Activation of effector immune cells promotes tumor stochastic extinction: A homotopy analysis approach

In this article we provide homotopy solutions of a cancer nonlinear model describing the dynamics of tumor cells in interaction with healthy and effector immune cells. We apply a semi-analytic technique for solving strongly nonlinear systems - the Step Homotopy Analysis Method (SHAM). This algorithm, based on a modification of the standard homotopy analysis method (HAM), allows to obtain a one-parameter family of explicit series solutions. By using the homotopy solutions, we first investigate the dynamical effect of the activation of the effector immune cells in the deterministic dynamics, showing that an increased activation makes the system to enter into chaotic dynamics via a period-doubling bifurcation scenario. Then, by adding demographic stochasticity into the homotopy solutions, we show, as a difference from the deterministic dynamics, that an increased activation of the immune cells facilitates cancer clearance involving tumor cells extinction and healthy cells persistence. Our results highlight the importance of therapies activating the effector immune cells at early stages of cancer progression

The EEG in acute ischaemic cerebrovascular disease

The electroencephalogram (EEG) is a neurophysiological technique with high temporal resolution and sensibility in the evaluation of brain function in real time. Besides this, EEG is the gold standard for the identification of epileptogenesis and ictogenesis biomarkers. Epileptic seizures and Cerebrovascular disease are two of the most frequent neurological disorders imposing important mutual challenges. Furthermore, in recent years, stroke care has evolved remarkably and, facing a new paradigm of acute standard of care (centred on multidisciplinary Stroke Units), epileptic seizures (as stroke complications) deserve to be rethought. The EEG is an essential neurophysiological exam in the evaluation of patients with epileptic seizures, status epilepticus and/or epilepsy, both for diagnosis and classification, as well as for the establishment of a correct treatment or outcome prediction. Furthermore, EEG has been previously used in cerebrovascular disease with different purposes. However, its clinical usefulness in the differential diagnosis of transient neurological symptoms, specifically in the differentiation between a transient ischaemic attack and some epileptic seizures, and also in the diagnosis or prediction of post-stroke seizures or in post-stroke prognosis prediction, remains uncertain. In this work, we aim to use the clinical model of acute ischaemic cerebrovascular disease to study the value of EEG in the differential diagnosis of transient neurological symptoms, in the diagnosis and prediction of post-stroke seizures and epilepsy, as well as to analyse if electroencephalographic abnormalities and/or epileptic seizures are independent predictors of an anterior circulation ischaemic stroke outcome. Furthermore, since the gold standard of acute stroke care (namely intravenous alteplase treatment) is associated with a reduction of mortality and incapacity of treated patients with possible consequences in post-stroke seizure frequency, but a pro-convulsive and an epileptogenic effect of alteplase has also been described, we aim to test the hypothesis that ischaemic stroke patients treated with intravenous alteplase have a different frequency of epileptic (clinic and/or electroencephalographic) manifestations compared to non-treated patients. Different research methodologies were used in this thesis. A systematic review and meta-analysis of observational studies was performed to evaluate both the frequency of post-stroke (ictal and interictal) epileptiform activity in the EEG, and the quality of studies about this subject. Furthermore, different types of observational studies (including clinical case report, case series and cohort studies) were completed to answer relevant clinical questions. We performed a prospective longitudinal study of possible transient ischaemic attacks (TIA) patients evaluated at a tertiary centre during 36 months, with 1-3 months follow-up and also of acute anterior circulation ischaemic stroke patients, consecutively admitted to a Stroke Unit over 24 months and followed-up for one year. In both studies, patients underwent standardized clinical, diagnostic and neurophysiological assessment. A short duration (≤60 minutes) video-EEG protocol with an extended montage including 64 EEG, two electrooculogram, one electrocardiogram and at least one electromyogram channel was established. Different electroencephalographic investigation technics including visual, back-average and quantitative analysis were used in the clinical workup of patients with possible and definite, transient and established, cerebrovascular disease as tools for the differential diagnosis and for brain functional assessment, concerning not only epileptic manifestations detection and prediction but also to search for predictors of ischaemic stroke functional outcome and vital prognosis. Although epileptic seizures were the most frequent defined final diagnosis (n=13; 16.3%) in our series of 80 patients with difficult-to-diagnose transient neurological symptoms, visual inspection of EEG supported this diagnosis only in 7.5% (n=6) of patients with possible TIA. Moreover, the majority (n=6; 53.8%) of patients with the final diagnosis of epileptic seizures did not have interictal epileptiform activity in an early EEG. Furthermore, early focal slow wave activity, the most frequent EEG abnormality in this patient’s series, did not distinguished between TIA and seizure patients. Our systematic review and random-effects meta-analysis showed that the pooled frequency of post-stroke ictal and interictal epileptiform activity was 7% (95%CI: 3%-12%) and 8% (95%CI: 4%-13%) respectively. Only 2 out of 17 included studies (11.7%) attained the maximum quality score. Moreover, no study exclusively enrolled ischaemic stroke patients, highlighting the need for higher quality studies in the evaluation of epileptiform activity frequency in this type of cerebrovascular disease. Furthermore, due to detection bias, it was not possible to correlate clinical and electrographic seizures. In our prospective cohort of 151 anterior circulation acute stroke patients, we identified different post-stroke, clinical and electroencephalographic, epileptic manifestations including 22.7% (5/22) of acute symptomatic seizures that were exclusively electrographic and therefore could not otherwise be recognised. Furthermore, only EEG back-average analysis allowed the diagnosis of cortical myoclonus during intravenous alteplase perfusion in one clinical vignette included in this work and the recognition of epilepsia partialis continua as a chronic complication of this stroke type in 1.7% of patients. This original work also showed that studied clinical and EEG epileptic manifestations were not significantly different between intravenous alteplase treated and non-treated patients. This thesis work established which abnormalities of an early EEG after acute stroke (background activity asymmetry and the presence of interictal epileptiform activity) are independent predictors of epilepsy in the year after (even when adjusted for clinical and imaging stroke severity). Besides this, early (within the first 72h) post-stroke EEG features, extracted from visual (background activity diffuse slowing and asymmetry) and quantitative (such as delta-theta to alpha-beta ratio and alfa relative power) analysis were recognized as independent predictors of death or functional dependency, at hospital discharge and at 12 months after stroke. Furthermore, outcome models that incorporate delta-theta to alpha-beta ratio or alpha relative power were better than models based exclusively on clinical and imaging-related ischaemic stroke severity at hospital admission. Additionally, post-stroke acute symptomatic seizures and epilepsy were independently associated to death and to an unfavourable outcome 1 year after an acute anterior circulation ischaemic stroke, respectively. Globally, these research projects have shown the value of EEG in the current paradigm of stroke patient’s care. Furthermore, they expand the knowledge both about the EEG role as a complementary neurophysiological tool in general Neurology and about different aspects of the diagnosis and outcome of two of the most prevalent neurological disorders, Cerebrovascular Diseases and Epilepsy, in particular. Beyond the value of specific results, with this work several other research questions about EEG and seizures in ischaemic cerebrovascular disease emerge. Therefore, new possibilities of future research, ideally multicentric, clinical or translational arise

Managing Student Suicidality on Campus: Perspectives from Diverse Student Affairs Staff

Suicidal behavior is a substantial public health issue faced by college campuses. College counseling professionals often interact with a variety of other student affairs professionals who may be involved in the management of suicidality on campus. However, research on their experiences and perspectives on this topic is scarce. In this study, we build on literature related to management of suicidality on campus, which is predominantly focused on campus counseling professionals. Fifteen semi-structured qualitative interviews were conducted with student affairs professionals to explore how professionals on campuses might better work together to prevent crises and support students at elevated risk for suicide. Recurrent and emerging themes included barriers impeding their ability to best serve suicidal students, their perceptions on what factors make students vulnerable to suicide, and suggestions for future research. We conclude with a discussion of options to increase quantity and quality of service provision on campus for suicidal students

Imagen social del bibliotecario : Indagación de la imagen social del bibliotecario que construye el usuario de bibliotecas

This work is based on the investigation of the image that is currently having the / the library / as by library users. Inquire about this in a society where the book is not the mainstay of the information, and new technologies (internet, virtual databases, digital archives, etc.) come increasingly different views is necessary for informational revalue the importance of human contact. In the theoretical literature outlines a path in various authors on the capabilities and roles of the traditional figure of the drive current and librarian. We find that the emphasis is on what should be, and the negative image that is mentioned librarian. In the methodological part is chosen to survey library users "Jean Jeaurés" Luján and Leandro N. Alem of General Rodriguez. We decided to compare two pieces of information to view in contrasting claims users see differences and similarities in the perception of / librarians. Also, we analyze the total vision users scored both libraries

Coffee industrial waste as a natural source of bioactive compounds with antibacterial and antifungal activities

Coffee is one of the most popular and consumed beverages in the world, which leads to a high contents of solid residue known as spent coffee grounds (SCG). As is known, coffee beans contain several classes of health related chemicals, including phenolic compounds, melanoidins, diterpenes, xanthines and carotenoids which are associated with therapeutic and pharmaceutical effects, due to antimicrobial, antioxidant, anti-infectious and antitumour activities. Considering that this coffee industrial waste has no commercial value and are currently disposed as a solid waste or employed as fertilizers, we intend to highlight the use of SCG as a raw material with potential interest to the food and pharmaceutical industries. Moreover, this work seems to be valuable to promote the use of SCG as natural and an inexpensive food supplements or pharmaceutical additive. The phytochemical compounds content among the crude aqueous extracts of SCG followed this order: phenolics > flavonoids > carotenoids (mg/ g dry waste), respectively. Caffeine content found in SCG was ~ 0.82 g/100 g dry waste, 70 % lower than coffee roasting beans. Coffee ground extracts showed inhibition to S. aureus and E. coli growth for concentrations of 1.0 mg/ mL and a stronger inhibition was also observed against C. albicans, C. krusei and C. parapsilosis growth using lower concentration (0.5 mg/ mL).info:eu-repo/semantics/publishedVersio

Holistic tourism: Motivations, self-image and satisfaction

Holistic tourism has become a new and alternative form of tourism and an important trend among tourists who seek programs and experiences that would allow them to achieve balance between mind, body and soul. Choosing holistic tourism means that a tourist can enjoy a different and full experience which goes beyond the simple contact with cultures, people, places or landscapes. It focuses on self-transformation and on an attempt of people understanding more about themselves. It is crucial we understand each person´s view about this new type of tourism since this perspective will surely bring potential new investors to this product. Knowing what every tourist values, feels and needs- in terms of personal fulfillment- can turn this new type of tourism into a competitive one. This study includes an empirical research conducted through questionnaires to 300 holistic tourists in four different Portuguese destinations: Azores, Gerês, Lisbon and Algarve. The results allowed a better understanding of the holistic tourists’ characteristics, their main motivations, self-image perception and satisfaction levels while taking part in holistic tourism.Polytechnic Institute of Viseu, the Center for Studies in Education, Technologies and Health (CI&DETS) and the Portuguese Foundation for Science and Technology (FCT).info:eu-repo/semantics/publishedVersio

Inactive trans-sialidase expression in iTS-null Trypanosoma cruzi generates virulent trypomastigotes

Disclosing virulence factors from pathogens is required to better understand the pathogenic mechanisms involved in their interaction with the host. In the case of Trypanosoma cruzi several molecules are associated with virulence. Among them, the trans-sialidase (TS) has arisen as one of particular relevance due to its effect on the immune system and involvement in the interaction/invasion of the host cells. The presence of conserved genes encoding for an inactive TS (iTS) isoform is puzzlingly restricted to the genome of parasites from the Discrete Typing Units TcII, TcV, and TcVI, which include highly virulent strains. Previous in vitro results using recombinant iTS support that this isoform could play a different or complementary pathogenic role to that of the enzymatically active protein. However, direct evidence involving iTS in in vivo pathogenesis and invasion is still lacking. Here we faced this challenge by transfecting iTS-null parasites with a recombinant gene that allowed us to follow its expression and association with pathological events. We found that iTS expression improves parasite invasion of host cells and increases their in vivo virulence for mice as shown by histopathologic findings in heart and skeletal muscle.Fil: Pascuale, Carla Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Burgos, Juan Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Postan, Miriam. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; ArgentinaFil: Lantos, Andrés Bernardo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Bertelli, Adriano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Campetella, Oscar Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Leguizamon, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentin

Coffee industrial waste as a natural source of bioactive compounds with antibacterial and antifungal activities

Coffee is one of the most popular and consumed beverages in the world, which leads to a high contents of solid residue known as spent coffee grounds (SCG). As is known, coffee beans contain several classes of health related chemicals, including phenolic compounds, melanoidins, diterpenes, xanthines and carotenoids which are associated with therapeutic and pharmaceutical effects, due to antimicrobial, antioxidant, anti-infectious and antitumour activities. Considering that this coffee industrial waste has no commercial value and are currently disposed as a solid waste or employed as fertilizers, we intend to highlight the use of SCG as a raw material with potential interest to the food and pharmaceutical industries. Moreover, this work seems to be valuable to promote the use of SCG as natural and an inexpensive food supplements or pharmaceutical additive. The phytochemical compounds content among the crude aqueous extracts of SCG followed this order: phenolics > flavonoids > carotenoids (mg/ g dry waste), respectively. Caffeine content found in SCG was ~ 0.82 g/100 g dry waste, 70 % lower than coffee roasting beans. Coffee ground extracts showed inhibition to S. aureus and E. coli growth for concentrations of 1.0 mg/ mL and a stronger inhibition was also observed against C. albicans, C. krusei and C. parapsilosis growth using lower concentration (0.5 mg/ mL).info:eu-repo/semantics/publishedVersio

TGF-β2 dictates disseminated tumour cell fate in target organs through TGF-β-RIII and p38α/β signalling

In patients, non-proliferative disseminated tumour cells (DTCs) can persist in the bone marrow (BM) while other organs (such as lung) present growing metastasis. This suggested that the BM might be a metastasis ‘restrictive soil’ by encoding dormancy-inducing cues in DTCs. Here we show in a head and neck squamous cell carcinoma (HNSCC) model that strong and specific transforming growth factor-β2 (TGF-β2) signalling in the BM activates the MAPK p38α/β, inducing an (ERK/p38)low signalling ratio. This results in induction of DEC2/SHARP1 and p27, downregulation of cyclin-dependent kinase 4 (CDK4) and dormancy of malignant DTCs. TGF-β2-induced dormancy required TGF-β receptor-I (TGF-β-RI), TGF-β-RIII and SMAD1/5 activation to induce p27. In lungs, a metastasis ‘permissive soil’ with low TGF-β2 levels, DTC dormancy was short-lived and followed by metastatic growth. Importantly, systemic inhibition of TGF-β-RI or p38α/β activities awakened dormant DTCs, fuelling multi-organ metastasis. Our work reveals a ‘seed and soil’ mechanism where TGF-β2 and TGF-β-RIII signalling through p38α/β regulates DTC dormancy and defines restrictive (BM) and permissive (lung) microenvironments for HNSCC metastasis.Fil: Bragado, Paloma. Mount Sinai School of Medicine. Tisch Cancer Institute; Estados UnidosFil: Estrada, Yeriel. Mount Sinai School of Medicine. Tisch Cancer Institute; Estados UnidosFil: Parikh, Falguni. Mount Sinai School of Medicine. Tisch Cancer Institute; Estados UnidosFil: Krause, Sarah. University Hospital of Schleswig-Holstein; AlemaniaFil: Capobianco, Carla Sabrina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Farina, Hernán Gabriel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schewe, Denis M.. Mount Sinai School of Medicine. Tisch Cancer Institute; Estados UnidosFil: Aguirre Ghiso, Julio A.. Mount Sinai School of Medicine. Tisch Cancer Institute; Estados Unido

Sexualidade da pessoa com deficiência intelectual - Atitudes de pais e profissionais

Dissertação de Mestrado em Psicologia Educacional, apresentada ao ISPA - Instituto UniversitárioTendo em conta que as atitudes dos pais e profissionais face à sexualidade das pessoas com deficiência intelectual têm um papel preponderante na disponibilização de oportunidades de vivências e experiências sexuais e na passagem de informação correcta acerca da sexualidade (Brown & Pirtle, 2008), o presente estudo pretende conhecer e analisar as atitudes e necessidades que ambos têm, bem como verificar se existem diferenças estatisticamente significativas entre elas. Tendo sido utilizada uma abordagem mista através da utilização do questionário ASQ-ID- Attitudes to Sexuality Questionnaire (Individuals with an Intellectual Disability) e de uma entrevista semi-estruturada, o presente estudo contou com uma amostra de 130 participantes (80 profissionais e 50 pais), dos quais três mães e três profissionais foram entrevistados. Os resultados obtidos confirmaram a nossa hipótese de que existem diferenças estatisticamente significativas nas atitudes dos pais e profissionais, demonstrando que os profissionais têm atitudes mais liberais. Através das entrevistas, verificámos que os profissionais têm necessidades de formação no que toca à capacidade para intervirem de forma adequada nas várias manifestações sexuais dos seus clientes, tendo sido enfatizada a necessidade do envolvimento da família neste processo, a consideração das diferenças individuais e a promoção de contextos favoráveis nas instituições para as vivências e experiências sexuais desta população. Por fim, atestou-se ainda através do discurso dos inquiridos, a falta de um consenso dentro das instituições acerca daquilo que devem fazer em situações onde os clientes necessitam de resposta.ABSTRACT: Given that the attitudes of parents and professionals towards sexuality of people with intellectual disabilities have a role in providing opportunities for experiences and sexual experiences and pass correct information about sexuality (Brown & Pirtle, 2008), this study seeks to examine and analyze the attitudes and needs that both have and see if there are statistically significant differences between them. Having used a mixed approach by using the questionnaire ASQ-ID-Attitudes to Sexuality Questionnaire (Individuals with an Intellectual Disability) and a semi-structured interview, this study involved a sample of 130 participants (80 professionals and 50 parents), of which three mothers and three professionals were interviewed. The results confirmed our hypothesis that there are significant differences in the attitudes of parents and professionals, demonstrating that professionals have more liberal attitudes. Through the interviews, we found that professionals have training needs in relation to the ability to intervene appropriately in various sexual manifestations of its customers, having emphasized the need to involve the family in this process, consideration of individual differences and promoting favorable contexts in institutions for sexual experiences and the experiences of this population. Finally, it is also attested by the discourse of the respondents, the lack of consensus within institutions about what they should do in situations where customers need to be answered