 patients older than 18 diagnosed with DM II who were treated with 1700 mg/day of metformin for more than six months were studied. Five polymorphisms in the SLC22A1 gene were analyzed as well as glycemia, HbA1c level, liver function, and lipid and kidney profiles. HbA1c and glycemia levels were higher in patients with the R61C, G401S, M420del and G465R polymorphisms; although the difference was statistically significant only for HbA1c in patients with the M420del and G465R variants (p=0.0273 and 0.0018, respectively). Polymorphisms with reduced activity in the SLC22A1 gene affect blood glucose levels and HbA1c in patients with DM II when they are treated with metformin.

O diabetes mellitus tipo II (DM II) é uma doença que afeta uma grande quantidade de indivíduos. Um medicamento utilizado no tratamento dos doentes é a metformina. Esse medicamento é transportado no interior dos hepatócitos por um transportador codificado pelo gene SLC22A1. Variantes no gene com atividade reduzida podem diminuir a quantidade de Metformina disponível no fígado e reduzir a resposta terapêutica. Propôs-se avaliar diferentes parâmetros bioquímicos em relação à dose da metformina e à presença de variantes no transportador. Foram estudados 103 pacientes maiores de 18 anos com diagnóstico de DM II tratados com 1700 mg/dia de metformina por mais de 6 meses. Foram analisados 5 polimorfismos no gene SLC22A1; glicemia, HbA1c, função hepática, perfil lipídico e renal. Os níveis de HbA1c e de glicemia foram superiores em doentes que apresentavam os polimorfismos R61C, G401S, M420del e G465R; embora a diferença seja estatisticamente significativa apenas para o HbA1c nos doentes que apresentavam as variantes M420del e G465R (p=0,0273 e 0,0018; respectivamente). A presença de polimorfismos com atividade reduzida no gene SLC22A1 afeta os níveis da glicemia e do HbA1c em doentes com DM II quando são tratados com metformina.

Analysis of DNA structure and sequence requirements for Pseudomonas aeruginosa MutL endonuclease activity.

The hallmark of the mismatch repair system in bacterial and eukaryotic organisms devoid of MutH is the presence of a MutL homologue with endonuclease activity. The aim of this study was to analyse whether different DNA structures affect Pseudomonas aeruginosa MutL (PaMutL) endonuclease activity and to determine if a specific nucleotide sequence is required for this activity. Our results showed that PaMutL was able to nick covalently closed circular plasmids but not linear DNA at high ionic strengths, while the activity on linear DNA was only found below 60 mM salt. In addition, single strand DNA, ss/ds DNA boundaries and negatively supercoiling degree were not required for PaMutL nicking activity. Finally, the analysis of the incision sites revealed that PaMutL, as well as Bacillus thuringiensis MutL homologue, did not show DNA sequence specificity.

Do gender and race/ethnicity influence acute myocardial infarction quality of care in a hospital with a large Hispanic patient and provider representation?

Background. Disparities in acute myocardial infarction (AMI) care for women and minorities have been extensively reported in United States but with limited information on Hispanics. Methods. Medical records of 287 (62%) Hispanic and 176 (38%) non-Hispanic white (NHW) patients and 245 women (53%) admitted with suspected AMI to a southern California nonprofit community hospital with a large Hispanic patient and provider representation were reviewed. Baseline characteristics, outcomes (mortality, CATH, PCI, CABG, and use of pertinent drug therapy), and medical insurance were analyzed according to gender, Hispanic and NHW race/ethnicity when AMI was confirmed. For categorical variables, 2 × 2 chi-square analysis was conducted. Odds ratio and 95% confidence interval for outcomes adjusted for gender, race/ethnicity, cardiovascular risk factors, and insurance were obtained. Results. Women and Hispanics had similar drug therapy, CATH, PCI, and mortality as men and NHW when AMI was confirmed (n = 387). Hispanics had less private insurance than NHW (31.4% versus 56.3%, P < 0.001); no significant differences were found according to gender. Conclusions. No differences in quality measures and outcomes were found for women and between Hispanic and NHW in AMI patients admitted to a facility with a large Hispanic representation. Disparities in medical insurance showed no influence on these findings.

A simple allele-specific polymerase chain reaction method to detect the Gly143Glu polymorphism in the human carboxylesterase 1 gene: importance of genotyping for pharmacogenetic treatment.

Human carboxylesterases 1 and 2 (CES1 and CES2) catalyze the hydrolysis of many exogenous compounds. Alterations in CES sequences could lead to variability in both the inactivation of drugs and the activation of prodrugs. The human CES1 gene encodes for the enzyme carboxylesterase 1, a serine esterase governing both metabolic deactivation and activation of numerous therapeutic agents. Some of theses drugs are the antiviral oseltamivir used to treat some types of influenza infections and the methylphenidate employed in the treatment of patients with attention deficit. The Gly143Glu polymorphism in CES1 gene has been shown to reduce enzyme activity. The aim of the present study was to develop an easy and cheap method to detect this polymorphism. For this, we studied a group of people from Córdoba, a Mediterranean area from Argentina. Our results show that our methodology could detect the presence of this polymorphism with a frequency around 1.8%, only in the heterozygote form. These results could be relevant to patients before the treatment with some drugs where the CES1 enzyme is involved.