Physical activity levels and sedentary behaviour according to sex, age, BMI, academic year, and country among medical students in Latin America.

Physical inactivity represents a global challenge in public health, being the second most significant factor contributing to mortality. In Latin America, the prevalence of physical inactivity and sedentary behaviour is notable, affecting medical students as well, who play a crucial role as behavioural role models for the population. This study addresses the prevalence of physical activity and sedentary behaviour among medical students in Latin America during the year 2023. A total of 864 participants from 12 institutions across eight countries were surveyed using the Global Physical Activity Questionnaire. Significant variations in physical activity and sedentary behaviour were observed according to sex, age, body mass index, academic year, and country. Notably, Costa Rica exhibited the highest levels of moderate physical activity in leisure time (90 min/day). Strength training was more common among men (60 min/day) and in Argentina (60 min/day). Sedentary behaviour was higher in women (420 min/day) and during the first academic year (485 min/day). Uruguay stood out with high levels of sedentary behaviour (600 min/day). Correlations indicated positive moderate associations between academic year and moderate leisure-time PA (r:0,128, p:0,007). In conclusion, there are associations between the level of physical activity and sedentary behaviour with the variables studied in this research, with the main findings being that the female sex has more time spent in sedentary behaviour (minutes/day) and less time spent in strength training (minutes/day). Additionally, there are higher levels of sedentary behaviour in the early years of medical study compared to the later years of the program.

Antibacterial activity of plant extracts against Streptococcus equi subsp. zooepidemicus isolates from guinea pigs with lymphadenitis in Ecuador.

Lymphadenitis is a commonly occurring and contagious disease in guinea pigs caused by different pathogens, including Streptococcus sp., Staphylococcus sp., and Corynebacterium sp. This study aimed to characterize the bacteria isolated from pus extracted from abscessed mandibular lymph nodes of diseased guinea pigs in Ecuador in 2019 and evaluate the in vitro antibacterial activity of the total extracts of three plant species. Isolates were recovered from three diseased guinea pigs with Lymphadenitis on a farm in Imbabura, Ecuador province. The bacteria were characterized through microbiological, biochemical, and molecular tests as Streptococcus equi subsp. zooepidemicus. Furthermore, the susceptibility of S. equi subsp. zooepidemicus to three plant extracts belonging to the Asteraceae family, Acmella ciliata, Bidens andicola, and Gazania splendens collected in Ecuador, were assessed in vitro by the microdilution method. Our data indicate that all the evaluated extracts showed activity, with a Minimum Inhibitory Concentration (MIC) of 22.50 mg/mL for Acmella ciliata, 11.25 mg/mL for Bidens andicola, and 5.60 mg/mL for Gazania splendens. Bidens andicola extract showed the highest efficacy with a % inhibition of 63.90 at the highest tested concentration (45 mg/mL). This is the first report on the bioactivity of these plant species against S. equi subsp. zooepidemicus.

Evolution and functional role prediction of the CYP6DE and CYP6DJ subfamilies in Dendroctonus (Curculionidae: Scolytinae) bark beetles.

Dendroctonus-bark beetles are natural components and key ecological agents of coniferous forests. They spend most of their lives under the bark, where they are exposed to highly toxic terpenes present in the oleoresin. Cytochrome P450 (CYP) is a multigene family involved in the detoxification of these compounds. It has been demonstrated that CYP6DE and CYP6DJ subfamilies hydroxylate monoterpenes, whose derivatives can act as pheromone synergist compounds or be pheromones themselves in these insects. Given the diversity and functional role of CYPs, we investigated whether these cytochromes have retained their function throughout the evolution of these insects. To test this hypothesis, we performed a Bayesian phylogenetic analysis to determine phylogenetic subgroups of cytochromes in these subfamilies. Subgroups were mapped and reconciled with the Dendroctonus phylogeny. Molecular docking analyses were performed with the cytochromes of each subgroup and enantiomers of α-pinene and ß-pinene, (+)-3-carene, ß-myrcene and R-(+)-limonene. In addition, functional divergence analysis was performed to identify critical amino acid sites that influence changes in catalytic site conformation and/or protein folding. Three and two phylogenetic subgroups were recovered for the CYP6DE and CYP6DJ subfamilies, respectively. Mapping and reconciliation analysis showed different gain and loss patterns for cytochromes of each subgroup. Functional predictions indicated that the cytochromes analyzed are able to hydroxylate all monoterpenes; however, they showed preferential affinities to different monoterpenes. Functional divergence analyses indicated that the CYP6DE subfamily has experimented type I and II divergence, whereas the CYP6DJ subfamily has evolved under strong functional constraints. Results suggest cytochromes of the CYP6DE subfamily evolve to reinforce their detoxifying capacity hydroxylating mainly α- and ß-pinene to (+) and (-)-trans-verbenol, being the negative enantiomer used as a pheromone by several Dendroctonus species; whereas cytochromes of the CYP6DJ subfamily appear to retain their original function related to the detoxification of these compounds.

A polyphasic taxonomy analysis reveals the presence of an ecotype of Rahnella contaminans associated with the gut of Dendroctonus-bark beetles.

Species belonging to the genus Rahnella are dominant members of the core gut bacteriome of Dendroctonus-bark beetles, a group of insects that includes the most destructive agents of pine forest in North and Central America, and Eurasia. From 300 isolates recovered from the gut of these beetles, 10 were selected to describe an ecotype of Rahnella contaminans. The polyphasic approach conducted with these isolates included phenotypic characteristics, fatty acid analysis, 16S rRNA gene, multilocus sequence analyses (gyrB, rpoB, infB, and atpD genes), and complete genome sequencing of two isolates, ChDrAdgB13 and JaDmexAd06, representative of the studied set. Phenotypic characterization, chemotaxonomic analysis, phylogenetic analyses of the 16S rRNA gene, and multilocus sequence analysis showed that these isolates belonged to Rahnella contaminans. The G + C content of the genome of ChDrAdgB13 (52.8%) and JaDmexAd06 (52.9%) was similar to those from other Rahnella species. The ANI between ChdrAdgB13 and JaDmexAd06 and Rahnella species including R. contaminans, varied from 84.02 to 99.18%. The phylogenomic analysis showed that both strains integrated a consistent and well-defined cluster, together with R. contaminans. A noteworthy observation is the presence of peritrichous flagella and fimbriae in the strains ChDrAdgB13 and JaDmexAd06. The in silico analysis of genes encoding the flagellar system of these strains and Rahnella species showed the presence of flag-1 primary system encoding peritrichous flagella, as well as fimbriae genes from the families type 1, α, ß and σ mainly encoding chaperone/usher fimbriae and other uncharacterized families. All this evidence indicates that isolates from the gut of Dendroctonus-bark beetles are an ecotype of R. contaminans, which is dominant and persistent in all developmental stages of these bark beetles and one of the main members of their core gut bacteriome.

Flexible IrOx neural electrode for mouse vagus nerve stimulation.

Vagus nerve stimulation (VNS) is being actively explored as a treatment for multiple conditions as part of bioelectronic medicine research. Reliable and safe VNS in mouse models is a critical need for understanding mechanisms of these. We report on the development and evaluation of a microfabricated cuff electrode (MouseFlex) constructed of polyimide (PI) and with iridium oxide (IrOx) electrodes that is thermoformed to 86 µm ± 12 µm radius to interface the mouse cervical vagus nerve (r ≈ 50 µm). Innovative bench-top methods were used to evaluate the stimulation stability and electrochemical properties of electrodes. Our aggressive stimulation stability (Stim-Stab) test utilized 1 billion pulses at a 1000 Hz with a current density of 6.28 A/cm2 (1.51 mC/cm2/phase) delivering 3023 × 103 C/cm2 to evaluate electrode lifetimes, and all electrodes remained functional. We also investigated the effects of thermoforming on their impedance, charge storage capacity (CSC), and charge injection capacity (CIC). The modest changes in electrochemical properties indicate that the thermoforming process was well tolerated. Thermoformed electrode safety and efficacy were evaluated in-vivo by performing acute VNS in mice and monitoring their heart and respiration rate as biomarkers. Their electrochemical properties were also measured before, during and after VNS. Bradycardia and bradypnea were reliably induced at stimulation currents of 100 to 200 µA, well below the in-vivo CIC of ∼1250 µA (∼0.5 mC/cm2), supporting their safety and efficacy. The electrode impedance increased and CIC decreased during in-vivo use, but largely reversed these changes in in-vitro testing after enzymatic cleaning, supporting their tolerance for surgical use. STATEMENT OF SIGNIFICANCE: Vagus nerve stimulation (VNS) is a rapidly growing aspect of healthcare and bioelectronic medicine research. Reliable and safe VNS in mice with small diameter (d ≈ 100 µm) nerves has been a challenge due to achieving intimate contact with the nerve, and the stimulation stability of commonly used electrodes. We demonstrate a microfabricated (MouseFlex) cuff electrode constructed of polyimide with IrOx electrodes that is thermoformed to contact the mouse cervical vagus. Bench studies highlight the stimulation stability exceeded 109 pulses at 6.28 A/cm2 and their electrochemical properties were measured before, during, and after bench and nerve stimulation. Nerve stimulation induced bradycardia and bradypnea at currents below the in-vivo charge injection capacity, supporting their safety, efficacy, and tolerance for surgical handling.

Neuropsychological Genotype-Phenotype in Patients with Williams Syndrome with Atypical Deletions: A Systematic Review.

Williams syndrome (WS) is a neurodevelopmental disorder caused by a microdeletion in the q11.23 region of chromosome 7. Recent case series reports and clinical case studies have suggested that the cognitive, behavioral, emotional, and social profile in WS could depend on the genes involved in the deletion. The objective of this systematic review was to analyze and synthesize the variability of the cognitive and behavioral profile of WS with atypical deletion and its probable relationship with the affected genes. The medical subject headings searched were "Williams syndrome," "genotype," "phenotype," "cognitive profile," and "atypical deletion." The studies included were in English or Spanish, with children and adults, and published between January 2000 and October 2022. Twenty-three studies are reported. The characteristics of the participants, the genes involved, the neuropsychological domains and instruments, and the prevalence of the WS cognitive profile criteria were used for the genotype-phenotype analysis. The genes with a major impact on the cognitive profile of WS were (a) LIMK1 and those belonging to the GTF2I family, the former with a greater influence on visuospatial abilities; (b) GTF2IRD1 and GTF2I, which have an impact on intellectual capacity as well as on visuospatial and social skills; (c) FZD9, BAZ1B, STX1A, and CLIP2, which influence the cognitive profile if other genes are also effected; and (d) GTF2IRD2, which is related to the severity of the effect on visuospatial and social skills, producing a behavioral phenotype like that of the autism spectrum. The review revealed four neuropsychological phenotypes, depending on the genes involved, and established the need for more comprehensive study of the neuropsychological profile of these patients. Based on the results found, we propose a model for the investigation of and clinical approach to the WS neuropsychological phenotype.

IgY Antibodies as Biotherapeutics in Biomedicine.

Since the discovery of antibodies by Emil Von Behring and Shibasaburo Kitasato during the 19th century, their potential for use as biotechnological reagents has been exploited in different fields, such as basic and applied research, diagnosis, and the treatment of multiple diseases. Antibodies are relatively easy to obtain from any species with an adaptive immune system, but birds are animals characterized by relatively easy care and maintenance. In addition, the antibodies they produce can be purified from the egg yolk, allowing a system for obtaining them without performing invasive practices, which favors the three "rs" of animal care in experimentation, i.e., replacing, reducing, and refining. In this work, we carry out a brief descriptive review of the most outstanding characteristics of so-called "IgY technology" and the use of IgY antibodies from birds for basic experimentation, diagnosis, and treatment of human beings and animals.

Rahnella sp., a Dominant Symbiont of the Core Gut Bacteriome of Dendroctonus Species, Has Metabolic Capacity to Degrade Xylan by Bifunctional Xylanase-Ferulic Acid Esterase.

Rahnella sp. ChDrAdgB13 is a dominant member of the gut bacterial core of species of the genus Dendroctonus, which is one of the most destructive pine forest bark beetles. The objectives of this study were identified in Rahnella sp. ChDrAdgB13 genome the glycosyl hydrolase families involved in carbohydrate metabolism and specifically, the genes that participate in xylan hydrolysis, to determine the functionality of a putative endo-1,4-ß-D-xylanase, which results to be bifunctional xylanase-ferulic acid esterase called R13 Fae and characterize it biochemically. The carbohydrate-active enzyme prediction revealed 25 glycoside hydrolases, 20 glycosyl transferases, carbohydrate esterases, two auxiliary activities, one polysaccharide lyase, and one carbohydrate-binding module (CBM). The R13 Fae predicted showed high identity to the putative esterases and glycosyl hydrolases from Rahnella species and some members of the Yersiniaceae family. The r13 fae gene encodes 393 amino acids (43.5 kDa), containing a signal peptide, esterase catalytic domain, and CBM48. The R13 Fae modeling showed a higher binding affinity to ferulic acid, α-naphthyl acetate, and arabinoxylan, and a low affinity to starch. The R13 Fae recombinant protein showed activity on α-naphthyl acetate and xylan, but not on starch. This enzyme showed mesophilic characteristics, displaying its optimal activity at pH 6.0 and 25°C. The enzyme was stable at pH from 4.5 to 9.0, retaining nearly 66-71% of its original activity. The half-life of the enzyme was 23 days at 25°C. The enzyme was stable in the presence of metallic ions, except for Hg2+. The products of R13 Fae mediated hydrolysis of beechwood xylan were xylobiose and xylose, manifesting an exo-activity. The results suggest that Rahnella sp. ChDrAdgB13 hydrolyze xylan and its products could be assimilated by its host and other gut microbes as a nutritional source, demonstrating their functional role in the bacterial-insect interaction contributing to their fitness, development, and survival.

Three new endemic species of Lepanthes (Orchidaceae, Pleurothallidinae) from the highlands of Ecuador.

Three new species of Lepanthes from Ecuador are described and illustrated. These additions to the Ecuadorean flora were recorded in evergreen montane forest and páramo as part of three different research projects conducted during the last five years (2016-2021). Lepanthesoro-lojaensis was discovered in the southwest of El Oro province and is similar to L.jimburae, differing mainly in the much smaller plants, inflorescences and floral parts. Lepanthesmicroprosartima from the western slopes of Pichincha volcano in northern Ecuador resembles L.obandoi but differs in the coloration of the leaves, the inflorescence that are shorter than the leaves and the smaller floral appendix. Lepanthescaranqui, found in eastern Pichincha and Imbabura, is most similar to L.pachychila but differs from it in its much larger plants and different shape of the petals and the floral appendix. Preliminary assessments of the conservation status of the three taxonomic novelties are provided, using the IUCN Red List Categories and Criteria.

The Bark Beetle Dendroctonus rhizophagus (Curculionidae: Scolytinae) Has Digestive Capacity to Degrade Complex Substrates: Functional Characterization and Heterologous Expression of an α-Amylase.

Dendroctonus-bark beetles are natural agents contributing to vital processes in coniferous forests, such as regeneration, succession, and material recycling, as they colonize and kill damaged, stressed, or old pine trees. These beetles spend most of their life cycle under stem and roots bark where they breed, develop, and feed on phloem. This tissue is rich in essential nutrients and complex molecules such as starch, cellulose, hemicellulose, and lignin, which apparently are not available for these beetles. We evaluated the digestive capacity of Dendroctonusrhizophagus to hydrolyze starch. Our aim was to identify α-amylases and characterize them both molecularly and biochemically. The findings showed that D. rhizophagus has an α-amylase gene (AmyDr) with a single isoform, and ORF of 1452 bp encoding a 483-amino acid protein (53.15 kDa) with a predicted signal peptide of 16 amino acids. AmyDr has a mutation in the chlorine-binding site, present in other phytophagous insects and in a marine bacterium. Docking analysis showed that AmyDr presents a higher binding affinity to amylopectin compared to amylose, and an affinity binding equally stable to calcium, chlorine, and nitrate ions. AmyDr native protein showed amylolytic activity in the head-pronotum and gut, and its recombinant protein, a polypeptide of ~53 kDa, showed conformational stability, and its activity is maintained both in the presence and absence of chlorine and nitrate ions. The AmyDr gene showed a differential expression significantly higher in the gut than the head-pronotum, indicating that starch hydrolysis occurs mainly in the midgut. An overview of the AmyDr gene expression suggests that the amylolytic activity is regulated through the developmental stages of this bark beetle and associated with starch availability in the host tree.

Effects of Bisphenol A on Foxl2 gene expression and DNA damage in adult viviparous fish Goodeaatripinnis.

Bisphenol A (BPA) is an emerging pollutant of global concern. Viviparous fish Goodea atripinnis is endemic to the Central Mexican Plateau where BPA was detected; however, few studies examined the influence of this chemical on native viviparous fish. The effects of BPA (sublethal dose) were determined on DNA integrity and Foxl2 expression in G. atripinnis gonads, and interactions of BPA with FOXL2 protein. Genotoxicity analysis revealed that % comets, at 14 and 28 days and comet tail length (at 14 days) were significantly higher in exposed compared to controls. In general, the % DNA tail was not markedly higher in BPA-treated fish; however, tail moment related to tail length exhibited significant increases in DNA damage. RT-qPCR assays showed Foxl2 overexpression after 14 and 28 days of exposure in females; while in males, Foxl2 was overexpressed after 28 days. In silico analysis demonstrated that BPA interacted with seven residues located in FOXL2 homeodomain. In summary, sublethal BPA doses induced DNA damage and changes in Foxl2 expression in gonadal cells of G. atripinnis, which may adversely affect reproduction in BPA-exposed wild populations. Foxl2 overexpression and BPA-FOXL2 interaction suggested alterations in processes involving Foxl2. Viviparous fish may thus serve as potential non-conventional models for assessing pollutants effects.

The Differential Expression of Mevalonate Pathway Genes in the Gut of the Bark Beetle Dendroctonus rhizophagus (Curculionidae: Scolytinae) Is Unrelated to the de Novo Synthesis of Terpenoid Pheromones.

Bark beetles commonly produce de novo terpenoid pheromones using precursors synthesized through the mevalonate pathway. This process is regulated by Juvenile Hormone III (JH III). In this work, the expression levels of mevalonate pathway genes were quantified after phloem feeding-to induce the endogenous synthesis of JH III-and after the topical application of a JH III solution. The mevalonate pathway genes from D. rhizophagus were cloned, molecularly characterized, and their expression levels were quantified. Also, the terpenoid compounds produced in the gut were identified and quantified by Gas Chromatography Mass Spectrometry (GC-MS). The feeding treatment produced an evident upregulation, mainly in acetoacetyl-CoA thiolase (AACT), 3-hydroxy-3-methylglutaryl-CoA synthase (HMGS), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), phosphomevalonate kinase (PMK), and isopentenyl diphosphate isomerase (IPPI) genes, and males reached higher expression levels compared to females. In contrast, the JH III treatment did not present a clear pattern of upregulation in any sex or time. Notably, the genes responsible for the synthesis of frontalin and ipsdienol precursors (geranyl diphosphate synthase/farnesyl diphosphate synthase (GPPS/FPPS) and geranylgeranyl diphosphate synthase (GGPPS)) were not clearly upregulated, nor were these compounds further identified. Furthermore, trans-verbenol and myrtenol were the most abundant compounds in the gut, which are derived from an α-pinene transformation rather than de novo synthesis. Hence, the expression of mevalonate pathway genes in D. rhizophagus gut is not directed to the production of terpenoid pheromones, regardless of their frequent occurrence in the genus Dendroctonus.

Changes in the Microbial Community of Pinus arizonica Saplings After Being Colonized by the Bark Beetle Dendroctonus rhizophagus (Curculionidae: Scolytinae).

The death of trees is an ecological process that promotes regeneration, organic matter recycling, and the structure of communities. However, diverse biotic and abiotic factors can disturb this process. Dendroctonus bark beetles (Curculionidae: Scolytinae) are natural inhabitants of pine forests, some of which produce periodic outbreaks, killing thousands of trees in the process. These insects spend almost their entire life cycle under tree bark, where they reproduce and feed on phloem. Tunneling and feeding of the beetles result in the death of the tree and an alteration of the resident microbiota as well as the introduction of microbes that the beetles vector. To understand how microbial communities in subcortical tissues of pines change after they are colonized by the bark beetle Dendroctonus rhizophagus, we compare both the bacterial and fungal community structures in two colonization stages of Pinus arizonica (Arizona pine) employing Illumina MiSeq. Our findings showed significant differences in diversity and the dominance of bacterial community in the two colonization stages with Shannon (P = 0.004) and Simpson (P = 0.0006) indices, respectively, but not in species richness with Chao1 (P = 0.19). In contrast, fungal communities in both stages showed significant differences in species richness with Chao1 (P = 0.0003) and a diversity with Shannon index (P = 0.038), but not in the dominance with the Simpson index (P = 0.12). The ß-diversity also showed significant changes in the structure of bacterial and fungal communities along the colonization stages, maintaining the dominant members in both cases. Our results suggest that microbial communities present in the Arizona pine at the tree early colonization stage by bark beetle change predictably over time.

Estudio piloto sobre la utilización de la Estimulación Rítmica Auditiva empleando tango para mejorar la marcha y la calidad de vida en pacientes con Enfermedad de Parkinson que experimentan trastornos de la marcha / PILOT STUDY OF THE USE OF RHYTHMIC AUDITORY STIMULATION USING ARGENTINE TANGO, IN ORDER TO IMPROVE GAIT DISORDERS AND QUALITY OF LIFE, IN PARKINSON´S DISEASE PATIENTS

La Estimulación Rítmica Auditiva (ERA) es una técnica que facilita la rehabilitación de movimientos que son intrínseca y biológicamente rítmicos, como la marcha. Utiliza los efectos fisiológicos del ritmo auditivo sobre el sistema motor y funciona como un estímulo de sincronización y como facilitador para lograr patrones de marchas fisiológicos. El objetivo de este estudio piloto fue comparar los parámetros de marcha y calidad de vida antes y después de la implementación de ERA en pacientes con Enfermedad de Parkinson (EP) que sufrían trastornos de la marcha. Para el estudio se reclutaron 10 pacientes con EP "clínicamente establecida o probable" según criterios diagnósticos internacionales de entre 60 y 85 años de edad, con trastornos de la marcha leves. El entrenamiento con ERA duró 6 semanas y utilizó piezas de tango para sincronizar la marcha a rentes niveles de cadencia. Los resultados muestran una mejoría significativa de la marcha y el equilibrio (escala de Tinetti) luego del entrenamiento con ERA, la cual fue acompañada por una tendencia a la mejoría de la calidad de vida (escala PDQ-39). Estos resultados sugieren que la ERA fue capaz de mejorar la marcha y esto se tradujo en mejorías funcionales. Se requieren estudios aleatorizados, ciego y controlados en un mayor número de pacientes para continuar estudiando la potencial eficacia de la ERA

Rhythmic Auditory Stimulation (RAS) is a technique that facilitates the rehabilitation of movements that are intrinsically and biologically rhythmic, such as gait. It uses the physiological effects of perceived rhythm on the motor system and functions as a synchronization stimulus and as a facilitator to improved gait patterns. The objective of this pilot study was to compare gait parameters and quality of life before and after the implementation of RAS in patients with Parkinson's Disease (PD) with gait difficulties. For the study, 10 patients with clinically established or probable PD according to international diagnostic criteria, between 60 and 85 years of age, who suffered from mild gait disorders were recruited. Training with RAS lasted 6 weeks and used tango pieces to synchronize gait to different levels of cadence. The results show a significant improvement in gait and balance (Tinetti scale) after training with RAS, which was accompanied by a tendency to improve the quality of life (PDQ-39 scale). These results suggest that RAS was able to improve gait, which translated into functional improvements. Randomized, blinded, controlled trials in a larger number of patients are required to further assess the potential efficacy of RAS.

Cambio de personalidad como primera manifestación de una esclerosis múltiple / Personality change as an onset symptom of multiple sclerosis

Introducción. La esclerosis múltiple es una enfermedad neurológica autoinmune, de etiología compleja y de curso crónico, que afecta con mayor frecuencia a población adulta joven, sobre todo a mujeres. El cuadro clínico incluye toda una serie de síntomas neurológicos, cognitivos y psiquiátricos, que van a afectar a casi todas las áreas del funcionamiento del individuo, provocando una serie de discapacidades tanto físicas como mentales, que a su vez traerán como consecuencia importantes cambios emocionales y en el estilo de vida. El desarrollo de clínica psiquiátrica relacionada con el afecto y la conducta se presenta a lo largo de la evolución de la enfermedad, sobre todo en fases avanzadas, siendo poco frecuente su aparición en el debut de la esclerosis múltiple. Caso clínico. Se expone el caso de un paciente en el que el inicio de la esclerosis múltiple estaba asociado a la aparición de clínica psiquiátrica; en concreto, presentaba cambios en sus rasgos de personalidad, confabulaciones y alteraciones de conducta de 3 años de evolución que fueron atribuidos inicialmente a un trastorno psiquiátrico, lo que trajo como consecuencia un retraso en el diagnóstico de su enfermedad neurológica. Conclusiones. La aparición de clínica psiquiátrica atípica, o los cambios en la expresión clínica de la enfermedad psiquiátrica de un paciente, deben constituir un signo de alarma que conduzca a realizar las exploraciones complementarias necesarias para descartar la presencia de una enfermedad orgánica subyacente (AU)

Introduction. Multiple sclerosis is a chronic, autoimmune neurological disease. Its pathogenesis has been shown to be complex and it more often affects young females. Its symptoms include neurological, cognitive, and psychiatric manifestations that can cause physical and mental disabilities with great impact on emotional state and life style. The development of psychiatric symptoms related with affectivity and behaviour are usually observed in advanced stages, being infrequent in the initial stages of the disease. Clinical case. The case is presented on a patient with psychiatric symptoms since multiple sclerosis onset. These symptoms included change in personality traits, confabulations, and behavioural disorders. The patient suffered these manifestations for three years, and were initially attributed to a psychiatric disorder. As a result, there was a delay in the diagnosis of the neurological disease. Conclusions. The appearance of atypical psychiatric symptoms, or a change in the clinical expression of a psychiatric disease, must be a warning sign for all physicians, and requires performing supplementary tests in order to rule out potentially serious medical diseases (AU)

Utilización de heparinas de bajo peso molecular para la profilaxis y el tratamiento de la enfermedad tromboembólica en pacientes embarazadas / Use of low molecular weight heparin for thromboprophylaxis and treatment of venous thromboembolism in pregnant women

Estudio observacional que valoró la seguridad de heparina de bajo peso molecular (HBPM) administrada para la profilaxis o el tratamiento de complicaciones tromboembólicas durante el embarazo. Diseño: Se revisaron retrospectivamente historias clínicas y se recogió el resultado del embarazo y los acontecimientos adversos. El riesgo tromboembólico (ETEV) se analizó mediante la clasificación del Royal College of Obstetrics and Gynaecologist. Resultados: Se incluyeron 127 pacientes (131 fetos) con edad media de 32,3 ± 4,3 años. La HBPM se indicó por ETEV aguda en 11 (8,6%) pacientes y por profilaxis en 116 (91,4%). En el grupo de profilaxis hubo 38 (30,0%), 49 (38,6%) y 29 (22,8%) pacientes con riesgo de ETEV alto, moderado y bajo respectivamente. Los nacidos vivos fueron 127 (97%) —19 (15,1%) pretérmino—. Una paciente con déficit de antitrombina desarrolló ETEV. Hubo 25 casos de sangrado (18 [72%] hematomas subcutáneos). Conclusión: La HBPM es bien tolerada y segura para la profilaxis y el tratamiento de las complicaciones tromboembólicas del embarazo (AU)

This observational study evaluated the safety of low molecular weight heparin (LMWH) for the prophylaxis and treatment of thromboembolic complications in pregnancy. Study Design: The medical records of pregnant women were identified and reviewed retrospectively. Information was extracted on LMWH use, pregnancy outcome, and adverse events. The Guidelines of the Royal College of Obstetrics and Gynaecologists were used to evaluate the thromboembolic risk. Results: Data were collected on 127 pregnancies (131 fetuses); the mean age was 32.3 ± 4.3. LMWH was prescribed for acute venous thromboembolism in 11 patients (8.6%) and for prophylaxis in 116 (91.4%). For the prophylaxis group, there were 38 (30.0%), 49 (38.6%) and 29 (22.8%) patients with high, moderate and low venous thromboembolism risk, respectively. There were 127 (97%) live births (19 preterm [15.1%]). In the prophylaxis group, one venous thromboembolism occurred in a patient with antithrombin deficiency. Safety outcomes included 25 cases of bleeding (18 [72%] were injection site hematomas). Conclusion: We found that LMWH was well tolerated and safe for the prophylaxis and treatment of thromboembolic complications during pregnancy (AU)

Auxin Biosynthesis, Accumulation, Action and Transport are Involved in Stress-Induced Microspore Embryogenesis Initiation and Progression in Brassica napus.

Isolated microspores are reprogrammed in vitro by stress, becoming totipotent cells and producing embryos and plants via a process known as microspore embryogenesis. Despite the abundance of data on auxin involvement in plant development and embryogenesis, no data are available regarding the dynamics of auxin concentration, cellular localization and the expression of biosynthesis genes during microspore embryogenesis. This work involved the analysis of auxin concentration and cellular accumulation; expression of TAA1 and NIT2 encoding enzymes of two auxin biosynthetic pathways; expression of the PIN1-like efflux carrier; and the effects of inhibition of auxin transport and action by N-1-naphthylphthalamic acid (NPA) and α-(p-chlorophenoxy) isobutyric acid (PCIB) during Brassica napus microspore embryogenesis. The results indicated de novo auxin synthesis after stress-induced microspore reprogramming and embryogenesis initiation, accompanying the first cell divisions. The progressive increase of auxin concentration during progression of embryogenesis correlated with the expression patterns of TAA1 and NIT2 genes of auxin biosynthetic pathways. Auxin was evenly distributed in early embryos, whereas in heart/torpedo embryos auxin was accumulated in apical and basal embryo regions. Auxin efflux carrier PIN1-like gene expression was induced in early multicellular embryos and increased at the globular/torpedo embryo stages. Inhibition of polar auxin transport (PAT) and action, by NPA and PCIB, impaired embryo development, indicating that PAT and auxin action are required for microspore embryo progression. NPA also modified auxin embryo accumulation patterns. These findings indicate that endogenous auxin biosynthesis, action and polar transport are required in stress-induced microspore reprogramming, embryogenesis initiation and progression.

Diversity and expression of P450 genes from Dendroctonus valens LeConte (Curculionidae: Scolytinae) in response to different kairomones.

Bark beetles (Curculionidae: Scolytinae) are major cause of woody plants death in the world. They colonize the stem and other parts of trees recognizing host-produced specific compounds (kairomones) and insect pheromones. Bark beetle's antennae and alimentary canal participate in the host selection identifying chemical compounds produced by trees and insects, and also in the metabolism and detoxification of these compounds. The red turpentine beetle (RTB), Dendroctonus valens LeConte, is an unaggressive species that colonize > 40 pine species (Pinaceae) in North and Central America. Several studies suggest that bark beetle cytochrome P450 enzymes are involved in monoterpene oxidation. In this study we identified by means of PCR, cloning, sequencing, and bioinformatic analysis, eleven full-length genes: five CYP4, four CYP6, and two CYP9 in the antennae and gut region of RTB, after stimulation with vapors of monoterpenes: (±)-α-pinene, (R)-(+)-α-pinene, (S)-(-)-ß-pinene, (S)-(-)-α-pinene and (+)-3-carene; pine trees volatiles used by RTB as kairomones. The recovered cDNA of these genes vary from 1.5 kb to 1.8 kb and the open frame encodes from 496 to 562 amino acid proteins. The bioinformatic analysis suggests that the majority of P450 proteins encoded by these genes are membrane anchored in the endoplasmic reticulum. RT-qPCR assays showed differential expression of all CYP genes between male and female. The gene expression was dependent of monoterpenes and exposure time, with some of them sex, antennae and gut region specific. Significant differences among monoterpenes, gut region, antennae and exposure time were found. Our results suggest that some of these genes may be involved in the detoxification process of these compounds during tree colonization.

Isolation and expression of cytochrome P450 genes in the antennae and gut of pine beetle Dendroctonus rhizophagus (Curculionidae: Scolytinae) following exposure to host monoterpenes.

Bark beetles oxidize the defensive monoterpenes of their host trees both to detoxify them and convert them into components of their pheromone system. This oxidation is catalyzed by cytochrome P450 enzymes and occurs in different tissues of the insect, including the gut (i.e., the site where the beetle's pheromones are produced and accumulated) and the antennae (i.e., the olfactory organs used for perception of airborne defensive monoterpenes as well as other host-associated compounds and pheromones). We identified ten new CYP genes in the pine beetle Dendroctonus rhizophagus in either antennae or gut tissue after stimulation with the vapors of major host monoterpenes α-pinene, ß-pinene and 3-carene. Five genes belong to the CYP4 family, four to the CYP6 family and one to the CYP9 family. Differential expression of almost all of the CYP genes was observed between sexes, and within these significant differences among time, stimuli, anatomical region, and their interactions were found upon exposure to host monoterpenes. Increased expression of cytochrome P450 genes suggests that they play a role in the detoxification of monoterpenes released by this insect's host trees.

Regulatory regions of SERPINC1 gene: identification of the first mutation associated with antithrombin deficiency.

Antithrombin is the main endogenous anticoagulant. Impaired function or deficiency of this molecule significantly increases the risk of thrombosis. We studied the genetic variability of SERPINC1 , the gene encoding antithrombin, to identify mutations affecting regulatory regions with functional effect on its levels. We sequenced 15,375 bp of this gene, including the potential promoter region, in three groups of subjects: five healthy subjects with antithrombin levels in the lowest (75%) and highest (115%) ranges of our population, 14 patients with venous thrombosis and a moderate antithrombin deficiency as the single thrombophilic defect, and two families with type I antithrombin deficiency who had neither mutations affecting exons or flanking regions, nor gross gene deletions. Our study confirmed the low genetic variability of SERPINC1 , particularly in the coding region, and its minor influence in the heterogeneity of antithrombin levels. Interestingly, in one family, we identified a g.2143 C>G transversion, located 170 bp upstream from the translation initiation codon. This mutation affected one of the four regions located in the minimal promoter that have potential regulatory activity according to previous DNase footprinting protection assays. Genotype-phenotype analysis in the affected family and reporter analysis in different hepatic cell lines demonstrated that this mutation significantly impaired, although it did not abolish, the downstream transcription. Therefore, this is the first mutation affecting a regulatory region of the SERPINC1 gene associated with antithrombin deficiency. Our results strongly sustain the inclusion of the promoter region of SERPINC1 in the molecular analysis of patients with antithrombin deficiency.