Escherichia coli induced matrix metalloproteinase-9 activity and type IV collagen degradation is regulated by progesterone in human maternal decidual.

BACKGROUND: Escherichia coli (E. coli) is one of the main bacteria associated with preterm premature rupture of membranes by increasing pro-matrix metalloproteinase 9 (proMMP-9) and degradation of type IV collagen in human feto-maternal interface (HFMi). proMMP-9 is regulated by progesterone (P4) but it is unclear whether P4 inhibits proMMP in human maternal decidual (MDec). This study aimed to determine a role of P4 on proMMP-2 and - 9 and type IV collagen induced by E. coli infection in MDec. METHODS: Nine HFMi were mounted in a Transwell system. MDec was stimulated with P4 or E. coli for 3-, 6-, or 24-hours. proMMP-2, -9 and type IV collagen were assessed. RESULTS: Gelatin zymography revealed an increase in proMMP-9 after 3, 6, and 24 h of stimulating MDec with E. coli. Using immunofluorescence, it was confirmed the increase in the HFMi tissue and a reduction on the amount of type IV collagen leading to the separation of fetal amniochorion and MDEc. The degradative activity of proMMP-9 was reduced by 20% by coincubation with P4. CONCLUSIONS: P4 modulates the activity of proMMP-9 induced by E. coli stimulation but it was unable to completely reverse the degradation of type IV collagen in human MDec tissue.

Endothelial biomarkers (Von willebrand factor, BDCA3, urokinase) as predictors of mortality in COVID-19 patients: cohort study.

BACKGROUND: SARS-CoV-2 is a systemic disease that affects endothelial function and leads to coagulation disorders, increasing the risk of mortality. Blood levels of endothelial biomarkers such as Von Willebrand Factor (VWF), Thrombomodulin or Blood Dendritic Cell Antigen-3 (BDCA3), and uUokinase (uPA) increase in patients with severe disease and can be prognostic indicators for mortality. Therefore, the aim of this study was to determine the effect of VWF, BDCA3, and uPA levels on mortality. METHODS: From May 2020 to January 2021, we studied a prospective cohort of hospitalized adult patients with polymerase chain reaction (PCR)-confirmed COVID-19 with a SaO2 ≤ 93% and a PaO2/FiO2 ratio < 300. In-hospital survival was evaluated from admission to death or to a maximum of 60 days of follow-up with Kaplan-Meier survival curves and Cox proportional hazard models as independent predictor measures of endothelial dysfunction. RESULTS: We recruited a total of 165 subjects (73% men) with a median age of 57.3 ± 12.9 years. The most common comorbidities were obesity (39.7%), hypertension (35.4%) and diabetes (30.3%). Endothelial biomarkers were increased in non-survivors compared to survivors. According to the multivariate Cox proportional hazard model, those with an elevated VWF concentration ≥ 4870 pg/ml had a hazard ratio (HR) of 4.06 (95% CI: 1.32-12.5) compared to those with a lower VWF concentration adjusted for age, cerebrovascular events, enoxaparin dose, lactate dehydrogenase (LDH) level, and bilirubin level. uPA and BDCA3 also increased mortality in patients with levels ≥ 460 pg/ml and ≥ 3600 pg/ml, respectively. CONCLUSION: The risk of mortality in those with elevated levels of endothelial biomarkers was observable in this study.

Oxidative Stress and Air Pollution: Its Impact on Chronic Respiratory Diseases.

Redox regulation participates in the control of various aspects of metabolism. Reactive oxygen and nitrogen species participate in many reactions under physiological conditions. When these species overcome the antioxidant defense system, a distressed status emerges, increasing biomolecular damage and leading to functional alterations. Air pollution is one of the exogenous sources of reactive oxygen and nitrogen species. Ambient airborne particulate matter (PM) is important because of its complex composition, which includes transition metals and organic compounds. Once in contact with the lungs' epithelium, PM components initiate the synthesis of inflammatory mediators, macrophage activation, modulation of gene expression, and the activation of transcription factors, which are all related to the physiopathology of chronic respiratory diseases, including cancer. Even though the pathophysiological pathways that give rise to the development of distress and biological damage are not fully understood, scientific evidence indicates that redox-dependent signaling pathways are involved. This article presents an overview of the redox interaction of air pollution inside the human body and the courses related to chronic respiratory diseases.

Seasonal and Spatial Variability of PM2.5 Concentration, and Associated Metal(loid) Content in the Toluca Valley, Mexico.

This study provides evidence of the seasonal and spatial variation of metal(lloid)s in particulate matter minor to 2.5 microns (PM2.5) in the Toluca Valley Metropolitan Area (TVMA), the fifth largest urban center in Mexico. Four sites were sampled between 2013 and 2014, which included urban and industrial areas, in the dry-cold (November-February) and dry-hot (March-May) seasons; PM2.5 was collected using high- and medium-volume samplers. Metal(lloid) concentrations in PM2.5 were analyzed using inductively coupled plasma‒mass spectrometry (ICP‒MS). The highest 24-hour PM2.5 concentration in the northern area was observed, and the PM2.5 concentrations were independent of the season. Five metal(lloid)s with a recovery percentage above 80% were considered to be reported (Co, Cr, Cu, Mn, and Sb). The maximum concentrations of metal(lloid)s were observed during the dry-cold season, and concentrations were up to one hundred or thousand fold with respect to the dry-hot season. The 24-hour PM2.5 and metal(lloid) concentrations exceeded national and international guidelines to protect population health.

Neuron numbers increase in the human amygdala from birth to adulthood, but not in autism.

Remarkably little is known about the postnatal cellular development of the human amygdala. It plays a central role in mediating emotional behavior and has an unusually protracted development well into adulthood, increasing in size by 40% from youth to adulthood. Variation from this typical neurodevelopmental trajectory could have profound implications on normal emotional development. We report the results of a stereological analysis of the number of neurons in amygdala nuclei of 52 human brains ranging from 2 to 48 years of age [24 neurotypical and 28 autism spectrum disorder (ASD)]. In neurotypical development, the number of mature neurons in the basal and accessory basal nuclei increases from childhood to adulthood, coinciding with a decrease of immature neurons within the paralaminar nucleus. Individuals with ASD, in contrast, show an initial excess of amygdala neurons during childhood, followed by a reduction in adulthood across nuclei. We propose that there is a long-term contribution of mature neurons from the paralaminar nucleus to other nuclei of the neurotypical human amygdala and that this growth trajectory may be altered in ASD, potentially underlying the volumetric changes detected in ASD and other neurodevelopmental or neuropsychiatric disorders.

Acute Stroke Care Is at Risk in the Era of COVID-19: Experience at a Comprehensive Stroke Center in Barcelona.

BACKGROUND AND PURPOSE: The purpose of the study is to analyze how the coronavirus disease 2019 (COVID-19) pandemic affected acute stroke care in a Comprehensive Stroke Center. METHODS: On February 28, 2020, contingency plans were implemented at Hospital Clinic of Barcelona to contain the COVID-19 pandemic. Among them, the decision to refrain from reallocating the Stroke Team and Stroke Unit to the care of patients with COVID-19. From March 1 to March 31, 2020, we measured the number of emergency calls to the Emergency Medical System in Catalonia (7.5 million inhabitants), and the Stroke Codes dispatched to Hospital Clinic of Barcelona. We recorded all stroke admissions, and the adequacy of acute care measures, including the number of thrombectomies, workflow metrics, angiographic results, and clinical outcomes. Data were compared with March 2019 using parametric or nonparametric methods as appropriate. RESULTS: At Hospital Clinic of Barcelona, 1232 patients with COVID-19 were admitted in March 2020, demanding 60% of the hospital bed capacity. Relative to March 2019, the Emergency Medical System had a 330% mean increment in the number of calls (158 005 versus 679 569), but fewer Stroke Code activations (517 versus 426). Stroke admissions (108 versus 83) and the number of thrombectomies (21 versus 16) declined at Hospital Clinic of Barcelona, particularly after lockdown of the population. Younger age was found in stroke admissions during the pandemic (median [interquartile range] 69 [64-73] versus 75 [73-80] years, P=0.009). In-hospital, there were no differences in workflow metrics, angiographic results, complications, or outcomes at discharge. CONCLUSIONS: The COVID-19 pandemic reduced by a quarter the stroke admissions and thrombectomies performed at a Comprehensive Stroke Center but did not affect the quality of care metrics. During the lockdown, there was an overload of emergency calls but fewer Stroke Code activations, particularly in elderly patients. Hospital contingency plans, patient transport systems, and population-targeted alerts must act concertedly to better protect the chain of stroke care in times of pandemic.

Obesity and pro-inflammatory mediators are associated with acute kidney injury in patients with A/H1N1 influenza and acute respiratory distress syndrome.

BACKGROUND: The obesity has been shown to increase the severity of A/H1N1 infection and the development of acute respiratory distress syndrome (ARDS) and organ involvement. METHODS: Circulating levels of C-peptide, insulin, glucagon, leptin, acute phase reactants (procalcitonin, C-reactive protein, tissue plasminogen activator, and serum amyloids A and P), were measured in samples from 32 critically ill patients with A/H1N1 virus infection, 17 of whom had ARDS complicated by acute kidney injury (AKI) and 15 of whom had ARDS but did not develop AKI. RESULTS: Patients with ARDS and AKI (ARDS/AKI) had higher BMI and higher levels of C-peptide, insulin, leptin, procalcitonin and serum amyloid A compared to those ARDS patient who did not develop AKI. Adjusting for confounding variables using logistic regression analysis, higher levels of C-peptide (>0.75 ng/mL) (OR=64.8, 95% CI = 2.1-1980, p = 0.0006) and BMI>30 Kg/m(2) (OR = 42.0, 95% CI = 1.2-1478, p = 0.04) were significantly associated with the development of AKI in ARDS patients. CONCLUSION: High levels of C-peptide and BMI>30 kg/m(2) were associated with the development of AKI in ARDS patients due to A/H1N1 infection. These metabolic/obesity indicators, together with the profiles of pro-inflammatory acute phase proteins, may be important links between obesity and poor outcomes in A/H1N1 09 infection.

Regulation of Cancer-Associated miRNAs Expression under Hypoxic Conditions.

Solid tumors frequently experience hypoxia or low O2 levels. In these conditions, hypoxia-inducible factor 1 alpha (HIF-1α) is activated and acts as a transcription factor that regulates cancer cell adaptation to O2 and nutrient deprivation. HIF-1α controls gene expression associated with various signaling pathways that promote cancer cell proliferation and survival. MicroRNAs (miRNAs) are 22-nucleotide noncoding RNAs that play a role in various biological processes essential for cancer progression. This review presents an overview of how hypoxia regulates the expression of multiple miRNAs in the progression of cancer cells.

Risk of adverse perinatal outcomes among women with clinical and subclinical histopathological chorioamnionitis.

Introduction: Histologic chorioamnionitis (HCA) is a placental inflammatory condition associated with adverse perinatal outcomes (APOs). This historical cohort study explores the risk of APOs in pregnant women with HCA and compares the impact of clinical chorioamnionitis (CCA) with subclinical chorioamnionitis (SCCA). Methodology: Placentas were evaluated by a perinatal pathologist tand all women with HCA were included. Two groups were integrated: (1) women with clinical chorioamnionitis (CCA) and (2) women with subclinical chorioamnionitis (SCCA). Additionally, we conducted a secondary analysis to compare the prevalence of APOs among stage 1, 2 and 3 of HCA and the risk of APOs between grades 1 and 2 of HCA. The APOs analyzed were preterm birth, stillbirth, neonatal weight < 1,500 g, neonatal sepsis. Relative risk with 95% confidence interval was calculated. Results: The study included 41 cases of CCA and 270 cases of SCCA. The mean gestational age at diagnosis and birth was 30.2 ± 5.4 weeks and 32.5 ± 5.1 weeks, for group 1 and 2, respectively. The study also found that women with HCA stage 3 and grade 2 had a higher prevalence and risk of adverse perinatal outcomes. Discussion: The findings of this study suggest the importance of placental histological study to excluded SCCA, which represents a significant risk to both maternal and neonatal health, contributing to high morbidity and mortality.

Progesterone modulates extracellular heat-shock proteins and interlukin-1ß in human choriodecidual after Escherichia coli infection.

INTRODUCTION: Chorioamnionitis is an adverse condition in human pregnancy caused by many bacterial pathogens including Escherichia coli (E. coli); which has been associated with higher risk of preterm birth. We recently reported that human maternal decidua (MDec) tissue responds to E. coli infection by secreting extracellular heat-shock proteins (eHsp)-60, -70 and interlukin-1ß (IL-1ß). Previous studies have shown that progesterone (P4) regulates the immune response, but it is unknown whether P4 inhibits the secretion of eHsp. The aim of this investigation was to determine the role of P4 on the secretion of eHsp-27, -60, -70 and IL-1ß in MDec after 3, 6, and 24 h of E. coli infection. METHODS: Nine human feto-maternal interface (HFMi) tissues were included and mounted in the Transwell culture system. Only the maternal decidua (MDec) was stimulated for 3, 6 and 24 h with E. coli alone or in combination with progesterone and RU486. After each treatment, the HFMi tissue was recovered to determine histological changes and the culture medium recovered to evaluate the levels of eHsp-27, -60, -70 and IL-1ß by ELISA and mRNA expression by RT-PCR. RESULTS: No structural changes were observed in the HFMi tissue treated with P4 and RU486. However, stimulation with E. coli produces diffuse inflammation and ischemic necrosis. E. coli induced infection decreases, in time- and dose-dependent manner, eHsp-27 and increases eHsp-60, eHsp-70 and IL-1ß levels. In contrast, incubation of HFMi tissue with E. coli + P4 reversed eHsp and IL-1ß secretion levels relative to E. coli stimulation group but not relative to the control group. The same profile was observed on the expression of eHsp-27 and eHsp-60. DISCUSSION: we found that progesterone modulates the anti-inflammatory (eHsp-27) and pro-inflammatory (eHsp-60 and eHsp-70) levels of eHsp induced by E. coli infection in human choriodecidual tissue. eHsp-60 and eHsp-70 levels were not completely reversed; maintaining the secretion of IL-1ß, which has been associated with adverse events during pregnancy.

Effect of smoking on the redox status of knee osteoarthritis: A preliminary study.

Even though smoking has been scarcely studied in osteoarthritis (OA) etiology, it is considered a controversial risk factor for the disease. Exposure to tobacco smoke has been reported to promote oxidative stress (OS) as part of the damage mechanism. The aim of this study was to assess whether smoking increases cartilage damage through the generation of OS. Peripheral blood (PB) and synovial fluid (SF) samples from patients with OA were analyzed. The samples were stratified according to smoking habit, Kellgren-Lawrence score, pain, and cotinine concentrations in PB. Malondialdehyde (MDA), methylglyoxal (MGO), advanced protein oxidation products (APOPs), and myeloperoxidase (MPO) were assessed; the activity of antioxidant enzymes such as gamma-glutamyl transferase (GGT), glutathione S-transferase (GST) and catalase (CAT), as well as the activity of arginase, which favors the destruction of cartilage, was determined. When stratified by age, for individuals <60 years, the levels of MDA and APOPs and the activity of MPO and GST were higher, as well as antioxidant system activity in the smoking group (OA-S). A greater degree of pain in the OA-S group increased the concentrations of APOPs and arginase activity (P < 0.01 and P < 0.05, respectively). Arginase activity increased significantly with a higher degree of pain (P < 0.01). Active smoking can be an important risk factor for the development of OA by inducing systemic OS in young adults, in addition to reducing antioxidant enzymes in older adults and enhancing the degree of pain and loss of cartilage.

Air pollution: impact and prevention.

Air pollution is becoming a major health problem that affects millions of people worldwide. In support of this observation, the World Health Organization estimates that every year, 2.4 million people die because of the effects of air pollution on health. Mitigation strategies such as changes in diesel engine technology could result in fewer premature mortalities, as suggested by the US Environmental Protection Agency. This review: (i) discusses the impact of air pollution on respiratory disease; (ii) provides evidence that reducing air pollution may have a positive impact on the prevention of disease; and (iii) demonstrates the impact concerted polices may have on population health when governments take actions to reduce air pollution.

[Progressive myositis ossificans: Case report]. / Miositis osificante progresiva: reporte de un caso.

Background: Myositis ossificans progressiva (MOP) is a low prevalence hereditary connective tissue disease (1:2,000,000 habitants). It is characterized by heterotopic ossification with an uncertain behavior that has been exceptionally related to neoplasms. The objective was to know the coexistence of MOP with neoplasms of mesodermal origin, so that they can be considered in the diagnosis of other patients, as well as formulate hypotheses to clarify their association. Clinical case: 27-year-old female with right gluteal and ischitiobial muscle pain that increased with exercise, without remission with analgesics until limiting the mobility of both extremities. A bone series was requested where areas of heterogeneous radiolucency were evidenced in the region of, both, thighs and pelvis in an irregular manner, similar to bone density, which was compatible with the ultrasound and tomographic findings; we concluded that they were images of myositis ossificans of the hip. The patient reported gastric symptoms and an endoscopy was requested, which histopathologically reported diffuse gastric carcinoma with signet ring cells; cabinet images showed an ovarian tumor. Conclusion: MOP is a low prevalence disease, which is why its knowledge and suspicion are essential for the diagnosis. We found little literature that involves the three entities; therefore, their pathophysiology and understanding is limited. Regarding MOP, at this moment there is no curative treatment; however, an accurate diagnosis allows to start rehabilitation in a timely manner with an improvement in the quality of life.

Introducción: la miositis osificante progresiva (MOP) es una enfermedad hereditaria del tejido conectivo de baja prevalencia (1:2,000,000 habitantes). Se caracteriza por osificación heterotópica con un comportamiento incierto que excepcionalmente se ha relacionado con neoplasias. Se buscó conocer la coexistencia de la MOP con neoplasias de origen mesodérmico, para que sean consideradas en el diagnóstico de otros pacientes, así como formular hipótesis para esclarecer su asociación. Caso clínico: mujer de 27 años con dolor de músculo isquitiobial y glúteo derecho que incrementaba con el ejercicio, sin remisión con analgésicos hasta limitar la movilidad de ambas extremidades. Se solicitó una serie ósea donde se evidenciaron zonas de radiolucidez heterogénea en la región de ambos muslos y pelvis de manera irregular, semejante a densidad ósea, que fue compatible con los hallazgos ecográficos y tomográficos; se concluyó que eran imágenes relacionadas con miositis osificante de cadera. La paciente refirió sintomatología gástrica y se solicitó una endoscopía que histopatológicamente reportó carcinoma gástrico difuso con células en anillo de sello; las imágenes de gabinete mostraron tumoración ovárica. Conclusión: la MOP es una patología de baja prevalencia, por lo que su conocimiento y sospecha son fundamentales para el diagnóstico. Hay poca literatura que involucre a las tres entidades; por ende, su fisiopatología y comprensión es limitada. En cuanto a la MOP, aún no hay un tratamiento curativo; sin embargo, el diagnóstico certero permite iniciar rehabilitación de manera oportuna con mejoría de la calidad de vida.

Plasma Endothelial and Oxidative Stress Biomarkers Associated with Late Mortality in Hospitalized COVID-19 Patients.

BACKGROUND: Coronavirus infectious disease 2019 (COVID-19) is a significant public health problem worldwide. COVID-19 increases the risk of non-pulmonary complications such as acute myocardial injury, renal failure, thromboembolic events, and multi-organic damage. Several studies have documented increased inflammation molecules, endothelial dysfunction biomarkers, and dysregulation of coagulation factors in COVID-19 patients. In addition, endothelium dysfunction is exacerbated by the oxidative stress (OxS) promoted by endocrine and cardiovascular molecules. Our objective was to evaluate whether endothelial and OxS biomarkers were associated with mortality in hospitalized COVID-19 patients. METHODS: A prospective cohort study was performed. Patients ≥18 years old with confirmed COVID-19 that required hospitalization were included in a prospective cohort study. Endothelium and oxidative stress biomarkers were collected between 3 and 5 days after admission. RESULTS: A total of 165 patients were evaluated; 56 patients succumbed. The median follow-up was 71 days [23-129]. Regarding endothelial dysfunction and OxS biomarkers, patients who did not survive had higher levels of nitrates (0.4564 [0.1817-0.6761] vs. 0.2817 [0.0517-0.5], p = 0.014), total nitrates (0.0507 [-0.0342-0.1809] vs. -0.0041 [-0.0887-0.0909], p = 0.016), sE-Selectin (1.095 [0.86-1.495] vs. 0.94 [0.71-1.19], p = 0.004), and malondialdehyde (MDA) (0.50 [0.26-0.72] vs. 0.36 [0.23-0.52], p = 0.010) compared to patients who survived. Endothelial and OxS biomarkers independently associated with mortality were sE-selectin (HR:2.54, CI95%; from 1.11 to 5.81, p = 0.027), nitrates (HR:4.92, CI95%; from 1.23 to 19.63, p = 0.024), and MDA (HR: 3.05, CI95%; from 1.14 to 8.15, p = 0.025). CONCLUSIONS: Endothelial dysfunction (sE-selectin and nitrates) and OxS (MDA) are independent indicators of a worse prognosis in COVID-19 patients requiring hospitalization.

Effect of Hypoxia in the Transcriptomic Profile of Lung Fibroblasts from Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an aging-associated disease characterized by exacerbated extracellular matrix deposition that disrupts oxygen exchange. Hypoxia and its transcription factors (HIF-1α and 2α) influence numerous circuits that could perpetuate fibrosis by increasing myofibroblasts differentiation and by promoting extracellular matrix accumulation. Therefore, this work aimed to elucidate the signature of hypoxia in the transcriptomic circuitry of IPF-derived fibroblasts. To determine this transcriptomic signature, a gene expression analysis with six lines of lung fibroblasts under normoxia or hypoxia was performed: three cell lines were derived from patients with IPF, and three were from healthy donors, a total of 36 replicates. We used the Clariom D platform, which allows us to evaluate a huge number of transcripts, to analyze the response to hypoxia in both controls and IPF. The control's response is greater by the number of genes and complexity. In the search for specific genes responsible for the IPF fibroblast phenotype, nineteen dysregulated genes were found in lung fibroblasts from IPF patients in hypoxia (nine upregulated and ten downregulated). In this sense, the signaling pathways revealed to be affected in the pulmonary fibroblasts of patients with IPF may represent an adaptation to chronic hypoxia.

Uric acid levels are relevant in patients with stroke treated with thrombolysis.

BACKGROUND AND PURPOSE: Uric acid (UA) is a neuroprotective antioxidant that improves the benefits of alteplase in experimental ischemia. However, it is unknown whether endogenous UA also influences the response to thrombolysis in patients with stroke. METHODS: A total of 317 consecutive patients treated with thrombolysis were included in a prospective stroke registry. Demographics, laboratory data, neurological course, and infarction volume were prospectively collected. Excellent outcome was defined as achieving a modified Rankin Scale score <2 at 90 days. Binary and ordinal logistic regression models were used to analyze modified Rankin Scale score at 90 days. RESULTS: UA levels were significantly higher in patients with an excellent outcome than in patients with a poor outcome (5.82 [1.39] versus 5.42 [1.81], P=0.029). In multivariate models, increased UA levels (OR, 1.23; 95% CI, 1.03 to 1.49; P=0.025) were associated with an excellent outcome and with an increased risk of shifting to a better category across the modified Rankin Scale (OR, 1.19; 95% CI, 1.04 to 1.38; P=0.014) independently of the effect of confounders. The levels of UA and the volume of final infarction were inversely correlated (r=-0.216, P<0.001) and the inverse correlation remained after adjustment for age, sex, and baseline National Institutes of Health Stroke Scale score (t value=-2.54, P=0.01). Significantly lower UA levels were found in patients with malignant middle cerebral artery infarction and parenchymal hemorrhage post-thrombolysis. CONCLUSIONS: Increased UA serum levels are associated with better outcome in patients with stroke treated with reperfusion therapies. These results support the assessment of the potential neuroprotective role of the exogenous administration of UA in patients with stroke treated with thrombolysis.

Multimodal CT-assisted thrombolysis in patients with acute stroke: a cohort study.

BACKGROUND AND PURPOSE: The value of multimodal CT to assist thrombolysis has received little attention in stroke. METHODS: We assessed prospectively the impact derived from the routine application of CT perfusion and CTA in patients with acute stroke treated consecutively with alteplase. The safety and efficacy of thrombolytic therapy were compared in 106 patients assisted with CT/CTA/CT perfusion (multimodal CT group) and 262 patients assisted without full multimodal brain imaging (control group) during a 5-year period (2005-2009). RESULTS: Good outcome (modified Rankin scale score ≤2) at 3 months was increased in the multimodal group compared with controls (adjusted OR, 2.88; 95% CI, 1.50-5.52). Multimodal-assisted thrombolysis yielded superior benefits in patients treated beyond 3 hours (adjusted OR, 4.48; 95% CI, 1.68-11.98) than treated within 3 hours (adjusted OR, 1.31; 95% CI, 0.80-2.16; interaction test P=0.043). Mortality (14% and 15%) and symptomatic hemorrhage (5% and 7%) were similar in both groups. CONCLUSIONS: Multimodal CT use in routine clinical practice may heighten the overall efficacy of thrombolytic therapy in acute ischemic stroke. The benefits seem greater in patients treated >3 hours after stroke onset, but further randomized clinical trials are needed to confirm these findings.

Osteopontin's relationship with malnutrition and oxidative stress in adolescents. A pilot study.

Osteopontin (OPN) is a protein involved in inflammatory illnesses such as fibrosis and cancer; its overexpression in cardiovascular diseases promotes the biomineralization of blood vessels and other soft tissues. Moreover, there is an active component of oxidative stress related with those diseases. The present study relates serum OPN levels with nutritional condition and oxidative stress in a group of adolescents. Anthropometric measurements were performed, and fasting blood samples were analyzed to determine OPN concentrations, blood chemistry parameters (glucose, triglycerides, total cholesterol, urea, uric acid, and creatinine) and oxidative stress biomarkers (Paraoxonase-1, Glutathione S-Transferase, Catalase, NAD(P)H Quinone Oxidoreductase, free carbonyl groups and malondialdehyde). Adolescents were categorized according to body mass index (BMI) and metabolic syndrome (MetS) criteria. We found increased OPN serum concentrations in overweight and obese adolescents, as well as in adolescents with MetS. Rises in OPN correlated with arm circumference and biomarkers of lipid peroxidation; with regard to serum glucose there was a trend to positive correlation. Our results suggest that serum OPN is associated to nutritional status and could be considered as an early biomarker of low-grade inflammation and probably the early biomineralization of soft tissues in adolescence.

Physiological Network From Anthropometric and Blood Test Biomarkers.

Currently, research in physiology focuses on molecular mechanisms underlying the functioning of living organisms. Reductionist strategies are used to decompose systems into their components and to measure changes of physiological variables between experimental conditions. However, how these isolated physiological variables translate into the emergence -and collapse- of biological functions of the organism as a whole is often a less tractable question. To generate a useful representation of physiology as a system, known and unknown interactions between heterogeneous physiological components must be taken into account. In this work we use a Complex Inference Networks approach to build physiological networks from biomarkers. We employ two unrelated databases to generate Spearman correlation matrices of 81 and 54 physiological variables, respectively, including endocrine, mechanic, biochemical, anthropometric, physiological, and cellular variables. From these correlation matrices we generated physiological networks by selecting a p-value threshold indicating statistically significant links. We compared the networks from both samples to show which features are robust and representative for physiology in health. We found that although network topology is sensitive to the p-value threshold, an optimal value may be defined by combining criteria of stability of topological features and network connectedness. Unsupervised community detection algorithms allowed to obtain functional clusters that correlate well with current medical knowledge. Finally, we describe the topology of the physiological networks, which lie between random and ordered structural features, and may reflect system robustness and adaptability. Modularity of physiological networks allows to explore functional clusters that are consistent even when considering different physiological variables. Altogether Complex Inference Networks from biomarkers provide an efficient implementation of a systems biology approach that is visually understandable and robust. We hypothesize that physiological networks allow to translate concepts such as homeostasis into quantifiable properties of biological systems useful for determination and quantification of health and disease.

Catecholamines, infection, and death in acute ischemic stroke.

Experimental studies have recently suggested that acute ischemia may facilitate the appearance of fatal infections as part of a brain-induced immunodepression syndrome. However, the mechanisms and neurological consequences of infections complicating acute ischemic stroke have received much less attention at the bedside. The incidence of infection and death after non-septic stroke was compared in this prospective study with longitudinal changes of cytokines, leukocytes, normetanephrine (NMN) and metanephrine (MN) in 75 consecutive patients. In multivariate analysis, infection, n = 13 (17%), was associated with the upper quartile of MN (OR 3.51, 95% CI 1.30-9.51), neurological impairment (NIHSS) on admission (OR 3.99, 95% CI 1.34-11.8), monocyte count (OR 1.78, 95% CI 1.13-2.79), and increased interleukin (IL)-10 (OR 1.54, 95% CI 1.00-2.38). Mortality at 3 months, n = 16 (21%), was associated with increased levels of NMN on admission (OR 2.34 95% CI 1.15-4.76), NIHSS score (OR 2.57, 95% CI 1.29-5.11), and higher IL-6 levels (OR 1.29, 95% 1.00-1.67). These findings suggest that acute ischemic stroke is associated with an early activation of the sympathetic adrenomedullar pathway that lowers the threshold of infection and increases the risk of death. Moreover, these findings are independent of the blood borne effects of pro- and anti-inflammatory cytokines, and circulating leukocytes.