"Direct and indirect impacts of the COVID-19 pandemic on operational conduct of pediatric vaccine clinical trials".

The coronavirus 2019 (COVID-19) pandemic, as well as the resulting public health measures, impacted many aspects of society. The conduct of important pediatric vaccine trials was among these. Analyzing data from six ongoing non-COVID-19 pediatric vaccine trials we aimed to assess the operational impact of the COVID-19 pandemic using descriptive analyses. We identified multiple operational disruptions in trial conduct. Additionally, we identified higher percentages of missed routine vaccinations than investigational vaccines throughout the observation period. Overall, the impact of the COVID-19 pandemic was most apparent early in the pandemic period while adaptations to the pandemic were developed; however, some disruptions persisted throughout the observation period. Pediatric vaccine clinical trials are critical to developing new and/or improved vaccines for the pediatric population. Continued evaluation of the impacts of COVID-19 on pediatric vaccine clinical trials is warranted.

Correction: Coppock et al. Pharmacologic Ascorbic Acid as Early Therapy for Hospitalized Patients with COVID-19: A Randomized Clinical Trial. Life 2022, 12, 453.

The authors wish to make a change to the author names (deleting one author-Constantine Daskalakis) for this paper [...].

Pharmacologic Ascorbic Acid as Early Therapy for Hospitalized Patients with COVID-19: A Randomized Clinical Trial.

Despite the widespread availability of effective vaccines, new cases of infection with severe acute respiratory syndrome coronavirus-2, the cause of coronavirus disease 2019 (COVID-19), remain a concern in the settings of vaccine hesitancy and vaccine breakthrough. In this randomized, controlled, phase 2 trial, we hypothesized that high-dose ascorbic acid delivered intravenously to achieve pharmacologic concentrations may target the high viral phase of COVID-19 and thus improve early clinical outcomes. Sixty-six patients admitted with COVID-19 and requiring supplemental oxygen were randomized to receive either escalating doses of intravenous ascorbic acid plus standard of care or standard of care alone. The demographic and clinical characteristics were well-balanced between the two study arms. The primary outcome evaluated in this study was clinical improvement at 72 h after randomization. While the primary outcome was not achieved, point estimates for the composite outcome and its individual components of decreased use of supplemental oxygen, decreased use of bronchodilators, and the time to discharge were all favorable for the treatment arm. Possible favorable effects of ascorbic acid were most apparent during the first 72 h of hospitalization, although these effects disappeared over the course of the entire hospitalization. Future larger trials of intravenous ascorbic acid should be based on our current understanding of COVID-19 with a focus on the potential early benefits of ascorbic in hospitalized patients.

Phytostimulant properties of highly stable silver nanoparticles obtained with saponin extract from Chenopodium quinoa.

BACKGROUND: Quinoa (Chenopodium quinoa Willd) is an Andean original pseudocereal with high nutritional value. During quinoa processing, large amounts of saponin-rich husks byproducts are obtained. Quinoa saponins, which are biologically active, could be used for various agriculture purposes. Silver nanoparticles have increasingly attracted attention for the management of crop diseases in agriculture. In this work, silver nanoparticles are synthesized by a sustainable and green method, using quinoa husk saponin extract (QE) to evaluate their potential for application in agriculture as biostimulants. RESULTS: Quinoa extract was obtained and characterized by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Sixteen saponin congeners were successfully identified and quantified. The QE obtained was used as a reducing agent for silver ions to synthesize silver nanoparticles (QEAgNPs) under mild conditions. The morphology, particle size, and stability of Ag nanoparticles were investigated by transmission electron microscopy (TEM), ultraviolet-visible spectroscopy (UV-visible), energy-dispersive X-ray (EDS), zeta potential, and Fourier transform infrared spectroscopy with attenuated total reflection (FTIR-ATR). Ultraviolet-visible spectroscopy measurements confirmed the formation of silver nanoparticles in the presence of QE, with estimated particle sizes in a range between 5 and 50 nm. According to the zeta potential values, highly stable nanoparticles were formed. The QE and QEAgNPs (200-1000 µg/mL) were also tested in radish seed bioassay to evaluate their phytotoxicity. The seed germination assays revealed that QEAgNPs possessed a phytostimulant effect on radish seeds in a dose-dependent manner, and no phytotoxicity was observed for both QE and QEAgNPs. CONCLUSION: Silver nanoparticles obtained by a so-called 'green' method could be considered as good candidates for application in the agricultural sector for seed treatment, or as foliar sprays and plant-growth-promoters. © 2020 Society of Chemical Industry.

Successfully Treated Norovirus- and Sapovirus-Associated Diarrhea in Three Renal Transplant Patients.

OBJECTIVES: To examine the burden of norovirus- and sapovirus-related diarrhea in renal transplant patients and to propose the use of nitazoxanide as a therapeutic option for treatment. METHODS: We reviewed three renal transplant patients with viral diarrhea requiring hospitalization due to acute renal failure and signs of graft rejection. All three patients were treated with nitazoxanide. We examined their clinical courses after therapy and compared time to resolution of symptoms and viral shedding. RESULTS: In all three renal transplant patients, improvement of diarrheal illness was witnessed within one week of nitazoxanide initiation. CONCLUSIONS: Infectious diarrhea remains an underestimated yet significant cause of morbidity in solid organ transplant patients. Norovirus and sapovirus are often responsible for this presentation. Nitazoxanide was used as a treatment modality with success in reduction of symptoms, decreased duration of illness, and cessation of viral shedding.

The First Reported Case of Majocchi's Granuloma with Malbranchea sp. in an Immunocompetent Patient.

Majocchi's granuloma is a rare condition in which a dermatophyte invades the deeper layers of the dermis and subcutaneous tissue and can often be misidentified and treated as eczema. It has a variable presentation ranging from cutaneous lesions to deeper infections in immunocompromised patients. No prior cases have described the formation of Majocchi's granuloma with the deuteromycetes, Malabranchea.

Soil legacy data rescue via GlobalSoilMap and other international and national initiatives.

Legacy soil data have been produced over 70 years in nearly all countries of the world. Unfortunately, data, information and knowledge are still currently fragmented and at risk of getting lost if they remain in a paper format. To process this legacy data into consistent, spatially explicit and continuous global soil information, data are being rescued and compiled into databases. Thousands of soil survey reports and maps have been scanned and made available online. The soil profile data reported by these data sources have been captured and compiled into databases. The total number of soil profiles rescued in the selected countries is about 800,000. Currently, data for 117, 000 profiles are compiled and harmonized according to GlobalSoilMap specifications in a world level database (WoSIS). The results presented at the country level are likely to be an underestimate. The majority of soil data is still not rescued and this effort should be pursued. The data have been used to produce soil property maps. We discuss the pro and cons of top-down and bottom-up approaches to produce such maps and we stress their complementarity. We give examples of success stories. The first global soil property maps using rescued data were produced by a top-down approach and were released at a limited resolution of 1km in 2014, followed by an update at a resolution of 250m in 2017. By the end of 2020, we aim to deliver the first worldwide product that fully meets the GlobalSoilMap specifications.

Cryptococcal Infection of the Ventriculoperitoneal Shunt in an Immunocompetent Patient.

BACKGROUND: Ventriculoperitoneal shunting is an effective treatment for hydrocephalus. Ventriculoperitoneal shunt (VPS) infection is a common complication. Cryptococcus neoformans as an implicated organism is rare. In this report, we describe a patient with cryptococcal VPS infection. CASE REPORT: A 52-year-old male with normal pressure hydrocephalus, status post implantation of VPS one year prior to the presentation; who was admitted with a fever, lethargy and confusion for three days. He was treated empirically with intravenous cefepime and vancomycin for VPS infection. The CSF analysis from both the lumbar puncture and the VPS was significant for a low white blood count, low glucose and high protein. Other work-up including India ink and cryptococcal antigen was unrevealing. He remained febrile despite antibiotic treatment for 5 days. The CSF from the shunt was sent for analysis again and it demonstrated similar results from the prior study, but the culture was now positive for Cryptococcus neoformans. The patient was started on oral flucytosine and intravenous liposomal amphotericin B. The VPS was removed and an externalized ventricular catheter was placed. The patient showed rapid resolution of the symptoms. CONCLUSIONS: To date, there was a total of nine reported cases of cryptococcal VPS infection upon review of the literature. Our presenting case and the literature review highlight the difficulties in making an accurate diagnosis of cryptococcal shunt infection. There were case reports of false negative cryptococcal antigen tests with culture proven cryptococcal meningitis. The CSF culture from the shunt remains a mainstay for identifying cryptococcal shunt infection. Cryptococcal shunt infections are rare and early diagnosis and treatment is essential for patient management which involves shunt replacement with concomitant administration of intravenous antifungal medication. High clinical suspicion is crucial and shunt culture preferably from the valve is recommended.

Biofilm en lentes de contacto hidrofílicas / Biofilm in hydrophilic contact lenses

INTRODUCCIÓN: Los biofilms son colecciones de microorganismos sésiles rodeadas de una matriz extracelular (exopolisacáridos) que ellos mismos generan. Se hallan de alguna manera, involucrados en la mayoría de los procesos infecciosos. La capacidad de generar biofilm por parte de algunos microorganismos sobre la superficie de las lentes de contacto (LC), dan a esta estructura un lugar relevante en la prevención de queratitis bacterianas en usuarios de lentes de contacto. OBJETIVO: Nuestro objetivo fue evidenciar cualitativamente, de manera reproducible mediante técnicas sencillas, el desarrollo de biofilm bacteriano sobre la superficie de lentes de contacto hidrofílicas usadas. METODOLOGÍA: Se realizó un estudio prospectivo descriptivo, utilizando 17 lentes de contacto hidrofílicas usadas (LCHU) sobre las cuales se evaluó el desarrollo de biofilm de Pseudomonas aeruginosa (ATTC 27853). RESULTADO: Se evidenció la formación de biofilm a las 8 horas de incubación, siendo más evidente a las 10 horas. Los resultados se evaluaron mediante microscopia óptica, de difracción y confocal. CONCLUSIÓN: El reconocimiento del biofilm como responsable de procesos infecciones oculares, entre ellos, las queratitis bacterianas en usuarios de lentes de contacto, posibilita la búsqueda de enfoques novedosos para su tratamiento y prevención.

INTRODUCTION: Biofilms are collections of microorganisms surrounded by a sessile extracellular matrix (exopolysaccharides) generate by themselves. They are involved in most of infectious processes. The ability to generate biofilm by some microorganisms on the surface of contact lenses, gives to bioflim structure an important rol in the prevention of bacterial keratitis in contact lens wearers. OBJECTIVE: Our objective was to show the development of bacterial biofilm on the surface of hydrophilic contact lenses. METHODS: We performed a prospective descriptive study, we evaluated the development of biofilm by Pseudomonas aeruginosa (ATTC 27853) on the surface of 17 hydrophilic contact lenses. After 8 hour of incubation, the formation of biofilm was cleared observed and became more evident 2 hour later. CONCLUSION:The results were evaluated by optical, diffraction and confocal microscopy.

Risk factors for surgical site infections following spinal fusion procedures: a case-control study.

BACKGROUND: Spinal fusion procedures are associated with a significant rate of surgical site infection (SSI) (1%-12%). The goal of this study was to identify modifiable risk factors for spinal fusion SSIs at a large tertiary care center. METHODS: A retrospective, case-control (1:3 ratio) analysis of SSIs following posterior spine fusion procedures was performed over a 1-year period. Clinical and surgical data were collected through electronic database and chart review. Variables were evaluated by univariate analysis and multivariable logistic regression. RESULTS: In total, 57 deep SSIs were identified out of 1587 procedures (3.6%). Infections were diagnosed a mean of 13.5 ± 8 days postprocedure. Staphylococcus aureus was the predominant pathogen (63%); 1/3 of these isolates were methicillin resistant. Significant patient risk factors for infection by univariate analysis included ASA score >2 and male gender. Among surgical variables, infected cases had significantly higher proportions of staged procedures and thoracic level surgeries and had a greater number of vertebrae fused. Notably, infected fusion procedures had a longer duration of closed suction drains than controls (5.1 ± 2 days vs 3.4 ± 1 day, respectively; P < .001). Drain duration (unit odds ratio [OR], 1.6 per day drain present; 95% confidence interval [CI], 1.3-1.9), body mass index (OR, 1.1; 95% CI, 1.0-1.1), and male gender (OR, 2.7; 95% CI, 1.4-5.6) were significant risk factors in the multivariate analysis. CONCLUSIONS: Prolonged duration of closed suction drains is a strong independent risk factor for SSI following instrumented spinal fusion procedures. Therefore, removing drains as early as possible may lower infection rates.

[Psychopharmacological treatment of bipolar disorder in Latin American]. / Tratamiento psicofarmacológico del trastorno bipolar en América Latina.

OBJECTIVE: This study assessed the treatment preferences among Latin-American psychiatrists for their bipolar disorder patients and if these preferences reflect the current guidelines. METHODS: We designed a survey comprised of fourteen questions. All the questions were aimed at the treatment of bipolar I patients only. We distributed the survey by hand or e-mail to psychiatrists in eight different countries: Argentina, Brasil, Colombia, Costa Rica, Ecuador, México, Perú and Venezuela. Between May 2008 and June 2009, we were able to gather 1143 surveys. RESULTS: As the initial choice of treatment for a bipolar patient who debuts with mania, 61.3% choose a combination of an atypical antipsychotic and a mood stabilizer. Lithium Carbonate (50%) was the first choice for a mood stabilizer in a manic episode. Olanzapine (55.4%) was the initial antipsychotic of choice for the treatment of acute mania. For the treatment of acute bipolar depression, 27% choose Lamotrigineas their first choice. Most of the psychiatrists (74.8%) prescribe antidepressants for the treatment of bipolar depression. For maintenance treatment of bipolar depression most psychiatrists first choice would be Lamotrigine (50.3%). Most of the psychiatrists (89.1%) prescribed two or more psychotropic drugs for the maintenance treatment of their bipolar patients. CONCLUSIONS: There were some similarities with the studies previously done in the US. It seems that for the most part the Latin-American psychiatrists don't strictly follow the literature guidelines that are published, but rather adapt the treatment to the specific case. More longitudinal studies of prescribing patterns in bipolar disorder are needed to corroborate these findings.

Development of laser-induced choroidal neovascularization in rats after retinal damage by sodium iodate injection.

PURPOSE: To determine the role of the retinal pigment epithelium (RPE) in the development of laser-induced choroidal neovascularization (CNV) by selective damage with sodium iodate (SI). METHODS: In group 1, diode laser photocoagulation was applied to the right eye of Long-Evans rats (n = 11). In group 2 (n = 11), SI was administered intravenously at a dose of 40 mg/kg of body weight 2 days after photocoagulation. In group 3 (n = 10), SI was injected 2 days before laser was applied. In group 4 (n = 10), SI was injected immediately after photocoagulation. RESULTS: CNV ingrowth developed in 42 of 93 burns (45%) of the laser group and in 46 of 75 burns (61%) when SI was administered 2 days after laser (p = 0.036). No CNV developed in the other groups. CONCLUSIONS: The angiogenic effect of the RPE is essential during the first hours after the onset of the laser-induced CNV process. When the RPE was damaged before or at the time of photocoagulation, CNV was not induced. These results suggest that RPE integrity is a decisive element in CNV formation.

Role of adenosine transport in gestational diabetes-induced L-arginine transport and nitric oxide synthesis in human umbilical vein endothelium.

Gestational diabetes is associated with increased L-arginine transport and nitric oxide (NO) synthesis, and reduced adenosine transport in human umbilical vein endothelial cells (HUVEC). Adenosine increases endothelial L-arginine/NO pathway via A(2) purinoceptors in HUVEC from normal pregnancies. It is unknown whether the effect of gestational diabetes is associated with activation of these purinoceptors or altered expression of human cationic amino acid transporter 1 (hCAT-1) or human equilibrative nucleoside transporter 1 (hENT1), or endothelial NO synthase (eNOS) in HUVEC. Cells were isolated from normal or gestational diabetic pregnancies and cultured up to passage 2. Gestational diabetes increased hCAT-1 mRNA expression (2.4-fold) and activity, eNOS mRNA (2.3-fold), protein level (2.1-fold), and phosphorylation (3.8-fold), but reduced hENT1 mRNA expression (32%) and activity. Gestational diabetes increased extracellular adenosine (2.7 microM), and intracellular L-arginine (1.9 mM) and L-citrulline (0.7 mM) levels compared with normal cells (0.05 microM, 0.89 mM, 0.35 mM, respectively). Incubation of HUVEC from normal pregnancies with 1 microM nitrobenzylthioinosine (NBMPR) mimicked the effect of gestational diabetes, but NBMPR was ineffective in diabetic cells. Gestational diabetes and NBMPR effects involved eNOS, PKC and p42/44(mapk) activation, and were blocked by the A(2a) purinoceptor antagonist ZM-241385. Thus, gestational diabetes increases the L-arginine/NO pathway involving activation of mitogen-activated protein (MAP) kinases, protein kinase C (PKC) and NO cell signalling cascades following activation of A(2a) purinoceptors by extracellular adenosine. A functional relationship is proposed between adenosine transport and modulation of L-arginine transport and NO synthesis in HUVEC, which could be determinant in regulating vascular reactivity in diabetes mellitus.

Cardiologia fetal. Experiencia en Cali / Fetal cardiology. Experience in Cali

Objetivo: mostrar la experiencia de cardiología fetal en una clínica de tercer nivel. Materiales y métodos: estudio descriptivo, prospectivo, realizado desde junio de 1997 a junio de 2000, en una clínica de tercer nivel de la ciudad de Cali, Colombia. Se estudiaron 34 pacientes embarazadas remitidas por el servicio de ginecoobstetricia con quienes se determinó el estado cardiovascular del feto. Resultados: según la edad de las pacientes el mayor porcentaje (59 por ciento) se encontró entre los 20 y los 29 años; Según la edad gestacional 65 por ciento se presentó entre las semanas 20 y 29; la indicación del estudio con mayor porcentaje (58 por ciento) fue la sospecha de patología cardíaca en un estudio ecográfíco de tercer nivel realizado por el médico obstetra. De acuerdo con el diagnóstico encontrado, el mayor porcentaje lo mostraron las cardiopatías congénitas con cortocircuito de izquierda a derecha. Conclusión: teniendo en cuenta las limitaciones del estudio, podemos observar de acuerdo con los resultados, que es importante la sensibilización de los médicos obstetras y radiólogos para aumentar la posibilidad diagnóstica de las cardiopatías congénitas y además realizar el esfuerzo en la toma completa del estudio ecocardiográfico fetal y no solamente la imagen de cuatro cámaras

Validación de la Brief Psychiatric Rating Scale (BPRS) en el Perú / Validation of the Brief Psychiatric Rating Scale (BPRS) in Perú

Introducción: La Brief Psychiatric Rating Scale (BPRS) es utilizada como uno de los principales indicadores de evolución en los ensayos clínicos sobre esquizofrenia. Debido a su utilidad, la validez y la confiabilidad de la escala han sido probadas en muchos países e idiomas, sin embargo, no existe un estudio similar en nuestro medio. Este trabajo evalúa la validez y la confiabilidad interevaluador de la BPRS traducida al español en pacientes peruanos. Método: Cuarenta pacientes hospitalizados con síndrome psicótico fueron examinados en 2 oportunidades separadas por un intervalo de por lo menos 2 semanas. En cada una de las evaluaciones, 2 psiquiátras familiarizados con el uso de la BPRS aplicaron simultáneamente la escala; además, el médico tratante de cada paciente calificó la severidad de su trastorno mediante la Clinical Global Impression (CGI). Resultados: el coeficiente de correlación de Pearson (R) para los puntajes de la BPRS entre los 2 evaluadores fue 0.8677 (p<0.001) en la segunda evaluación. La correlación entre la BPRS y la CGI fue R= 0.6989 (p<0.001) y R=0.3178 (p=0.045) en la primera y segunda evaluación, respectivamente. Entre las 2 evaluaciones hubo variación significativa en los puntajes obtenidos tanto en la BPRS como en la CGI. El R entre las variaciones de la BPRS y de la CGI fue 0.3558 (p=0.024). Conclusión: La versión en castellano de la BPRS es psicométricamente aceptable y puede ser utilizada como un instrumento para medir la evolución de nuestros pacientes psicóticos.