维持性血液透析患者认知功能特点研究

Objective: To study the episodic memory, semantic memory, cognitive planning ability and inhibition ability in MHD patients. Method: Neuropsychological research methods such as Action memory of verb-object phrase, Trail Making Test (A and B), Verbal Fluency Test, Go-No/Go test and Stroop Color Naming Task were used to investigate Episodic Memory 、Semantic Memory、Executive Function of 40 MHD and 40 NC. Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale(SDS), Social Support Scale, Life Satisfaction Scale, and biochemical examination were applied and their relationships with cognitive function were analized. The mean age and education level of MHD group and NC group have no significant difference. Result: 1.Action memory of verb-object phrase differed significantly between MHD group and NC group. 2.Two tests of Verbal Fluency differed significantly between MHD group and NC group. 3.Trail Making Test A, Trail Making Test B, the baseline condition of Go-No/Go Test and Stroop Color Naming Test differed significantly between MHD group and NC group. 4.There is no significant difference between MHD group and NC group on the correct rate of No/Go Test and the baseline condition. Both groups showed Stroop Effect in Go-No/Go test, but MHD group performed significantly worse. 5.In Stroop Color Naming Task Test, NC group showed Stroop Effect, significant Repeated Distraction Promotion Effect and significant Negative Priming Effect,while MHD group showed only Stroop Effect and no Repeated Distraction Promotion Effect and no Negative Priming Effect. There is significant difference in Stroop Effect between MHD group and NC group. Conclusion: 1.Comparing with NC group, episodic memory, semantic memory, cognitive planning ability, and inhibition ability of MHD group were impaired significantly. 2.The pathological aging of Executive Function in MHD group showed: executive Function should be a unitary system. 3.Cognitive impairment is negatively correlated with serum creatinine, blood pressure and anxiety score in MHD patients; and is related with hemoglobin, hematocrit, social support and life satisfaction. Keyword: maintenance hemodialysis, episodic memory, semantic memory, cognitive planning, inhibition ability.

阿片药物依赖的神经机制---内侧前额叶与药物的心理依赖

Mental dependence, characterized by craving and impulsive seeking behavior, is the matter of intensive study in the field of drug addiction. The mesolimbic dopamine system has been suggested to play an important role in rewarding of drugs and relapse. Although chronic drug use can induce neuroadaptations of the mesolimbic system and changes of drug reinforcement, these mechanisms cannot fully account for the craving and the compulsive drug-using behavior of addicts. Acknowledging the reinforcement effects of drugs, most previous studies have studied the impact of environmental cues and conditioned learning on addiction behavior, often using established classical or operant conditioning model. These studies, however, paid little attention to the role of cognitive control and emotion in addiction. These mental factors that are believed to have an important influence on conditioned learning. The medial prefrontal cortex (mPFC) has close anatomic and functional connections with the mesolimbic dopamine system. A number of the cognitive neurological studies demonstrate that mPFC is involved in motivation, emotional regulation, monitoring of responses and other executive functions. Thus we speculated that the function of abnormality in mPFC following chronic drug use would cause related to the abnormal behavior in addicts including impulse and emotional changes. In the present study of a series of experiments, we used functional magnetic resonance imaging to examine the hemodynamic response of the mPFC and related circuits to various cognitive and emotional stimuli in heroin addicts and to explore the underlying dopamine neuromechnism by microinjection of tool drugs into the mPFC in laboratory animals. In the first experiment, we found that heroin patients, relative to the normal controls, took a much shorter time and committed more errors in completing the more demanding of cognitive regulation in the reverse condition of the task, while the neural activity in anterior cingulate cortex (ACC) was attenuated. In the second experiment, the scores of the heroin patients in self-rating depression scale (SDS) and Self-rating anxiety scale (SAS) were significantly higher than the normal controls and they rated the negative pictures more aversive than the normal controls. Being congruent with the behavioral results, hemodynamic response to negative pictures showed significant difference between the two groups in bilateral ventral mPFC (VMPFC), amygdala, and right thalamus. The VMPFC of patients showed increased activation than normal controls, whereas activation in the amygdala of patients was weaker than that in normal subjects. Our third experiment showed that microinjection of D1 receptor agonist SKF38393 into the mPFC of rats decreased hyperactivity, which was induced by morphine injection, in contrast, D1 receptor antagonist SCH23390 increased the hyperactivity, These findings suggest: (1) The behavior and neural activity in ACC of addicts changed in chronic drug users. Their impulsive behavior might result from the abnormal neural activity in the mPFC especially the ACC. (2) Heroine patients were more depress and anxiety than normal controls. The dysfunction of the mPFC---amygdala circuit of heroine addicts might be related to the abnormal emotion response. (3) Dopamine in the mPFC has an inhibitory effect on morphine induced behavior. The hyperactivity induced by chronic morphine was reduced by dopamine increase with D1 receptor agonist, confirm the first experiment that the neuroadaption of mPFC system induced by chronic morphine administration appears to be the substrate the impulse behavior of drug users.

语音意识缺陷儿童的言语知觉技能

Considerable studies find that developmental dyslexia is associated with deficits in phonological processing skills, especially phonological awareness. In order to explore the nature of phonological awareness deficits in dyslexia, researchers have begun to investigate the role of speech perception. The findings about speech perception abilities in dyslexics are inconsistent. The heterogeneity of dyslexia may be responsible for the inconsistency of findings. Considering the general suggestion that phonological awareness deficits in dyslexia are attributed to categorical perception deficits, it is more direct to examine whether children with phonological awareness difficulties or phonological dyslexia show speech categorization deficits consistently. The present study would investigate whether Chinese children with phonological awareness deficits or phonological dyslexia showed abnormal speech perception. The whole study consisted of two parts. Part I screened children with phonological-awareness deficits from Year 3 kindergartens and examined their abilities of perceiving native category continuum, nonnative category contrasts and non-speech sound series. Part II selected phonological dyslexics from an elementary school as participants, and further explored the relation between phonological deficits and speech perception. The first two experiments of Part II examined separately the abilities to label stimuli in native category continuum and brief stops in different contexts, the last experiment investigated the adaptation effects of different participant groups. The main conclusions are as follows: 1) Children with phonological dyslexia showed categorical perception deficits: they had lower consistency than controls when perceiving stimuli within phonetic categories, especially for the stimuli which were not natural sounds. 2) Children with phonological dyslexia exhibited a general difficulty of perceiving brief segments of stops from different contexts. 3) Children with phonological dyslexia did not show adaptation to repeatedly presented stimuli. Based on the present conclusions and the findings of previous studies, we suggested that the representations of sound stimuli in phonological dyslexics’ brains are different from those in normal children’s; the representations of sound stimuli in dyslexics’ cortical neural networks are more diffuse and inconsistent.

精神分裂症患者及其未患病一级亲属的面孔情绪知觉研究

Schizophrenia is a heritable disorder. However, molecular genetics and related research area have not unmasked the nature and mechanisms of this disorder. Therefore, many researchers begin to explore the pathology mechanism from other approaches. High-risk study is one of the promising approaches. In this study, we mainly focused on facial emotion perception in schizophrenia and their non-psychotic first-degree relatives, and attempted to explore whether facial emotion perception is the potential biological marker of schizophrenia. This dissertation comprises 4 studies. In the first study, we conducted a meta-analysis on behavioral data of facial emotion perception in schizophrenia. Our findings showed that patients demonstrated general deficits in both facial emotion perception and facial processing tasks. In the second study, sixty-nine patients with schizophrenia and 56 of their first-degree relatives (33 parents and 23 siblings), and 92 healthy controls (67 younger and 25 older healthy controls) completed a set of facial emotion perception tasks. The results validated that patients with schizophrenia displayed general deficits in facial emotion perception. Study two also demonstrated that siblings of patients performed equally well compared to the corresponding younger healthy controls in all the facial emotion perception tasks, while the parents of patients behaved significantly worse than the corresponding older healthy controls in the composite index of facial emotion perception tasks. The results suggest that relatives of patients display more severely declining in facial emotion perception with the increasing of age. In the third study, we used an automated voxel-wise technique, activation likelihood estimation (ALE) to provide an objective, quantitative evaluation of facial emotion processing in schizophrenia. Our findings demonstrated a marked under-recruitment of the amygdala, accompanied by a substantial limitation in activation in schizophrenia throughout a ventral temporal-basal ganglia-prefrontal cortex ‘social-brain’ system may be central to the difficulties patients experience when processing facial emotion. In the last study, we did an fMRI study about facial emotion perception in 12 patients with schizophrenia, 12 non-psychotic siblings of patients and 12 healthy controls. The results suggest that siblings of patients demonstrate abnormal activation in a variety of brain areas, including prefrontal gyrus, insula, parahippocampal gyrus and superior temporal gyrus. Taken together, the current findings suggest facial emotion perception may be a potential biological marker of schizophrenia.

Centenarians and their hearts: a prospective registry with comprehensive geriatric assessment, electrocardiogram, echocardiography, and follow-up

Background Data on the cardiac characteristics of centenarians are scarce. Our aim was to describe electrocardiogram (ECG) and echocardiography in a cohort of centenarians and to correlate them with clinical data. Methods We used prospective multicenter registry of 118 centenarians (28 men) with a mean age of 101.5 ± 1.7 years. Electrocardiogram was performed in 103 subjects (87.3%) and echocardiography in 100 (84.7%). All subjects underwent a follow-up for at least 6 months. Results Centenarians with abnormal ECG were less frequently females (72% vs 93%), had higher rates of previous consumption of tobacco (14% vs 0) and alcohol (24% vs 12%), and scored lower in the perception of health status (6.8 ± 2.0 vs 8.3 ± 6.8). Centenarians with significant abnormalities in echocardiography were less frequently able to walk 6 m (33% vs 54%). Atrial fibrillation/flutter was found in 27 subjects (26%). Mean left ventricular (LV) ejection fraction was 60.0 ± 10.5%. Moderate or severe aortic valve stenosis was found in 16%, mitral valve regurgitation in 15%, and aortic valve regurgitation in 13%. Diastolic dysfunction was assessed in 79 subjects and was present in 55 (69.6%). Katz index and LV dilation were independently associated with the ability to walk 6 m. Age, Charlson and Katz indexes, and the presence of significant abnormalities in echocardiography were associated with mortality. Conclusions Centenarians have frequent ECG alterations and abnormalities in echocardiography. More than one fifth has atrial fibrillation, and most have diastolic dysfunction. Left ventricular dilation was associated with the ability to walk 6 m. Significant abnormalities in echocardiography were associated with mortality.

Research into error recovery for sensory robots

Lee, M., Barnes, D. P., Hardy, N. (1985). Research into error recovery for sensory robots. Sensor Review, 5 (4), 194-197.

Model-based detection of spiculated lesions in mammograms

R. Zwiggelaar, T.C. Parr, J.E. Schumm. I.W. Hutt, S.M. Astley, C.J. Taylor and C.R.M. Boggis, 'Model-based detection of spiculated lesions in mammograms', Medical Image Analysis 3 (1), 39-62 (1999)

Depolarization of sperm membrane potential is a common feature of men with subfertility and is associated with low fertilization rate at IVF

STUDY QUESTION. Are significant abnormalities in outward (K+) conductance and resting membrane potential (Vm) present in the spermatozoa of patients undertaking IVF and ICSI and if so, what is their functional effect on fertilization success? SUMMARY ANSWER. Negligible outward conductance (≈5% of patients) or an enhanced inward conductance (≈4% of patients), both of which caused depolarization of Vm, were associated with a low rate of fertilization following IVF. WHAT IS KNOWN ALREADY. Sperm-specific potassium channel knockout mice are infertile with defects in sperm function, suggesting that these channels are essential for fertility. These observations suggest that malfunction of K+ channels in human spermatozoa might contribute significantly to the occurrence of subfertility in men. However, remarkably little is known of the nature of K+ channels in human spermatozoa or the incidence and functional consequences of K+ channel defects. STUDY DESIGN, SIZE AND DURATION. Spermatozoa were obtained from healthy volunteer research donors and subfertile IVF and ICSI patients attending a hospital assisted reproductive techniques clinic between May 2013 and December 2015. In total, 40 IVF patients, 41 ICSI patients and 26 normozoospermic donors took part in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS. Samples were examined using electrophysiology (whole-cell patch clamping). Where abnormal electrophysiological characteristics were identified, spermatozoa were further examined for Ca2+ influx induced by progesterone and penetration into viscous media if sufficient sample was available. Full exome sequencing was performed to specifically evaluate potassium calcium-activated channel subfamily M α 1 (KCNMA1), potassium calcium-activated channel subfamily U member 1 (KCNU1) and leucine-rich repeat containing 52 (LRRC52) genes and others associated with K+ signalling. In IVF patients, comparison with fertilization rates was done to assess the functional significance of the electrophysiological abnormalities. MAIN RESULTS AND THE ROLE OF CHANCE. Patch clamp electrophysiology was used to assess outward (K+) conductance and resting membrane potential (Vm) and signalling/motility assays were used to assess functional characteristics of sperm from IVF and ICSI patient samples. The mean Vm and outward membrane conductance in sperm from IVF and ICSI patients were not significantly different from those of control (donor) sperm prepared under the same conditions, but variation between individuals was significantly greater (P< 0.02) with a large number of outliers (>25%). In particular, in ≈10% of patients (7/81), we observed either a negligible outward conductance (4 patients) or an enhanced inward current (3 patients), both of which caused depolarization of Vm. Analysis of clinical data from the IVF patients showed significant association of depolarized Vm (≥0 mV) with low fertilization rate (P= 0.012). Spermatozoa with electrophysiological abnormities (conductance and Vm) responded normally to progesterone with elevation of [Ca2+]i and penetration of viscous medium, indicating retention of cation channel of sperm (CatSper) channel function. LIMITATIONS, REASONS FOR CAUTION. For practical, technical, ethical and logistical reasons, we could not obtain sufficient additional semen samples from men with conductance abnormalities to establish the cause of the conductance defects. Full exome sequencing was only available in two men with conductance defects. WIDER IMPLICATIONS OF THE FINDINGS. These data add significantly to the understanding of the role of ion channels in human sperm function and its impact on male fertility. Impaired potassium channel conductance (Gm) and/or Vm regulation is both common and complex in human spermatozoa and importantly is associated with impaired fertilization capacity when the Vm of cells is completely depolarized.

Human papillomavirus detection in women with and without human immunodeficiency virus infection in Colombia

Background: HIV infection leads to a decreasing immune response, thereby facilitating the appearance of other infections, one of the most important ones being HPV. However, studies are needed for determining associations between immunodeficiency caused by HIV and/or the presence of HPV during the course of cervical lesions and their degree of malignancy. This study describes the cytological findings revealed by the Papanicolaou test, laboratory characteristics and HPV molecular profile in women with and without HIV infection. Methods: A total of 216 HIV-positive and 1,159 HIV-negative women were invited to participate in the study; PCR was used for the molecular detection of HPV in cervical samples. Statistical analysis (such as percentages, Chi-square test and Fisher's exact test when applicable) determined human papillomavirus (HPV) infection frequency (single and multiple) and the distribution of six types of high-risk-HPV in women with and without HIV infection. Likewise, a logistic regression model was run to evaluate the relationship between HIV-HPV infection and different risk factors. Results: An association was found between the frequency of HPV infection and infection involving 2 or more HPV types (also known as multiple HPV infection) in HIV-positive women (69.0% and 54.2%, respectively); such frequency was greater than that found in HIV-negative women (44.3% and 22.7%, respectively). Statistically significant differences were observed between both groups (p = 0.001) regarding HPV presence (both in infection and multiple HPV infection). HPV-16 was the most prevalent type in the population being studied (p = 0.001); other viral types had variable distribution in both groups (HIV-positive and HIV-negative). HPV detection was associated with <500 cell/mm(3) CD4-count (p = 0.004) and higher HIV-viral-load (p = 0.001). HPV-DNA detection, <200 cell/mm(3) CD4-count (p = 0.001), and higher HIV-viral-load (p = 0.001) were associated with abnormal cytological findings. Conclusions: The HIV-1 positive population in this study had high multiple HPV infection prevalence. The results for this population group also suggested a greater association between HPV-DNA presence and cytological findings. HPV detection, together with low CD4 count, could represent useful tools for identifying HIV-positive women at risk of developing cervical lesions.

Relação entre a Infeção por Escherichia coli Aderente-Invasina e a Doença de Crohn

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas

Alterações do Funcionamento da Glândula da Tiróide

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas

Distúrbios do metabolismo do cobre, ferro e zinco

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas

QUANTITATIVE THREE DIMENSIONAL ELASTICITY IMAGING

Neoplastic tissue is typically highly vascularized, contains abnormal concentrations of extracellular proteins (e.g. collagen, proteoglycans) and has a high interstitial fluid pres- sure compared to most normal tissues. These changes result in an overall stiffening typical of most solid tumors. Elasticity Imaging (EI) is a technique which uses imaging systems to measure relative tissue deformation and thus noninvasively infer its mechanical stiffness. Stiffness is recovered from measured deformation by using an appropriate mathematical model and solving an inverse problem. The integration of EI with existing imaging modal- ities can improve their diagnostic and research capabilities. The aim of this work is to develop and evaluate techniques to image and quantify the mechanical properties of soft tissues in three dimensions (3D). To that end, this thesis presents and validates a method by which three dimensional ultrasound images can be used to image and quantify the shear modulus distribution of tissue mimicking phantoms. This work is presented to motivate and justify the use of this elasticity imaging technique in a clinical breast cancer screening study. The imaging methodologies discussed are intended to improve the specificity of mammography practices in general. During the development of these techniques, several issues concerning the accuracy and uniqueness of the result were elucidated. Two new algorithms for 3D EI are designed and characterized in this thesis. The first provides three dimensional motion estimates from ultrasound images of the deforming ma- terial. The novel features include finite element interpolation of the displacement field, inclusion of prior information and the ability to enforce physical constraints. The roles of regularization, mesh resolution and an incompressibility constraint on the accuracy of the measured deformation is quantified. The estimated signal to noise ratio of the measured displacement fields are approximately 1800, 21 and 41 for the axial, lateral and eleva- tional components, respectively. The second algorithm recovers the shear elastic modulus distribution of the deforming material by efficiently solving the three dimensional inverse problem as an optimization problem. This method utilizes finite element interpolations, the adjoint method to evaluate the gradient and a quasi-Newton BFGS method for optimiza- tion. Its novel features include the use of the adjoint method and TVD regularization with piece-wise constant interpolation. A source of non-uniqueness in this inverse problem is identified theoretically, demonstrated computationally, explained physically and overcome practically. Both algorithms were test on ultrasound data of independently characterized tissue mimicking phantoms. The recovered elastic modulus was in all cases within 35% of the reference elastic contrast. Finally, the preliminary application of these techniques to tomosynthesis images showed the feasiblity of imaging an elastic inclusion.

Modeling the Possible Influences of Eye Movements on the Refinement of Cortical Direction Selectivity

The second-order statistics of neural activity was examined in a model of the cat LGN and V1 during free-viewing of natural images. In the model, the specific patterns of thalamocortical activity required for a Bebbian maturation of direction-selective cells in VI were found during the periods of visual fixation, when small eye movements occurred, but not when natural images were examined in the absence of fixational eye movements. In addition, simulations of stroboscopic reming that replicated the abnormal pattern of eye movements observed in kittens chronically exposed to stroboscopic illumination produced results consistent with the reported loss of direction selectivity and preservation of orientation selectivity. These results suggest the involvement of the oculomotor activity of visual fixation in the maturation of cortical direction selectivity.

The role of metabolism in the pathogenesis of adherent invasive Escherichia coli (AIEC)

Crohn’s disease (CD) is a chronic, relapsing inflammatory condition affecting the gastrointestinal tract of humans, of which there is currently no cure. The precise etiology of CD is unknown, although it has become widely accepted that it is a multifactorial disease which occurs as a result of an abnormal immune response to commensal enteric bacteria in a genetically susceptible host. Recent studies have shown that a new group of Escherichia coli, called Adherent Invasive Escherichia coli (AIEC) are present in the guts of CD patients at a higher frequency than in healthy subjects, suggesting that they may play a role in the initiation and/or maintenance of the inflammation associated with CD. Two phenotypes define an AIEC and differentiate them from other groups of E. coli. Firstly, AIEC can adhere to and invade epithelial cells; and secondly, they can replicate in macrophages. In this study, we use a strain of AIEC which has been isolated from the colonic mucosa of a CD patient, called HM605, to examine the relationship between AIEC and the macrophage. We show, using a systematic mutational approach, that while the Tricarboxylic acid (TCA) cycle, the glyoxylate pathway, the Entner-Doudoroff (ED) pathway, the Pentose Phosphate (PP) pathway and gluconeogenesis are dispensable for the intramacrophagic growth of HM605, glycolysis is an absolute requirement for the ability of this organism to replicate intracellularly. We also show that HM605 activates the inflammasome, a major driver of inflammation in mammals. Specifically, we show that macrophages infected with HM605 produce significantly higher levels of the pro-inflammatory cytokine IL-1β than macrophages infected with a non-AIEC strain, and we show by immunoblotting that this is due to cleavage of caspase-1. We also show that macrophages infected with HM605 exhibit significantly higher levels of pyroptosis, a form of inflammatory cell death, than macrophages infected with a non-AIEC strain. Therefore, AIEC strains are more pro-inflammatory than non-AIEC strains and this may have important consequences in terms of CD pathology. Moreover, we show that while inflammasome activation by HM605 is independent of intracellular bacterial replication, it is dependent on an active bacterial metabolism. Through the establishment of a genetic screen aimed at identifying mutants which activate the inflammasome to lower levels than the wild-type, we confirm our observation that bacterial metabolism is essential for successful inflammasome activation by HM605 and we also uncover new systems/structures that may be important for inflammasome activation, such as the BasS/BasR two-component system, a type VI secretion system and a K1 capsule. Finally, in this study, we also identify a putative small RNA in AIEC strain LF82, which may be involved in modulating the motility of this strain. Overall this works shows that, in the absence of specialised virulence factors, the ability of AIEC to metabolise within the host cell may be a key determinant of its pathogenesis.