Recommendations of the Society of Thoracic Surgery and the Section of Cardiothoracic and Vascular Surgery of the Spanish Society of Anesthesia, Resuscitation and Pain Therapy, for patients undergoing lung surgery included in an intensified recovery program.

In recent years, multidisciplinary programs have been implemented that include different actions during the pre, intra and postoperative period, aimed at reducing perioperative stress and therefore improving the results of patients undergoing surgical interventions. Initially, these programs were developed for colorectal surgery and from there they have been extended to other surgeries. Thoracic surgery, considered highly complex, like other surgeries with a high postoperative morbidity and mortality rate, may be one of the specialties that most benefit from the implementation of these programs. This review presents the recommendations made by different specialties involved in the perioperative care of patients who require resection of a lung tumor. Meta-analyzes, systematic reviews, randomized and non-randomized controlled studies, and retrospective studies conducted in patients undergoing this type of intervention have been taken into account in preparing the recommendations presented in this guide. The GRADE scale has been used to classify the recommendations, assessing on the one hand the level of evidence published on each specific aspect and, on the other hand, the strength of the recommendation with which the authors propose its application. The recommendations considered most important for this type of surgery are those that refer to pre-habilitation, minimization of surgical aggression, excellence in the management of perioperative pain and postoperative care aimed at providing rapid postoperative rehabilitation.

Gut microbiota alterations in critically ill older patients: a multicenter study.

BACKGROUND: Aging generates changes in the gut microbiota, affecting its functionality. Little is known about gut microbiota in critically ill older adults. The objective of this study was to describe the profile of gut microbiota in a cohort of critically ill older adults. METHODS: This observational study was conducted in five health institutions. Over a 6-month study period, critically ill patients over 18 years old who were admitted to the intensive care unit were enrolled. Fecal microbiota profiles were determined from 155 individuals, over 60 years old (n = 72) and under 60 years old (n = 83). Gut microbiota was analyzed by sequencing the V3-V4 region of the 16S rRNA gene. Alpha and beta diversity, operational taxonomic units and the interaction of gut microbiota with variables under study were analyzed. Amplicon sequence variants (ASVs) specifically associated with age were recovered by including gender, discharge condition, BMI, ICU stay and antibiotics as covariates in a linear mixed model. RESULTS: In older adults, sepsis, malnutrition, antibiotic prescription and severity (APACHE and SOFA scores) were higher than in the group under 60 years of age. Alpha diversity showed lower gut microbiota diversity in those over 60 years of age (p < 0.05); beta diversity evidenced significant differences between the groups (PERMANOVA = 1.19, p = 0.038). The microbiota of the adults under 60 years old showed greater abundance of Murdochiella, Megasphaera, Peptoniphilus and Ezakiella, whereas those over 60 years old Escherichia-Shigella and Hungatella were more abundant. CONCLUSION: The gut microbial community was altered by different factors; however, age significantly explained the variability in critically ill patients. A lower presence of beneficial genera and a higher abundance of pathogens was observed in adults over 60 years old.

Afrontamiento y adaptación en cuidadores principales de niños hospitalizados, según el modelo de Callista Roy / Coping and adaptation in primary caregivers of hospitalized children, based on Callista Roy's model / Enfrentamento e adaptação em cuidadores primários de crianças hospitalizadas, segundo o modelo Callista Roy

Objetivo: identificar el nivel de afrontamiento y adaptación de los cuidadores principales de niños hospitalizados en dos centros de Medellín, desde el modelo Callista Roy, durante el año 2019. Metodología: estudio transversal descriptivo prospectivo. El tamaño de muestra fue de 400 cuidadores principales. Se incluyeron mayores de 18 años, quienes firmaron el consentimiento informado. Se utilizó una encuesta sociodemográfica y la Escala de Medición del Proceso de Afrontamiento y Adaptación, versión en español (EsCAPS, abreviada), previa autorización. Las variables cualitativas se presentan en frecuencias absolutas y relativas, y las cuantitativas en mediana acompañada del rango intercuartílico (RIC). Resultados: todos los cuidadores eran mujeres, con mediana de edad de 30 años y RIC 25-37, 119 (29,5%) tenían un nivel educativo técnico y tecnólogo, su estrato socioeconómico estaba entre los estratos uno, dos y tres (84.6%). De ellas, 160 (39.7%) vivían en unión libre. En cuanto a los niños, la mediana de edad fue de 24 meses (RIC 2-72). El diagnóstico principal fue de afecciones respiratorias, 113/398 (28.4%). La mediana del puntaje de afrontamiento global fue 56 (RIC 50-60), lo que ubica a la mayoría en un nivel de afrontamiento bajo. Conclusión: los cuidadores principales de niños hospitalizados tienen un grado bajo de afrontamiento, es necesario fortalecer los planes de cuidado para mejorar el bienestar de los cuidadores.

Objective: To identify the level of coping and adaptation of primary caregivers of hos-pitalized children during 2019 in two centers of Medellin, based on Callista Roy's model.Methodology: Prospective descriptive cross-sectional study. The sample size was made up of 400 primary caregivers. Participants over 18 years who signed the informed consent were included. A sociodemographic survey and the Coping Adaptation Processing Scale version in Spanish (abbreviated EsCAPS) were used, with prior authorization. Qualitative variables were expressed in absolute and relative frequencies, while quantitative ones were expressed using median and interquartile range (IQR).Results: All the caregivers were women, with a median age of 30 years and IQR: 25-37. 119 (29.5%) were technicians and technologists, who belonged to socioeconomic strata 1, 2, and 3 (84.6%). 160 (39.7%) of them lived in a common-law marriage. Amongst hospitalized children, the median age was 24 months and the IQR 2-72; the most frequent diagnosis was respiratory disorders, 113/398 (28.4%). The median global score was 56, with an IQR of 50-60, placing most of them in a low coping level.Conclusion: Primary caregivers of hospitalized children have a low level of coping. It is necessary to strengthen the care plans for the welfare of caregivers.

Objetivo: identificar o nível de enfrentamento e adaptação dos cuidadores principais de crianças hospitalizadas em dois centros de Medellín, a partir do modelo Callista Roy, durante 2019.Metodologia: estudo transversal descritivo prospectivo. O tamanho da amostra foi de 400 cuidadores principais. Foram incluídos os maiores de 18 anos que assinaram o Termo de Consentimento Livre e Esclarecido. Utilizou-se um levantamento sociodemográfico e a Escala de Medição do Processo de Enfrentamento e Adaptação, versão em espanhol (EsCAPS, abreviatura), com autorização prévia. As variáveis qualitativas são apresentadas em frequências absolutas e relativas e as variáveis quantitativas em mediana acompan-hadas do intervalo interquartil (IQR).Resultados: todos os cuidadores eram mulheres, com mediana de idade de 30 anos e IQR 25-37, 119 (29,5%) possuíam escolaridade técnica e tecnológica, estrato socioe-conômico entre os estratos um, dois e três (84,6%). Destes, 160 (39,7%) viviam em união estável. Em relação às crianças, a mediana de idade foi de 24 meses (IQR 2-72). O diagnóstico principal foram doenças respiratórias, 113/398 (28,4%). A pontuação geral mediana de enfrentamento foi de 56 (IQR 50-60), o que coloca a maioria em um nível de enfrentamento baixo.Conclusão: os cuidadores principais de crianças hospitalizadas apresentam baixo grau de enfrentamento, é necessário fortalecer os planos de cuidado para melhorar o bem-estar dos cuidadores.

Recommendations of the Society of Thoracic Surgery and the Section of Cardiothoracic and Vascular Surgery of the Spanish Society of Anesthesia, Resuscitation and Pain Therapy, for patients undergoing lung surgery included in an intensified recovery program. / Recomendaciones de la Sociedad Española de Cirugía Torácica y de la Sección de Cardiotorácica y Cirugía Vascular de la Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor, para los pacientes sometidos a cirugía pulmonar incluidos en un programa de recuperación intensificada.

In recent years, multidisciplinary programs have been implemented that include different actions during the pre, intra and postoperative period, aimed at reducing perioperative stress and therefore improving the results of patients undergoing surgical interventions. Initially, these programs were developed for colorectal surgery and from there they have been extended to other surgeries. Thoracic surgery, considered highly complex, like other surgeries with a high postoperative morbidity and mortality rate, may be one of the specialties that most benefit from the implementation of these programs. This review presents the recommendations made by different specialties involved in the perioperative care of patients who require resection of a lung tumor. Meta-analyses, systematic reviews, randomized and non-randomized controlled studies, and retrospective studies conducted in patients undergoing this type of intervention have been taken into account in preparing the recommendations presented in this guide. The GRADE scale has been used to classify the recommendations, assessing on the one hand the level of evidence published on each specific aspect and, on the other hand, the strength of the recommendation with which the authors propose its application. The recommendations considered most important for this type of surgery are those that refer to pre-habilitation, minimization of surgical aggression, excellence in the management of perioperative pain and postoperative care aimed at providing rapid postoperative rehabilitation.

Impact of Pneumococcal Vaccination in the Nasopharyngeal Carriage of Streptococcus pneumoniae in Healthy Children of the Murcia Region in Spain.

BACKGROUND: An epidemiological study of Streptococcus pneumoniae nasopharyngeal carriage in healthy children was carried out five years after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13). OBJECTIVES: Study the impact of pediatric vaccination with PCV13, and other associated epidemiological factors on the status of nasopharyngeal carriage, the circulating pneumococcal serotypes, and the antibiotic susceptibility to more frequently used antibiotics. METHODS: A multi-center study was carried out in Primary Health Care, which included 1821 healthy children aged 1 to 4 years old. All isolates were sent to the Spanish Pneumococcal Reference Laboratory for serotyping and antimicrobial susceptibility testing. RESULTS: At least one dose of PCV13 had been received by 71.9% of children and carriage pneumococcal prevalence was 19.7%. The proportion of PCV13 serotypes was low (14.4%), with an observed predominance of non-vaccine serotypes, 23B, 11A, 10A, 35B/F, and 23A were the five most frequent. A high rate of resistance to penicillin, erythromycin, and trimethoprim sulfamethoxazole was found. CONCLUSIONS: A low proportion of PCV13 serotypes were detected, confirming the impact of pediatric vaccination for reducing the serotypes vaccine carriage. High resistance rates to clinically important antibiotics were observed.

A Risk Assessment Framework for Seed Degeneration: Informing an Integrated Seed Health Strategy for Vegetatively Propagated Crops.

Pathogen buildup in vegetative planting material, termed seed degeneration, is a major problem in many low-income countries. When smallholder farmers use seed produced on-farm or acquired outside certified programs, it is often infected. We introduce a risk assessment framework for seed degeneration, evaluating the relative performance of individual and combined components of an integrated seed health strategy. The frequency distribution of management performance outcomes was evaluated for models incorporating biological and environmental heterogeneity, with the following results. (1) On-farm seed selection can perform as well as certified seed, if the rate of success in selecting healthy plants for seed production is high; (2) when choosing among within-season management strategies, external inoculum can determine the relative usefulness of 'incidence-altering management' (affecting the proportion of diseased plants/seeds) and 'rate-altering management' (affecting the rate of disease transmission in the field); (3) under severe disease scenarios, where it is difficult to implement management components at high levels of effectiveness, combining management components can be synergistic and keep seed degeneration below a threshold; (4) combining management components can also close the yield gap between average and worst-case scenarios. We also illustrate the potential for expert elicitation to provide parameter estimates when empirical data are unavailable. [Formula: see text] Copyright © 2017 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

Multiparametric evaluation of preoperative MRI in early stage breast cancer: prognostic impact of peri-tumoral fat

Purpose. Obesity is associated with adverse outcomes in breast cancer patients. Fat-specific cytokines (adipokines) have been proposed as key drivers of breast cancer progression, invasion, and metastasis. We aimed at assessing correlations between peri-tumoral fat, quantified on magnetic resonance imaging (MRI) and pathologic factors potentially impacting therapy recommendations. Methods. We retrospectively reviewed records of 63 patients with early stage breast cancer who underwent preoperative MRI imaging using appropriately weighted series for breast and tumor contouring. Fat volumes were generated through voxel intensity filtering. The peri-tumoral region was defined as the intersection of a 1-cm spherical extension around the tumor and the breast contour. Peri-tumoral fat was defined as the fraction of a fat content in this volume. Surgical pathology records were used to extract clinical data. Statistical analyses were conducted using Pearson and Spearman correlation coefficients. Results. Among reviewed patients, 45 had T1 tumors (1.22 ± 0.85 cm diameter) and 18 had T2 tumors (2.08 ± 1.06 cm). Axillary lymph nodes were dissected in 31 and positive in 17 patients analyzed. Peri-tumoral fat ratio ranged between 25 and 99 %. Peri-tumoral fat ratio significantly correlated with the nodal-positive ratio of positive axillary lymph nodes (r = 0.532). Peri-tumoral fat ratio demonstrated optimally prominent correlation among obese patients upon body mass index categorical stratification. Conclusions. In women with early stage breast cancer, peri-tumoral fat correlates positively with the ratio of pathologically involved axillary nodes. This work highlights a novel method for quantitating peri-tumoral fat content. Preoperative breast MRI may be utilized to predict extent of axillary disease (AU)

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Cerebral Temperature Dysregulation: MR Thermographic Monitoring in a Nonhuman Primate Study of Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Cerebral thermoregulation remains poorly understood. Temperature dysregulation is deeply implicated in the potentiation of cerebrovascular ischemia. We present a multiphasic, MR thermographic study in a nonhuman primate model of MCA infarction, hypothesizing detectable brain temperature disturbances and brain-systemic temperature decoupling. MATERIALS AND METHODS: Three Rhesus Macaque nonhuman primates were sourced for 3-phase MR imaging: 1) baseline MR imaging, 2) 7-hour continuous MR imaging following minimally invasive, endovascular MCA stroke induction, and 3) poststroke day 1 MR imaging follow-up. MR thermometry was achieved by multivoxel spectroscopy (semi-localization by adiabatic selective refocusing) by using the proton resonance frequency chemical shift. The relationship of brain and systemic temperatures with time and infarction volumes was characterized by using a mixed-effects model. RESULTS: Following MCA infarction, progressive cerebral hyperthermia was observed in all 3 subjects, significantly outpacing systemic temperature fluctuations. Highly significant associations were observed for systemic, hemispheric, and global brain temperatures (F-statistic, P = .0005 for all regressions) relative to the time from stroke induction. Significant differences in the relationship between temperature and time following stroke onset were detected when comparing systemic temperatures with ipsilateral (P = .007), contralateral (P = .004), and infarction core (P = .003) temperatures following multiple-comparisons correction. Significant associations were observed between infarction volumes and both systemic (P ≤ .01) and ipsilateral (P = .04) brain temperatures, but not contralateral brain temperature (P = .08). CONCLUSIONS: Successful physiologic and continuous postischemic cerebral MR thermography was conducted and prescribed in a nonhuman primate infarction model to facilitate translatability. The results confirm hypothesized temperature disturbance and decoupling of physiologic brain-systemic temperature gradients. These findings inform a developing paradigm of brain thermoregulation and the applicability of brain temperature as a neuroimaging biomarker in CNS injury.

Multiparametric evaluation of preoperative MRI in early stage breast cancer: prognostic impact of peri-tumoral fat.

PURPOSE: Obesity is associated with adverse outcomes in breast cancer patients. Fat-specific cytokines (adipokines) have been proposed as key drivers of breast cancer progression, invasion, and metastasis. We aimed at assessing correlations between peri-tumoral fat, quantified on magnetic resonance imaging (MRI) and pathologic factors potentially impacting therapy recommendations. METHODS: We retrospectively reviewed records of 63 patients with early stage breast cancer who underwent preoperative MRI imaging using appropriately weighted series for breast and tumor contouring. Fat volumes were generated through voxel intensity filtering. The peri-tumoral region was defined as the intersection of a 1-cm spherical extension around the tumor and the breast contour. Peri-tumoral fat was defined as the fraction of a fat content in this volume. Surgical pathology records were used to extract clinical data. Statistical analyses were conducted using Pearson and Spearman correlation coefficients. RESULTS: Among reviewed patients, 45 had T1 tumors (1.22 ± 0.85 cm diameter) and 18 had T2 tumors (2.08 ± 1.06 cm). Axillary lymph nodes were dissected in 31 and positive in 17 patients analyzed. Peri-tumoral fat ratio ranged between 25 and 99 %. Peri-tumoral fat ratio significantly correlated with the nodal-positive ratio of positive axillary lymph nodes (r = 0.532). Peri-tumoral fat ratio demonstrated optimally prominent correlation among obese patients upon body mass index categorical stratification. CONCLUSIONS: In women with early stage breast cancer, peri-tumoral fat correlates positively with the ratio of pathologically involved axillary nodes. This work highlights a novel method for quantitating peri-tumoral fat content. Preoperative breast MRI may be utilized to predict extent of axillary disease.

Clinical protocol for the management of malignant hyperthermia. / Protocolo clínico asistencial de manejo de la hipertermia maligna.

Malignant hyperthermia is a hypermetabolic syndrome that appears in susceptible patients after exposure to certain anaesthetic drugs (succinylcholine, inhalation anaesthetics). Its incidence in Spain is 1 in 40,000 adults, with a 10% mortality rate. It is induced by an abnormal regulation of the ryanodine receptors, producing a massive release of calcium from the sarcoplasmic reticulum in the striate muscle. Clinical manifestations include: CO2 increase, tachycardia, haemodynamic instability, metabolic and respiratory acidosis, profuse sweating, hyperpyrexia, CPK increase, myoglobinuria, kidney failure, disseminated intravascular coagulation (DIC), and ending in cardiac arrest. Dantrolene sodium is a ryanodine receptor antagonist, and inhibits the release of intracellular calcium. Definitive diagnosis is achieved by the exposure of muscle fibres to caffeine and halothane. Protocols can help guarantee a reliable and secure management when this severe event occurs.

Tissue-type plasminogen activator induces synaptic vesicle endocytosis in cerebral cortical neurons.

The release of the serine proteinase tissue-type plasminogen activator (tPA) from the presynaptic terminal of cerebral cortical neurons plays a central role in the development of synaptic plasticity, adaptation to metabolic stress and neuronal survival. Our earlier studies indicate that by inducing the recruitment of the cytoskeletal protein ßII-spectrin and voltage-gated calcium channels to the active zone, tPA promotes Ca(2+)-dependent translocation of synaptic vesicles (SVs) to the synaptic release site where they release their load of neurotransmitters into the synaptic cleft. Here we used a combination of in vivo and in vitro experiments to investigate whether this effect leads to depletion of SVs in the presynaptic terminal. Our data indicate that tPA promotes SV endocytosis via a mechanism that does not require the conversion of plasminogen into plasmin. Instead, we show that tPA induces calcineurin-mediated dynamin I dephosphorylation, which is followed by dynamin I-induced recruitment of the actin-binding protein profilin II to the presynaptic membrane, and profilin II-induced F-actin formation. We report that this tPA-induced sequence of events leads to the association of newly formed SVs with F-actin clusters in the endocytic zone. In summary, the data presented here indicate that following the exocytotic release of neurotransmitters tPA activates the mechanism whereby SVs are retrieved from the presynaptic membrane and endocytosed to replenish the pool of vesicles available for a new cycle of exocytosis. Together, these results indicate that in murine cerebral cortical neurons tPA plays a central role coupling SVs exocytosis and endocytosis.

An Enhanced Model of Middle Cerebral Artery Occlusion in Nonhuman Primates Using an Endovascular Trapping Technique.

BACKGROUND AND PURPOSE: Current nonhuman primate stroke models are limited by either stroke variability or survivability. A new nonhuman primate stroke model was developed by using endovascular trapping techniques to limit collateral vessels with serial MR imaging and neurologic assessments. MATERIALS AND METHODS: Eight adult rhesus monkeys (female, 7-13 years of age) underwent MR imaging and Spetzler neurologic assessment followed by endovascular stroke induction consisting of superselective endovascular placement of surgical silk sutures into the right MCA by using a trapping technique. Two initial subjects were euthanized immediately following postocclusion MR imaging. The subsequent 6 subjects recovered and underwent follow-up MR imaging and Spetzler neurologic assessments at 48 hours, with 4 being followed to 96 hours. Stroke infarct volumes were measured, and the longitudinal Spetzler clinical neurologic scores were assessed. The brain tissues were harvested and prepared with hematoxylin-eosin staining. RESULTS: Focal permanent cerebral ischemia was induced in the targeted right MCA territory in all subjects. The volumes of the ischemic lesions at 6, 48, and 96 hours were 3.18 ± 1.007 mL (standard error of the mean) (n = 8), 6.70 ± 1.666 mL (standard error of the mean) (n = 6), and 7.23 ± 1.371 mL (standard error of the mean) (n = 4). For the survival animals, the immediate postsurgical Spetzler grading score improved from 60.7 at 24 hours to 68.7 at 48 hours. CONCLUSIONS: We report a trapping modification to an established endovascular suture stroke model that yielded reproducible ischemia and clinically quantifiable neurologic deficits with no strokes in nontarget areas. This technique may be useful in evaluating translational stroke and penumbral imaging research in addition to preclinical testing of neuroprotective therapies.

Application of a topical vapocoolant spray decreases pain at the site of initial intradermal anaesthetic injection during ultrasound-guided breast needle biopsy.

AIM: To assess whether the application of a topical vapocoolant spray immediately prior to initial intradermal anaesthetic injection during ultrasound-guided breast biopsy decreases pain at the site of the initial injection. MATERIALS AND METHODS: In this institutional review board-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant study, 50 women aged 49.1 ± 1.6 years (mean ± standard error) were recruited and provided written informed consent. Participants served as their own controls and were blinded as to whether a topical vapocoolant spray or a placebo was used immediately prior to the initial local anaesthetic injection at two separate biopsy sites. With the exception of the application of vapocoolant or placebo, the entire ultrasound-guided procedure was performed according to a routine protocol. Participants recorded pain at initial injection site on a visual analogue scale. General linear mixed models for repeated measures analysis of variance and a 0.05 significance level were used. RESULTS: Application of topical vapocoolant spray was shown to significantly decrease pain at the site of initial intradermal anaesthetic injection as compared to placebo (p<0.001). Treatment effect was independent of age of the subject, race/ethnicity, operator, type of biopsy device, and histopathology result. No complications from vapocoolant spray use were reported. CONCLUSION: Application of a topical vapocoolant spray immediately prior to initial intradermal anaesthetic injection during ultrasound-guided breast biopsy significantly decreases pain at the site of the initial injection and could contribute to improve the patient's overall procedural experience.

[Antibiotic susceptibility of Streptococcus pneumoniae in healthy carrier children in Murcia (Spain)]. / Sensibilidad de Streptococcus pneumoniae en niños portadores sanos en Murcia (España).

INTRODUCTION AND OBJECTIVES: Streptococcus pneumoniae (SP) is a human pathogen that involves a high use of antibiotics. The objective of the study was to determine the susceptibility to commonly used antibiotics and their associated risk factors, in order to promote rational use of antibiotics. PATIENTS AND METHODS: In A multicentre study was conducted in summer 2009 and winter 2010 on children attending paediatric clinics in the Region of Murcia. A nasopharyngeal sample was collected and an epidemiological questionnaire was completed. The study included 1562 children aged 1 and 4 years old. RESULTS: Almost one-third (31.3%, 489/1562) of children were nasal carriers. A sensitivity study was carried out on 376 isolates, of which 343 were serotyped. Almost two-thirds (61.7%, 964/1562) of children had received at least one dose of PCV7 (heptavalent pneumococcal conjugate vaccine), and 12.8% (44/343) of the isolates belonged to PCV7 serotypes. The prevalence rates of penicillin resistance (meningitis infections criteria CMI>0.06mg/L) were 28.1%; however, this percentage was 54% in PCV7 serotypes. None of the isolates had (MIC >2mg/L), so prevalence rates of susceptibility with non-meningitis infections criteria were 100%. There was a high percentage of erythromycin resistance (45.7%). The factors favouring resistance to penicillin and cefotaxime were the consumption of antibiotics in the previous month and the carrying of vaccine serotypes. On the other hand, the age of 4 years old was a protective factor of resistance. The 14, 35B, 19A, 15A, and 19F serotypes were less susceptible to penicillin. CONCLUSIONS: Both oral amoxicillin given to outpatients and intravenous penicillin or ampicillin to hospitalized patients are excellent options for the treatment of non-meningeal infections, as seen with pneumonia in these kinds of environments, where there is low incidence of isolates highly resistant to penicillin (CMI ≥ 2mg/L).

Tissue-type plasminogen activator mediates neuroglial coupling in the central nervous system.

The interaction between neurons, astrocytes and endothelial cells plays a central role coupling energy supply with changes in neuronal activity. For a long time it was believed that glucose was the only source of energy for neurons. However, a growing body of experimental evidence indicates that lactic acid, generated by aerobic glycolysis in perivascular astrocytes, is also a source of energy for neuronal activity, particularly when the supply of glucose from the intravascular space is interrupted. Adenosine monophosphate-activated protein kinase (AMPK) is an evolutionary conserved kinase that couples cellular activity with energy consumption via induction of the uptake of glucose and activation of the glycolytic pathway. The uptake of glucose by the blood-brain barrier is mediated by glucose transporter-1 (GLUT1), which is abundantly expressed in endothelial cells and astrocytic end-feet processes. Tissue-type plasminogen activator (tPA) is a serine proteinase that is found in endothelial cells, astrocytes and neurons. Genetic overexpression of neuronal tPA or treatment with recombinant tPA protects neurons from the deleterious effects of metabolic stress or excitotoxicity, via a mechanism independent of tPA's ability to cleave plasminogen into plasmin. The work presented here shows that exposure to metabolic stress induces the rapid release of tPA from murine neurons but not from astrocytes. This tPA induces AMPK activation, membrane recruitment of GLUT1, and GLUT1-mediated glucose uptake in astrocytes and endothelial cells. Our data indicate that this is followed by the synthesis and release of lactic acid from astrocytes, and that the uptake of this lactic acid via the monocarboxylate transporter-2 promotes survival in neurons exposed to metabolic stress.