957 resultados para Clear majority
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Dissertação para obtenção do grau de Mestre em Arquitetura, apresentada na Universidade de Lisboa - Faculdade de Arquitetura.
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Tese (doutorado)—Universidade de Brasília, Faculdade de Educação, Programa de Pós-Graduação em Educação, 2016.
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The emerging concept of psychobiotics—live microorganisms with a potential mental health benefit—represents a novel approach for the management of stress-related conditions. The majority of studies have focused on animal models. Recent preclinical studies have identified the B. longum 1714 strain as a putative psychobiotic with an impact on stress-related behaviors, physiology and cognitive performance. Whether such preclinical effects could be translated to healthy human volunteers remains unknown. We tested whether psychobiotic consumption could affect the stress response, cognition and brain activity patterns. In a within-participants design, healthy volunteers (N=22) completed cognitive assessments, resting electroencephalography and were exposed to a socially evaluated cold pressor test at baseline, post-placebo and post-psychobiotic. Increases in cortisol output and subjective anxiety in response to the socially evaluated cold pressor test were attenuated. Furthermore, daily reported stress was reduced by psychobiotic consumption. We also observed subtle improvements in hippocampus-dependent visuospatial memory performance, as well as enhanced frontal midline electroencephalographic mobility following psychobiotic consumption. These subtle but clear benefits are in line with the predicted impact from preclinical screening platforms. Our results indicate that consumption of B. longum 1714 is associated with reduced stress and improved memory. Further studies are warranted to evaluate the benefits of this putative psychobiotic in relevant stress-related conditions and to unravel the mechanisms underlying such effects.
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Transparent thin films can now be site-selectively patterned and positioned on surface using mask-defined electrodeposition of one oxide and overcoating with a different solution-processed oxide, followed by thermal annealing. Annealing allows an interdiffusion process to create a new oxide that is entirely transparent. A primary electrodeposited oxide can be patterned and the secondary oxide coated over the entire substrate to form high color contrast coplanar thin film tertiary oxide. The authors also detail the phase formation and chemical state of the oxide and how the nature of the electrodeposited layer and the overlayer influence the optical clearing of the patterned oxide film.
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Projeto de Graduação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de licenciada em Enfermagem
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O estilo de vida, atualmente, tem bastante influência na higiene do sono. São diversos os fatores que contribuem tanto para a sua manutenção como para a sua falha. O trabalho por turnos está frequentemente associado a elevadas cargas de stresse e fadiga devido a situações imprevisíveis e perigosas que possam advir da área profissional, da rotatividade do horário laboral, a um sono deficiente, à falta de atividades desportivas e de lazer, bem como à má alimentação. Estilo de vida, este, que reduz a qualidade de vida em geral e aumenta drasticamente a probabilidade de surgir doenças quer ao nível físico como mental. O sono, por sua vez, é um fenómeno universal de grande importância para o desenvolvimento humano. A qualidade do sono é determinada por vários fatores, entre eles as rotinas de sono. Torna-se, assim, importante estudar as rotinas de forma a incrementar o conhecimento sobre este determinante. A alternância do dia-noite –claro/escuro -, os horários de trabalho, os horários de lazer, as atividades familiares são todos fatores exógenos que sincronizam o ciclo sono-vigília. Estudar a qualidade de sono em profissionais que trabalham por turnos é de extrema relevância visto tratar-se de uma população cada vez mais em risco e em que se considera que o sono seja um dos fatores mais comprometidos. O presente estudo tem como objetivo caraterizar e avaliar a qualidade do sono em profissionais, em função dos horários de trabalho. A metodologia utilizada é quantitativa e centrou-se na aplicação do questionário IQSP – Índice de Qualidade do Sono de Buysse et al. (1989), adaptado e traduzido para português. O questionário foi aplicado a 50 indivíduos pertencentes à Polícia Marítima, na Zona Norte de Portugal Continental, na maioria (92%) homens com idades compreendidas entre os 36 e os 55 anos. Do total de participantes, 76% (n=38) encontra-se a trabalhar por turnos. A análise dos dados foi efetuada através do Statistical Package for the Social Sciences, versão 22, tendo sido realizadas análises descritivas, inferenciais e correlacionais. Com maior relevância, no presente estudo, conclui-se que não existem diferenças estatisticamente significativas na qualidade do sono entre aqueles que trabalham por turnos e os que têm horário fixo, bem como, que a qualidade do sono também não se diferencia em função da idade, do tempo de profissão e da existência de filhos pequenos. Conclui-se, ainda, que a qualidade do sono parece estar relacionada com a satisfação com o horário de trabalho.
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This study examined whether instrumental and normative learning contexts differentially influence 4- to 7-year-old children’s social learning strategies; specifically, their dispositions to copy an expert versus a majority consensus. Experiment 1 (N = 44) established that children copied a relatively competent “expert” individual over an incompetent individual in both kinds of learning context. In experiment 2 (N = 80) we then tested whether children would copy a competent individual versus a majority, in each of the two different learning contexts. Results showed that individual children differed in strategy, preferring with significant consistency across two different test trials to copy either the competent individual or the majority. This study is the first to show that children prefer to copy more competent individuals when shown competing methods of achieving an instrumental goal (Experiment 1) and provides new evidence that children, at least in our “individualist” culture, may consistently express either a competency or majority bias in learning both instrumental and normative information (Experiment 2). This effect was similar in the instrumental and normative learning contexts we applied.
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The gammacoronavirus, Infectious Bronchitis Virus (IBV), is a respiratory pathogen of chickens. IBV is a constant threat to poultry production as established vaccines are often ineffective against emerging strains. This requires constant and rapid vaccine production by a process of viral attenuation by egg passage, but the essential forces leading to attenuation in the virus have not yet been characterised. Knowledge of these factors will lead to the development of more effective, rationally attenuated, live vaccines and reduction of the mortality and morbidity caused by this pathogen. M41 CK strain was egg passaged four times many years ago at Houghton Poultry Research Station and stored as M41-CK EP4 (stock virus at The Pirbright Institute since 1992). It was the first egg passage to have its genome pyrosequenced and was therefore used as the baseline reference. The overall aim of this project was to analyse deep sequence data obtained from four IBV isolates (called A, A1, C and D) each originating from the common M41-CK EP4 (ep4) and independently passaged multiple times in embryonated chicken eggs (figure 1.1). Highly polymorphic encoding regions of the IBV genome were then identified which are likely involved in the attenuation process through the formation of independent SNPs and/or SNP clusters. This was then used to direct targeted investigation of SNPs during the attenuation process of the four IBV passages. A previously generated deep sequence dataset was used as a preliminary map of attenuation for one virulent strain of IBV. This investigation showed the nucleocapsid and spike as two highly polymorphic encoding regions within the IBV genome with the highest proportion of SNPs compared to encoding region size. This analysis then led to more focussed studies of the nucleocapsid and spike encoding region with the ultimate aim of mapping key attenuating regions and nucleotide positions. The 454 pyrosequencing data and further investigation of nucleocapsid and spike encoding regions have identified the SNPs present at the same nucleotide positions within analysed A, A1, C and D isolates. These SNPs probably play a crucial role in viral attenuation and universal vaccine production but it is not clear if independent SNPs are also involved in loss of virulence. The majority of SNPs accumulated at different nucleotide positions without further continuation in Sanger sequenced egg passages presenting S2 subunit (spike) and nucleocapsid as polymorphic encoding regions which in nature remain highly conserved.
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Breast cancer, the most commonly diagnosed type of cancer in women, is a major cause of morbidity and mortality in the western world. Well-established risk factors of breast cancer are mostly related to women’s reproductive history, such as early menarche, late first pregnancy and late menopause. Survival rates have improved due to a combination of factors, including better health education, early detection with large-scale use of screening mammogram, improved surgical techniques, as well as widespread use of adjuvant therapy. At initial presentation, clinicopathological features of breast cancer such as age, nodal status, tumour size, tumour grade, and hormonal receptor status are considered to be the standard prognostic and predictive markers of patient survival, and are used to guide appropriate treatment strategies. Lymphovascular invasion (LBVI), including lymphatic (LVI) and blood (BVI) vessel invasion, has been reported to be prognostic and merit accurate evaluation, particularly in patients with node negative tumours who might benefit from adjuvant chemotherapy. There is a lack of standard assessment and agreement on distinguishing LVI from BVI despite the major challenges in the field. A systematic review of the literatures, examining methods of detection and the prognostic significance of LBVI, LVI and BVI, was carried out. The majority of studies used haematoxylin and eosin (H&E) and classical histochemistry to identify LVI and BVI. Only few recent studies used immunohistochemistry (IHC) staining of the endothelium lining lymphatic and blood vessels, and were able to show clear differences between LVI and BVI. The prognostic significance of LBVI and LVI was well-documented and strongly associated with aggressive features of breast tumours, while the prognostic value and the optimal detection method of BVI were unclear. Assessment and prognostic value of LBVI on H&E sections (LBVIH&E) was examined and compared to that of LVI and BVI detected using IHC with D2-40 for LVI (LVID2–40) and Factor VIII for BVI (BVIFVIII) in patients with breast cancer including node negative and triple negative patients (n=360). LBVIH&E, LVID2–40 and BVIFVIII were present in 102 (28%), 127 (35%) and 59 (16%) patients respectively. In node negative patients (206), LBVIH&E, LVID2–40 and BVIFVIII were present in 41 (20%), 53 (26%) and 21 (10%) respectively. In triple negative patients (102), LBVIH&E, LVID2–40 and BVIFVIII were present in 35 (29%), 36 (35%) and 14 (14%) respectively. LBVIH&E, LVID2–40 and BVIFVIII were all significantly associated with tumour recurrence in all cohorts. On multivariate survival analysis, only LVID2–40 and BVIFVIII were independent predictors of cancer specific survival (CSS) in the whole cohort (P=0.022 and P<0.001 respectively), node negative (P=0.008 and P=0.001 respectively) and triple negative patients (P=0.014 and P<0.001 respectively). Assessment of LVI and BVI by IHC, using D2-40 and Factor VIII, improves prediction of outcome in patients with node negative and triple negative breast cancer and was superior to the conventional detection method. Breast cancer is recognised as a complex molecular disease and histologically identical tumours may have highly variable outcomes, including different responses to therapy. Therefore, there is a compelling need for new prognostic and predictive markers helpful of selecting patients at risk and patients with aggressive diseases who might benefit from adjuvant and targeted therapy. It is increasingly recognised that the development and progression of human breast cancer is not only determined by genetically abnormal cells, but also dependent on complex interactions between malignant cells and the surrounding microenvironment. This has led to reconsider the features of tumour microenvironment as potential predictive and prognostic markers. Among these markers, tumour stroma percentage (TSP) and tumour budding, as well as local tumour inflammatory infiltrate have received recent attention. In particular, the local environment of cytokines, proteases, angiogenic and growth factors secreted by inflammatory cells and stromal fibroblasts has identified crucial roles in facilitating tumour growth, and metastasis of cancer cells through lymphatic and/or blood vessel invasion. This might help understand the underlying process promoting tumour invasion into these vessels. An increase in the proportion of tumour stroma and an increase in the dissociation of tumour cells have been associated with poorer survival in a number of solid tumours, including breast cancer. However, the interrelationship between these variables and other features of the tumour microenvironment in different subgroups of breast cancer are not clear. Also, whether their prognostic values are independent of other components of the tumour microenvironment have yet to be identified. Therefore, the relationship between TSP, clinicopathological characteristics and outcome in patients with invasive ductal breast cancer, in particular node negative and triple negative disease was examined in patients with invasive ductal breast cancer (n=361). The TSP was assessed on the haematoxylin and eosin-stained tissue sections. With a cut-off value of 50% TSP, patients with ≤50% stroma were classified as the low-TSP group and those with >50% stroma were classified as the high-TSP group. A total of 109 (30%) patients had high TSP. Patients with high TSP were old age (P=0.035), had involved lymph node (P=0.049), Her-2 positive tumours (P=0.029), low-grade peri-tumoural inflammatory infiltrate (P=0.034), low CD68+ macrophage infiltrate (P<0.001), low CD4+ (P=0.023) and low CD8+ T-lymphocytes infiltrate (P=0.017), tumour recurrence (P=0.015) and shorter CSS (P<0.001). In node negative patients (n=207), high TSP was associated with low CD68+ macrophage infiltrate (P=0.001), low CD4+ (P=0.040) and low CD8+ T-lymphocytes infiltrate (P=0.016) and shorter CSS (P=0.005). In triple negative patients (n=103), high TSP was associated with increased tumour size (P=0.017) high tumour grade (P=0.014), low CD8+ T-lymphocytes infiltrate (P=0.048) and shorter CSS (P=0.041). The 15-year cancer specific survival rate was 79% vs 21% in the low-TSP group vs high-TSP group. On multivariate survival analysis, a high TSP was associated with reduced CSS in the whole cohort (P=0.007), node negative patients (P=0.005) and those who received systemic adjuvant therapy (P=0.016), independent of other pathological characteristics including local host inflammatory responses. Therefore, a high TSP in invasive ductal breast cancer was associated with recurrence and poorer long-term survival. The inverse relation with the tumour inflammatory infiltrate highlights the importance of the amount of tumour stroma on immunological response in patients with invasive ductal breast cancer. Implementing this simple and reproducible parameter in routine pathological examination may help optimise risk stratification in patients with breast cancer. Similarly, the relationship between tumour budding, clinicopathological characteristics and outcome was examined in patients with invasive ductal breast cancer (n=474), using routine pathological sections. Tumour budding was associated with several adverse pathological characteristics, including positive lymph node (P=0.009), presence of LVI (P<0.001), and high TSP (P=0.001) and low-grade general peri-tumural inflammatory infiltrative (P=0.002). In node negative patients, a high tumour budding was associated with presence of LVI (P<0.001) and low-grade general peri-tumural inflammatory infiltrative (P=0.038). On multivariate survival analysis, tumour budding was associated with reduced CSS (P=0.001), independent of nodal status, tumour necrosis, CD8+ and CD138+ inflammatory cells infiltrate, LVI, BVI and TSP. Furthermore, tumour budding was independently associated with reduced CSS in node negative patients (P=0.004) and in those who have low TSP (P=0.003) and high-grade peri-tumoural inflammatory infiltrative (P=0.012). A high tumour budding was significantly associated with shorter CSS in luminal B and triple negative breast cancer subtypes (all P<0.001). Therefore, tumour budding was a significant predictor of poor survival in patients with invasive ductal breast cancer, independent of adverse pathological characteristics and components of tumour microenvironment. These results suggest that tumour budding may promote disease progression through a direct effect on local and distant invasion into lymph nodes and lymphatic vessels. Therefore, detection of tumour buds at the stroma invasive front might therefore represent a morphologic link between tumour progression, lymphatic invasion, spread of tumour cells to regional lymph nodes, and the establishment of metastatic dissemination. Given the potential importance of the tumour microenvironment, the characterisation of intracellular signalling pathways is important in the tumour microenvironment and is of considerable interest. One plausible signalling molecule that links tumour stroma, inflammatory cell infiltrate and tumour budding is the signal transducer and activator of transcription (STAT). The relationship between total and phosphorylated STAT1 (ph-STAT1), and total and ph-STAT3 tumour cell expression, components of tumour microenvironment and survival in patients with invasive ductal breast cancer was examined. IHC of total and ph-STAT1/STAT3 was performed on tissue microarray of 384 breast cancer specimens. Cellular STAT1 and cellular STAT3 expression at both cytoplasmic and nuclear locations were combined and identified as STAT1/STAT3 tumour cell expression. These results were then related to CSS and phenotypic features of the tumour and host. A high ph-STAT1 and a high ph-STAT3 tumour cell expression was associated with increased ER (P=0.001 and P<0.001 respectively) and PR (all P<0.05), reduced tumour grade (P=0.015 and P<0.001 respectively) and necrosis (all P=0.001). Ph-STAT1 was associated with increased general peri-tumoural inflammatory infiltrate (P=0.007) and ph-STAT3 was associated with lower CD4+ T-lymphocyte infiltrate (P=0.024). On multivariate survival analysis, including both ph-STAT1 and ph-STAT3 tumour cell expression, only high ph-STAT3 tumour cell expression was significantly associated with improved CSS (P=0.010) independent of other tumour and host-based factors. In patients with high necrosis grade, high ph-STAT3 tumour cell expression was independent predictor of improved CSS (P=0.021). Ph-STAT1 and ph-STAT3 were also significantly associated with improved cancer specific survival in luminal A and B subtypes. STAT1 and STAT3 tumour cell expression appeared to be an important determinant of favourable outcome in patients with invasive ductal breast cancer. The present results suggest that STATs may affect disease outcome through direct impact on tumour cells, and the surrounding microenvironment. The above observations of the present thesis point to the importance of the tumour microenvironment in promoting tumour budding, LVI and BVI. The observations from STATs work may suggest that an important driving mechanism for the above associations is the presence of tumour necrosis, probably secondary to hypoxia. Further work is needed to examine the interaction of other molecular pathways involved in the tumour microenvironment, such as HIF and NFkB in patients with invasive ductal breast cancer.
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Las preferencias en elección de pareja de hombres y mujeres interesados en establecer relaciones a largo plazo con personas de su mismo sexo biológico ha sido un tema de interés para el análisis evolucionista, ya que existe debate frente a los resultados de las investigaciones y los planteamientos de las teorías de inversión parental y estrategias sexuales. Con el objetivo de identificar qué características son preferidas por hombres y mujeres interesados en establecer una relación a largo plazo con personas de su mismo sexo biológico y contribuir a esta discusión, se llevó a cabo un estudio descriptivo en el que analizamos el contenido de 732 perfiles de hombres y mujeres (H=491; M=241) que buscaban una relación estable con parejas de su mismo sexo biológico. Las categorías analizadas fueron: edad, atractivo físico (apariencia, contextura, estatura y peso), estatus socioeconómico (situación laboral, nivel educativo y zona de residencia buscada), estado civil, número de hijos y hábitos saludables (fumar y beber). Los resultados encontrados muestran que los hombres presentan rangos amplios en las características deseadas en una pareja (edad=16.87; estatura=11.37; peso=15.23) y además buscan personas menores a la edad ofrecida (M=-4.17 años). En las mujeres se encontró que los rangos son más restringidos (edad=13.85; estatura=9.83; peso=12.77) y además prefieren parejas mayores (M=2.89 años). A nivel general, se evidencia que los resultados encontrados en la mayoría de las variables podrían indicar congruencia con los planteamientos de la teoría de inversión parental y estrategias sexuales; sin embargo, en otras variables los resultados no son claros.
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The lower crustal structure beneath the Western Alps -- including the Moho -- bears the signature of past and present geodynamic processes. It has been the subject of many studies until now. However, its current knowledge still leaves significant open questions. In order to derive new information, independent from previous determinations, here I wish to address this topic using a different method --- ambient seismic noise autocorrelation --- that is for the first time applied to reveal Moho depth in the Western Alps. Moho reflections are identified by picking reflectivity changes in ambient seismic noise autocorrelations. The seismic data is retrieved from more than 200 broadband seismic stations, from the China--Italy--France Alps (CIFALPS) linear seismic network, and from a subset of the AlpArray Seismic Network (AASN). The automatically-picked reflectivity changes along the CIFALPS transect in the southwestern Alps show the best results in the 0.5--1 Hz frequency band. The autocorrelation reflectivity profile of the CIFALPS transect shows a steeper subduction profile,~55 to ~70 km, of the European Plate underneath the Adriatic Plate. The dense spacing of the CIFALPS network facilitates the detection of lateral continuity of crustal structure, and of the Ivrea mantle wedge reaching shallow crustal depths in the southwestern Alps. The data of the AASN stations are filtered in the 0.4--1 and 0.5--1 Hz frequency bands. Although the majority of the stations give the same Moho depth for the different frequency bands, the few stations with different Moho depths shows the care that has to be taken when choosing the frequency band for filtering the autocorrelation stacks. The new Moho depth maps by using the AASN stations are a compilation of the first and second picked reflectivity changes. The results show the complex crust-mantle structure with clear differences between the northwestern and southwestern Alps.
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Clear cell sarcoma of the kidney (CCSK) is the second most common pediatric renal tumor, characterized in 90% of cases by the presence of internal tandem duplications (ITDs) localized at the last exon of BCOR gene. BCOR protein constitute a core component of the non-canonical Polycomb Repressive Complex1 (PRC1.1), which performs a fundamental silencing activity. ITDs in the last BCOR exon at the level of PUFD domain have been identified in many tumor subtypes and could affect PCGF1 binding and the subsequent PRC1.1 activity, although the exact oncogenic mechanism of ITD remains poorly understood. This project has the objective of investigating the molecular mechanisms underlying the oncogenesis of CCSK, approaching the study with different methodologies. A first model in HEK-293 allowed to obtain important informations about BCOR functionality, suggesting that the presence of ITD generates an altered activity which is very different from a loss-of-function. It has also been observed that BCOR function within the PRC1.1 complex varies with different ITDs. Moreover, it allowed the identification of molecular signatures evoked by the presence of BCOR-ITD, including its role in extracellular matrix interactions and invasiveness promotion. The parallel analysis of WTS data from 8 CCSK cases permitted the identification of a peculiar signature for metastatic CCSKs, highlighting a 20-fold overexpression of FGF3. This factor promoted a significant increase in invasive ability in the cellular model. In order to study BCOR-ITD effects over cell stemness and differentiation, an inducible model is being obtained in H1 cells. This way, it will be possible to study the functionality of BCOR-ITD in a context more similar to the origin of CCSKs, evaluating both the specific interactome and phenotypic consequences caused by the mutation.
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Continuum parallel robots (CPRs) are manipulators employing multiple flexible beams arranged in parallel and connected to a rigid end-effector. CPRs promise higher payload and accuracy than serial CRs while keeping great flexibility. As the risk of injury during accidental contacts between a human and a CPR should be reduced, CPRs may be used in large-scale collaborative tasks or assisted robotic surgery. There exist various CPR designs, but the prototype conception is rarely based on performance considerations, and the CPRs realization in mainly based on intuitions or rigid-link parallel manipulators architectures. This thesis focuses on the performance analysis of CPRs, and the tools needed for such evaluation, such as workspace computation algorithms. In particular, workspace computation strategies for CPRs are essential for the performance assessment, since the CPRs workspace may be used as a performance index or it can serve for optimal-design tools. Two new workspace computation algorithms are proposed in this manuscript, the former focusing on the workspace volume computation and the certification of its numerical results, while the latter aims at computing the workspace boundary only. Due to the elastic nature of CPRs, a key performance indicator for these robots is the stability of their equilibrium configurations. This thesis proposes the experimental validation of the equilibrium stability assessment on a real prototype, demonstrating limitations of some commonly used assumptions. Additionally, a performance index measuring the distance to instability is originally proposed in this manuscript. Differently from the majority of the existing approaches, the clear advantage of the proposed index is a sound physical meaning; accordingly, the index can be used for a more straightforward performance quantification, and to derive robot specifications.
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The scope of this paper is to analyze the self-declared symptoms and state of well-being of participants in the Yoga and Promotion of Health program, which consisted of hatha yoga lessons. It includes body exercises and breathing techniques, as well as ethical and philosophical content, administered to two groups of lecturers, workers and students of a public university in the State of São Paulo from August to December 2011 and March to June 2012. The participants filled out the adapted version of the Measure Yourself Medical Outcome Profile form at the beginning and end of the program. Of the 20 participants in Group 1, eight filled out the form and half of them reported the improvement of self-declared symptoms; as regards the state of well being, three of them felt they had improved. In Group 2, which also had 20 participants, nine completed the program and all of them reported improvements of self-declared symptoms and well-being. In conclusion, yoga is a mind-body practice which exerts an important therapeutic effect on most practitioners and also promotes health for the majority of them, expanding their capacity of self perception and self care. However, it should be noted that it doesn't achieve the same positive effect for all practitioners as some yoga traditions advocate.
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Hippocampal sclerosis (HS) is considered the most frequent neuropathological finding in patients with mesial temporal lobe epilepsy (MTLE). Hippocampal specimens of pharmacoresistant MTLE patients that underwent epilepsy surgery for seizure control reveal the characteristic pattern of segmental neuronal cell loss and concomitant astrogliosis. However, classification issues of hippocampal lesion patterns have been a matter of intense debate. International consensus classification has only recently provided significant progress for comparisons of neurosurgical and clinic-pathological series between different centers. The respective four-tiered classification system of the International League Against Epilepsy subdivides HS into three types and includes a term of gliosis only, no-HS. Future studies will be necessary to investigate whether each of these subtypes of HS may be related to different etiological factors or with postoperative memory and seizure outcome. Molecular studies have provided potential deeper insights into the pathogenesis of HS and MTLE on the basis of epilepsy-surgical hippocampal specimens and corresponding animal models. These include channelopathies, activation of NMDA receptors, and other conditions related to Ca(2+) influx into neurons, the imbalance of Ca(2+)-binding proteins, acquired channelopathies that increase neuronal excitability, paraneoplastic and non-paraneoplastic inflammatory events, and epigenetic regulation promoting or facilitating hippocampal epileptogenesis. Genetic predisposition for HS is clearly suggested by the high incidence of family history in patients with HS, and by familial MTLE with HS. So far, it is clear that HS is multifactorial and there is no individual pathogenic factor either necessary or sufficient to generate this intriguing histopathological condition. The obvious variety of pathogenetic combinations underlying HS may explain the multitude of clinical presentations, different responses to clinical and surgical treatment. We believe that the stratification of neuropathological patterns can help to characterize specific clinic-pathological entities and predict the postsurgical seizure control in an improved fashion.