Local analysis of strains and rotations for macromolecular electron microscopy maps.

Macromolecular complexes perform their physiological functions by local rearrangements of their constituents and biochemically interacting with their reaction partners. These rearrangements may involve local rotations and the induction of local strains causing different mechanical efforts and stretches at the different areas of the protein. The analysis of these local deformations may reveal important insight into the way proteins perform their tasks. In this paper we introduce a method to perform this kind of local analysis using Electron Microscopy volumes in a fully objective and automatic manner. For doing so, we exploit the continuous nature of the result of an elastic image registration using B-splines as its basis functions. We show that the results obtained by the new automatic method are consistent with previous observations on these macromolecules.

Substituent and solvent effects on the UV-vis absorption spectrum of the photoactive yellow protein chromophore.

Solvent effects on the UV-vis absorption spectra and molecular properties of four models of the photoactive yellow protein (PYP) chromophore have been studied with ASEP/MD, a sequential quantum mechanics/molecular mechanics method. The anionic trans-p-coumaric acid (pCA(-)), thioacid (pCTA(-)), methyl ester (pCMe(-)), and methyl thioester (pCTMe(-)) derivatives have been studied in gas phase and in water solution. We analyze the modifications introduced by the substitution of sulfur by oxygen atoms and hydrogen by methyl in the coumaryl tail. We have found some differences in the absorption spectra of oxy and thio derivatives that could shed light on the different photoisomerization paths followed by these compounds. In solution, the spectrum substantially changes with respect to that obtained in the gas phase. The n → π1* state is destabilized by a polar solvent like water, and it becomes the third excited state in solution displaying an important blue shift. Now, the π → π1* and π → π2* states mix, and we find contributions from both transitions in S1 and S2. The presence of the sulfur atom modulates the solvent effect and the first two excited states become practically degenerate for pCA(-) and pCMe(-) but moderately well-separated for pCTA(-) and pCTMe(-).

Study on the Properties of PLA- and PP-Based Films for Food Applications Incorporating Orange Peel Extract from Agricultural by-Products.

The aim of this work was to develop active packaging based on polypropylene (PP) and polylactic acid (PLA) matrices using a high value by-product extracted from orange peel as an active compound for food packaging applications. Different films with and without orange peel extract (OPE) based on PP and PLA were obtained via cast extrusion and characterized in terms of their mechanical, thermal, optical, and sealing properties. The films obtained were transparent, but when OPE was incorporated, the transmittance spectrum decreased, causing slight coloration. Mechanical properties were affected by the incorporation of OPE, as elongation at break and tensile strength increased in the cross-direction of the PP film, although the main differences found were related to the polymer itself. In addition, sealing strength also increased via the incorporation of OPE in the PP matrix. However, thermal properties were not affected by OPE in the PP matrix but slightly decreased stability in PLA. Regarding antimicrobial activity in in vitro studies, no inhibition of the growth of Listeria innocua, Saccharomyces cerevisiae, Aspergillus niger, or Escherichia coli was observed. Finally, antioxidant activity was observed in in vitro studies with 2,2-Diphenyl-1picrylhydrazyl (DPPH) radical. The results of this study showed that the obtention of materials with OPE incorporated into the PLA and PP matrix is feasible. The new materials obtained can be used for applications of oxidation-sensitive fresh products.

Clinical characteristics and outcome of hospitalized elderly patients with COVID- 19 after vaccine failure.

We described clinical characteristics and outcome of 160 patients over 65 years (01 September to 31 August 2021) who had a first positive SARS-CoV-2 PCR- test more than 14 days after full vaccination and were hospitalized with COVID-19. Median age of included patients was 84 years, 61.2% were over 80 years; 50.6% were male and most (82.5%) has at least one comorbidity. Up to 84% received specific treatment against COVID-19, including 76.9% low-flow oxygen therapy. We found that overall mortality was 25.6% and 30.6% in those older than 80 years. A higher mortality was significantly associated with older age and treatment with tocilizumab. Our data showed that although COVID-19 vaccines continue protecting elderly patients against hospitalization and death and might improve the prognosis after hospitalization in patients with breakthrough infections, mortality in this population -especially in those older than 80 years- remains very high.

Storm impacts on a coupled human-natural coastal system: Resilience of developed coasts.

Human occupation of and alteration of the world's coast has transformed large stretches of it into Coupled Human-Natural Systems (CHANS) in which humans both influence and are influenced by coastal evolution. In such systems, human activity is as critical on natural resilience as processes and sediment supply derived from the natural setting. Pre- and post-storm observations of these interactions on the intensively developed Atlantic coast of the Gulf of Cádiz, (Spain and Portugal) are examined to determine natural and engineering resilience. Three case studies are used in three CHANS, showing that human interventions interact in complex ways with the natural system influencing post-storm recovery. In natural coasts, storm impact is assessed in terms of geomorphological response; on developed coasts, it is quantified as damage to infrastructure or loss of amenity. Preparedness, availability of resources, choice of response and the speed at which human agencies respond affect resilience for post-storm beach behaviour. Results show in some sites natural resilience adjusting by post-storm sediment transfers and an equilibrium morphology that may differ from pre-storm morphology; engineering resilience ensured that CHANS regained their pre-storm human infrastructure and amenity. Their management requires a fundamentally different approach to that of natural coastlines. The current immature stage of understanding of CHANS (especially the human preparedness and response components) is illustrated by the case studies presented where short-term political decisions and reactions to storms play a strong role in post-storm response. The nature and extent of many developed coasts as CHANS is slowly becoming more widely acknowledged, but to increase natural resilience and decrease vulnerability in CHANS better planning is required so that future storms are anticipated and when they happen, pre-planned human response actions are activated. Storms are an integral and inevitable element in the behaviour of coastal CHANS, not a disaster or emergency.

Social distancing to combat COVID-19 led to a marked decrease in food-borne infections and sexually transmitted diseases in Spain.

Data from a recent epidemiological surveillance network showed a decrease in the reported number of sexually transmitted diseases (STDs) and food-borne infections. We reflect on the possible drivers and consequences of a decrease in these transmittable infectious diseases linked to human contact in relation to social distancing due to the COVID-19 pandemic in Madrid (Spain).

[Prevalence of osteoarticular infections by Enterobacteria producing extended-spectrum -lactamases]. / Prevalencia de infecciones osteoarticulares por enterobacterias productoras de -lactamasas de espectro extendido.

INTRODUCTION: Infections of enterobacteria producing extended-spectrum -lactamases place a heavy burden on health systems. Little is known in osteoarticular infections, so this work studied the prevalence of these infections in a third-level hospital. MATERIAL AND METHODS: Prevalence study in patients of a Traumatology Service during 2016, with infection criteria provided by the CDC in Atlanta, Georgia. The VITEK® 2 AST-N272 (bioMérieux) system was used for bacterial identification at the species level and for antimicrobial susceptibility tests. RESULTS: 7.85% (n = 86) were reported with osteoarticular infections; 22.09% (n = 19) were by enterobacteria BLEEs. An average of 77.1 days of hospitalization (SD 37.7) (46-200 days); isolation of the microorganism occurred 15 days after entry. Sixteen (84.2%) patients had osteomyelitis, three (15.8%) had a prosthetic knee or hip infection. The average number of treatment days was 60 days (21-129 days). Eighteen patients (94.7%) were discharged with resolution of their infectious picture; one patient died with infection over aggregated pneumonia due to carbapenem-resistant K. pneumoniae. DISCUSSION: The prevalence of osteoarticular infections by enterobacteria BLEEs could not be accurately calculated, but we consider it to be within what is expected, infection control measures require higher standards and there is a lack of development programs to use antimicrobials rationally to control the emergence of these pathologies.

INTRODUCCIÓN: Las infecciones por enterobacterias productoras de -lactamasas de espectro extendido (BLEEs) ocasionan una gran carga a los sistemas de salud. Poco se conoce de las infecciones osteoarticulares, por lo que este trabajo estudió la prevalencia de estas infecciones en un hospital de tercer nivel. MATERIAL Y MÉTODOS: Estudio de prevalencia en pacientes de un servicio de traumatología durante 2016, con criterios de infección proporcionados por el CDC de Atlanta, Georgia. Se utilizó el sistema VITEK® 2 AST-N272 (bioMérieux) para la identificación bacteriana a nivel de especie y para las pruebas de susceptibilidad antimicrobiana. RESULTADOS: Se reportaron 7.85% (n = 86) con infecciones osteoarticulares; 22.09% (n = 19) fueron por enterobacterias BLEEs. Con un promedio de 77.1 días de hospitalización (DE 37.7) (46-200 días); el aislamiento del microorganismo se produjo 15 días posteriores al ingreso; 16 (84.2%) pacientes presentaron osteomielitis, tres (15.8%) tuvieron infección protésica de rodilla o cadera. El promedio de días de tratamiento fue de 60 días (21-129 días); 18 pacientes (94.7%) fueron dados de alta con resolución de su cuadro infeccioso; un paciente falleció con infección sobreagregada por neumonía debida a K. pneumoniae resistente a carbapenémicos. DISCUSIÓN: La prevalencia de infecciones osteoarticulares por enterobacterias BLEEs no se pudo calcular con precisión, pero consideramos que se encuentra dentro de lo esperado, las medidas de control de infecciones requieren tener estándares más elevados y falta desarrollar programas de uso racional de antimicrobianos para controlar la aparición de estas patologías.

Comparación de vía mediastinal posterior versus vía retroesternal para el reemplazo de esófago con ascenso gástrico parcial. Motivo de un cambio de estrategia / Comparison of posterior mediastinal versus retrosternal route for esophageal replacement with partial gastric pull-up. Rationale for a change in strategy

Introducción: existen dos rutas para realizar el reemplazo de esófago (RE), la retroesternal (RRE) y la mediastinal posterior (RMP). El objetivo del estudio es comparar los pacientes que recibieron un ascenso gástrico parcial empleando estas dos rutas. Material y métodos: Se revisaron las historias clínicas de 51 pacientes con ascenso gástrico parcial, en 27 años en el Hospital Garrahan. Se utilizó la vía RRE en 25 casos y la RMP en 26. Fueron comparados los datos epidemiológicos de los grupos y las variables para valorar la dificultad del acto quirúrgico, evolución inmediata y alejada. El estudio es comparativo, retro-prospectivo y longitudinal. Resultados: las características generales de los pacientes fueron similares. Los que recibieron el ascenso gástrico por vía RMP presentaron una menor incidencia de dehiscencia (p=0,017), de enfermedad por reflujo gastroesofágico (ERGE) (p=0,001) y de dumping (p=0,0001). No hubo diferencias estadísticamente significativas entre los dos grupos al comparar la duración del procedimiento, días de internación total y en Unidad de Cuidados Intensivos (UCI), días de permanencia en asistencia respiratoria mecánica (ARM), inicio de alimentación oral y estenosis de la anastomosis. Se observó una tendencia clínicamente relevante, que no alcanzó significancia estadística en las complicaciones intraquirúrgicas y número de dilataciones postoperatorias. No hubo necrosis del ascenso. Fallecieron 2 pacientes. Conclusiones: considerando la menor incidencia de dehiscencia, ERGE y dumping reemplazados por RMP, elegimos a ésta como nuestra primera opción para el reemplazo esofágico en la infancia (AU)

Introduction: The two routes for esophageal replacement (ER) are retrosternal (RRE) and posterior mediastinal (PMR). The aim of the study was to compare patients who received a partial gastric pull-up using either of these two routes. Material and methods: The clinical records of 51 patients who underwent partial gastric pull-up over 27 years at the Garrahan Hospital were reviewed. The RRE route was used in 25 and the RMP in 26 cases. The epidemiological data of the groups and the variables to evaluate the complexity of the surgical procedure, and shortand long-term outcome were compared. A comparative, retroprospective, and longitudinal study was conducted. Results: the general characteristics of the patients were similar. Those who underwent gastric pull-up via PMR had a lower incidence of dehiscence (p=0.017), gastroesophageal reflux disease (GERD) (p=0.001), and dumping (p=0.0001). No statistically significant differences were found between the two groups when comparing the duration of the procedure, days of total hospital and intensive care unit (ICU) stay, days on mechanical ventilation (MV), initiation of oral feeding and stenosis of the anastomosis. A clinically relevant trend, which did not reach statistical significance, was observed in intraoperative complications and number of postoperative dilatations. There was no necrosis of the pull-up. Two patients died. Conclusions: considering the lower incidence of dehiscence, GERD, and dumping associated with PMR, this was our first choice for esophageal replacement in infancy (AU)

Zika virus infection during the Olympic Games in Rio: A fear or an actual risk? / Infección por virus Zika durante los Juegos Olímpicos de Río: ¿alarma o riesgo real?

The recent outbreak of Zika virus infection in Brazil has aroused considerable media interest due to its association with neurological malformations in children born from mothers infected by the virus and to its association with Guillain-Barre syndrome in adults. This relationship has led to the World Health Organisation declaring the current epidemic as a "Public Health Emergency of International Concern". Controversy also emerged on the advisability of delaying or changing the location of the Olympic and Paralympic Games, which were held in August at various locations in Brazil. In this article, we review the available evidence on the risk of Zika and dengue virus infection in individuals who travel to endemic countries, especially for multitudinous events.

Recombinant X chromosome in a prenatal diagnosis.

The prenatal cytogenetic study of an amniotic fluid sample of a 39-year-old female showed one X chromosome with a fragment of extra material in the short arm. The G-band pattern suggested that the extra material could be the long arm of an X chromosome. Several complementary studies were performed in order to better clarify the origin of the material. These studies included parental karyotypes, microsatellite typing and comparative genomic hybridization (CGH). The results obtained allowed us to conclude that the derivative chromosome arose de novo as a recombinant X chromosome with duplication of Xq and partial deletion of Xp. Once informed, the parents decided to continue with the pregnancy, after which a healthy girl was born with no apparent disorders.

The role of metallothionein and zinc in hepatic copper accumulation in cattle.

The role of metallothionein (MT) and zinc (Zn) in hepatic copper (Cu) accumulation in calves from a region in North-West Spain has been investigated. In this region there is intensive pig farming, and animals with liver Cu concentrations above normal are not uncommon. Concentrations of hepatic MT were not related to Cu accumulation but were strongly dependent on the Zn status of the animal. When analysing the metal content bound to MT it was observed that Cu-MT values, in the same way as Zn-MT, were directly correlated with MT concentrations in the liver, indicating that although Cu is a poor inducer of MT synthesis, it can compete with Zn for MT binding sites. The ability of Cu to displace Zn from MT is highly dependent on the Cu:Zn ratio in the cell, Cu being the main metal in MT at the higher levels of Cu exposure in Galician cattle. In spite of this, the percentage of the total hepatic Cu bound to MT is very low in these animals, indicating that cattle have a very limited capacity to accumulate Cu-MT in the liver, and may therefore have a greater susceptibility to Cu toxicosis.

Mapping of Friedreich's ataxia locus by identification of recombination events in patients homozygous by descent.

The Friedreich's ataxia locus (FRDA) maps on chromosome 9q13. Genetic data, obtained from a small number of recombination events, indicated that the FRDA locus might be located centromeric to the D9S15/D9S5 linkage group, the most probable order being cen-FRDA-D9S5-D9S111-D9S15-D9S110-qter. Recently, new centromeric markers have been reported. Analysis of these markers allowed us to localize the recombination breakpoint in some of the recombinant families. However, only one proximal recombination has been found with these markers. To increase the genetic information from FRDA families, we have analyzed the centromeric markers FR1, FR2, FR7, FR8, and FR5 in patients homozygous by descent. These were ascertained because parents were consanguineous or because they were homozygous for the entire haplotype D9S15 or D9S111-D9S5-D9S411E-D9S202. Haplotype divergence for, at least, two contiguous markers was observed in two patients homozygous for the core D9S111-FR2 haplotype and in one third-degree consanguineous family homozygous for haplotype D9S411E-FR5. Interpretation of divergence as the result of ancient meiotic crossovers allowed the definition of three new recombination events which place the FRDA locus within the interval defined by markers D9S411E and FR8. A consanguineous family with first-cousin parents showed homozygosity only at D9S202 and FR2. Further investigations are needed to discern whether two different mutations are segregating in the family or whether two recombinations, one distal and one proximal, have taken place.

Evidence for a common origin of most Friedreich ataxia chromosomes in the Spanish population.

Haplotype analysis is a powerful approach to understand the spectrum of mutations accounting for a disease in a homogeneous population. We show that haplotype variation for 10 markers linked to the Friedreich ataxia locus (FRDA) argues in favor of an important mutation homogeneity in the Spanish population, and positions the FRDA locus in the region where it has been recently isolated. We also report the finding of a new single nucleotide polymorphism called FAD1. The new marker shows a very strong linkage disequilibrium with Friedreich ataxia (FA) in both the Spanish and French populations. suggesting the existence of an ancient and widespread FRDA mutations. Inclusion of FAD1 in the extended haplotype analysis has allowed to postulate that this main FRDA mutation could account for 50-90% of the disease chromosomes. The results indicate that FA, despite clinical heterogeneity, could have originated from a few initial mutations.

Hormonal regulation of FHG22 mRNA in Syrian hamster harderian glands: role of estradiol.

The regulation of the FHG22 gene by sex steroids has been studied in Syrian hamster Harderian gland, an organ with sexual dimorphism in which the FHG22 mRNA is female-specific. Testosterone treatment of females caused irregular inhibitory effects on the FHG22 mRNA levels, whereas male castration originated transitory increases during less than 2 weeks. Treatment of 15 day-castrated males for 1 or 2 days with beta-estradiol-3-benzoate caused a marked stimulation in the FHG22 mRNA levels. The results found in vivo may be explained considering those found in female Harderian gland serum-free primary cell cultures. In the absence of hormones, the FHG22 mRNA levels decreased along the time and neither progesterone, testosterone, or 5 alpha-dihydrotestosterone affected the expression. However, estradiol stimulated the FHG22 mRNA expression in a time and dose-dependent manner: increasing effects were detected between 8-96 h of treatment and the EC50 was about 10(-9) M. The estradiol effect was reverted by the antiestrogen ICI 164,384 or by cycloheximide. We conclude that estradiol stimulates FHG22 mRNA expression in Harderian gland, although other agents may also control the expression in vivo.

Localization of a gene for X-linked nonspecific mental retardation (MRX24) in Xp22.2-p22.3.

Nonspecific X-linked mental retardation (MRX) includes several distinct genetic entities in which mental retardation is not associated with additional distinguishing physical changes. We report linkage data in a Spanish family with MRX, using polymorphic DNA markers distributed over the X chromosome. Two-point linkage analysis demonstrated close linkage between the MRX locus and DXS85 in Xp22.3 with a peak lod score of 2.28 at a theta = 0.00. Analysis of multiple informative meioses suggested a localization of the MRX locus (MRX24) between DXS278 and DXS207. Multipoint linkage analysis resulted in a maximum LOD score of 2.45 at 3 cM proximal to DXS85, and allowed us to reject a localization of the MRX24 gene in all other regions from Xp21-Xqter. These findings localize the MRX24 gene in the chromosomal region Xp22.2-p22.3.

Gene localization in a family with X-linked syndromal mental retardation (Prieto syndrome).

A mapping study was performed on a 3-generation Spanish family with X-linked syndromal mental retardation. Affected males have a typical facial appearance, ear malformations, abnormal growth of teeth, clinodactyly, dimpled skin at the lower back, and patellar luxation. In pneumoencephalography a marked subcortical cerebral atrophy was evident. In the linkage studies with polymorphic DNA markers, no recombination was found between the disease locus and the loci OTC and DXS148, both assigned to Xp21.1. One or more recombinants were observed between the disease locus and loci from the distal part of Xp and the pericentromeric region. Close linkage to loci of Xq has also been excluded. The analysis of multiple informative meioses suggests that the disease locus maps between DXS255 (Xp11.22) and DXS84 (Xp21.1) on Xp.

Localization of non-specific X-linked mental retardation gene (MRX73) to Xp22.2.

Clinical and molecular studies are reported on a family (MRX73) of five males with non-specific X-linked mental retardation (XLMR). A total of 33 microsatellite and RFLP markers was typed. The gene for this XLMR condition was been linked to DXS1195, with a lod score of 2.36 at theta = 0. The haplotype and multipoint linkage analyses suggest localization of the MRX73 locus to an interval of 2 cM defined by markers DXS8019 and DXS365, in Xp22.2. This interval contains the gene of Coffin-Lowry syndrome (RSK2), where a missense mutation has been associated with a form of non-specific mental retardation. Therefore, a search for RSK2 mutations was performed in the MRX73 family, but no causal mutation was found. We hypothesize that another unidentified XLMR gene is located near RSK2.

Isolation and identification of sex-specific cDNA clones from the Syrian hamster harderian gland.

Syrian hamster Harderian glands show a typical sexual dimorphism, with males having two secretory cell types and females having one cell type and intraluminal porphyrin accretions, among other differences. Since these differences may be due to the expression of specific genes, our interest is to identify those genes and their role on the development and control of the sexual dimorphism. The experimental approach was to construct cDNA libraries for male and female Syrian hamster Harderian glands and then subtracted libraries for male vs. female and for female vs. male. By this method, cDNA libraries enriched either in male-specific or in female-specific clones were obtained. Clones from those libraries were checked for differential expression by using double colony hybridization with [32P]-cDNA from male and female glands. Then, the selected clones were checked again for expression in Harderian glands by Northern hybridization, using poly(A+) RNA from males, castrated males, and females. Finally, the clones were sequenced and compared to search for significant homologies. One of the male-specific clones showed strong homology with rat cytochrome p450b/e. Among the female-specific clones, homologies were found to the complement C3 fragment from several species, to sequences from the mouse mammary tumor virus, and to the subunits C1 and C2 of the rat prostatic steroid binding protein. Several other clones showed no significant homologies and need further characterization.