Multifunctional Organometallic Compounds Active against Infective Trypanosomes: Ru(II) Ferrocenyl Derivatives with Two Different Bioactive Ligands.

Human African trypanosomiasis (HAT, sleeping sickness) and American trypanosomiasis (Chagas disease) are endemic zoonotic diseases caused by genomically related trypanosomatid protozoan parasites (Trypanosoma brucei and Trypanosoma cruzi, respectively). Just a few old drugs are available for their treatment, with most of them sharing poor safety, efficacy, and pharmacokinetic profiles. Only fexinidazole has been recently incorporated into the arsenal for the treatment of HAT. In this work, new multifunctional Ru(II) ferrocenyl compounds were rationally designed as potential agents against these pathogens by including in a single molecule 1,1'-bis(diphenylphosphino)ferrocene (dppf) and two bioactive bidentate ligands: pyridine-2-thiolato-1-oxide ligand (mpo) and polypyridyl ligands (NN). Three [Ru(mpo)(dppf)(NN)](PF6) compounds and their derivatives with chloride as a counterion were synthesized and fully characterized in solid state and solution. They showed in vitro activity on bloodstream T. brucei (EC50 = 31-160 nM) and on T. cruzi trypomastigotes (EC50 = 190-410 nM). Compounds showed the lowest EC50 values on T. brucei when compared to the whole set of metal-based compounds previously developed by us. In addition, several of the Ru compounds showed good selectivity toward the parasites, particularly against the highly proliferative bloodstream form of T. brucei. Interaction with DNA and generation of reactive oxygen species (ROS) were ruled out as potential targets and modes of action of the Ru compounds. Biochemical assays and in silico analysis led to the insight that they are able to inhibit the NADH-dependent fumarate reductase from T. cruzi. One representative hit induced a mild oxidation of low molecular weight thiols in T. brucei. The compounds were stable for at least 72 h in two different media and more lipophilic than both bioactive ligands, mpo and NN. An initial assessment of the therapeutic efficacy of one of the most potent and selective candidates, [Ru(mpo)(dppf)(bipy)]Cl, was performed using a murine infection model of acute African trypanosomiasis. This hit compound lacks acute toxicity when applied to animals in the dose/regimen described, but was unable to control parasite proliferation in vivo, probably because of its rapid clearance or low biodistribution in the extracellular fluids. Future studies should investigate the pharmacokinetics of this compound in vivo and involve further research to gain deeper insight into the mechanism of action of the compounds.

DistilIQA: Distilling Vision Transformers for no-reference perceptual CT image quality assessment.

No-reference image quality assessment (IQA) is a critical step in medical image analysis, with the objective of predicting perceptual image quality without the need for a pristine reference image. The application of no-reference IQA to CT scans is valuable in providing an automated and objective approach to assessing scan quality, optimizing radiation dose, and improving overall healthcare efficiency. In this paper, we introduce DistilIQA, a novel distilled Vision Transformer network designed for no-reference CT image quality assessment. DistilIQA integrates convolutional operations and multi-head self-attention mechanisms by incorporating a powerful convolutional stem at the beginning of the traditional ViT network. Additionally, we present a two-step distillation methodology aimed at improving network performance and efficiency. In the initial step, a "teacher ensemble network" is constructed by training five vision Transformer networks using a five-fold division schema. In the second step, a "student network", comprising of a single Vision Transformer, is trained using the original labeled dataset and the predictions generated by the teacher network as new labels. DistilIQA is evaluated in the task of quality score prediction from low-dose chest CT scans obtained from the LDCT and Projection data of the Cancer Imaging Archive, along with low-dose abdominal CT images from the LDCTIQAC2023 Grand Challenge. Our results demonstrate DistilIQA's remarkable performance in both benchmarks, surpassing the capabilities of various CNNs and Transformer architectures. Moreover, our comprehensive experimental analysis demonstrates the effectiveness of incorporating convolutional operations within the ViT architecture and highlights the advantages of our distillation methodology.

Exodoncia de premolar inferior supernumerario con posterior colocación de Fibrina Rica en Plaquetas y Leucocitos (L-PRF)

Los dientes supernumerarios son una anomalía odontogénica, consiste en aumento del número dentario con respecto a la cantidad normal. La Fibrina rica en Plaquetas y Leucocitos (L-PRF) es una matriz rica en plaquetas y glóbulos blancos, que promueve la curación y regeneración de los tejidos. La exodoncia de un tercer premolar inferior supernumerario con posterior colocación de membrana de L-PRF. Paciente de sexo masculino de 27 años de edad con un probable premolar supernumerario por lingual. Se programó la cirugía incluyendo L-PRF. Se realizó extracción de sangre para preparar la membrana de L-PRF, anestesia, incisión lineal, despegamiento mucoperióstico, osteotomía, exodoncia, tratamiento del lecho quirúrgico colocando la membrana de L-PRF y sutura interdental. Se prescribió medicación antibiótica, antiinflamatoria y analgésica. La técnica con L-PRF es sencilla y económica. Los resultados postoperatorios fueron favorables, observándose una buena cicatrización, ausencia de dolor, edema o infección.

Supernumerary teeth are an odontogenic anomaly, involving an increase in the number of teeth compared to the normal amount. Platelet-Rich Fibrin (L-PRF) is a matrix rich in platelets and white blood cells that promotes tissue healing and regeneration. The Extraction of a supernumerary lower third premolar followed by placement of L-PRF membrane. A 27-year-old male patient with a probable lingual supernumerary premolar. Surgery was scheduled, including L-PRF. Blood was extracted to prepare the L-PRF membrane, followed by anesthesia, linear incision, mucoperiosteal detachment, osteotomy, extraction, treatment of the surgical site with L-PRF membrane placement, and interdental suturing. Antibiotic, anti-inflammatory, and analgesic medication was prescribed. The L-PRF technique is simple and cost-effective. Postoperative results were favorable, with good healing, absence of pain, swelling, or infection was observed.

Guillain-Barré syndrome in a COVID-19 patient / Síndrome de Guillain-Barré en paciente con COVID-19

Abstract Coronavirus type 2 is a P-coronavirus whose infection is characterized by a predominantly respiratory clinical picture. However, neurological symptoms are garnering great interest related to pulmonary infection and direct viral invasion of the central nervous system, with a possible association between Guillain-Barré syndrome and SARS-CoV-2 infection. This report describes this relationship in a 44-year-old female patient with classical Guillain-Barré syndrome signs and symptoms on admission, and respiratory signs and symptoms six days prior to the onset of neurological symptoms. There were positive SARS-CoV IgG and IgM blood tests and an epidemiological link of direct contact with people infected with SARS-CoV-2. She required ICU care due to the risk of respiratory failure, along with immunoglobulin treatment, but did not need mechanical ventilation; she improved and was discharged. One month later she consulted again and was thought to have had a Guillain-Barré relapse. She was hospitalized and treated until she progressed and her symptoms resolved. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2204).

Resumen El coronavirus tipo 2 es un P-coronavirus cuya infección se caracteriza por clínica de predominio respiratorio; sin embargo, la sintomatologia neurológica está cobrando gran interés asociada a la infección pulmonar e invasión directa del virus al sistema nervioso central. Siendo posible la aso ciación entre el síndrome de Guillain-Barré y la infección por virus SARS-CoV-2. En este reporte se describe dicha asociación en una paciente femenina de 44 años de edad, con clínica clásica de síndrome de Guillain-Barré al ingreso y clínica respiratoria seis días previos a la instalación de los síntomas neurológicos. Reportándose serologías IgG e IgM para SARS-CoV-positivas y nexo epidemiológico de contacto directo con personas infectadas por SARS-CoV-2. Requirió manejo en UCI por riesgo de falla respiratoria, manejo con inmunoglobulinas, sin requerimiento de ventilación mecánica, presentando mejoría y otorgándose salida. Un mes después reconsulta, se considera recaída de Guillain-Barré, se hospitaliza, se inicia manejo hasta evolución y resolución de síntomas. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2204).

Caracterización clínica de la peritonitis secundaria en una institución de tercer nivel y factores relacionados con mortalidad / Clinical characterization of secondary peritonitis in a tertiary level of care institution and factors related to mortality

Introducción. La peritonitis secundaria es una enfermedad con altos índices de mortalidad, por lo que se considera de gran importancia identificar los factores que inciden en ella. Método. Se realizó un estudio analítico entre 2019 y 2020 en el que se incluyeron pacientes con peritonitis secundaria, se caracterizaron las variables más relacionadas con el pronóstico, como aspectos demográficos y clínicos, y se analizó la asociación entre la mortalidad y estas variables. Resultados. La mortalidad hospitalaria fue del 30,7 %, encontrando como condiciones relacionadas con la mortalidad la ubicación de la fuente séptica en abdomen superior, la presencia de dolor en abdomen superior, atención en UCI, control del foco en la primera intervención, pacientes que cursaron con falla renal, edad del paciente y valores de hemoglobina. Conclusiones. En la cohorte estudiada se encontraron índices de mortalidad dos veces superiores a los reportados en Suramérica y 1,5 veces a los del resto del país. El mayor poder predictivo de mortalidad en el análisis bivariado fue dado por la presencia de falla renal y el valor de la hemoglobina.

Introduction. Secondary peritonitis is a disease with high mortality rates, so it is considered of great importance to identify the factors that affect it. Methods. An analytical study was carried out between 2019 and 2020 in which patients with secondary peritonitis were included, the variables most related to prognosis were characterized, such as demographic and clinical aspects, and the association between mortality and these variables was analyzed. Results. Hospital mortality was 30.7%, finding conditions related to mortality to be the location of the septic source in the upper abdomen, the presence of pain in the upper abdomen, care in the ICU, control of the focus in the first intervention, patients who underwent kidney failure, patient age, and hemoglobin values. Conclusion. Mortality rates were found in the studied cohort twice higher than those reported in South America and 1.5 times higher than those of the rest of the country. The greatest predictive power of mortality in the bivariate analysis was given by the presence of kidney failure and hemoglobin.

Factores de riesgo cardiovascular y anomalías electrocardiográficas en estudiantes universitarios de Itá, Paraguay / Cardiovascular risk factors and electrocardiographic anomalies in university students from Itá, Paraguay

Introducción: La determinación de los factores de riesgo cardiovascular debe realizarse en etapas precoces como en la edad universitaria. Esto tiene como propósito identificar los factores modificables, sobre todo en edades tempranas de la vida. Objetivos: Determinar la frecuencia de alteraciones antropométricas, hipertensión arterial, hiperglicemia, hábito de fumar, sedentarismo, ingesta de alcohol y alteraciones electrocardiográficas en los alumnos de la Universidad Gran Asunción (Itá, Paraguay) en los años 2017 y 2018. Materiales y métodos: Estudio observacional prospectivo realizado en varones y mujeres, mayores de 18 años, estudiantes de todas las carreras universitarias, que acudieron en los años 2017 y 2018. Se realizó examen clínico y electrocardiográfico previo consentimiento informado. Se aplicó estadística descriptiva para la descripción de las variables. Resultados: Se incluyeron 121 mujeres (edad media 21±4 años) y 62 varones (edad media 20±3 años). Se hallaron las siguientes frecuencias: sobrepeso 27%, obesidad 14%, circunferencia abdominal aumentada 26%, índice de conicidad aumentado 45%, hipertensión arterial 18%, sedentarismo 80%, hábito de fumar 0,5% e ingesta de alcohol 15%. Las anomalías electrocardiográficas se detectaron en 19% siendo la más frecuente la bradicardia sinusal. Se detectaron dos casos de síndrome QTc prolongado en pacientes asintomáticos. Conclusión: Los factores de riesgo cardiovascular más frecuentes fueron el sedentarismo, el sobrepeso y la hipertensión arterial. Las anomalías electrocardiográficas se detectaron en 19% siendo la bradicardia sinusal la más frecuente.

Introduction: The determination of cardiovascular risk factors should be carried out in early life stages such as university age. The purpose of this is to identify modifiable factors, especially at early ages of life. Objectives: To determine the frequency of anthropometric alterations, arterial hypertension, hyperglycemia, smoking habit, sedentary lifestyle, alcohol intake and electrocardiographic alterations in the students of the Gran Asunción University (Itá, Paraguay) in the years 2017 and 2018. Materials and methods: Prospective observational study carried out in males and females, over 18 years old, students of all university careers, who attended the university in the years 2017 and 2018. A clinical and electrocardiographic examination was performed with informed consent. Descriptive statistics was applied for the description of the variables. Results: One hundred twenty one women were included (average age 21±4 years) and 62 men (average age 20±3 years). The following frequencies were found: overweight 27%, obesity 14%, increased abdominal circumference 26%, conicity index increased 45%, hypertension 18%, sedentary lifestyle 80%, smoking habit 0.5% and alcohol intake 15%. The electrocardiographic anomalies were detected in 19%, with sinus bradycardia being the most frequent. Two cases of prolonged QTc syndrome were detected in asymptomatic patients. Conclusion: The most frequent cardiovascular risk factors were sedentary lifestyle, overweight and high blood pressure. Electrocardiographic abnormalities were detected in 19%, with sinus bradycardia being the most frequent.

Injuria renal aguda secundaria a crisis hipercalcémica: a propósito de un caso / Acute renal injury secondary to hypercalcemic crisis: a case report / Lesão ou injúria renal aguda secundária a crise hipercalcêmica: relatório de caso clínico

La injuria renal aguda es una entidad clínica compleja, caracterizada por la disminución abrupta de la función renal. La hipercalcemia como etiología de la misma es poco frecuente. Los mecanismos involucrados en su desarrollo son múltiples y poco estudiados. Se presenta el caso de un paciente varón de 59 años que desarrolló un cuadro severo de falla renal aguda como complicación de crisis hipercalcémica por un adenoma de paratiroides. Se observó alteración en los marcadores de daño y función renal. La bioquímica urinaria mostró una necrosis tubular aguda. Los niveles de calcio, parathormona y calciuria se asociaron a endocrinopatía. La ecografía, el centellograma y la biopsia paratiroidea mostraron la presencia de un adenoma. Se presentaron otras complicaciones sistémicas concomitantes como pancreatitis y complicaciones cardíacas. El tratamiento paliativo fue la hemodiálisis y el definitivo la paratiroidectomía. El síndrome de hueso hambriento se presentó como una complicación postquirúrgica. Tras el alta, la recuperación de la función renal nunca fue total. El daño renal agudo asociado a disfunción sistémica por hipercalcemia puede llevar a una recuperación parcial de la función renal. Se debe considerar el desarrollo de enfermedad renal crónica posterior a la falla renal aguda por hipercalcemia como complicación de la misma.

Acute renal injury is a complex clinical entity, characterized by the abrupt worsening in renal function. Hypercalcemia as its etiology is rare. The mechanisms involved in its development are multiple and rarely studied. The case of a 59-year-old male patient who developed a severe acute renal failure as a complication of an hypercalcemic crisis due to a parathyroid adenoma is presented here. Alterations in markers of damage and renal function were observed. Urinary biochemistry showed acute tubular necrosis. Calcium, parathormone and urine calcium levels were associated with endocrinopathy. The ultrasound, the scintigraphy and the parathyroid biopsy showed the presence of an adenoma. There were other concomitant systemic complications such as pancreatitis and cardiac complications. Hemodialysis was the palliative treatment, while the definitive treatment was parathyroidectomy. The hungry bone syndrome occurred as a postoperative complication. After discharge, recovery of renal function was never complete. Acute renal damage associated with systemic dysfunction due to hypercalcemia can lead to a partial recovery of renal function. The development of chronic kidney disease after acute renal failure due to hypercalcemia should be considered one of its complications.

A Lesão renal aguda é uma entidade clínica complexa, caracterizada pela diminuição abrupta da função renal. A hipercalcemia como etiologia da mesma não é muito frequente. Os mecanismos que participam no seu desenvolvimento são múltiplos e pouco estudados. Apresenta-se o caso de um paciente, homem, de 59 anos, que desenvolveu um quadro severo de insuficiência renal aguda como complicação de crise hipercalcêmica por um adenoma da paratireóide. Foi observada alteração nos marcadores de dano e função renal. A bioquímica urinária mostrou uma necrose tubular aguda. Os níveis de cálcio, paratormona e calciúria foram associados a endocrinopatia. A ultra-sonografia, a cintilografia, e a biópsia da paratireóide mostraram a presença de um adenoma. Apresentaram-se outras complicações sistêmicas concomitantes como pancreatite e cardíacas. O tratamento paliativo foi hemodiálise e o definitivo, a paratireoidectomia. A síndrome do osso faminto apresentou-se como uma complicação pós-operatória. Após a alta, a recuperação da função renal nunca foi total. O dano renal agudo associado à disfunção sistêmica por hipercalcemia pode levar para uma recuperação parcial da função renal. Deve ser considerado o desenvolvimento da doença renal crônica posterior à insuficiência renal aguda por hipercalcemia como complicação da mesma.