Tumor budding as a risk factor for lymph node metastases in cutaneous squamous cell carcinoma: a systematic review and meta-analysis.

BACKGROUND: Current staging systems have limitations in stratifying high-risk cases of cutaneous squamous cell carcinoma (cSCC). Tumor budding (TB) has emerged as a potential prognostic factor in various cancers. OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the prognostic significance of TB in predicting lymph node metastases (NM) in cSCC. METHODS: A comprehensive search of the PubMed, Web of Science, EMBASE, and Cochrane databases was conducted. Studies investigating the association of TB using a 5-bud cut-off and NM in cSCC were included. A meta-analysis was performed using odds ratios (OR) to evaluate the association between TB and NM. RESULTS: Six retrospective studies comprising 793 cSCC patients were included. The random-effects analysis showed a significant association between high TB (≥5 buds) and NM (OR = 13.29, 95% CI = 5.55; 31.86). DISCUSSION: Tumor budding is a promising histopathologic feature for predicting NM in cSCC. The results show a strong association between high TB and NM, supporting its utility as a risk factor for NM in cSCC. Its inclusion in clinical practice and cSCC staging might be helpful in the stratification of high-risk cases and guide optimal management strategies for each patient. However, further investigation is needed to determine standardized reporting guidelines for TB in cSCC.

Exploring the genetic background of the botulism neurotoxin BoNT/B2 in Spain.

To determine whether the neurotoxin BoNT/B2 causing botulism in Spain is clonal, the genetic diversity and phylogenetic relationships of Clostridium botulinum from food-borne episodes and infant cases of the condition were explored. The botulinum toxin gene (bont) subtype, the variable region of the flagellin gene (flaVR), and a seven-gene multi-locus sequence type were examined by sequencing 37 BoNT-positive cultures obtained over the period 2010 to 2022. Out of 37 botulism events, 16 food-borne episodes and 16 infant cases were associated with bont/b2. Eight bont/b2 alleles were detected [nucleotide distance range 0.0259-0.415%, Hunter and Gaston discrimination index (HGDI) 0.71]. The most common bont/b2 allele corresponded to that of strain Prevot 25 NCASE and its single and double locus variations (87.5%). Four known flaVR types were identified (HGDI 0.79), along with one previously unknown (flaVR-15). Sixteen sequence types (STs) (HGDI 0.89) were recorded including seven new STs (ST164-ST170; 10 new alleles) and five new STs (ST171-ST175; with new allele combinations) were also noted. Correlations among some STs and flaVR types were seen. Overall, the present results show that the combined analysis of bont/b2-flaVR-ST at the nucleotide level could be used to track botulism events in Spain. The neurotoxin BoNT/B2 has largely been responsible for human botulism in Spain. The polymorphism analysis of bont/b2, flaVR typing, and sequence type determinations, revealed a wide variety of clones to be responsible for human botulism, ruling out a common source of acquisition. IMPORTANCE Botulism, a potentially fatal disease, is classically characterized by a symmetrical descending flaccid paralysis, which if left untreated can lead to respiratory failure and death. Botulinum neurotoxin (BoNT), produced by certain species of Clostridium, is the most potent biological toxin known, and the direct cause of botulism. This study characterizes the acquisition in Spain of two forms of botulism, i.e., food-borne and infant botulism, which are largely caused by the main neurotoxin BoNT/B2. Polymorphism analysis of the bont/b2 gene, typing of the flagellin variable region sequence (flaVR), and multilocus sequence typing, were used to explore the genetic background of Clostridium botulinum group I. To our knowledge, this is the first phylogenetic and typing study of botulism undertaken in Spain.

Did COVID-19 lockdown delay actually worsen melanoma prognosis?

Abstract Background: The COVID-19 lockdown possibly meant a delay in the diagnosis and treatment of melanoma and therefore, worsening its prognosis. This unique situation of diagnosis deferral is an exceptional opportunity to investigate melanoma biology. Objectives: To evaluate the immediate and mid-term impact of diagnosis delay on melanoma. Methods: A retrospective observational study of melanoma diagnosed between March 14th 2019 and March 13th 2021. We compared the characteristics of melanomas diagnosed during the first 6-month period after the lockdown instauration and a second period after recovery of normal activity with the same periods of the previous year, respectively. Results: A total of 119 melanomas were diagnosed. There were no differences in age, sex, incidence, location, presence of ulceration or mitoses, and in situ/invasive melanoma rate (p > 0.05). After the recovery of the normal activity, Breslow thickness increased in comparison with the previous year (2.4 vs 1.9 mm, p < 0.05) resulting in a significant upstaging according to the AJCC 8th ed. (p < 0.05). Study limitations: The main limitation is that this is a single-center study. Conclusions: The COVID-19 lockdown implied a diagnosis delay leading to a mid-term increase in Breslow thickness and an upstaging of invasive melanomas. However, the detection deferral did not result in a higher progression of in situ to invasive melanoma, in our sample.

Recent advances in sensing the inter-biomolecular interactions at the nanoscale - A comprehensive review of AFM-based force spectroscopy.

Biomolecular interactions underpin most processes inside the cell. Hence, a precise and quantitative understanding of molecular association and dissociation events is crucial, not only from a fundamental perspective, but also for the rational design of biomolecular platforms for state-of-the-art biomedical and industrial applications. In this context, atomic force microscopy (AFM) appears as an invaluable experimental technique, allowing the measurement of the mechanical strength of biomolecular complexes to provide a quantitative characterization of their interaction properties from a single molecule perspective. In the present review, the most recent methodological advances in this field are presented with special focus on bioconjugation, immobilization and AFM tip functionalization, dynamic force spectroscopy measurements, molecular recognition imaging and theoretical modeling. We expect this work to significantly aid in grasping the principles of AFM-based force spectroscopy (AFM-FS) technique and provide the necessary tools to acquaint the type of data that can be achieved from this type of experiments. Furthermore, a critical assessment is done with other nanotechnology techniques to better visualize the future prospects of AFM-FS.

Did COVID-19 lockdown delay actually worsen melanoma prognosis?

BACKGROUND: The COVID-19 lockdown possibly meant a delay in the diagnosis and treatment of melanoma and therefore, worsening its prognosis. This unique situation of diagnosis deferral is an exceptional opportunity to investigate melanoma biology. OBJECTIVES: To evaluate the immediate and mid-term impact of diagnosis delay on melanoma. METHODS: A retrospective observational study of melanoma diagnosed between March 14th 2019 and March 13th 2021. We compared the characteristics of melanomas diagnosed during the first 6-month period after the lockdown instauration and a second period after recovery of normal activity with the same periods of the previous year, respectively. RESULTS: A total of 119 melanomas were diagnosed. There were no differences in age, sex, incidence, location, presence of ulceration or mitoses, and in situ/invasive melanoma rate (p>0.05). After the recovery of the normal activity, Breslow thickness increased in comparison with the previous year (2.4 vs 1.9mm, p<0.05) resulting in a significant upstaging according to the AJCC 8th ed. (p<0.05). STUDY LIMITATIONS: The main limitation is that this is a single-center study. CONCLUSIONS: The COVID-19 lockdown implied a diagnosis delay leading to a mid-term increase in Breslow thickness and an upstaging of invasive melanomas. However, the detection deferral did not result in a higher progression of in situ to invasive melanoma, in our sample.

Early-Life Stress Reprograms Stress-Coping Abilities in Male and Female Juvenile Rats.

Prenatal stress (PS) is a major risk factor for the development of emotional disorders in adulthood that may be mediated by an altered hypothalamic-pituitary-adrenal axis response to stress. Although the early onset of stress-related disorders is recognized as a major public health problem, to date, there are relatively few studies that have examined the incidence of early-life stressors in younger individuals. In this study, we assessed PS impact on the stress-coping response of juvenile offspring in behavioral tests and in the induced molecular changes in the hippocampus. Furthermore, we assessed if pregnancy stress could be driving changes in patterns of maternal behavior during early lactation. We found that PS modified stress-coping abilities of both sex offspring. In the hippocampus, PS increased the expression of bdnf-IV and crfr1 and induced sex difference changes on glucocorticoids and BDNF mRNA receptor levels. PS changed the hippocampal epigenetic landscape mainly in male offspring. Stress during pregnancy enhanced pup-directed behavior of stressed dams. Our study indicates that exposure to PS, in addition to enhanced maternal behavior, induces dynamic neurobehavioral variations at juvenile ages of the offspring that should be considered adaptive or maladaptive, depending on the characteristics of the confronting environment. Our present results highlight the importance to further explore risk factors that appear early in life that will be important to allow timely prevention strategies to later vulnerability to stress-related disorders.

Protein O-Fucosyltransferase 1 Undergoes Interdomain Flexibility in Solution.

Protein O-fucosyltransferase 1 (PoFUT1) is a GT-B fold enzyme that fucosylates proteins containing EGF-like repeats. GT-B glycosyltransferases have shown a remarkable grade of plasticity adopting closed and open conformations as a way of tuning their catalytic cycle, a feature that has not been observed for PoFUT1. Here, we analyzed Caenorhabditis elegans PoFUT1 (CePoFUT1) conformational behavior in solution by atomic force microscopy (AFM) and single-molecule fluorescence resonance energy transfer (SMF-FRET). Our results show that this enzyme is very flexible and adopts mainly compact conformations and to a lesser extend a highly dynamic population that oscillates between compact and highly extended conformations. Overall, our experiments illustrate the inherent complexity of CePoFUT1 dynamics, which might play a role during its catalytic cycle.

Enhanced Molecular Spin-Photon Coupling at Superconducting Nanoconstrictions.

We combine top-down and bottom-up nanolithography to optimize the coupling of small molecular spin ensembles to 1.4 GHz on-chip superconducting resonators. Nanoscopic constrictions, fabricated with a focused ion beam at the central transmission line, locally concentrate the microwave magnetic field. Drops of free-radical molecules have been deposited from solution onto the circuits. For the smallest ones, the molecules were delivered at the relevant circuit areas by means of an atomic force microscope. The number of spins Neff effectively coupled to each device was accurately determined combining Scanning Electron and Atomic Force Microscopies. The collective spin-photon coupling constant has been determined for samples with Neff ranging between 2 × 106 and 1012 spins, and for temperatures down to 44 mK. The results show the well-known collective enhancement of the coupling proportional to the square root of Neff. The average coupling of individual spins is enhanced by more than 4 orders of magnitude (from 4 mHz up to above 180 Hz), when the transmission line width is reduced from 400 µm down to 42 nm, and reaches maximum values near 1 kHz for molecules located on the smallest nanoconstrictions.

Non-invasive biomarkers of fetal brain development reflecting prenatal stress: An integrative multi-scale multi-species perspective on data collection and analysis.

Prenatal stress (PS) impacts early postnatal behavioural and cognitive development. This process of 'fetal programming' is mediated by the effects of the prenatal experience on the developing hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS). We derive a multi-scale multi-species approach to devising preclinical and clinical studies to identify early non-invasively available pre- and postnatal biomarkers of PS. The multiple scales include brain epigenome, metabolome, microbiome and the ANS activity gauged via an array of advanced non-invasively obtainable properties of fetal heart rate fluctuations. The proposed framework has the potential to reveal mechanistic links between maternal stress during pregnancy and changes across these physiological scales. Such biomarkers may hence be useful as early and non-invasive predictors of neurodevelopmental trajectories influenced by the PS as well as follow-up indicators of success of therapeutic interventions to correct such altered neurodevelopmental trajectories. PS studies must be conducted on multiple scales derived from concerted observations in multiple animal models and human cohorts performed in an interactive and iterative manner and deploying machine learning for data synthesis, identification and validation of the best non-invasive detection and follow-up biomarkers, a prerequisite for designing effective therapeutic interventions.

In Vivo and In Vitro Neuronal Plasticity Modulation by Epigenetic Regulators.

Prenatal stress (PS) induces molecular changes that alter neural connectivity, increasing the risk for neuropsychiatric disorders. Here we analyzed -in the hippocampus of adult rats exposed to PS- the epigenetic signature mediating the PS-induced neuroplasticity changes. Furthermore, using cultured hippocampal neurons, we investigated the effects on neuroplasticity of an epigenetic modulator. PS induced significant modifications in the mRNA levels of stress-related transcription factor MEF2A, SUV39H1 histone methyltransferase, and TET1 hydroxylase, indicating that PS modifies gene expression through chromatin remodeling. In in vitro analysis, histone acetylation inhibition with apicidin increased filopodium density, suggesting that the external regulation of acetylation levels might modulate neuronal morphology. These results offer a way to enhance neural connectivity that could be considered to revert PS effects.

Prenatal stress increases adult vulnerability to cocaine reward without affecting pubertal anxiety or novelty response.

Prenatal stress (PS) induces long-lasting molecular alterations in brain circuits of the offspring and increases the propensity to develop neuropsychiatric diseases during adulthood, including mood disorders and drug addiction. A major goal of this study was to assess the impact of PS on pubertal behaviour and adult vulnerability to cocaine-induced conditioning place preference (CPP). We therefore evaluated pubertal novelty response and anxiety-like behaviour in control (C) and PS rats, and then, we examined cocaine-induced CPP in those animals during adulthood. We found no differences between C and PS groups on pubertal behaviour, however, only PS rats showed a significant cocaine-induced CPP. To further analyze our results, we classified cocaine-treated rats regarding their CPP score in Low CPP or High CPP and we then analysed their pubertal behaviour. We found different relations of anxiety-like behaviour to cocaine reward as a function of PS exposure: for C group, High CPP and Low CPP had shown similar levels of anxiety-like behaviour at puberty; on the contrary, for PS group, High CPP had shown lower anxiety-like behaviour than Low CPP rats. This study underscores the importance of considering prenatal exposure to stress when analysing the relationship between anxiety and cocaine vulnerability. Moreover, the evaluation of behavioural traits at puberty opens the possibility of early intervention and will allow the development of specific prevention strategies to avoid the devastating consequences of drug addiction later in life.

Molecular basis for the integration of environmental signals by FurB from Anabaena sp. PCC 7120.

FUR (Ferric uptake regulator) proteins are among the most important families of transcriptional regulators in prokaryotes, often behaving as global regulators. In the cyanobacterium Anabaena PCC 7120, FurB (Zur, Zinc uptake regulator) controls zinc and redox homeostasis through the repression of target genes in a zinc-dependent manner. In vitro, non-specific binding of FurB to DNA elicits protection against oxidative damage and avoids cleavage by deoxyribonuclease I. The present study provides, for the first time, evidence of the influence of redox environment in the interaction of FurB with regulatory zinc and its consequences in FurB-DNA-binding affinity. Calorimetry studies showed that, in addition to one structural Zn(II), FurB is able to bind two additional Zn(II) per monomer and demonstrated the implication of cysteine C93 in regulatory Zn(II) coordination. The interaction of FurB with the second regulatory zinc occurred only under reducing conditions. While non-specific FurB-DNA interaction is Zn(II)-independent, the optimal binding of FurB to target promoters required loading of two regulatory zinc ions. Those results combined with site-directed mutagenesis and gel-shift assays evidenced that the redox state of cysteine C93 conditions the binding of the second regulatory Zn(II) and, in turn, modulates the affinity for a specific DNA target. Furthermore, differential spectroscopy studies showed that cysteine C93 could also be involved in heme coordination by FurB, either as a direct ligand or being located near the binding site. The results indicate that besides controlling zinc homeostasis, FurB could work as a redox-sensing protein probably modifying its zinc and DNA-binding abilities depending upon environmental conditions.

Glutaminolysis drives membrane trafficking to promote invasiveness of breast cancer cells.

The role of glutaminolysis in providing metabolites to support tumour growth is well-established, but the involvement of glutamine metabolism in invasive processes is yet to be elucidated. Here we show that normal mammary epithelial cells consume glutamine, but do not secrete glutamate. Indeed, low levels of extracellular glutamate are necessary to maintain epithelial homoeostasis, and provision of glutamate drives disruption of epithelial morphology and promotes key characteristics of the invasive phenotype such as lumen-filling and basement membrane disruption. By contrast, primary cultures of invasive breast cancer cells convert glutamine to glutamate which is released from the cell through the system Xc- antiporter to activate a metabotropic glutamate receptor. This contributes to the intrinsic aggressiveness of these cells by upregulating Rab27-dependent recycling of the transmembrane matrix metalloprotease, MT1-MMP to promote invasive behaviour leading to basement membrane disruption. These data indicate that acquisition of the ability to release glutamate is a key watershed in disease aggressiveness.

Prenatal Stress and Neurodevelopmental Plasticity: Relevance to Psychopathology.

Prenatal development constitutes a critical time for shaping adult behaviour and may set the stage for vulnerability to disease later in life. A wealth of information from humans as well as from animal research has revealed that exposure to hostile conditions during gestation may result in a series of coordinated biological responses aimed at enhancing the probability of survival, but could also increase the susceptibility to mental illness. Prenatal stress has been linked to abnormal cognitive, behavioural and psychosocial outcomes both in animals and in humans, but the underlying molecular and physiological mechanisms remain largely unknown. In this chapter, we shall review experimental data from studies reported for rats, since more information is available for them than for other species. The major focus of the present chapter is to update and discuss data on behavioural, functional and morphological effects of prenatal stress in rats that may have counterparts in prospective and/or retrospective studies of gestational stress in humans. This work contributes to understanding the role of neuronal plasticity in the long-term effects of developmental adversity on brain function and its implications for vulnerability to disease.

Long-term consequences of prenatal stress and neurotoxicants exposure on neurodevelopment.

There is a large consensus that the prenatal environment determines the susceptibility to pathological conditions later in life. The hypothesis most widely accepted is that exposure to insults inducing adverse conditions in-utero may have negative effects on the development of target organs, disrupting homeostasis and increasing the risk of diseases at adulthood. Several models have been proposed to investigate the fetal origins of adult diseases, but although these approaches hold true for almost all diseases, particular attention has been focused on disorders related to the central nervous system, since the brain is particularly sensitive to alterations of the microenvironment during early development. Neurobiological disorders can be broadly divided into developmental, neurodegenerative and neuropsychiatric disorders. Even though most of these diseases share genetic risk factors, the onset of the disorders cannot be explained solely by inheritance. Therefore, current understanding presumes that the interactions of environmental input, may lead to different disorders. Among the insults that can play a direct or indirect role in the development of neurobiological disorders are stress, infections, drug abuse, and environmental contaminants. Our laboratories have been involved in the study of the neurobiological impact of gestational stress on the offspring (Dr. Antonelli's lab) and on the effect of gestational exposure to toxicants, mainly methyl mercury (MeHg) and perfluorinated compounds (PFCs) (Dr. Ceccatelli's lab). In this focused review, we will review the specialized literature but we will concentrate mostly on our own work on the long term neurodevelopmental consequences of gestational exposure to stress and neurotoxicants.

Unravelling the Link Between Prenatal Stress, Dopamine and Substance Use Disorder.

Substance use disorder (SUD) refers to the detrimental use of psychoactive substances and it is related to a cluster of behavioural, cognitive and physiological dysfunctions indicating that the individual continues using the substance despite significant substance-related problems. Although it is one of the most prevalent neuropsychiatric diseases affecting society worldwide, the mechanism underlying the vulnerability of certain individuals is not well understood yet. It is now widely accepted that, in addition to genetic factors, environmental adversities during critical stages of development of an organism could also be considered as risk factors that contribute to SUD. It has been suggested that prenatal stress (PS) could play an important role in the causal mechanisms of SUD, since it was shown that PS leads individuals to poor stress management and behavioural problems, both of which increase the risk of SUD. It is widely accepted that gestational stress exposure in rats interferes with the correct progeny development. In particular, research in this field points out that the development of the mesocorticolimbic dopaminergic (DA) system is sensitive to disruption by exposure to early stressors. Interestingly, PS induces behavioural abnormalities that are similar to those observed in individuals that present SUD. Since dysfunction of mesocorticolimbic DA pathway has been reported in both prenatally stressed and SUD individuals, in this review we will summarise the current knowledge supporting that PS may serve as a strong candidate to explain the vulnerability of certain individuals to develop SUD following repeated drug exposure. We will also propose a mechanistic hypothesis to explain PS-induced changes on mesocorticolimbic DA system.

A proactive role of water molecules in acceptor recognition by protein O-fucosyltransferase 2.

Protein O-fucosyltransferase 2 (POFUT2) is an essential enzyme that fucosylates serine and threonine residues of folded thrombospondin type 1 repeats (TSRs). To date, the mechanism by which this enzyme recognizes very dissimilar TSRs has been unclear. By engineering a fusion protein, we report the crystal structure of Caenorhabditis elegans POFUT2 (CePOFUT2) in complex with GDP and human TSR1 that suggests an inverting mechanism for fucose transfer assisted by a catalytic base and shows that nearly half of the TSR1 is embraced by CePOFUT2. A small number of direct interactions and a large network of water molecules maintain the complex. Site-directed mutagenesis demonstrates that POFUT2 fucosylates threonine preferentially over serine and relies on folded TSRs containing the minimal consensus sequence C-X-X-S/T-C. Crystallographic and mutagenesis data, together with atomic-level simulations, uncover a binding mechanism by which POFUT2 promiscuously recognizes the structural fingerprint of poorly homologous TSRs through a dynamic network of water-mediated interactions.

[Surveillance of resistance of Staphylococcus aureus to antibiotics in Galicia: 2007-2012]. / Vigilancia de la resistencia a los antibióticos en Staphylococcus aureus en Galicia: 2007-2012.

INTRODUCTION: Since 2007 the Galician Surveillance Program on Antimicrobial Resistance has been collected data of Staphylococcus aureus susceptibility patterns. The data from 2007 to 2012 have been analyzed and are reported. METHODS: A total of 4,577 different isolates of S. aureus from cerebrospinal fluid and blood cultures were included. The Institutions involved provided the information about the susceptibility patterns, the assay methods used and the interpretative guidelines followed, and demographic data of patients. RESULTS: The rate of methicillin-resistance S. aureus (MRSA) was 22% in 2007-2010 and 26% in 2011-2012, although in some areas the percentage reached 57% (2007- 2010) or 66% (2011-2012). The higher rates of resistance were found in patients older than 75 years. Gentamycin resistance was less than 9% and for quinolones were about 25%. A strong association between methicillin and quinolone-resistance were observed (91%). The resistance against linezolid and glycopeptides were exceptional. CONCLUSIONS: The percentage of MRSA has evolved slightly along the period of this study reaching no significant differences between Galicia and the global data in Spain in 2012. Nevertheless, there are significant differences among the geographic areas studied. Most MRSA isolates were recovered from hospitalized patients, but an increase in the number of MRSA among outpatients was observed, while old patients from nursing homes are included in the outpatient group, so the MRSA rate in this group could be overestimated.

Vigilancia de la resistencia a los antibióticos en Staphylococcus aureus en Galicia: 2007-2012 / Surveillance of resistance of Staphylococcus aureus to antibiotics in Galicia: 2007-2012

Introducción. Desde 2007 el Programa Gallego de Vigilancia de Resistencias Antimicrobianas recogió datos de los patrones de sensibilidad de Staphylococcus aureus. Se analizaron e informaron los datos entre 2007 y 2012. Métodos. Se incluyeron 4.577 aislamientos de S. aureus procedentes de líquido cefalorraquídeo o de sangre. Los distintos centros enviaron información sobre los patrones de sensibilidad, los métodos de ensayo, los criterios de interpretación seguidos y datos demográficos de los pacientes. Resultados. El porcentaje de aislamientos S. aureus resistentes a meticillina (SARM) fue del 22% (2007-2010) y del 26% (2011-2012), aunque en determinada área el porcentaje alcanzó el 57% (2007-2010) o 66% (2011-2012). Las tasas más altas de resistencias se encontraron en los mayores de 75 años. La resistencia a gentamicina fue menor del 9% y la de quinolonas sobre el 25%. Existe fuerte asociación entre resistencias a meticilina y quinolonas (91%). La resistencia frente a linezolid y glicopéptidos fue excepcional. Conclusiones. El porcentaje de SARM a lo largo del periodo de estudio ha presentado ciertas fluctuaciones alcanzándose en 2012 una situación similar en Galicia a la del conjunto de España. No obstante, hay importantes diferencias entre las áreas geográficas estudiadas. La mayoría de los SARM fueron aislados en pacientes hospitalizados, pero se observó un incremento entre ambulatorios. Dado que los pacientes mayores institucionalizados fueron incluidos en el grupo de los ambulatorios es posible que las tasas de SARM en este grupo hayan sido sobreestimadas (AU)

Introduction. Since 2007 the Galician Surveillance Program on Antimicrobial Resistance has been collected data of Staphylococcus aureus susceptibility patterns. The data from 2007 to 2012 have been analyzed and are reported. Methods. A total of 4,577 different isolates of S. aureus from cerebrospinal fluid and blood cultures were included. The Institutions involved provided the information about the susceptibility patterns, the assay methods used and the interpretative guidelines followed, and demographic data of patients. Results. The rate of methicillin-resistance S. aureus (MRSA) was 22% in 2007-2010 and 26% in 2011-2012, although in some areas the percentage reached 57% (2007-2010) or 66% (2011-2012). The higher rates of resistance were found in patients older than 75 years. Gentamycin resistance was less than 9% and for quinolones were about 25%. A strong association between methicillin and quinolone-resistance were observed (91%). The resistance against linezolid and glycopeptides were exceptional. Conclusions. The percentage of MRSA has evolved slightly along the period of this study reaching no significant differences between Galicia and the global data in Spain in 2012. Nevertheless, there are significant differences among the geographic areas studied. Most MRSA isolates were recovered from hospitalized patients, but an increase in the number of MRSA among outpatients was observed, while old patients from nursing homes are included in the outpatient group, so the MRSA rate in this group could be overestimated (AU)

Glutamate neurotransmission is affected in prenatally stressed offspring.

Previous studies from our laboratory have shown that male adult offspring of stressed mothers exhibited higher levels of ionotropic and metabotropic glutamate receptors than control rats. These offspring also showed long-lasting astroglial hypertrophy and a reduced dendritic arborization with synaptic loss. Since metabolism of glutamate is dependent on interactions between neurons and surrounding astroglia, our results suggest that glutamate neurotransmitter pathways might be impaired in the brain of prenatally stressed rats. To study the effect of prenatal stress on the metabolism and neurotransmitter function of glutamate, pregnant rats were subjected to restrain stress during the last week of gestation. Brains of the adult offspring were used to assess glutamate metabolism, uptake and release as well as expression of glutamate receptors and transporters. While glutamate metabolism was not affected it was found that prenatal stress (PS) changed the expression of the transporters, thus, producing a higher level of vesicular vGluT-1 in the frontal cortex (FCx) and elevated levels of GLT1 protein and messenger RNA in the hippocampus (HPC) of adult male PS offspring. We also observed increased uptake capacity for glutamate in the FCx of PS male offspring while no such changes were observed in the HPC. The results show that changes mediated by PS on the adult glutamatergic system are brain region specific. Overall, PS produces long-term changes in the glutamatergic system modulating the expression of glutamate transporters and altering synaptic transmission of the adult brain.