Remote ischemic conditioning in ST-elevation myocardial infarction as adjuvant to primary angioplasty (RIC-STEMI): study protocol for a randomized controlled trial

BACKGROUND: ST-elevation myocardial infarction (STEMI) accounts for nearly one third of acute coronary syndromes. Despite improved STEMI patient care, mortality remains high, contributing significantly to the ischemic heart disease burden. This may partly be related to ischemia-reperfusion injury (IRI). Remote ischemic conditioning (RIC), through short cycles of ischemia-reperfusion applied to a limb, has been shown to reduce IRI in various clinical settings. Our primary hypothesis is that RIC will reduce adverse events related to STEMI when applied as adjunctive therapy to primary percutaneous coronary intervention (PCI). METHODS/DESIGN: "Remote ischemic conditioning in ST-elevation myocardial infarction as adjuvant to primary angioplasty" (RIC-STEMI) is an ongoing prospective, single-center, open-label, randomized controlled trial to assess whether RIC as an adjunctive therapy during primary PCI in patients presenting with STEMI can improve clinical outcomes. After enrollment, participants are randomized according to a computer-generated randomization schedule, in a ratio of 1:1 to RIC or no intervention, in blocks of four individuals. RIC is begun at least 10 min before the estimated time of the first balloon inflation and its duration is 30 min. Ischemia is induced by three cycles of inflation of a blood pressure cuff placed on the left lower limb to 200 mmHg and then deflation to 0 mmHg for another 5 min. Primary endpoint is a combined endpoint of death from cardiac cause or hospitalization for heart failure (HF) on follow-up (including device implantation: implantable cardioverter defibrillator, cardiac resynchronization and left ventricular assist device). Secondary endpoints are myocardial infarction (MI) size (estimated by the 48 h area under the curve of serum troponin I levels), development of Q-wave MI, left ventricular function (assessed by echocardiography within the first 3 days after admission), contrast-induced nephropathy, in-hospital mortality, all-cause mortality and, finally, major adverse cardiovascular events. Patients will have a minimum follow-up period of 12 months. From 11 March 2013 to 31 December 2014, 324 patients have been enrolled and randomized. We expect to complete enrollment of the 494 patients deemed necessary within 3 years.info:eu-repo/semantics/publishedVersio

Indifferentiated osteoclastic-type giant cell carcinoma

Initially described 40 years ago (Rosai), the undifferentiated osteoclastic-type giant cell carcinoma (IOGCC) is a variant of ductal adenocarcinoma and accounts for less than 1% of exocrine pancreatic tumors. Its extreme rarity, with consequent existence of few reports and clinical experience, leads to the arousal of doubts with regard to its histogenesis, types of approach and therapeutical attitudes. It is important to note that in Portugal no similar case is registered in medical literature. A 61 year old patient admitted to the Internal Medicine Ward 3 at Coimbra University Hospital presents with a volumous intra-abdominal mass in the left hypochondrium and microcytic anemia. During the investigation, a pancreatic neoplasm was identified, and the patient was submitted to surgical resection, the anatomo-pathological study of the tumor having revealed IOGCC. The particularities of the case, current available therapeutical options and its evolution are discussed, as well as a revision of the existing literature

Can ePROMs improve the understanding and management of lung cancer patients’ Quality of Life? A Scoping review (Preprint)

Background: Electronic patient-reported outcome measures (ePROMs) are essential for clinical practice and research. The growth of electronic health technologies has provided unprecedented opportunities to collect information systematically through ePROMs. They are widely used in scientific research, but we need more evidence if they will also be used, with their implementation, in daily clinical practice. For example, patients with lung cancer have an advanced stage of the disease when diagnosed. This entails tremendous suffering due to high mortality and losses in the different dimensions of the human being. In this case, monitoring symptoms and other outcomes expressly represent great utility in improving a patient's quality of life. Objective: ePROMs provided unprecedented opportunities to collect information systematically. The authors aim to prove that ePROMs are more helpful in managing patient symptoms, lung cancer, and overall survival than their alternatives, such as non-electronic PROMs. Methods: This scoping review considered articles published between 2017 and 2022 identified through searches in PubMed, Scopus, Cochrane, CINAHL, and PsycINFO. We found 5,097 articles; after eliminating duplicates, we reduced them to 3,315, and after reading the abstract, we were left with 56; finally, after applying the exclusion criteria, we reviewed 12. Arksey and O'Malley's five-step framework was used to refine the initial search results with the following research questions: 1) Do ePROMs help physician-patient communication? 2) To what extent do they improve decision-making? 3) Are institutions and their digitization policies barriers or enablers for this process? 4) What else is needed for routine implementation?. Results: Twelve articles were included in this review. The answers to our questions were: 1) ePROMs are an integrative and facilitative communication tool, highlighting their importance in the relationship between palliative care and medical oncology. 2) ePROMs help assess patient symptoms and functionality more accurately and facilitate clinical decision-making. In addition, it allows more precise predictions of overall patient survival and the adverse effects of their treatments. 3) The main institutional obstacles are the initial investment, which can be costly, and the data protection policy. However, as enablers, we have better funding through the development of telemedicine, support from institutional leaders to overcome resistance to change, and transparent policies to ensure the safe and secure use of ePROMs. 4) More than evidence for its routine application, its implementation must overcome physicians' inertia and safeguard the confidentiality of the data obtained. Conclusions: Routine collection of remote ePROMs is an effective and valuable strategy for providing real-time clinical feedback. In addition, it provides satisfaction to patients and professionals. Optimizing ePROMs in lung cancer patients leads to a more accurate view of health outcomes and ensures quality patient follow-up. It also allows us to stratify patients based on their morbidity, creating specific follow-ups for their needs. However, data privacy and security are concerns when using ePROMs to ensure compliance with local entities. At least four barriers were identified: cost, complex programming within health systems, security, and socio-health literacy.info:eu-repo/semantics/publishedVersio

Bioprospecting of yeasts for amylase production in solid state fermentation and evaluation of the catalytic properties of enzymatic extracts

Profiling microorganisms with potential for amylase production in low cost culture media has been widely recognized due to its broad applicability. The aim of this study was to select yeast strains with potential to produce amylolytic enzymes by solid state fermentation. Fifty-four (54) strains were assessed and three exhibited ability to produce amylases: Candida parapsilosis with 14.68 U/mL (146.8 U/g substrate); Rhodotorula mucilaginosa with 25.0 U/mL (250 U/g substrate), and Candida glabrata with 25.39 U/mL (253.9 U/g substrate), in solid state fermentation, for 120 h at 28°C, using wheat bran with 70% moisture. The enzymes exhibited maximum activity at a pH of 7.0 and at 60°C. Amylases demonstrated satisfactory structural stability, maintaining their catalytic activity after 1 h at 50°C. All enzymes were ethanol tolerant and retained more than 70% of their original activities in 15% ethanol solution. Corn starch was efficiently hydrolyzed by enzymes and the extracts produced by C. parapsilosis and C. glabrata exhibited dextrinizing activity, while those produced by R. mucilaginosa exhibited saccharifying activity. Key words: Candida parapsilosis, Candida glabrata, Rhodotorula mucilaginosa, dextrinizing and saccharifying activit

Idea representation and elaboration in design inspiration and fixation experiments

Design fixation experiments often report that participants exposed to an example solution generate fewer ideas than those who were not. This reduced ‘idea fluency’ is generally explained as participants’ creativity being constrained by the example they have seen. However, the inclusion of an example also introduces other factors that might affect idea fluency in the experiments. We here offer an additional explanation for these results: participants not exposed to the example tend to generate ideas with little elaboration, while the level of detail in the example encourages a similar level of elaboration among stimulated participants. Because idea elaboration is time consuming, non-stimulated participants record more ideas overall. We investigated this hypothesis by reanalyzing data from three different studies; in two of them we found that non-stimulated participants generated more ideas and more ideas containing only text, whilst stimulated participants generated ideas that were more elaborated. Based on the creativity literature, we provide several explanations for the differences in results found across studies. Our findings and explanations have implications for the interpretation of creativity experiments reported to date and for the design of future studies.The CAPES Foundation, Ministry of Education of Brazil (BEX11468/13-0); The UK’s Engineering and Physical Sciences Research Council (EP/K008196/1

Scotogenic dark matter and Dirac neutrinos from unbroken gauged B−LB-L symmetry

We propose a simple extension of the standard model where neutrinos get naturally small "scotogenic" Dirac masses from an unbroken gauged $B-L$ symmetry, ensuring dark matter stability. The associated gauge boson gets mass through the Stueckelberg mechanism. Two scenarios are identified, and the resulting phenomenology briefly sketched.Comment: 9 pages, 3 tables, 1 figur

Rationale, design and methodology for Intraventricular Pressure Gradients Study: a novel approach for ventricular filling assessment in normal and falling hearts

<p>Abstract</p> <p>Background</p> <p>Intraventricular pressure gradients have been described between the base and the apex of the left ventricle during early diastolic ventricular filling, as well as, their increase after systolic and diastolic function improvement. Although, systolic gradients have also been observed, data are lacking on their magnitude and modulation during cardiac dysfunction. Furthermore, we know that segmental dysfunction interferes with the normal sequence of regional contraction and might be expected to alter the physiological intraventricular pressure gradients. The study hypothesis is that systolic and diastolic gradients, a marker of normal left ventricular function, may be related to physiological asynchrony between basal and apical myocardial segments and they can be attenuated, lost entirely, or even reversed when ventricular filling/emptying is impaired by regional acute ischemia or severe aortic stenosis.</p> <p>Methods/Design</p> <p><it>Animal Studies: </it>Six rabbits will be completely instrumented to measuring apex to outflow-tract pressure gradient and apical and basal myocardial segments lengthening changes at basal, afterloaded and ischemic conditions. Afterload increase will be performed by abruptly narrowing or occluding the ascending aorta during the diastole and myocardial ischemia will be induced by left coronary artery ligation, after the first diagonal branch.</p> <p><it>Patient Studies: </it>Patients between 65-80 years old (n = 12), both genders, with severe aortic stenosis referred for aortic valve replacement will be selected as eligible subjects. A high-fidelity pressure-volume catheter will be positioned through the ascending aorta across the aortic valve to measure apical and outflow-tract pressure before and after aortic valve replacement with a bioprosthesis. Peak and average intraventricular pressure gradients will be recorded as apical minus outflow-tract pressure and calculated during all diastolic and systolic phases of cardiac cycle.</p> <p>Discussion</p> <p>We expect to validate the application of our method to obtain intraventricular pressure gradients in animals and patients and to promote a methodology to better understand the ventricular relaxation and filling and their correlation with systolic function.</p

Intervention effects of Ganoderma lucidum spores on epileptiform discharge hippocampal neurons and expression of Neurotrophin-4 and N-Cadherin

Epilepsy can cause cerebral transient dysfunctions. Ganoderma lucidum spores (GLS), a traditional Chinese medicinal herb, has shown some antiepileptic effects in our previous studies. This was the first study of the effects of GLS on cultured primary hippocampal neurons, treated with Mg2+ free medium. This in vitro model of epileptiform discharge hippocampal neurons allowed us to investigate the anti-epileptic effects and mechanism of GLS activity. Primary hippocampal neurons from <1 day old rats were cultured and their morphologies observed under fluorescence microscope. Neurons were confirmed by immunofluorescent staining of neuron specific enolase (NSE). Sterile method for GLS generation was investigated and serial dilutions of GLS were used to test the maximum non-toxic concentration of GLS on hippocampal neurons. The optimized concentration of GLS of 0.122 mg/ml was identified and used for subsequent analysis. Using the in vitro model, hippocampal neurons were divided into 4 groups for subsequent treatment i) control, ii) model (incubated with Mg2+ free medium for 3 hours), iii) GLS group I (incubated with Mg2+ free medium containing GLS for 3 hours and replaced with normal medium and incubated for 6 hours) and iv) GLS group II (neurons incubated with Mg2+ free medium for 3 hours then replaced with a normal medium containing GLS for 6 hours). Neurotrophin-4 and N-Cadherin protein expression were detected using Western blot. The results showed that the number of normal hippocampal neurons increased and the morphologies of hippocampal neurons were well preserved after GLS treatment. Furthermore, the expression of neurotrophin-4 was significantly increased while the expression of N-Cadherin was decreased in the GLS treated group compared with the model group. This data indicates that GLS may protect hippocampal neurons by promoting neurotrophin-4 expression and inhibiting N-Cadherin expression

Altered thymic differentiation and modulation of arthritis by invariant NKT cells expressing mutant ZAP70

Various subsets of invariant natural killer T (iNKT) cells with different cytokine productions develop in the mouse thymus, but the factors driving their differentiation remain unclear. Here we show that hypomorphic alleles of Zap70 or chemical inhibition of Zap70 catalysis leads to an increase of IFN-gamma-producing iNKT cells (NKT1 cells), suggesting that NKT1 cells may require a lower TCR signal threshold. Zap70 mutant mice develop IL-17-dependent arthritis. In a mouse experimental arthritis model, NKT17 cells are increased as the disease progresses, while NKT1 numbers negatively correlates with disease severity, with this protective effect of NKT1 linked to their IFN-gamma expression. NKT1 cells are also present in the synovial fluid of arthritis patients. Our data therefore suggest that TCR signal strength during thymic differentiation may influence not only IFN-gamma production, but also the protective function of iNKT cells in arthritis

Volatile constituents and behavioral change induced by Cymbopogon winterianus leaf essential oil in rodents

Cymbopogon winterianus Jowitt (‘Java citronella’) is an important essential oil yielding aromatic grass cultivated in India and Brazil and its volatile essential oils extracted from its leaves are used in perfumery, cosmetics, pharmaceuticals and flavoring industries. However, there is no report on any psychopharmacological study of C. winterianus leaf essential oil (LEO) available to date. In this study, the pharmacological effects of the LEO were investigated in animal models and its phytochemical analyses. GC-MS analysis showed a mixture of monoterpenes, as citronellal (36.19%), geraniol (32.82%) and citronellol (11.37%). LEO exhibited an inhibitory effect on the locomotor activity of mice, an antinociceptive effect by increasing the reaction time in the writhing and capsaicin tests. All doses induced a significant increase in the sleeping time of animals not having modified however, the latency. The LEO did not alter the remaining time of the animals on the rota-rod apparatus. These results suggest a possible central effect.Key words: Cymbopogon winterianus, essential oil, CNS, behavioral effects, analgesic