Breast cancer (BC) is a malignant disease with a high prevalence worldwide. The main cause of death is not the primary tumor, but instead the spread of tumor cells to distant sites. The aim of the ...present study was to examine a new method for the detection of cancer cells in aqueous medium using bioimpedance spectroscopy assisted with magnetic nanoparticles (MNP's) exposure to a constant magnetic field. The spectroscopic patterns were identified for three breast cancer cell lines. Each BC cell line represents a different pathologic stage: the early stage (MCF-7), invasive phase (MDA-MB-231) and metastasis (SK-BR-3). For this purpose, bioimpedance measurements were carried out at a certain frequency range with the aid of nanoprobes, consisting of magnetic nanoparticles (MNPs) coupled to a monoclonal antibody. The antibody was specific for the predominant cell surface protein for each cell line, which was identified by using RT-qPCR and flow cytometry. Accordingly, EpCAM corresponds to MCF-7, MUC-1 to MDA-MB-231, and HER-2 to SK-BR-3. Despite their low concentrations, BC cells could be detected by impedance spectroscopy. Hence, this methodology should permit the monitoring of circulating tumor cells (CTC) and therefore help to prevent recurrences and metastatic processes during BC treatment.
Tuberculosis is the leading cause of death by an infectious microorganism worldwide. Conventional treatment lasts at least six months and has adverse effects; therefore, it is important to find ...therapeutic alternatives that reduce the bacterial load and may reduce the treatment duration. The immune response against tuberculosis can be modulated by several mechanisms, including extracellular vesicles (EVs), which are nano-sized membrane-bound structures that constitute an efficient communication mechanism among immune cells.
The EVs released by the J774A.1 mouse macrophage cell line, both spontaneously (S-EV) and after infection with
H37Rv (Mtb-EV), were purified by ultra-centrifugation and size-exclusion chromatography. The size distribution and chemical composition of these EVs were evaluated, and their effect on the bacterial load and the production of cytokines was determined in both in vitro and in vivo models of
infection.
Mtb-EV are larger than S-EV, they contain
-specific antigens (not detected in EVs released from
-infected J774A.1 cells) and are rich in phosphatidylserine, present in their outer membrane layer. S-EV, but not Mtb-EV, reduced the bacterial load and the production of MCP-1 and TNF-α in
-infected macrophages, and these effects were reversed when phosphatidylserine was blocked with annexin V. Both S-EV and Mtb-EV significantly reduced the lung bacterial load in mice infected with
after 60 days of treatment, but they had no effect on survival or on the lung pneumonic area of these mice.
J774A.1 macrophages infected with
H37Rv released EVs that differed in size and phosphatidylserine content from spontaneously released EVs, and these EVs also had different biological effects: S-EV reduced the mycobacterial load and the cytokine production in vitro (through a phosphatidylserine-dependent mechanism), while both EVs reduced the lung bacterial load in vivo. These results are the basis for further experiments to evaluate whether EVs improve the efficiency of the conventional treatment for tuberculosis.
Nick Shackleton's research on piston cores from the Iberian margin highlighted the importance of this region for providing high-fidelity records of millennial-scale climate variability, and for ...correlating climate events from the marine environment to polar ice cores and European terrestrial sequences. During the Integrated Ocean Drilling Program (IODP) Expedition 339, we sought to extend the Iberian margin sediment record by drilling with the D/V JOIDES Resolution. Five holes were cored at Site U1385 using the advanced piston corer (APC) system to a maximum depth of ~155.9 m below sea floor (m b.s.f.). Immediately after the expedition, cores from all holes were analyzed by core scanning X-ray fluorescence (XRF) at 1 cm spatial resolution. Ca/Ti data were used to accurately correlate from hole-to-hole and construct a composite spliced section, containing no gaps or disturbed intervals to 166.5 m composite depth (mcd). A low-resolution (20 cm sample spacing) oxygen isotope record confirms that Site U1385 contains a continuous record of hemipelagic sedimentation from the Holocene to 1.43 Ma (Marine Isotope Stage 46). The sediment profile at Site U1385 extends across the middle Pleistocene transition (MPT) with sedimentation rates averaging ~10 cm kyr−1. Strong precession cycles in colour and elemental XRF signals provide a powerful tool for developing an orbitally tuned reference timescale. Site U1385 is likely to become an important type section for marine–ice–terrestrial core correlations and the study of orbital- and millennial-scale climate variability.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Objectives The goal of this trial was to study the long-term effects of intravenous (IV) metoprolol administration before reperfusion on left ventricular (LV) function and clinical events. Background ...Early IV metoprolol during ST-segment elevation myocardial infarction (STEMI) has been shown to reduce infarct size when used in conjunction with primary percutaneous coronary intervention (pPCI). Methods The METOCARD-CNIC (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction) trial recruited 270 patients with Killip class ≤II anterior STEMI presenting early after symptom onset (<6 h) and randomized them to pre-reperfusion IV metoprolol or control group. Long-term magnetic resonance imaging (MRI) was performed on 202 patients (101 per group) 6 months after STEMI. Patients had a minimal 12-month clinical follow-up. Results Left ventricular ejection fraction (LVEF) at the 6 months MRI was higher after IV metoprolol (48.7 ± 9.9% vs. 45.0 ± 11.7% in control subjects; adjusted treatment effect 3.49%; 95% confidence interval CI: 0.44% to 6.55%; p = 0.025). The occurrence of severely depressed LVEF (≤35%) at 6 months was significantly lower in patients treated with IV metoprolol (11% vs. 27%, p = 0.006). The proportion of patients fulfilling Class I indications for an implantable cardioverter-defibrillator (ICD) was significantly lower in the IV metoprolol group (7% vs. 20%, p = 0.012). At a median follow-up of 2 years, occurrence of the pre-specified composite of death, heart failure admission, reinfarction, and malignant arrhythmias was 10.8% in the IV metoprolol group versus 18.3% in the control group, adjusted hazard ratio (HR): 0.55; 95% CI: 0.26 to 1.04; p = 0.065. Heart failure admission was significantly lower in the IV metoprolol group (HR: 0.32; 95% CI: 0.015 to 0.95; p = 0.046). Conclusions In patients with anterior Killip class ≤II STEMI undergoing pPCI, early IV metoprolol before reperfusion resulted in higher long-term LVEF, reduced incidence of severe LV systolic dysfunction and ICD indications, and fewer heart failure admissions. (Effect of METOprolol in CARDioproteCtioN During an Acute Myocardial InfarCtion. The METOCARD-CNIC Trial; NCT01311700 )
BACKGROUND Hydroxymethylglutaryl coenzyme A (HMGCoA) reductase inhibitors have beneficial effects beyond their cholesterol-lowering properties. The antioxidant mechanism of HMGCoA reductase ...inhibitors is not completely understood.
OBJECTIVES To elucidate the antioxidant effect of simvastatin.
METHODS We studied the influence of simvastatin treatment on the development of hypertension, modification of antioxidant systems, and reactivity of aortic rings in Wistar–Kyoto (WKY) and spontaneously hypertensive (SHR) rats.
RESULTS Simvastatin had no effect on blood pressure (BP). Simvastatin treatment (either 1 or 2 mg/kg body weight for 12 or 20 weeks) increased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in SHR rats compared with untreated control SHR rats. Carbachol-induced relaxation of aortic rings was impaired in control SHR rats and was restored by simvastatin treatment. Addition of SOD improved the response in control SHR rats and did not have any effect in treated SHR rats. Addition of diethyldithiocarbamic acid, a selective inhibitor of SOD, produced a mild non-significant impairment in carbachol-induced relaxation in control SHR rats, suggesting a deficient antioxidant system in these animals. However, in treated SHR and in WKY rats, impairment of the relaxation was marked, implying that SOD activity in these animals was important to maintain endothelial function. In aortic rings without endothelium from SHR rats, contraction induced by free radicals was substantially higher than in WKY rats. This effect was attenuated in 1-mg-treated rats and abolished in 2-mg-treated rats.
CONCLUSIONS Simvastatin promotes intracellular antioxidant systems, fundamentally SOD, restoring endothelial function but not having any effect on blood pressure.
Resumen ANTECEDENTES: el síndrome metabòlico agrupa factores de riesgo de diabetes mellitus 2 y enfermedad cardiovascular: obesidad central, hiperglucemia, hipertensión arterial, hipertrigliceridemia ...y colesterol de alta densidad (C-HDL) reducido. La obesidad y el síndrome metabòlico son afecciones en las que sobreviene inflamación subclínica crónica, factor de riesgo independiente de enfermedad cardiovascular y aterosclerosis. El índice neutrófilo/linfocito (INL) ha surgido como un marcador pronóstico asociado con un estado proinflamatorio que refleja el equilibrio entre la respuesta inmunitaria innata y adaptativa. OBJETIVO: definir la relación entre el índice neutrófilo/linfocito (INL) elevado y el síndrome metabólico en trabajadores activos adscritos al Hospital Central Norte de PEMEX. Los objetivos secundarios fueron establecer la relación entre el índice neutrófilo/linfocito y los componentes del síndrome metabólico individualmente. MATERIAL Y MÉTODO: estudio retrospectivo, transversal y observacional en el que se evaluaron trabajadores activos de PEMEX de 18 a 65 años de edad y se clasificaron en dos grupos de acuerdo con la existencia o ausencia de síndrome metabólico y se calculó el índice neutrófilo/linfocito de cada uno. RESULTADOS: se incluyeron 334 pacientes, 155 (46%) no cumplieron criterios para síndrome metabólico y 179 (54%) sí. De los pacientes en el cuartil más alto de índice neutrófilo/linfocito (>2.12) 57 correspondieron al grupo con síndrome metabólico (p=0.000). El coeficiente de correlación biserial puntual entre índice neutrófilo/ linfocito y síndrome metabólico fue de 0.235 (p=0.000); 69 de los 235 pacientes con obesidad central estaban en el cuartil más alto de índice neutrófilo/linfocito (p=0.001). CONCLUSIONES: los hallazgos sugieren que existe una relación significativa entre la elevación del índice neutrófilo/linfocito (>2.12) y la existencia de síndrome metabólico y obesidad central.
We conducted a multicentric national study (SEIMC-CEME-22), to describe the clinical and epidemiological profile of the mpox outbreak in Spain, including the management of the disease.
This was a ...retrospective national observational study conducted by Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC) and Foundation SEIMC-GESIDA. We included patients with a confirmed mpox diagnosis before 13 July 2022, and attended at the Spanish health network (the early phase of the outbreak). Epidemiological, clinical, and therapeutic data were collected.
Of a total of 1472 patients from 52 centers included, 99% of them were cisgender men, mostly middle-aged, and 98.6% were residents in Spain. The main suspected route of transmission was sexual exposure, primarily among MSM. Occupational exposure was reported in 6 patients. Immunosuppression was present in 40% of patients, mainly due to human immunodeficiency virus (HIV). Only 6.5% of patients had been vaccinated against orthopoxvirus. Virus sequencing was performed in 147 patients (all B.1 lineage). Rash was the most frequent symptom (95.7%), followed by fever (48.2%), adenopathies (44.4%) myalgias (20.7%), proctitis (17%), and headache (14.7%). Simultaneously diagnosed sexually transmitted infections included syphilis (n = 129), gonococcal infection (n = 91), HIV (n = 67), chlamydia (n = 56), hepatitis B (n = 14), and hepatitis C (n = 11). No therapy was used in 479 patients (33%). Symptomatic therapies and antibiotics were used in 50% of cases. The most used therapy regimens were systemic corticoids (90 patients), tecovirimat (6 patients), and cidofovir (13 patients). Smallpox immunoglobulins were used in 1 patient. Fifty-eight patients were hospitalized, and 1 patient died.
Mpox outbreak in Spain affected primarily middle-aged men who were sexually active and showed a high rate of HIV infection. A range of heterogeneous therapeutics options was performed.
Resumen ANTECEDENTES: existe incremento de la prevalência de diabetes mellitus 2 y del envejecimiento. Así, los riesgos asociados con control glucémico intensivo en esta población vulnerable se ...incrementan. Por ello, debe considerarse la posibilidad de un sobretratamiento en estos pacientes. OBJETIVO: determinar la prevalencia de control glucémico intensivo y sobretratamiento en pacientes con diabetes mellitus tipo 2 mayores de 60 años. MATERIAL Y MÉTODO: estudio retrospectivo, transversal, observacional y analítico. De 2013 a 2015 se evaluaron pacientes mayores de 60 años de edad con diabetes mellitus tipo 2, hemoglobina glucosilada (HbAlc) <7% y administración de hipoglucemiantes. Los pacientes se clasificaron en control glucémico intensivo (HbAlc 6.6-7%) y sobretratamiento (HbAlc <6.5%). Los porcentajes de ambos grupos y sus complicaciones cardiovasculares y no cardiovasculares asociadas se compararon utilizando una prueba Z. RESULTADOS: se incluyeron 13,229 pacientes con diabetes mellitus tipo 2 mayores de 60 años; en 2013, fueron 4,381, 16% (n=701) en control glucémico intensivo y 6% (n=256) en sobretratamiento; en 2014 fueron 4,383, 16% (n=697) en control glucémico intensivo y 6% (n=252) en sobretratamiento; en 2015 fueron 4,465, 16% (n=708) en control glucémico intensivo y 6% (n=260) con sobretratamiento. El control glucémico intensivo causó 5, 3 y 1% de complicaciones durante 2013, 2014 y 2015, respectivamente. En el grupo con sobretratamiento el porcentaje de complicaciones fue de 4% en 2013 y de 6% en 2015. Se obtuvo un valor Z de -2.90 (p<0.05), mostrando mayor número en sobretratamiento. CONCLUSIONES: de la población estudiada, 16% estaba en control glucémico intensivo y 6% en sobretratamiento, con incremento significativo de complicaciones en el grupo con sobretratamiento, la hipoglucemia fue la más frecuente.
Study objective We seek to examine the efficacy and safety of prereperfusion emergency medical services (EMS)–administered intravenous metoprolol in anterior ST-segment elevation myocardial ...infarction patients undergoing eventual primary angioplasty. Methods This is a prespecified subgroup analysis of the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction trial population, who all eventually received oral metoprolol within 12 to 24 hours. We studied patients receiving intravenous metoprolol by EMS and compared them with others treated by EMS but not receiving intravenous metoprolol. Outcomes included infarct size and left ventricular ejection fraction on cardiac magnetic resonance imaging at 1 week, and safety by measuring the incidence of the predefined combined endpoint (composite of death, malignant ventricular arrhythmias, advanced atrioventricular block, cardiogenic shock, or reinfarction) within the first 24 hours. Results From the total population of the trial (N=270), 147 patients (54%) were recruited during out-of-hospital assistance and transferred to the primary angioplasty center (74 intravenous metoprolol and 73 controls). Infarct size was smaller in patients receiving intravenous metoprolol compared with controls (23.4 SD 15.0 versus 34.0 SD 23.7 g; adjusted difference –11.4; 95% confidence interval CI –18.6 to –4.3). Left ventricular ejection fraction was higher in the intravenous metoprolol group (48.1% SD 8.4% versus 43.1% SD 10.2%; adjusted difference 5.0; 95% CI 1.6 to 8.4). Metoprolol administration did not increase the incidence of the prespecified safety combined endpoint: 6.8% versus 17.8% in controls (risk difference –11.1; 95% CI –21.5 to –0.6). Conclusion Out-of-hospital administration of intravenous metoprolol by EMS within 4.5 hours of symptom onset in our subjects reduced infarct size and improved left ventricular ejection fraction with no excess of adverse events during the first 24 hours.
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