Harmol used for the treatment of herpes simplex virus induced keratitis.

Herpes simplex virus type 1 (HSV-1) infection of the eyes results in herpes simplex keratitis (HSK), which has led to vision loss and even blindness in patients. However, the rate of drug resistance in HSV is on the rise; therefore, new antiviral agents with sufficient safety profiles must be developed. At present, we assessed the anti-HSV-1 activity of 502 natural compounds and their ability to reduce the HSV-1-induced cytopathic effect. We chose harmol for further studies because it exhibited the highest antiviral activity. We found that harmol inhibited both HSV-1 F and HSV-1/153 (a clinical drug-resistant strain) replication, with an EC50 of 9.34 µM and 5.84 µM, respectively. Moreover, harmol reduced HSV-1 replication in corneal tissues and viral progeny production in tears, and also alleviated early corneal surface lesions related to HSK. For example, harmol treatment preserved corneal thickness and nerve density in HSK mice. Interestingly, harmol also showed a promising antiviral effect on HSV-1/153 induced HSK in mouse model. Furthermore, harmol combined with acyclovir (ACV) treatment showed a greater antiviral effect than either one alone in vitro. Therefore, harmol may be a promising therapeutic agent for managing HSK.

Impacto de la inteligencia artificial en las métricas terapéuticas del ataque cerebrovascular durante la pandemia COVID-19 / Impact of artificial intelligence on therapeutic metrics of cerebrovascular attack during the COVID-19 pandemic

Resumen Introducción : El inicio de la pandemia COVID-19, obligó a implementar cambios en el sistema de aten ción de los servicios de emergencia. Coincidentemente, en nuestra institución, implementamos el software de inteligencia artificial (IA), RAPID.AI, para el análisis de imágenes en el ataque cerebrovascular isquémico (ACVi). Nuestro objetivo fue evaluar el impacto del uso de la IA junto a los cambios en el triage durante la pandemia por COVID-19 en pacientes con ACVi por oclusión de gran vaso cerebral (OGVC). Métodos : Se crearon 2 grupos de pacientes con ACVi por OGVC tratados con terapia de reperfusión endovenosa más endovascular o terapia endovascu lar directa. Grupo 1: pacientes de enero 2019 a junio 2020; Grupo 2: pacientes de julio 2020 a diciembre de 2021, estudiados con RAPID.AI. Se analizaron datos clínicos, y métricas temporales. Se compararon según hora de arribo de 08:00 a 20:00 h (diurno) vs. 20:01 a 7:59 h (nocturno). Resultados : El grupo 1 comprendió 153 pacientes y el grupo 2 133. En el grupo 2 la métrica puerta-imagen y adquisición de la imagen fueron menores, con menor tiempo puerta-inicio de imagen y puerta-recanalización; los pacientes en horario nocturno presentaron mayor NIHSS y tiempos inicio-ingreso con menor proporción de independencia funcional a 90 días. Conclusiones : El uso de la IA para el análisis de imá genes junto a un menor tiempo puerta-fin de imagen, permitió acortar el intervalo hasta la punción inguinal. En el análisis por horarios durante la pandemia, los pacientes ingresados en horario diurno presentaron métricas puerta-imagen, tiempo de imagen y puerta-recanalización significativamente menores.

Abstract Introduction : The start of the COVID-19 pandemic forced the implementation of changes in the emergency services care system. Concomitantly, at our institution, we implemented the artificial intelligence (AI) software, RAPID.AI, for image analysis in ischemic stroke (IS). Our objective was to evaluate the impact of the use of AI together with the changes in the triage during the COVID-19 pandemic in patients with stroke due to large vessel occlusion (LVO). Methods : We included patients with IS due to LVO treated with intravenous reperfusion therapy plus en dovascular or direct endovascular therapy. Results : Two groups were created. Group 1: patients from January 2019 to June 2020; Group 2: patients from July 2020 to December 2021, studied with RAPID.AI. Clini cal data and temporal metrics were analyzed. They were compared according to arrival time from 08:00 to 20:00 (daytime) vs 20:01 to 7:59 (night). Results: We included 286 patients, 153 in group 1 and 133 in group 2. In group 2, door-image metric and image duration were lower, with shorter door-image onset and door-recanalization times; patients who arrived at night had higher NIHSS and longer time from onset-to-door with lower propor tion of functional independence at 90 days (mRS ≤ 2). Conclusions : The use of AI for image analysis along with a shorter door to end of image time allowed to reduce the interval to groin puncture. In the analysis by hours during the pandemic, patients admitted in daytime hours had significantly lower door to image, image time acquisition, and door to recanalization metrics.

Utilidad de la secuencia de susceptibilidad como predictor de penumbra en la isquemia cerebral aguda / Utility of susceptibility sequence as a predictor of penumbra in acute cerebral ischemia

Resumen Objetivo: El objetivo del tratamiento en accidente cerebrovascular (ACV) isquémico agudo es restablecer la circulación en el área de la penumbra isquémica. La secuencia de susceptibilidad (SWI) puede detectar cambios en el calibre de las venas intracraneanas cuando se altera la relación desoxiHb/oxiHb en áreas hipoperfundidas, lo que permitiría una detección temprana de penumbra isquémica. Material y métodos: Estudio de cohorte retrospectivo. Se incluyeron pacientes con infartos agudos en territorio de la arteria cerebral media. Se evaluaron las secuencias difusión y SWI iniciales y un estudio de control a los siete días. La extensión del ACV se midió con la escala ASPECT en difusión y SWI del ingreso, y en el estudio de control. Se estableció una discordancia SWI/difusión > 2 puntos como variable predictora y la extensión final del infarto como variable de resultado. Resultados: Se incluyeron 31 pacientes, mediana de edad de 72 años (RIC: 61-81). En 13 pacientes se detectó una oclusión vascular proximal, ocho de los cuales tenían discordancia SWI/difusión > 2 puntos (p < 0,0001). En cinco pacientes encontramos incremento del infarto, cuatro con discordancia SWI/difusión (p = 0,01). Conclusión: La presencia de discordancia SWI/difusión puede ser un biomarcador de penumbra isquémica en pacientes con oclusión vascular proximal.

Abstract Objective: The goal of treatment in acute ischemic stroke is to restore circulation in the area of the ischemic penumbra. Susceptibility weighted imaging (SWI) can detect changes in the caliber of intracranial veins when the deoxyHb/oxyHb ratio is altered in hypoperfused areas, which would allow early detection of ischemic penumbra. Material and methods: Retrospective cohort study. Patients with acute infarcts in the territory of the middle cerebral artery were included. Initial diffusion and SWI sequences and a control study at seven days were evaluated. Stroke extension was measured with the ASPECT scale in diffusion and SWI on admission, and in the control study. An SWI/diffusion discrepancy > 2 points was established as a predictor variable and the final extension of the infarct as a result variable. Results: Thirty-one patients were included, median age 72 years (IQR: 61-81). Proximal vascular occlusion was detected in 13 patients, 8 of whom had SWI/diffusion discordance > 2 points (p < 0.0001). In 5 patients we found increased infarction, 4 with SWI/diffusion mismatch (p = 0.01). Conclusion: The presence of SWI/diffusion mismatch may be a biomarker of ischemic penumbra in patients with proximal vascular occlusion.

Correlation between preoperative Doppler ultrasonography-assessed specific accessory cephalic vein diameter-cephalic vein diameter ratio (r) and early dysfunction of Radial artery-Cephalic vein arteriovenous fistula: a single-center cross-sectional study.

Background: Accessory cephalic vein (ACV) ligation can circumvent immature arteriovenous fistula (AVF). However, no consensus has been reached on the definite timing of ACV ligation. This study aimed to retrospectively analyze the correlation between preoperative Doppler ultrasonography (DUS)-assessed specific ACV diameter-cephalic vein diameter ratio (r) and early dysfunction of Radial artery-Cephalic vein (RC)-AVF in order to improve the early maturity rate of RC-AVF. Methods: A total of 258 patients who underwent RC-AVF at The Third Affiliated Hospital, Sun Yat-sen University from 1 June 2018 to 31 March 2022 were included in this study. The inclusion criteria were as follows: (I) cephalic vein ≥2.0 mm and radial artery ≥1.5 mm, suitable for RC-AVF establishment; (II) presence of an ACV. As per the specific r determined using preoperative DUS assessment, all patients were classified into two groups: Group A (r<0.8) and Group B (r≥0.8). Furthermore, patients in each group were divided into intervention and non-intervention subgroups based on the presence or absence of intraoperative ACV ligation, respectively. Patient data including age, sex, underlying disease, AVF side, and radial diameter were compared. The difference of maturity rate between participants in the intervention group and non-intervention group with different r values was analyzed, so as to obtain the relationship between different r values and maturity rate. Results: No statistical differences were observed between the intervention and non-intervention subgroups in the two groups in terms of sex, age, comorbidities, complications, AVF side, radial artery, cephalic vein, and ACV diameters (P>0.05). When r<0.8, the maturity rates of the intervention group and the non-intervention group were 80% and 92.98%, respectively, χ2=4.561. The difference in maturation rate between the intervention and non-intervention subgroups was insignificant (P=0.075) when r<0.8. When r≥0.8, the maturity rates of the intervention group and the non-intervention group were 89.83% and 45.45%, respectively, χ2=25.943. The difference in maturation rates between the intervention and non-intervention subgroups was significant when r≥0.8 (P<0.001). Conclusions: Preoperative DUS suggested a correlation between r≥0.8 and early immaturity of RC-AVF. Therefore, concurrent intraoperative ACV ligation should be carried out when preoperative r is ≥0.8, as it may reduce the early power dysfunction of RC-AVF.

Effect of Cilostazol on Delayed Cerebral Infarction in Aneurysmal Subarachnoid Hemorrhage Using Explainable Predictive Modeling.

The studies interpreting DCI, a complication of SAH, and identifying correlations are very limited. This study aimed to investigate the effect of cilostazol on ACV and DCI after coil embolization for ruptured aneurysms (n = 432). A multivariate analysis was performed and explainable artificial intelligence approaches were used to analyze the contribution of cilostazol as a risk factor on the development of ACV and DCI with respect to global and local interpretation. The cilonimo group was significantly lower than the nimo group in ACV (13.5% vs. 29.3; p = 0.003) and DCI (7.9% vs. 20.7%; p = 0.006), respectively. In a multivariate logistic regression, the odds ratio for DCI for the cilonimo group, female sex, and aneurysm size was 0.556 (95% confidence interval (CI), 0.351-0.879; p = 0.012), 3.713 (95% CI, 1.683-8.191; p = 0.001), and 1.106 (95% CI, 1.008-1.214; p = 0.034). The risk of a DCI occurrence was significantly increased with an aneurysm size greater than 10 mm (max 80%). The mean AUC of the XGBoost and logistic regression models was 0.94 ± 0.03 and 0.95 ± 0.04, respectively. Cilostazol treatment combined with nimodipine could decrease the prevalence of ACV (13.5%) and DCI (7.9%) in patients with aSAH.

Three-dimensional heterogeneous electro-Fenton system with reduced graphene oxide based particle electrode for Acyclovir removal.

New pollutant pharmaceutical and personal care products (PPCPs), especially antiviral drugs, have received increasing attention not only due to their increase in usage after the outbreak of COVID-19 epidemics but also due to their adverse impacts on water ecological environment. Electro-Fenton technology is an effective method to remove PPCPs from water. Novel particle electrodes (MMT/rGO/Fe3O4) were synthesized by depositing Fe3O4 nanoparticles on reduced graphene oxide modified montmorillonite and acted as catalysts to promote oxidation performance in a three-dimensional Electro-Fenton (3D-EF) system. The electrodes combined the catalytic property of Fe3O4, hydrophilicity of montmorillonite and electrical conductivity of graphene oxides, and applied for the degradation of Acyclovir (ACV) with high efficiency and ease of operation. At optimal condition, the degradation rate of ACV reached 100% within 120 min, and the applicable pH range could be 3 to 11 in the 3D-EF system. The stability and reusability of MMT/rGO/Fe3O4 particle electrodes were also studied, the removal rate of ACV remained at 92% after 10 cycles, which was just slightly lower than that of the first cycle. Potential degradation mechanisms were also proposed by methanol quenching tests and FT-ICR-MS.

Surface-Enhanced Raman scattering (SERS) filter paper substrates decorated with silver nanoparticles for the detection of molecular vibrations of Acyclovir drug.

Acyclovir (ACV) drug, a common antiviral agent, is frequently used as the primary clinical treatment method for treating hepatitis B, herpes simplex, and varicella zoster viruses due to its potent therapeutic effect. In patients with compromised immune systems, this medication can stop cytomegalovirus infections, and high doses of this drug are required; however, such prescription leads to kidney toxicity. Therefore, timely and accurate detection of ACV is crucial in many areas. Surface-Enhanced Raman Scattering (SERS) is a reliable, rapid, and precise approach for the identification of trace biomaterials and chemicals. Filter paper substrates decorated with silver nanoparticles (AgNPs) were applied as SERS biosensors to detect ACV and control its adverse effects. Initially, a chemical reduction procedure was utilized to produce AgNPs. Afterward, UV-Vis, FE-SEM, XRD, TEM, DLS, and AFM were employed to examine the properties of prepared AgNPs. In order to prepare SERS-active filter paper substrates (SERS-FPS) to detect Molecular vibrations of ACV, AgNPs prepared by immersion method were coated on filter paper substrates. Moreover, the UV-Vis DRS analysis was carried out to assess the stability of filter paper substrates and SERS-FPS. The AgNPs reacted with ACV after being coated on SERS-active plasmonic substrates and could sensitively detect ACV in small concentrations. It was discovered that the limit of detection of SERS plasmonic substrates was 10-12 M. Moreover, the mean RSD for ten repeated tests was calculated as 4.19%. The enhancement factor for detecting ACV using the developed biosensors was calculated to be 3.024 × 105 and 3.058 × 105 experimentally and via simulation, respectively. According to the Raman results, SERS-FPS for the detection of ACV, fabricated by the present methods, showed promising results for SERS-based investigations. Furthermore, these substrates showed significant disposablity, reproducibility, and chemical stability. Therefore, the fabricated substrates are capable to be employed as potential SERS biosensors to detect trace substances.

Delayed acyclovir therapy for disseminated varicella zoster in an adult kidney transplant recipient: a case report and literature review.

Kidney transplant recipients are at increasing risk for reactivation of varicella-zoster virus (VZV) infection. Presentation of case: A 31-year-old male was admitted with fever, chest pain, and dyspnea. Also, the complaints accompanied by generalized maculopapular, vesicular, hemorrhagic, itching, and painful rash with pustules and crusts on an erythematous base fill the entire body for the last 10 days. Chest computed tomography scan showed diffuse miliary and ground-glass opacities. The patient had a previous history of chickenpox infection in childhood, no recent contact with individuals suffering from VZV infection, and no known pretransplant serology for VZV. Due to the high clinical suspicion of reactivated VZV with pneumonitis and severe disseminated form, we started the treatment with intravenous acyclovir (ACV) for 10 days followed by oral ACV for a total of 21 days, along with stopping mycophenolate mofetil and increasing the prednisolone dose to 10 mg/d. The clinical status was improved and the rash receded with a flaked surface for old lesions. Conclusion: We experienced a successful ACV treatment for delayed and severe VZV infection with a literature review of VZV pneumonitis among kidney transplant recipients. To the best of our knowledge, this is the first case that presented a disseminated skin form with pneumonitis of VZV from Syria. This case supports the initiation of antiviral therapy for transplant patients even after 72 hours the onset of the rash despite the lack of evidence in these circumstances.

Ethanol extract from Artemisia argyi leaves inhibits HSV-1 infection by destroying the viral envelope.

Herpes simplex virus type 1 (HSV-1) is a widely disseminated virus that establishes latency in the brain and causes occasional but fatal herpes simplex encephalitis. Currently, acyclovir (ACV) is the main clinical drug used in the treatment of HSV-1 infection, and the failure of therapy in immunocompromised patients caused by ACV-resistant HSV-1 strains necessitates the requirement to develop novel anti-HSV-1 drugs. Artemisia argyi, a Traditional Chinese Medicine, has been historically used to treat inflammation, bacterial infection, and cancer. In this study, we demonstrated the antiviral effect and mechanism of ethanol extract of A. argyi leaves (hereafter referred to as 'AEE'). We showed that AEE at 10 µg/ml exhibits potent antiviral effects on both normal and ACV-resistant HSV-1 strains. AEE also inhibited the infection of HSV-2, rotavirus, and influenza virus. Transmission electron microscopy revealed that AEE destroys the membrane integrity of HSV-1 viral particles, resulting in impaired viral attachment and penetration. Furthermore, mass spectrometry assay identified 12 major components of AEE, among which two new flavones, deoxysappanone B 7,3'-dimethyl ether, and 3,7-dihydroxy-3',4'-dimethoxyflavone, exhibited the highest binding affinity to HSV-1 glycoprotein gB at the surface site critical for gB-gH-gL interaction and gB-mediated membrane fusion, suggesting their involvement in inactivating virions. Therefore, A. argyi is an important source of antiviral drugs, and the AEE may be a potential novel antiviral agent against HSV-1 infection.

Endocarditis Infecciosa a hemocultivos y ecocardiograma negativos: ¿Con qué otra herramienta contamos? A propósito de un caso

La endocarditis infecciosa (EI) es una enfermedad frecuente, con elevada morbi-mortalidad, cuyo diagnóstico continúa siendo un desafío en la actualidad. El abordaje de la misma debe de ser realizado por un equipo multidisciplinario. La semiología, herramienta fundamental en la medicina clínica, juega un rol preponderante, nos permite mantener una alta sospecha diagnóstica a pesar de contar con estudios paraclínicos negativos. En estas situaciones han ganado importancia las nuevas técnicas de imagen como el PET-TC. Se presenta el caso de una mujer con cardiopatía predisponente en el que se llega al diagnóstico por PET-TC.

Infective endocarditis (IE) is a frequent disease, with high morbidity and mortality, whose diagnosis continues to be a challenge nowadays. The approach must be carried out by a multidisciplinary team. Semiology, a fundamental tool in clinical medicine, plays a preponderant role, allowing us to maintain a high diagnostic suspicion despite having negative paraclinical studies. In these situations, new imaging techniques such as PET-CT have gained importance. We present the case of a woman with predisposing heart disease in whom the diagnosis was made by PET-CT.

A endocardite infecciosa (EI) é uma doença frequente, com alta morbimortalidade, cujo diagnóstico continua sendo um desafio na atualidade. Sua abordagem deve ser realizada por uma equipe multidisciplinar. A semiologia, ferramenta fundamental na clínica médica, desempenha um papel preponderante, permitindo-nos manter uma elevada suspeição diagnóstica apesar dos estudos paraclínicos negativos. Nestas situações, novas técnicas de imagem como o PET-CT têm ganhado importância. Apresentamos o caso de uma mulher com cardiopatia predisponente cujo diagnóstico foi feito pelo PET-CT.

Nuevos paradigmas: 12 años de trombólisis sistémica. Unidad ACV, Hospital de Clínicas / New paradigms: 12 years of systemic thrombolysis. Stroke Unit, Clinicas Hospital / Novos paradigmas: 12 anos de trombólise sistêmica. Unidade AVC, Hospital de Clínicas

Introducción: el ACV constituye un problema de salud y la trombólisis sistémica una estrategia de reperfusión con alto nivel de evidencia para su tratamiento. Los reportes nacionales sobre su utilización son escasos. Objetivos: comunicar y analizar los resultados de esta terapia en el Hospital de Clínicas. Establecer predictores de buena evolución, hemorragia intracraneana y mortalidad. Métodos: estudio observacional analítico de los pacientes trombolizados en el Hospital de Clínicas (2010-2021). Resultados: se realizó trombólisis sistémica a 268 pacientes. La mediana del NIHSS al ingreso fue 12 puntos. Un 42% fueron infartos totales de la circulación anterior. La cardioembolia constituyó la etiopatogenia más frecuente. El 59,3% de los pacientes fueron externalizados con independencia funcional y 55,2% con déficit neurológico mínimo. Las tasas de hemorragia intracraneana sintomática y mortalidad fueron 7,1% y 18,7% respectivamente. El 57% de los pacientes se trataron con tiempo puerta aguja ≤60 minutos. El porcentaje de trombólisis en el total de ACV fue 18,9%. La edad, NIHSS al ingreso e internación en unidad de ACV se comportaron como variables importantes para predecir buena evolución, hemorragia intracraneana y muerte. Discusión y conclusiones: se comunicó la mayor casuística nacional sobre el tema. Los parámetros de efectividad y seguridad del tratamiento fueron comparables a los reportados internacionalmente. Se destacaron los buenos tiempos puerta aguja y tasa trombólisis sobre ACV totales como indicadores satisfactorios de calidad asistencial. La internación en unidad de ACV se comportó como un factor predictor de independencia funcional y protector frente a mortalidad hospitalaria.

Introduction: Strokes are a health problem and systemic thrombolysis constitutes a reperfusion strategy backed up by significant evidence on its positive therapeutic impact. National reports on its use are scarce. Objectives: To report and analyze results obtained with this therapeutic approach at the Clinicas Hospital. To establish predictive factors for a good evolution, intracranial hemorrhage and mortality. Method: Observational, analytical study of thrombolysed patients at Clinicas Hospital (2010-2021). Results: Systemic thrombolysis was performed in 268 patients. Average NIHSS score was 12 points when admitted to hospital.42 % of cases were total anterior circulation infarct (TACI). Cardioembolic ischaemmic stroke was the most frequent etiopahogenesis. 59.3% of patients were discharged with functional independence and 55.2% had minimal neurologic deficit. Symptomatic intracranial hemorrhage and mortality rates were 7.1% and 18.7% respectively. 57% of patients were assisted within ≤60 minutes they showed up at the ER. Thrombolysis percentage in total number of strokes was 18.9%. Age, NIHSS score upon arrival to hospital and admission to the stroke unit were significant variables to predict a good evolution, intracranial hemorrhage and death. Discussion and conclusions: The large number of cases in the country was reported. Effectiveness and safety parameters for this treatment were comparable to those reported internationally. The good door-to-needle time and thrombolysis rate versus total number of strokes stood out as satisfactory indicators of healthcare quality. Admission to the stroke unit behaved as a predictive factor of functional independence and it protected patients from hospital mortality.

Introdução: o AVC é um problema de saúde sendo a trombólise sistêmica uma estratégia de reperfusão com alto nível de evidência para seu tratamento. Os dados nacionais sobre seu uso são escassos. Objetivos: comunicar e analisar os resultados desta terapia no Hospital de Clínicas. Estabelecer preditores de boa evolução, hemorragia intracraniana e mortalidade. Métodos: estudo observacional analítico de pacientes trombolisados no Hospital de Clínicas (2010-2021). Resultados: a trombólise sistêmica foi realizada em 268 pacientes. A mediana do índice NIHSS na admissão foi de 12 pontos. 42% eram infartos totais da circulação anterior. A cardioembolia foi a etiopatogenia mais frequente. 59,3% dos pacientes tiveram alta da unidade com independência funcional e 55,2% com déficit neurológico mínimo. As taxas de hemorragia intracraniana sintomática e mortalidade foram de 7,1% e 18,7%, respectivamente. 57% dos pacientes foram tratados com tempo porta-agulha ≤60 minutos. A porcentagem de trombólise no AVC total foi de 18,9%. Idade, NIHSS na admissão e internação na unidade de AVC se comportaram como variáveis importantes para prever boa evolução, hemorragia intracraniana e óbito. Discussão e conclusões: este trabajo inclui a maior casuística nacional sobre o tema. Os parâmetros de eficácia e segurança do tratamento foram comparáveis aos descritos na bibliografia internacional. Foram destacados como indicadores satisfatórios da qualidade do atendimento os bons tempos porta-agulha e taxa de trombólise em relação ao AVC total. A internação em unidade de AVC comportou-se como preditor de independência funcional e protetor contra a mortalidade hospitalar.

Neurological disease in the time of COVID-19. A case series

Introduction: we present a series of patients with neurological problems and SARS-CoV-2 infection, and review the respective evidence. Patients and methods: a retrospective descriptive study of consecutive RT-PCR SARS-CoV-2-positive patients in a neurology department from August 1 to December 31, 2020. Results: we recorded 30 patients: 16 men (53%), with a mean age of 65±17.3. In 53%, the neu rological problem preceded the respiratory symptoms and SARS-CoV-2 infection diagnosis. At the syndromic level, the following were found: CVAs 43% (13), seizures 10% (3), posterior reversible encephalopathy 10% (3), encephalopathy 7% (2), brief psychotic disorder 7% (2), myelopathy 3% (1), Guillain-Barré syndrome 3% (1), headache 3% (1), vasculitis 3% (1), intracerebral hemorrhage 3% (1), myasthenic crisis 3% (1) and recurrent optic neuritis 3% (1). Conclusions: SARS-CoV-2 induced neurological problems produce a wide variety of symptoms and may be the first manifestation, even without the development of respiratory symptoms from this infection. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2233).

Introducción: se presenta una serie de pacientes con compromiso neurológico e infección por SARS-CoV-2 y se revisa la evidencia al respecto. Pacientes y métodos: estudio descriptivo, retrospectivo de pacientes consecutivos RT-PCR positivos para SARS-CoV-2 del servicio de neurología desde el 1° de agosto hasta 31 de diciembre de 2020. Resultados: registramos 30 pacientes, 16 hombres (53%), edad media: 65±17.3. En el 53% el compromiso neurológico antecedió los síntomas respiratorios y el diagnóstico de infección por SARS-CoV-2. A nivel sindromático se observó: ACV 43% (13), crisis convulsivas 10% (3), encefalopatía posterior reversible 10% (3), encefalopatía 7% (2), trastorno psicótico breve 7% (2), mielopatía 3% (1), síndrome de Guillain-Barré 3% (1), cefalea 3% (1), vasculitis 3% (1), hemorragia intracerebral 3% (1), crisis miasténica 3% (1) y neuritis óptica recurrente 3% (1). Conclusiones: el compromiso neurológico por el SARS-CoV-2 produce una gran variedad de síntomas y puede ser la primera manifestación incluso sin el desarrollo de síntomas respiratorios por esta infección. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2233).

Lesions in the Ventromedial Prefrontal Cortex and their Impact on Social Cognition / Lesiones en la Corteza Prefrontal Ventromedial y su Impacto en la Cognición Social

Abstract Aims: To identify the impact of ventromedial prefrontal cortex injury (vmPFc) on social cognition (SC) processes in a stroke patient in relation to a control group matched by age, gender, and schooling. Possible associations between post-injury behavior and impacted neuropsychological attributes of emotion recognition, Theory of Mind (TOM), and empathy are discussed. Method: One male patient (n = 1) (58 years old) with stroke in right vmpFC and 10 healthy participants completed different screening, neuropsychological assessment, and SC tests as: Addenbrooke's Cognitive Examination-Revised; The Trail Making Test; Raven's Matrices; Faux Pas Test; Reading Mind in the Eyes Test, among others. Results: Due single cases are reported, p< .05 values of a tail were considered statistically significant in all comparisons. Correlations were found between damage in vmPFC and alterations in affective TOM, working and retrograde memory, mood and relational alterations in the patient. Discrepancies were found with respect to other studies in relation to the laterality of the injury and the impact of cognitive and affective empathy that seems to be relatively intact. Conclusions: There is a need to clarify the role of affective TOM after acquired brain injury (ABI) in vmPFC. A protocol is needed to assess and intervene in aspects of TOM that would involve documenting strengths and deficits of TOM: inter and intrapersonal after an ABI. Similarly, there is a need to address the lateralization of different domains of function in vmPFC and their relationship to affective TOM.

Resumen Objetivo: Identificar el impacto de la lesión en la corteza prefrontal ventromedial (vmPFC por sus siglas en inglés) en los procesos de cognición social (SC por sus siglas en inglés) a un paciente con accidente cerebrovascular (ACV) en rela-ción a un grupo control pareado por edad, gènero y escolaridad. Se discuten las posibles asociaciones entre el comporta-miento posterior a la lesión y los atributos neuropsicológicos impactados de reconocimiento de emociones, Teoria de la Mente (TOM por sus siglas en inglés) y empatia. Método: Un paciente con ACV en el vmPFC derecho y 10 participantes sanos completaron diferentes pruebas de screening, evaluación neuropsicológica y SC. Resultados: Se encontraron correlaciones entre el dano en vmPFC y alteraciones en la TOM afectiva, memoria de trabajo y retrógrada, alteraciones animicas y relacionales en el paciente. Se hallaron discrepancias frente a otros estudios en relación con la lateralidad de la lesión y al impacto de la empatia cognitiva y afectiva la cual parece estar relativamente intacta. Conclusiones: Se requiere aclarar el panorama frente al deterioro de la TOM afectiva despuès de una lesión cerebral adquirida (ABI por sus siglas en inglés) en vmPFC. Se necesita un protocolo para evaluar e intervenir en aspectos de la TOM que involucraria documentar fortalezas y déficits de TOM: inter e intrapersonal despuès de un ABI. De igual manera, se requiere abordar la lateralización de diferentes dominios de la función en vmPFC y su relación con la TOM afectiva.

Psychometric Properties of the Action Research Arm Test (ARAT) Scale in Post-Stroke Patients-Spanish Population.

The validation of measuring instruments in the field of health is a requirement before they can be used safely and reliably. The action research arm test (ARAT) tool is an instrument validated in numerous countries and languages and for different populations, and its use is widespread. The objective of this research was to determine the psychometric properties of ARAT for a sample composed of post-stroke patients. To achieve this, a psychometric analysis was performed, where internal consistency tests were carried out using Cronbach's alpha, correlations between items and item-total and half-level tests to verify their reliability. Regarding validity, criteria validity tests were performed, taking the motor function dimension of the Fugl-Meyer scale as gold standard, and convergent validity tests were performed by correlation with the FIM-FAM, ECVI-38 and Lawton and Brody scales. The results showed very good internal consistency as well as good criterion and convergent validity. In conclusion, the ARAT can be considered a valid and reliable instrument for the evaluation of upper limb function in post-stroke patients.

Paciente joven con accidente cerebrovascular isquémico: ¿Se debe buscar una trombofilia? / Ischemic stroke in a young patient, is it needed to look for a thrombophilia?

Resumen El accidente cerebrovascular isquémico es un evento de gran importancia debido a las implicaciones y el impacto en la calidad de vida de la población afectada. Su incidencia es más alta en adultos mayores y en personas con factores de riesgo cardiovascular. Existe un grupo de pacientes jóvenes (18-44 años) sin factores de riesgo que presentan dicho evento, por lo que, en la práctica clínica, se tiende a evaluar rutinariamente las trombofilias hereditarias y adquiridas como factor etiológico principal para los eventos isquémicos en este grupo etario. No obstante, son pocos los casos donde se documenta algún trastorno de este tipo, ya que es más frecuente la presencia de otras etiologías como el cardioembolismo y trastornos vasculares. La evaluación de las trombofilias es compleja, dado el alto costo, las limitaciones técnicas para hacerlo y el impacto clínico y terapéutico incierto al documentarse estos estados. Se realiza esta revisión de tema con el fin de orientar al clínico acerca de la pertinencia de objetivar estas condiciones en el paciente joven con accidente cerebrovascular isquémico.

Abstract Acute ischemic stroke is a pathology of great complexity due to the implications and impact on the quality of life of the affected population. The incidence of this pathology is higher in older adults and in people with cardiovascular risk factors. There is a group of young patients with no risk factors who present these events. Therefore, in clinical practice, hereditary thrombophilias tend to be frequently evaluated as the main etiological factor for this age group. However, there are few cases where a disorder of this type is documented and the presence of other etiologies such as cardioembolism and vascular disorders are more frequent. Thus, the evaluation of thrombophilia is complex due to its high cost, technical limitations when evaluating, and its uncertain clinical and therapeutic impact when documented. For this reason, this review is carried out in order to guide the clinician about the relevance of objectifying these conditions in young patient with acute ischemic stroke

Imaging of arrhythmia: Real-time cardiac magnetic resonance imaging in atrial fibrillation.

Objectives: Quantitative evaluations of function, volume and mass are fundamental in the diagnostic workup of different cardiovascular diseases and can be exactly determined by CMRI in sinus rhythm. This does not hold true in arrhythmia as CMR is hampered by reconstruction artifacts caused by inconsistent data from multiple heartbeats. Real-time (RT) MRI at high temporal resolution might reduce these problems. Methods: Consecutive patients with atrial fibrillation were prospectively included and underwent RT and conventional CINE CMR in randomized order. 29 patients were studied at 1.5 T and 30 patients at 3 T. At 3 T a group of 20 subjects in sinus rhythm served as controls. RT and CINE image quality was evaluated in different planes and for different wall sections using a Likert scale (from zero to four). Volumetric analysis was performed using two types of software and differences between RT and CINE CMR were evaluated. Results: In patients with atrial fibrillation RT CMR short axis (SA) resulted in a significantly higher image quality compared to CINE imaging both at 1.5 T and 3 T (1.5 T: mid SA: 3.55 ± 0.5 RT vs 2.6 ± 0.9 CINE, p = 0.0001; 3 T: mid SA: 3.15 ± 0.9 RT vs 2.6 ±1.0 CINE, p = 0.03); This qualitative difference was more marked and significant for the long axis views (2CV and 4CV) at 1.5 T (1.5 T: 2CV: 3.2 ± 0.6 RT vs 2.65 ± 1.1 CINE; p = 0.011; 4CV: 2.9 ± 0.69 RT vs 2.4 ± 0.9 CINE; p = 0.0044). During sinus rhythm CINE images were superior concerning diagnostic quality (3 T mid SA: 3.35 ± 0.45 RT vs 3.8 ± 0.5 CINE, p = 0.008). Quantitative analysis was successful with both software packages and the results showed a good correlation (Pearson correlation between 0.679 and 0.921 for patients). RT CMR resulted in slightly lower functional volumes than CINE CMR (3 T: patients: EDVI 86 ± 29 ml/m2 RT vs 93 29 ml/m2± 29 CINE, Pearson r = 0.902) but similar ejection fractions (3 T: patients: EF 47 ± 16% RT vs 45 ± 13% CINE, Pearson r = 0679; controls: EF 63 ± 6 RT vs 63 ± 3 CINE, Pearson r = 0.695). Conclusion: RT CMR improves image quality in arrhythmic patients and renders studies more comfortable. Volumetric analysis is feasible with slightly lower values relative to CINE CMR, while ejection fractions are comparable.

Desempenho energético e pegada de carbono de um sistema de esgotamento sanitário centralizado no nordeste brasileiro / Energy performance and carbon footprint of a centralized sewage system in northeastern Brazil

RESUMO O objetivo do trabalho foi avaliar a operação e manutenção de um sistema de esgotamento sanitário centralizado, composto de três subsistemas, que atende 367 mil habitantes no Nordeste do Brasil. A avaliação do ciclo de vida considerou um inventário amplo de operação e manutenção do sistema de esgotamento sanitário com as redes de coleta, estações de tratamento de esgoto, disposição do esgoto tratado no corpo hídrico e gestão do lodo. O arranjo tecnológico das estações de tratamento de esgoto avaliadas incluiu o reator do tipo upflow anaerobic sludge blanket, seguido de lagoa aerada e lagoa de polimento em um subsistema, e upflow anaerobic sludge blanket seguido de reator de lodo ativado por aeração prolongada em dois subsistemas. O desempenho energético utilizou o método de demanda de energia acumulada e a pegada de carbono empregou o método de potencial de aquecimento global de 100 anos do Painel Intergovernamental sobre Mudanças Climáticas. O sistema de esgotamento sanitário avaliado demandou 5,12 MJ·m−3 e emitiu 4,08 kg CO2eq·m−3. As maiores contribuições do sistema de esgotamento sanitário avaliado foram a eletricidade, com 62% da demanda energética, e as emissões diretas para o ar, com 94% da pegada de carbono, sendo as emissões dos reatores upflow anaerobic sludge blanket com 76% da pegada de carbono. A identificação dos aspectos e impactos ambientais do sistema de esgotamento sanitário avaliado apoia a inovação tecnológica e gerencial para otimizar o desempenho energético e mitigar as emissões de gases de efeito estufa.

ABSTRACT This aim of this work was to evaluate the operation and maintenance of a centralized wastewater treatment system, composed of three subsystems, which serves 367 thousand inhabitants in northeastern Brazil. The life cycle assessment considered a comprehensive inventory of the wastewater treatment system operation and maintenance with the collection networks, wastewater treatment plants, disposal of the treated wastewater in the water body and sludge management. The technological arrangement of the evaluated wastewater treatment plants included the Upflow Anaerobic Sludge Blanket reactor, followed by aerated and polishing ponds in one subsystem, and Upflow Anaerobic Sludge Blanket followed by extended aeration activated sludge in two subsystems. The energy performance used the cumulative energy demand method and the carbon footprint used the global warming potential method for 100 years of the Intergovernmental Panel on Climate Change. The evaluated wastewater treatment system presented 5.12 MJ·m−3 and 4.08 kg CO2eq·m−3. The largest contribution of the evaluated wastewater treatment system was the electricity use with 62% of the energy demand and direct emissions to the air with 94% of the carbon footprint, being direct emissions from Upflow Anaerobic Sludge Blanket reactors with 76% of the carbon footprint. The identification of environmental aspects and impacts of the evaluated wastewater treatment system supports technological and management innovations to optimize its energy performance and mitigate greenhouse gases emission.

Promoter exchange of the cryptic nonribosomal peptide synthetase gene for oligopeptide production in Aspergillus oryzae.

Oligopeptides with functional activities are of current interest in the nutraceutical and medical sectors. The development of the biosynthetic process of oligopeptides through a nonribosomal peptide synthetase (NRPS) system has become more challenging. To develop a production platform for nonribosomal peptides (NRPs), reprogramming of transcriptional regulation of the acv gene encoded ACV synthetase (ACVS) was implemented in Aspergillus oryzae using the CRISPR-Cas9 system. Awakening silent acv expression was successfully achieved by promoter substitution. Among the three exchanged promoters, AoPgpdA, AoPtef1, and PtPtoxA, the replacement of the native promoter with AoPgpdA led to the highest ACV production in A. oryzae. However, the ACV production of the AoPGpdA strain was also dependent on the medium composition, in which urea was the best nitrogen source, and a C:N ratio of 20:1 was optimal for tripeptide production. In addition to cell growth, magnesium ions are an essential element for ACV production and might participate in ACVS activity. It was also found that ACV was the growth-associated product of the engineered strain that might be a result of constitutive transcriptional control by the AoPgpdA promoter. This study offers a potential strategy for nonribosomal ACV production using the fungal system, which is applicable for redesigning bioactive oligopeptides with industrial relevance.

Estabilidade dinâmica de pessoas com AVE durante o movimento de cabeceio simulado em um jogo digital / Estabilidad dinámica de personas con ACV durante el movimiento de cabeceo simulado en un juego digital / Dynamical stability of post-stroke volunteers during soccer headers simulated by a digital game

RESUMO A estabilidade postural é um objetivo de tratamento na fisioterapia que pode ser alcançado por meio de exercícios de transferência de peso bilateral. Os jogos digitais surgem como alternativa para execução desses exercícios, mas sua avaliação ainda necessita de aprimoramento. Propõe-se aqui o uso de variáveis biomecânicas para verificar o comportamento da estabilidade postural dinâmica durante um movimento de cabeceio, simulado por um jogo digital com diferentes exigências de velocidades. Para isso, 16 voluntários pós-acidente vascular encefálico (AVE) - 12 homens e 4 mulheres, com idade média de 56 anos - e 16 hígidos pareados por sexo e idade participaram da coleta experimental, na qual eles foram submetidos ao jogo digital "cabeceio", que tem cinco níveis de velocidade, do mais lento ao mais rápido, com duração de 30 segundos cada. A partir dos sinais cinemáticos foi possível calcular os indicadores de interesse, a área da base de suporte e a margem de estabilidade, definida como a menor distância entre as bordas da base de suporte e a projeção vertical do centro de massa (CM) extrapolado, que considera a velocidade do CM. Os valores da base de suporte não apresentaram diferenças entre os níveis de velocidade do jogo, mas sim entre grupos. A margem de estabilidade não diferiu entre níveis e grupos. Os níveis de velocidade do jogo, possivelmente, não estimularam os voluntários a buscar estratégias diferentes para manter a estabilidade, como dar um passo, mas os fizeram adotar bases de suporte diferentes, sendo que indivíduos com AVE adotaram uma base de suporte menor do que a dos hígidos.

RESUMEN La estabilidad postural es el objetivo del tratamiento en fisioterapia que puede lograrse mediante ejercicios de traslado de peso bilateral. Los juegos digitales son una alternativa para realizar estos ejercicios, pero aún necesita mejorar su evaluación. Se propone el uso de variables biomecánicas para verificar el comportamiento de estabilidad postural dinámica durante el movimiento de cabeceo, simulado por un juego digital con diferentes requerimientos de velocidad. Para ello, 16 voluntarios pos-accidente cerebrovascular (ACV) -12 hombres y 4 mujeres, con edad media de 56 años- y 16 individuos sanos pareados por sexo y edad participaron de la recolección experimental, en la que fueron sometidos al juego digital "cabeceo", que cuenta con cinco niveles de velocidad, del más lento al más rápido, con una duración de 30 segundos cada uno. A partir de las señales cinemáticas fue posible calcular los indicadores de interés, el área de base de apoyo y el margen de estabilidad, definido como la menor distancia entre los bordes de la base de apoyo y la proyección vertical del centro de masa (CM) extrapolado, que considera la velocidad del CM. Los valores de la base de apoyo no mostraron diferencias entre niveles de velocidad de juego, pero sí entre grupos. El margen de estabilidad no difirió entre niveles y grupos. Los niveles de velocidad de juego posiblemente no animaron a los voluntarios a buscar diferentes estrategias para mantener la estabilidad, como dar un paso, pero les hicieron adoptar diferentes bases de apoyo, llevando a los individuos con ACV a emplear una base de apoyo menor que la de los individuos sanos.

ABSTRACT Postural stability is a goal of physical therapy treatment which can be achieved by bilateral weight transfer exercises. Digital games come as an alternative to performing these exercises, and their evaluation still needs improvement. We proposed using biomechanical variables to assess postural stability behavior. We aimed to investigate dynamic postural stability during soccer headers simulated by a digital game with different speed requirements. For this, 16 post-stroke volunteers (12 men and 4 women with a mean age of 56 years) and 16 healthy volunteers, paired by sex and age, participated in the experimental collection, in which they were subjected to the digital game "Cabeceio" (Soccer Heading), which has five speed levels, from slowest to the fastest, lasting 30 seconds each. From the kinematic signals, we could estimate our indicators of interest: the area of the base of support and the margin of stability, the latter defined as the smallest distance between the edges of the base of support and the vertical projection of the extrapolated CM, considering CM speed. The values of the base of support failed to differ between game speed levels, but did so between groups. The margin of stability failed to differ between levels and groups. The speed levels of the game possibly failed to encourage volunteers to pursue different strategies to maintain dynamic stability, such as taking a step. Although they maintained different support bases, post-stroke individuals adopted a smaller base of support than healthy ones.

Importancia del sistema de preaviso y elección del centro asistencial en el accidente cerebrovascular agudo / Importance of the forewarning system and assistance center selection in acute stroke

Resumen El accidente cerebrovascular (ACV) es una urgencia tiempo dependiente, ya que las conductas de mayor impacto pronóstico dependen del tiempo trascurrido. El objetivo de este trabajo fue analizar nuestros tiempos puerta aguja (TPA), comienzo aguja (TCA) y el efecto que tiene sobre estos el sistema preaviso y la elección adecuada del centro asistencial. Se realizó un estudio observacional con datos obtenidos de histo rias clínicas de pacientes internados en la unidad de ACV. Analizamos el número de tratamientos trombolíticos endovenosos, entre agosto 2015 y diciembre 2019. Comparamos TPA según utilización de pre-aviso, llegada directa por sus propios medios vs. en ambulancia sin pre-aviso, y TCA según llegada directa al centro con unidad de ACV vs. llegada a otro centro para posterior derivación. De 265 pacientes en ventana terapéutica, se realizó tratamiento en 143. Llegaron 137 pacientes derivados de otro centro, 70 recibieron tratamiento trombolítico. El TPA con sistema preaviso y sin preaviso fue 41 ± 23 (media ± DE) y 81 ± 43 minutos, respectivamente (p = 0.001). El TPA con llegada directa por sus propios medios 79 ± 43 y en ambulancia sin preaviso 84 ± 44 minutos (p = 0.7) a unidad de ACV. El TCA en llegada directa a unidad de ACV fue 159 ± 59 y a otro centro para su derivación 199 ± 44 minutos (p = 0.001). La utilización de un sistema de preaviso y la elección directa de un centro con unidad de ACV son medidas clave para reducir los tiempos de tratamiento.

Abstract Acute ischemic stroke (AIS) is a time-dependent emergency, since the greatest impact depends on the time elapsed to treatment. The objective of this work was to analyze door to needle (DTN) and start treatment (STT) times and the effect of pre-notification system (PNS) and the appropriate choice of the healthcare center on these variables. An observational study with data obtained from records of patients admitted to the Stroke Unit (SU) was conducted between August 2015 to December 2019. We analyzed the number of intravenous thrombolytic treatments (IVT), DTN and STT and compared them according to PNS use, direct arrival at the center with SU or arrival at another center for subsequent referral. An overall of 472 patients were hospitalized during the studied period and the treatment was performed in 143 out of 265 patients. One hundred thirty-seven patients arrived from another center, 70 received IVT. Average DNT with PNS and without PNS were 41 ± 23 and 81 ± 44 minutes, respectively (p = 0.001). STT on direct arrival to SU was 159 ± 59 minutes and to another center for referral was 199 ± 44 (p = 0.001). The use of a PNS and the direct choice of a center where IVT is performed significantly improve treatment