COVID 19 y embarazo en Chile: Informe preliminar del estudio multicéntrico GESTACOVID / COVID-19 and pregnancy in Chile: preliminary report of the GESTACOVID multicenter study

INTRODUCCIÓN: En Chile, los efectos maternos y perinatales de la pandemia por SARS-CoV-2 son aún desconocidos. GESTACOVID es un estudio multicéntrico que incluye embarazadas y puérperas hasta el día 42 con COVID-19. El objetivo de este estudio es presentar un informe preliminar, describiendo el impacto de la enfermedad en las embarazadas, factores de riesgo asociados y resultados perinatales. MÉTODOS: Estudio de cohorte descriptivo que incluye 661 pacientes enroladas entre el 7 de marzo y el 6 de julio de 2020, en 23 centros hospitalarios del país. Se analizaron variables demográficas, comorbilidades, características clínicas y del diagnóstico de COVID-19 y resultado materno y perinatal. RESULTADOS: Las pacientes hospitalizadas por COVID-19 tuvieron mayor prevalencia de hipertensión arterial crónica [10% vs 3%; OR=3,1 (1,5-6,79); p=0,003] y de diabetes tipo 1 y 2 [7% vs 2%; OR=3,2 (1,3-7,7); p=0,009] que las pacientes manejadas ambulatoriamente. Un IMC >40 kg/mt2 se asoció con un riesgo dos veces mayor de requerir manejo hospitalizado [OR=2,4 (1,2 - 4,6); p=0,009]. Aproximadamente la mitad de las pacientes (54%) tuvo un parto por cesárea, y un 8% de las interrupciones del embarazo fueron por COVID-19. Hasta la fecha de esta publicación, 38% de las pacientes continuaban embarazadas. Hubo 21 PCR positivas en 316 neonatos (6,6%), la mayoría (17/21) en pacientes diagnosticadas por cribado universal. CONCLUSIONES: Las embarazadas con COVID-19 y comorbilidades como diabetes, hipertensión crónica y obesidad mórbida deben ser manejadas atentamente y deberán ser objeto de mayor investigación. La tasa de transmisión vertical requiere una mayor evaluación para diferenciar el mecanismo y tipo de infección involucrada.

INTRODUCTION: In Chile, effects of the SARS-CoV-2 infection in pregnant women are unknown. GESTACOVID is a multicenter collaborative study including pregnant women and those in the postpartum period (until 42 days) who have had COVID-19. The purpose of this study is to report our preliminary results describing the clinical impact of COVID-19 in pregnant women, the associated risk factors and perinatal results. METHODS: Descriptive cohort study including 661 patients between April 7th and July 6th, 2020, in 23 hospitals. Demographical, comorbidities, clinical and diagnostic characteristics of COVID-19 disease and maternal and perinatal outcomes were analyzed. RESULTS: Pregnant women with COVID-19 admitted to the hospital were more likely to have chronic hypertension [10% vs 3%; OR=3.1 (1.5-6.79); p=0,003] and diabetes type 1 and 2 [7% vs 2%; OR=3.2 (1.3-7.7); p=0.009] than those with outpatient management. A body mass index of >40 kg/mt2 was associated with two-fold higher risk of hospitalization [OR=2.4 (1.2-4.6); p=0.009]. Almost half of patients (54%) were delivered by cesarean section, and 8% of the medically indicated deliveries were due to COVID-19. So far, 38% of the patients are still pregnant. Among 316 newborns, there were 21 positive PCR tests (6.6%), mostly from asymptomatic mothers undergoing universal screening. CONCLUSIONS: Pregnant women with COVID-19 and comorbidities such as diabetes, chronic hypertension and morbid obesity need a close follow up and should be a matter for further research. Vertical transmission of COVID-19 should be thoroughly studied to define the mechanisms and type of infection involved.

Histological description of the interaction between muscle fibers and connective tissue of the fascia of the human trapezius muscle / Descripción histológica de la interacción entre las fibras musculares y tejido conectivo de la fascia del músculo trapecio humano

The skeletal muscle fascia corresponds to a condensation of connective tissue. Fascias are highly innervated and sensitive, and can cover non-expandable structures as well as musculature. It is suggested that fascias have a pivotal role in functions such as postural regulation, peripheral motor coordination and proprioception. Also, the presence of inflammation and microcalcification in fascia of patients with localized muscle pain has been described, suggesting a pathogenic role in pain. The aim was to describe the histological structure of the external deep fascia of the trapezius muscle, with emphasis on the content and arrangement of muscle fibers, type I collagen, and adipose tissue. Sample material was obtained from a male cadaver (60-70 years old), by dissection of the posterior cervical region of the superficial fascia of the trapezius muscle and fixed in buffered formalin. Samples were processed by routine histological techniques and embedded in paraffin, obtaining 5 µm-thick sections that were stained according to the van Gieson technique. The trapezius fascia is composed of type I collagen, organized into high-density collagen bundles and oriented in different directions, and by adipocytes disposed in longitudinal groups on the main axis of the fascia. Muscle fibers are organized into bundles that are inserted laterally on the thickness of the fascia. It is possible that lateral transmission of tensional forces between the fibers might be present.

La fascia del músculo esquelético corresponde a una condensación de tejido conectivo. Las fascias están inervadas y son sensibles y pueden cubrir estructuras no distensibles, así como las fibras musculares esqueléticas. Tienen un rol importante en la regulación de la postura, la coordinación motora periférica y la propiocepción. Además, se ha descrito la presencia de inflamación y microcalcificaciones en la fascia de los pacientes con dolor muscular localizado, lo que sugiere un rol patogénico en el dolor. El objetivo del trabajo fue describir la estructura histológica de la fascia externa profunda del músculo trapecio, con énfasis en el contenido y la disposición de las fibras musculares, colágeno tipo I y el tejido adiposo. Material y métodos: El material de la muestra fue obtenido de un cadáver de sexo masculino (60-70 años), por la disección de la región cervical posterior de la fascia superficial del músculo trapecio e inmediatamente fijado en formalina tamponada (pH 7,2) durante 48 horas. La muestra fue procesada por técnicas histológicas e impregnada en parafina (punto de fusión 56-58 C). Secciones de 5 µm de espesor fueron montadas en láminas silanizada para el desarrollo del protocolo de la técnica de van Gieson. Resultados y discusión: Se observa que la fascia del trapecio está compuesta por tejido conectivo denso irregular con abundante colágeno tipo I, organizado en paquetes grandes como verdaderos haces de colágeno de alta densidad orientada en diferentes direcciones; y por adipocitos dispuestos en grupos longitudinales en el eje principal de la fascia. Las fibras musculares estriadas están organizadas en paquetes que se insertan lateralmente en el espesor de la fascia. Es posible que la transmisión lateral de la tensión entre las fibras esté presente.

Measuring the Lyapunov exponent using quantum mechanics.

We study the time evolution of two wave packets prepared at the same initial state, but evolving under slightly different Hamiltonians. For chaotic systems, we determine the circumstances that lead to an exponential decay with time of the wave packet overlap function. We show that for sufficiently weak perturbations, the exponential decay follows a Fermi golden rule, while by making the difference between the two Hamiltonians larger, the characteristic exponential decay time becomes the Lyapunov exponent of the classical system. We illustrate our theoretical findings by investigating numerically the overlap decay function of a two-dimensional dynamical system.

Specific heat of multifractal energy spectra.

Motivated by the self-similar character of energy spectra demonstrated for quasicrystals, we investigate the case of multifractal energy spectra, and compute the specific heat associated with simple archetypal forms of multifractal sets as generated by iterated maps. We considered the logistic map and the circle map at their threshold to chaos. Both examples show nontrivial structures associated with the scaling properties of their respective chaotic attractors. The specific heat displays generically log-periodic oscillations around a value that characterizes a single exponent, the "fractal dimension," of the distribution of energy levels close to the minimum value set to 0. It is shown that when the fractal dimension and the frequency of log oscillations of the density of states are large, the amplitude of the resulting log oscillation in the specific heat becomes much smaller than the log-periodic oscillation measured on the density of states.

[Evolution of meningococcal disease in the community of Madrid. Effectiveness of antimeningococcal A+C vaccination]. / Evolución de la enfermedad meningocócica en la Comunidad de Madrid. Efectividad de la vacunación antimeningocócica A + C.

BACKGROUND: In 1997 (between 22 September and 14 November) an A + C meningococcal mass vaccination campaign was carried out in Madrid, targeting the age group of from 18 months to 19 years of age, in the face of an increase in the number of cases of meningococcal disease caused by serogroup C occurring in the 1996-97 season. This study forms a part of the impact assessment of that campaign. METHODS: The evolution of the meningococcal disease, by means of the comparison of rates of incidence; and the efficacy of the vaccination campaign was determined after one year (1997-98 season) and after two years (1997-98 and 1998-99 seasons) of monitoring. The vaccine efficacy has been calculated as [1-(Incidence rate in vaccinated/Incidence rate in unvaccinated)]* 100. RESULTS: A significant drop was registered in the incidence of serogroup C meningococcal disease on comparing the 1997-98 and 1998-99 seasons with the epidemic season (1996-97). The vaccine efficacy after two years of monitoring subsequent to the vaccination campaign was 76.9% for the global population between 18 months and 19 years of age and 88.5% in the group of vaccinated individuals between 15 and 19 years of age. CONCLUSIONS: The vaccine efficacy obtained is compatible with that described in the relevant literature. The significant reduction in the incidence of meningococcal disease caused by serogroup C was due to the vaccine efficacy obtained.

Isolation and expression of a barley beta-1,3-glucanase isoenzyme II gene.

A beta-1,3-glucanase gene from Hordeum vulgare was isolated by a PCR strategy, cloned and subsequently sequenced. The amplified sequence contained the entire coding region of the isoenzyme II, which is interrupted by a 165 bp intron at 73 bp downstream the starting codon. This intron contains all the elements required for the processing mechanism in monocots: a high A + U content, the appropriate splice sites in the 5' and 3' ends and four typical YUNAN consensus sequences. Transient transformation of wheat protoplasts with the complete beta-1,3-glucanase gene under the control of maize polyubiquitin promoter revealed that the intron sequence was spliced out. The gene was also expressed at high levels, probably due to an enhancer-like sequence found near the 3' end of the intron.

[Construction and validation of an attitude scale to primary health care]. / Construcción y validación de una escala de actitudes hacia la atención primaria de salud.

OBJECTIVES: To elaborate and validate a scale which can be used as an instrument to find the attitudes towards primary health care of doctors at the first care level. DESIGN: Validation study and questionnaire on attitudes. SETTING: The first care level in the Murcia region. Subjects were 155 doctors (27 family and 128 general doctors) in fixed and provisional posts working in the out-clinics and health centres. MEASUREMENTS AND RESULTS: A Likert-type attitudes scale was designed with five reply options. After the pilot-study on the initial scale and the full item-item correlation, the definitive 46-item survey was elaborated. Selection of subjects was through two-stage stratified randomised sampling, by specialty (general/family medicine) and health district. Reliability was high. Contents validity was reached through various consensus methods. To test validity of construction, a factorial analysis of the main components was performed, with 7 factors isolated: overall patient care, team-work, guidance on health problems, doctor's interest in in-work training, professional role, concern for the psychosocial aspects of the illness and inclusion of second level professionals. CONCLUSIONS: The scale designed is a valid instrument, both a reliable way of identifying PHC doctors' attitudes and the attitudes, which could be improved.

The quantized D-transformation.

We construct a new example of a quantum map, the quantized version of the D-transformation, which is the natural extension to two dimensions of the tent map. The classical, quantum and semiclassical behavior is studied. We also exhibit some relationships between the quantum versions of the D-map and the parity projected baker's map. The method of construction allows a generalization to dissipative maps which includes the quantization of a horseshoe. (c) 1996 American Institute of Physics.

Hygromycin resistance as an efficient selectable marker for wheat stable transformation.

A highly efficient method for stable wheat transformation using hygromycin resistance as a selectable marker is described. Young embryogenic calli growing from immature wheat embryos were transformed using a gunpowder-driven microparticle accelerator. Transgenic wheat plants were determined by PCR amplification of transgene fragments and confirmed by Southern hybridization, activity of the transgene expression and by analysis of the progeny. The hpt gene was as good as or a better selectable marker than the bar gene with an average efficiency (number of transgenic plants relative to the number of bombarded calli) of 5.5% compared with 2.6% for the bar gene.

Structure and characterization of the gene encoding the ferredoxin-NADP reductase-binding protein from Zea mays L.

A genomic clone encoding ferredoxin-NADP reductase binding protein (BP) from Zea mays L. was sequenced and characterized. The promoter region (692 bp) shows several motives resembling those involved in enhancement, tissue-specific expression and light regulation in plants, besides the typical TATA and CAAT boxes. The coding sequence is interrupted by two introns. The deduced amino acid (aa) sequence corresponds to 22.85 kDa for the precursor polypeptide, including a transit peptide of 64 aa and a mature protein of 148 aa.

Estudio clínico de disulfiram en suspensión inyectable: una nueva alternativa en el tratamiento del alcoholismo / Clinical study of disulfiram in intravenous suspension. A therapeutic alternative for alcoholism

A disulfiram suspension (propylenglycol and water) was used to treat 45 alcoholic patients. Inactive suspension was given to 8 control alcoholic patients. Pain, local inflammation, thirst and drowsiness were related to disulfiram suspension, but not to solvent administration. Patients receiving disulfiram who drank alcohol experimented the known reaction which was related to subsequent abstinence from alcohol. 67% of patients receiving disulfiram remained abstinent after 1 year of follow up

The chloroplast reductase-binding protein is identical to the 16.5-kDa polypeptide described as a component of the oxygen-evolving complex.

The N-terminal sequence of the spinach chloroplast reductase-binding protein was determined. The sequence is the same one of a 16.5-kDa polypeptide described as a component of the oxygen-evolving system. Antibodies against both proteins are equivalent as shown by immunoblots, Ouchterlony assays, precipitation of reductase-binding protein complex, and agglutination of thylakoids partially depleted of reductase. These results suggest both proteins are identical. Exposure of the binding protein on the stromal side of thylakoids is supported by agglutination of thylakoids partially depleted of reductase, proteolysis by trypsin, and by accessibility to Fab of anti-binding protein. The latter prevents rebinding of reductase supporting the functional role of the binding protein (16.5 kDa).

Protein phosphorylation in purple photosynthetic bacteria.

Endogenous protein phosphorylation was shown in both in vitro and in vivo experiments in R. rubrum and in other purple photosynthetic bacteria. Among the substrates of this protein kinase activity the apoproteins of the light harvesting complex were tentatively identified. Phosphoamino acid analysis revealed the presence of phosphoserine, phosphothreonine and phosphotyrosine in R. rubrum. A tyrosine kinase was partially purified in the same bacteria.

Immunodetection of the Ferredoxin-NADP Oxidoreductase-Binding Protein Complex in Thylakoids of Different Higher Plant Species.

Monospecific polyclonal antibodies against thylakoid ferredoxin-NADP(+) oxidoreductase and its binding protein from Spinacia oleracea were used to detect the presence of these proteins in different higher plants, including C(3), C(4), and Crassulacean acid metabolism species. A remarkable conservation of antigenic determinants in all the species analyzed was demonstrated for both the reductase and its binding protein. The association of these polypeptides in a complex was detected by immunoprecipitation.

Stromal serine protein kinase activity in spinach chloroplasts.

At least twelve 32P-labeled stromal proteins were detected by electrophoresis under denaturing conditions when intact chloroplasts were incubated with 32Pi, in the light but only three were detected in the presence of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) or in the dark. Incubation of isolated stroma with [gamma-32P]ATP resulted in the preferential phosphorylation of one of them, a 70-kDa polypeptide, in serine residues. Thylakoid membranes in the dark promoted the phosphorylation of two additional stromal polypeptides of 55 and 40 kDa. Illumination during the phosphorylation of stroma in the presence of thylakoids stimulated severalfold the labeling of the 40-kDa polypeptide but not when DCMU was added. The protein kinase activity present in isolated stroma phosphorylated exogenous substrates like histone III, phosvitin, histone II, and casein with specific activities of 3, 1.8, 0.7, and 0.2 pmol X mg-1 X min-1. Histone III polypeptides were phosphorylated differently by stroma and by thylakoids in the dark. Moreover, histone III phosphorylated by thylakoids in the dark yielded a pattern of phosphopeptides after V8 protease treatment that was different from the pattern obtained when histone III was phosphorylated by stroma.

Immunological studies of the binding protein for chloroplast ferredoxin-NADP+ reductase.

Monospecific rabbit antibodies against the ferredoxin-NADP+ reductase binding protein of spinach thylakoids were obtained and characterized. The immunoglobulin G (IgG) fraction gave single precipitation arcs with the purified antigen or with Triton X-100 extracts of thylakoids or the reductase binding protein complex. Antibodies against the flavoprotein behave similarly. Both antibodies agglutinated thylakoids and precipitated the diaphorase activity of a Triton X-100 extract of these membranes. Isolated Fab fragments of the IgG anti-binding protein inhibited NADP+ photoreduction in a time- and Fab concentration-dependent manner. The presence of ferredoxin diminished the rate of inhibition. In the light, the inactivation rate was higher than in dark and this effect was abolished in the presence of uncouplers. These results suggest that the binding protein is protruding from the thylakoids and could be sensing the proton gradient.

Localization and Quantitative Determination of Ferredoxin-NADP Oxidoreductase, a Thylakoid-Bound Enzyme in the Cyanobacterium Anabaena sp. Strain 7119.

Thylakoid membrane preparations obtained from mechanically disrupted (sonicated) cells of the cyanobacterium Anabaena sp. strain 7119 show a membrane-bound ferredoxin-NADP(+) oxidoreductase (EC 1.18.1.2) as determined either by specific antibodies or by using the ferredoxin-dependent NADPH-cytochrome c reductase activity, which is a specific test for this enzyme. However, in contrast with higher plant thylakoids, a low yield of the cyanobacterial reductase-only about 20% of the total amount of this protein estimated in whole cell homogenates-was obtained as a membrane-bound form when Mg(2+) was present during the disruption treatment. It is noteworthy that the addition of water-soluble nonionic polymers, namely polyethylene glycol and polyyinylpyrrolidone, dramatically increased the yield of the thylakoid-bound reductase, reaching values up to 80 to 85% of the total enzyme. Using these thylakoid membrane preparations, a quantitative determination of the reductase has been performed for the first time for cyanobacterial thylakoids. The value determined by immunoelectrophoresis-from 8 to 10 nanomoles per micromole of chlorophyll-is clearly higher than those reported for chloroplast thylakoids.

Evidence of the activity of tyrosine kinase(s) and of the presence of phosphotyrosine proteins in pea plantlets.

Homogenate fractions from etiolated pea plantlets showed tyrosine kinase activity when incubated with [32P]ATP and substrates like polyamino acid polymer (Glu-Ala-Tyr)n or [Val5]angiotensin II. When these tyrosine kinase substrates were recovered by high voltage electrophoresis, and analyzed by high pressure liquid chromatography after alkaline hydrolysis, yielded radioactive phosphotyrosine. The same product was obtained after acid hydrolysis of either endogenous or exogenous substrates. Phosphorylated polypeptides were extracted after sodium dodecyl sulfate gel electrophoresis of a pellet fraction incubated with [32P]ATP. After acid hydrolysis and high voltage electrophoresis, [32P]phosphotyrosine was found in gel bands with polypeptides of about 92 and 57 kDa. These results suggest that tyrosine kinase(s) and phosphotyrosine proteins are also present in higher plants.

Isolation and sequencing of an active-site peptide from spinach ferredoxin-NADP+ oxidoreductase after affinity labeling with periodate-oxidized NADP+.

Spinach ferredoxin-NADP+ oxidoreductase was inactivated by treatment with 2',3'-dialdehyde NADP+ (periodate-oxidized NADP+), which selectively modifies a lysine residue at the nucleotide-binding domain of the enzyme. The identity of the derivatized residue was ascertained by thin-layer chromatography of the protein hydrolysate. Reductase that had been labeled with periodate-oxidized NADP+ and NaB3H4 was treated with trypsin, and samples of the tryptic digest were subjected to reverse-phase high-performance liquid chromatography. The radioactivity profiles showed modification of one specific peptide. The primary structure of this peptide was found to be Gly-Glu-Lys*-Met-Tyr-Ile-Gln-Thr-Arg, where Lys* represents the derivatized lysine. The sequence obtained corresponds to residues 242-250 in the primary structure of spinach ferredoxin-NADP+ reductase recently reported [Karplus et al. (1984) Biochemistry 23, 6576-6583].

Identification of an essential arginine residue in the beta subunit of the chloroplast ATPase.

The ATPase activity of soluble chloroplast coupling factor (CF1) was irreversibly inactivated by phenylglyoxal, an arginine reagent. Under the conditions of inactivation, 2.48 mol of [14C]phenylglyoxal were incorporated per 400,000 g of enzyme when the ATPase was inactivated 50% by the reagent. Isolation of the component polypeptide subunits of the [14C]phenylglyoxal-modified enzyme revealed that the distribution of moles of labeled reagent/mol of subunit was the following: alpha, 0.37; beta, 0.40; gamma, 0.08; delta, none; epsilon, 0.03. CNBr treatment of the isolated alpha and beta subunits and fractionation of the peptides by gel electrophoresis revealed that the radioactivity bound to the alpha subunit was nonspecifically associated with several peptides, while a single peptide derived from the beta subunit contained the majority of the radioactivity associated with this subunit. After treating the isolated beta subunit with trypsin and Staphylococcus aureus protease, a major radioactive peptide was isolated with a sequence Arg-Ile-Thr-Ser-Ile-Lys. This sequence, when compared with the primary structure of the CF1 beta subunit as translated from the gene (Zurawski, G., Bottomley, W., and Whitfeld, P. R. (1982) Proc. Natl. Acad. Sci. U. S. A. 79, 6260-6264) indicated that the arginine marked with the asterisk, the predominant residue modified by phenylglyoxal when the ATPase activity of CF1 is inactivated by the reagent, is Arg 312.