Abstract INTRODUCTION The percentage of asymptomatic COVID-19 cases worldwide is estimated at 18–50%; 53% in Cuba specifically, and 58% in Havana, the Cuban capital and the 2020 epicenter of the country’s COVID-19 epidemic. These figures, however, do not represent the transmission capacity or behavior of asymptomatic cases. Understanding asymptomatic transmission’s contribution to SARS-CoV-2 spread is of great importance to disease control and prevention. OBJECTIVE Identify the epidemiological implications of asymptomatic SARS-CoV-2 infection in Havana, Cuba, during the first wave of the epidemic in 2020. METHODS We carried out a cross-sectional study of all confirmed COVID-19 cases diagnosed in Havana, Cuba, from March 16 through June 30, 2020. The information was obtained through review of the standardized form for investigation of suspected and confirmed cases. Examined variables included age, sex, occupation, case type and source of infection. Cases were divided into asymptomatic and symptomatic groups, and transmission was characterized through the creation of a contact matrix. Analysis was carried out in Epidat and R. RESULTS We studied 1287 confirmed cases, of which 57.7% (743) were asymptomatic, and 42.3% (544) were symptomatic. Symptomatic presentation was the most common for both imported and introduced cases, while asymptomatic presentation was more common in autochthonic cases and infections from an undetermined source. Asymptomatic infection was more common in groups aged <20 and 20–59 years, while symptomatic infection was more common in those aged >60 years. In the contact matrix, 34.6% of cases (445/1287) were not tied to other cases, and 65.4% (842/1287) were infectious–infected dyads, with symptomatic–symptomatic being the most common combination. The majority of primary cases (78.5%; 1002/1276) did not generate secondary cases, and 85.6% (658/743) of asymptomatic cases did not lead to other cases (although one asymptomatic superspreader led to 90 cases in a single event). However, 63.2% (344/544) of symptomatic primary cases generated secondary cases, and 11 symptomatic superspreaders spawned 100 secondary cases in different events. CONCLUSIONS Asymptomatic SARS-CoV-2 infection was the most common form of COVID-19 in Havana during the study period, but its capacity for contagion was lower than that of symptomatic individuals. Superspreader events under specific conditions played an important role in sustaining the epidemic.

Abstract Introduction: Chronic kidney disease (CKD) associated with pregnancy increases the risk of maternal and fetal complications. Objective: To determine perinatal morbidity and mortality of children born to mothers with mild and moderate CKD during pregnancy. Methods: Retrospective study of medical records of women with mild and moderate CKD during pregnancy cared for at La Raza National Medical Center between 2010 and 2016. Results: There were 142 patients, 99 (69.72 %) with mild CKD and 43 (30.28 %) with moderate CKD; 79 neonates (55.63 %) reached full term, 28 (19.71 %) had growth restriction; 44 (30.98 %), low birth weight and 54 (38.02 %) were admitted to the neonatal intensive care unit (NICU); four women (4.04 %) had an abortion; in four (2.81 %), their children had intrauterine death, and in 10 (7.04 %), neonatal death. High blood pressure (OR = 6.93) and hemoglobin < 11 g/dL (OR = 2.48) were risk factors for prematurity. Conclusion: A relationship was found between anemia and blood pressure levels and risk for prematurity, low Apgar and NICU admission.

Resumen Introducción: La enfermedad renal (ER) crónica asociada al embarazo incrementa el riesgo de complicaciones maternas y fetales. Objetivo: Determinar la morbilidad y mortalidad perinatal del hijo de madre con enfermedad renal leve y moderada del embarazo. Métodos: Estudio retrospectivo de expedientes de mujeres con ER leve y moderada del embarazo atendidas en el Centro Médico Nacional La Raza entre 2010 y 2016. Resultados: Se trató de 142 pacientes, 99 (69.72 %) con ER leve y 43 (30.28 %) con ER moderada; 79 (55.63 %) neonatos llegaron a término, 28 (19.71 %) presentaron restricción de crecimiento; 44 (30.98 %), peso bajo al nacimiento y 54 (38.02 %) ingresaron a la unidad de cuidados intensivos neonatales; cuatro (4.04 %) mujeres presentaron aborto, en cuatro (2.81 %) sus hijos presentaron muerte intrauterina y en 10 (7.04 %), muerte neonatal. La presión arterial alta (RM = 6.93) y la hemoglobina < 11g/dL (RM = 2.48) constituyeron factores de riesgo para prematurez. Conclusión: Se encontró relación entre la anemia y las cifras de tensión arterial como riesgo para prematurez, Apgar bajo e ingreso a unidad de cuidados intensivos neonatales.

The key step in the chemoenzymatic synthesis of apremilast was to produce the chiral alcohol (R)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethanol, (R)-3. Two enzymatic approaches were evaluated to obtain (R)-3, one using ketoreductases and the other lipases. Bioreduction of 1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethanone (2), using ketoreductase KRED-P2-D12, led to (R)-3 with 48% conversion and 93% enantiomeric excess (ee). Kinetic resolution of rac-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl acetate (rac-4), via hydrolysis reaction, with 20% of n-butanol, catalyzed by lipase from Aspergillus niger yielded (R)-3 with > 99% ee, 50% conversion and E-value (enantiomeric ratio) > 200. The reaction between enantiomerically pure (R)-3 and 4-acetylamino-isoindol-1,3-dione (8) afforded apremilast in 65% yield and 67% ee.

ABSTRACT Protein–energy malnutrition affects one in nine people worldwide and is most prevalent among children aged less than five years in low-income countries. Early childhood malnutrition can have damaging neurodevelopmental effects, with significant increases in cognitive, neurological and mental health problems over the lifespan, outcomes which can also extend to the next generation. This article describes a research collaboration involving scientists from five centers in Barbados, China, Cuba and the USA. It builds on longer-term joint work between the Barbados Nutrition Study (which, over a 45-year span, has extensively documented nutritional, health, behavioral, social and economic outcomes of individuals who experienced protein–energy malnutrition in the first year of life and healthy controls from the same classrooms and neighborhoods) and the Cuban Neuroscience Center (which has developed low-cost brain imaging methods that can be readily used in low income settings to identify biomarkers for early detection and treatment of adverse consequences of childhood malnutrition). This collaboration, which involved Barbadian, Cuban and US scientists began in the 1970s, when quantitative EEG techniques were applied to EEG data collected in 1977–78, at which time study participants were aged 5–11 years. These EEG records were never fully analyzed but were stored in New York and made available to this project in 2016. These data have now been processed and analyzed, comparing EEG findings in previously malnourished and control children, and have led to the identification of early biomarkers of long-term effects of early childhood protein–energy malnutrition. The next stage of the project will involve extending earlier work by collecting EEG recordings in the same individuals at ages 45–51 years, 40 years later, and comparing findings to earlier data and to these individuals’ behavioral and cognitive outcomes. Quantitative EEG biomarkers of the effects of protein–energy malnutrition may help identify children at greatest risk for early malnutrition’s adverse neurodevelopmental effects and inform development of targeted interventions to mitigate the long-term adverse effects of protein–energy malnutrition in developing countries.

Introduction: The use of solutions containing hypertonic glucose (3.86%/4.25%) has been postulated as the method of choice for study the peritoneal function, and permits a better evaluation of the ultrafiltration (UF) capacity. Objective: The aim of our study was to analyze the UF capacity and its relation with the peritoneal permeability and sieving of sodium, performing the peritoneal kinetic study with hypertonic glucose solutions. Patients and methods: We performed 184 peritoneal kinetic studies with hypertonic glucose solutions in stable patients on peritoneal dialysis (PD), with a mean time on PD of 16 ± 22 months. We measured the mass transfer coefficient of creatinine (CrMTC), dialysate to plasma ratio of creatinine (D/PCr), UF capacity and sieving of sodium at 60 minutes (difNa60). Results: The mean values were: CrMTC: 9.1 ± 4.5 ml/min, D/PCr: 0.71 ± 0.09, UF 759 ± 233 ml/4 h and difNa60: 4.7 ± 2.3. The best multivariate model that predicts the UF capacity included: difNa60, CrMTC, age and time on PD (r = 0.57; p >0.0001). In patients with UF lower than 600 ml/4 h (Percentil 25) the correlation between UF and CrMTC was lost, but remains the correlation with difNa 60 (r = 0.48). The patients with previous peritonitis (n = 38) showed no differences in UF, CrMTC or D/Pcr, but the had lower difNa 60 (3.7 ± 2.8 vs. 4.9 ± 2.1; p = 0.002) than the remaning patients. Conclusions: The peritoneal kinetic study performed with hypertonic glucose allows to standarize the UF capacity and by determination of sieving of sodium, the early detection of water transport alterations, before the UF capacity and small solutes permeability alteration develops.

Introducción: La utilización de soluciones con glucosa al 3,86%/4,25% se ha postulado como el método ideal para estudiar la función peritoneal, ya que permite evaluar mejor la capacidad de ultrafiltración (UF). Objetivo: El objetivo del estudio es analizar la UF y sus relaciones con la permeabilidad peritoneal y el cribado de sodio mediante la realización de cinéticas peritoneales con glucosa hipertónica. Pacientes y métodos: Realizamos 184 cinéticas con glucosa hipertónica en pacientes estables en diálisis peritoneal (DP), con un tiempo medio en DP de 16 ± 22 meses. Se midieron el coeficiente de transferencia de masa de creatinina (MTCcr), el cociente dializado/plasma de creatinina (D/Pcr), la UF y el cribado de sodio a los 60 minutos (difNa60). Resultados: Los valores medios fueron: MTC-Cr: 9,1 ± 4,5 ml/min, D/Pcr: 0,71 ± 0,09, UF 759 ± 233 ml/4 h y difNa60: 4,7 ± 2,3. El modelo que mejor explica la UF es el que incluye difNa60, MTCcr, edad y tiempo en DP (r = 0,57; p >0,0001). En los pacientes con UF menor de 600 ml (percentil 25) se pierde la correlación entre la UF y el MTCcr, pero se mantiene con difNa60 (r = 0,48). Los 38 pacientes con antecedentes de peritonitis no presentaron diferencias en UF, MTCcr o D/Pcr, pero tienen menor difNa60 (3,7 ± 2,8 frente a 4,9 ± 2,1; p = 0,002) que el resto de pacientes. Conclusiones: La cinética peritoneal realizada con glucosa hipertónica permite no sólo hacer una medida estandarizada de la UF sino también determinar el cribado de sodio, que es el parámetro más sensible para detectar alteraciones del transporte de agua.

A investigação fitoquímica do extrato metanólico das folhas de Annona dioica (Annonaceae) resultou na identificação dos flavonóides kaempferol (1), 3-O-[3",6"-di-O-p-hidroxicinamoil] -beta-galactopiranosil-kaempferol (2), 6"-O-p-hidroxicinamoil-beta-galactopiranosil-kaempferol (3) e 3-O-beta-galactopiranosil-kaempferol (4). As estruturas foram caracterizadas inequivocamente através de análises espectroscópicas utilizando-se RMN de ¹H e 13C uni e bi-dimensional. Os efeitos citotóxicos dos flavonóides e da fração flavonoídica (FF) foram avaliados frente a células do carcinoma de Ehrlich, utilizando-se o ensaio do MTT (brometo de 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolium). Os resultados indicaram que 1, 2, 3 e FF apresentam ação anti-proliferativa importante quando comparados com a quercetina. A ação inibitória dos flavonóides sobre as DNA-topoisomerases I e II foi avaliada utilizando-se o ensaio de relaxação sobre o plasmídeo pBR322. Os resultados indicaram ação não seletiva dos flavonóides sobre as DNA-topoisomerases I e II.

Chemical investigation of methanol extract leaves from Annona dioica (Annonaceae) resulted in the identification of flavonoids kaempferol (1), 3-O-[3",6"-di-O-p-hydroxycinnamoyl]-beta-galactopyranosyl-kaempferol (2), 6"-O-p-hydroxycinnamoyl-beta-galactopyranosyl-kaempferol (3) and 3-O-beta-galactopyranosyl-kaempferol (4). The structures were unequivocally characterized by ¹H and 13C NMR spectroscopic analyses using 1D and 2D experiments. The cytotoxic effects of the flavonoids and flavonoid fraction (FF) were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay against Ehrlich carcinoma cells. The results indicated that 1, 2, 3 and FF exhibit significant antiproliferative action when compared to quercetin. The inhibitory action on DNA-topoisomerase I and II of all the flavonoids was evaluated by relaxation assays on pBR322 plasmid DNA. The results indicated the inhibitory and non-selective effects of the flavonoids on DNA-topoisomerase I and II.