Pathological Ones Research Articles

Evaluation of Response by Color Doppler to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer: A Preliminary Study

INTRODUCTION: Locally advanced breast carcinomas represent a relatively heterogeneous group of clinical entities, biological and pathological ones. Neoadjuvant treatment offers several theoretical advantages over postoperative administration of treatment: - Early treatment of micrometastatic disease; - In vivo evaluation of treatment response; - Allowing conservative surgery. Therefore, the Doppler ultrasonography can serve as an independent functional method for objectively measure tumor response to chemotherapy. The objective of this study is to evaluate the applicability of power Doppler and pulsed Doppler as a predictor of tumor response to neoadjuvant chemotherapy in Locally Advanced Breast Cancer. MATERIALS AND METHODS: The population of this prospective observational study comprises 40 patients with Infiltrative Breast Carcinoma (not otherwise specified) by histological analysis and locally advanced (TNM 6th ed). The patients and were subjected to evaluation by Doppler before, after 2-3 cycles of chemotherapy and pre-surgery. Vascular density was calculated, the ratio between the number of colored pixels within the tumor area by total number of pixels in this area, and the response to treatment, according to RECIST criteria of 1.1(2009), was correlated with end pathological response. We calculated mean and standard deviation for quantitative variables. To study the association were used Fisher s exact test and Spearman correlation coefficient using SPSS-10 program and Bioestat.8.0. We adopted a significance level of a = 0.05 for all data analyzed. RESULTS: There was no statistical difference between responders and nonresponders in Dopplervelocimetric Response and Pathologic Response groups (p = 0.3348), and there was no difference between Morphological and Pathological responses (p = 0.0567), nor between morphological response and Dopplervelocimetric one (p = 0.6287). The sensitivity and specificity of vascular density were 85.7% and 50%, respectively, with negative predictive value of 50% and positive of 85.7%. DISCUSSION: These results show that the functional evaluation by Doppler has accompanied the morphological and pathological responses with good accuracy in the presence of active disease, which is very important to reduce the possibility of residual disease in conservative surgery, indicated in such locally advanced cases with good response to primary chemotherapy. CONCLUSION: We presented a method for functional evaluation of malignant mammary tumor response to cytotoxic treatments, cost / benefit extremely favorable compared to other methods already established as functional magnetic resonance imaging, scintimammography and positron emission tomography, it is not invasive, not requiring contrast medium or radiopharmaceuticals.

Adult Attention Deficit Hyperactivity Disorder (ADHD): public health implications

In 2008 NICE guidance recommended the identification and treatment of Attention Deficit Hyperactivity Disorder (ADHD) in adults. Previously, diagnosis and treatment of this condition had mainly been confined to children and young people. Dr Tamsin Newlove-Delgado and Professor Ken Stein from University of Exeter explain why adult ADHD is important and what the implications are for health improvement, commissioning and providing evidence based services Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder, with symptoms of inattention, hyperactivity and impulsivity causing significant impairment in functioning. The diagnostic criteria for ADHD currently require that symptoms must have been present before the age of seven years, and be apparent in more than one setting. There is no single cause; instead the condition appears to result from a complex interaction of genetic and environmental factors.1 ADHD is estimated to affect 3-5% of children of school age in the UK.1,2 Does ADHD exist in adults? Few studies have followed up young people with ADHD beyond the age of 25. A meta-analysis of data from follow-up studies suggested that although the rate of persistence of ADHD meeting the full diagnostic criteria at age 25 was only 15%, the persistence of symptoms was much higher at around 40-60%.3 Therefore, although the prevalence of ADHD certainly declines with age, a significant proportion of adults have still been found to be affected. ADHD in adults remains the subject of some debate, given the high rate of co-morbidities and the difficulty in distinguishing normal symptoms from pathological ones. However, in 2008 the National Institute for Health and Clinical Excellence (NICE) reviewed the evidence on adult ADHD, recommending recognition of the condition and establishment of services for assessment and management, with stimulant medication as the first-line treatment for adults with either moderate or severe levels of impairment.2 How many adults might suffer with ADHD? A meta-analysis of world literature produced a pooled prevalence estimate of 2.5%.4 The UK 2007 Adult Psychiatric Morbidity Survey5 used the six item Adult ADHD Self Report Scale (ASRS) to screen the sample for ADHD symptoms. Using this scale 8.2% of adults scored four or more, which was considered to warrant clinical assessment, and 0.6% scored all six, indicating a high likelihood of a positive diagnosis. NICE have estimated the number of men with ADHD at over 300,000 in England, and the number of women at over 80,000,6 indicating that there is a considerable population likely to be affected. Impact of adult ADHD Higher risk of other psychiatric disorders Adults with ADHD are at increased risk for other psychiatric disorders. Over a lifetime, it is estimated that over threequarters of those with ADHD will have a psychiatric co-morbidity;7 with depression and anxiety being most common. Substance misuse and smoking Substance misuse affects up to half of adults with ADHD.7 A significant proportion of those in contact with substance misuse services also have ADHD symptoms. High rates of smoking (up to 40%) in ADHD8 may be explained by genetic influences or self-medication with nicotine: the condition is also linked with earlier initiation of smoking and difficulty in quitting.9 Accidents Studies have reported that adolescents and adults with ADHD are more likely to be involved in road traffic collisions, to be stopped for speeding, and to report losses of concentration and control whilst driving.10 Similarly, both children and adults with ADHD appear to have more accidents and injuries in general, possibly due to impulsivity and risktaking behaviours.11 Educational and occupational underachievement Adults with ADHD experience higher job turnover and more periods of unemployment. A recent European study found they were twice as likely to be unemployed. …

Detection of obstructive sleep apnoea using dynamic filter-banked features

There is a need for developing simple signal processing algorithms for less costly, reliable and noninvasive Obstructive Sleep Apnoea (OSA) diagnosing. One of the promising directions is to provide the OSA analysis based on the heart rate variability (HRV), which clearly shows a non-stationary behavior. So, a feature extraction approach, being capable of capturing the dynamic heart rate information and suitable for OSA detection, remains an open issue. Grounded on discriminating capability of frequency bands of HRV activity between normal and OSA patients, features can be extracted. However, some HRV normal spectrograms resemble like pathological ones, and vice versa; so, prior to extract the feature set, the energy spatial contribution contained in each subŨband should be clarified. This paper presents a methodology for OSA detection based on a set of short-time feature banked features that are extracted from the spectrogram of the HRV time series. The methodology introduces the spectral splitting scheme, which searches for spectral components with alike stochastic behavior improving the OSA detection accuracy. Two different splitting approaches are considered (heuristic and relevance-based); both of them performing minute-by-minute classification comparable with other outcomes that are reported in literature, but avoiding more complex methods or more computed features. For validation purposes, the methodology is tested on 1-min HRV-segments estimated from 50 Physionet database recordings. Using a parallel combining k-nn classifier, the assessed dynamic feature set reaches as much as 80% value of accuracy, for both considered approaches of spectral splitting. Attained results can be oriented in research focused on finding alternative methods used for less costly and noninvasive OSA diagnosing with the additional benefit of easier clinical interpretation of HRV-derived parameters.

Sampling techniques for single-cell electrophoresis.

Cells are extraordinarily complex, containing thousands of different analytes with concentrations spanning at least nine orders of magnitude. Analyzing single cells instead of tissue homogenates provides unique insights into cell-to-cell heterogeneity and aids in distinguishing normal cells from pathological ones. The high sensitivity and low sample consumption of capillary and on-chip electrophoresis, when integrated with fluorescence, electrochemical, and mass spectrometric detection methods, offer an ideal toolset for examining single cells and even subcellular organelles; however, the isolation and loading of such small samples into these devices is challenging. Recent advances have addressed this issue by interfacing a variety of enhanced mechanical, microfluidic, and optical sampling techniques to capillary and on-chip electrophoresis instruments for single-cell analyses.

The biophysical bases of will-less behaviors

Are there distinctions at the neurophysiological level that correlate with voluntary and involuntary actions? Whereas the wide variety of involuntary behaviors (and here mostly the deviant or pathological ones will be considered) will necessarily be represented at some biophysical level in nervous system activity–for after all those cellular activity patterns manifest themselves as behaviors and thus there will be a multiplicity of them–there could be some general tendencies to be discerned amongst that assortment. Collecting observations derived from neurophysiological activity associated with several pathological conditions characterized by presenting will-less actions such as Parkinson's disease, seizures, alien hand syndrome and tics, it is proposed that a general neurophysiologic tendency of brain activity that correlates with involuntary actions is higher than normal synchrony in specific brain cell networks, depending upon the behavior in question. Wilful, considered normal behavior, depends on precise coordination of the collective activity in cell ensembles that may be lost, or diminished, when there are tendencies toward more than normal or aberrant synchronization of cellular activity. Hence, rapid fluctuations in synchrony is associated with normal actions and cognition while less variability in brain recordings particularly with regards to synchronization could be a signature of unconscious and deviant behaviors in general.

English

Numerous stressors such as environmental, nutritional, pathological or equipment related ones are operative in swine facilities. Among many factors, socking density increases social stress and influences pig performance. Many studies have reported that reducing space allowance could induce decreases in growth performance of pigs. In addition, high stocking density induces a behavioral problem and influences physiological stress during transport. Thus, the optimum stocking density has to be defined for improving pig production.   Key words: Performance, pigs, stocking density, stress.

Moonlighting proteins in neurological disorders

AbstractNoabstract.

Psicologia, formação de psicólogos e a escola: desafios contemporâneos

A atuação do psicólogo na educação cresce nos últimos anos, em instituições educativas e no atendimento à queixa escolar, mas ainda é comum, em diversos cursos de graduação, psicólogos se formarem sem ter tido contato direto com uma escola. Esse fato reduz os fenômenos escolares a questões meramente psicológicas e, sobretudo, patológicas, e coexiste com práticas apoiadas na compreensão dos elementos que constituem a subjetividade em sua relação com os processos educativos. Discutimos, a partir do relato de experiência docente, aspectos que são fundamentais para uma proposta de formação do psicólogo que tem como referência a inserção do estudante de psicologia em espaços educativos por meio de visitas a instituições e de estágios na área. Essa proposta desdobra-se em duas modalidades: a disciplina Problemas de Aprendizagem e o estágio Intervenção clínica em processos de aprendizagem. Tal inserção cria a possibilidade de o futuro psicólogo contactar-se com o cotidiano escolar e deparar-se com determinações que vão além da imediata relação dual psicólogo-usuário.

Exosomes as intercellular signalosomes and pharmacological effectors

Cell secretion is a general process involved in various biological responses. Exosomes are part of this process and have gained considerable scientific interest in the past five years. Several steps through investigations across the last 20 years can explain this interest. First characterized during reticulocyte maturation, they were next evidenced as a key player in the immune response and cancer immunotherapy. More recently they were reported as vectors of mRNAs, miRNAs and also lipid mediators able to act on target cells. They are the only type of vesicles released from an intracellular compartment from cells in viable conditions. They appear as a vectorized signaling system operating from inside a donor cell towards either the periphery, the cytosol, or possibly to the nucleus of target cells. Exosomes from normal cells trigger positive effects, whereas those from pathological ones, such as tumor cells or infected ones may trigger non-positive health effects. Therefore regulating the biogenesis and secretion of exosomes appear as a pharmacological challenge to intervene in various pathophysiologies. Exosome biogenesis and molecular content, interaction with target cells, utilisation as biomarkers, and functional effects in various pathophysiologies are considered in this review.

Physiologic and pathologic septal deviations: subjective and objective functional rhinologic findings

A high incidence of septal deviation with significant inter-rater variability has been reported. An explanation could be the presence of physiological septal deviation besides pathological ones. We differentiated an unselected cohort by their nasal resistance into groups with physiological normal and pathologically increased resistance to detect differences and analogies in comparison to healthy subjects and a pathological cohort. Prospective cohort study. A total of 356 patients were assessed using rhinoresistometry, acoustic rhinometry, endoscopy and visual analogue scales. After definition of a benchmark between physiological and pathological nasal resistance, group differences were calculated and correlations analysed. The normal one-sided inspiratory nasal resistance was defined as less or equal to 0.35 sPa/cm^3 at a flow-velocity of 250 cm^3/s (R250). Using this benchmark, the unselected group of non-rhinological patients was differentiated into 114 subjects with physiological nasal resistance and 44 with pathological septal deviation. Nasal resistance after decongestion was significantly lower for normal or patients with a physiological septal deviation in comparison to the rhinological one on both nasal sides. Healthy subjects and patients with physiological septal deviation showed similarities in objective rhinological parameters as well as rhinological patients and patients with pathological septal deviation derived from the unselected group of non-rhinological patients. Furthermore, this benchmark of nasal resistance shows significant correlations with subjective assessment of nasal breathing. Inspiratory nasal resistance obtained at a flow-velocity of 250 cm^3/s using rhinoresistometry may be useful to distinguish patients with physiological and pathological septal deviation. Correlation with subjective assessment and endoscopic findings is improved.

Investigation on three-dimensional temperature field of human knee considering anatomical structure

Inappropriate heat and mass transfer is an extremely important factor to cause rheumatics of human knee which however receives few attentions up to now. Understanding the thermal behaviors of pathological knee tissues can help diagnose its pathological status and find out the most efficient therapeutical way, which is hard to access otherwise. This paper is dedicated to develop a theoretical model for characterizing the three-dimensional temperature fields of human knee by taking its real anatomical structure into consideration. Based on the classical Pennes bioheat transfer equation, the temperature fields of normal knees and pathological ones under various thermal conditions were numerically simulated and compared, which would help better understand the disease mechanisms causing trouble for human knee. Meanwhile, a medical infrared image system was adopted to map the surface temperature of human knee which qualitatively verifies the theoretical prediction and its diagnostic value. Further, effects of heating from outside on the knee tissue and interventional hyperthermia based on vessel heating were also evaluated. Potential therapeutical strategies were suggested for the thermal rehabilitation of rheumatic knee in the near future.

Classification of Cardiac Arrhythmias using Biorthogonal Wavelets and Support Vector Machines

The classification of Electrocardiogram (ECG) is critical for diagnosis and treatment of patients with heart disorders. We present a technique for automatic the detection and classification of cardiac arrhythmias using biorthogonal wavelet functions and support vector machines (SVM). For feature extraction the biorthogonal wavelet transforms are applied to decompose the ECG signal into wavelet scales. Further, a soft thresholding technique is used to denoise and extract important cardiac events in the signal. Subsequently, we applied SVM classifier to discriminate the detected event features into normal or pathological ones. Numeric computations demonstrate that the efficient wavelet preprocessing provides an accurate estimation of important physiological features of ECG and its effect in the improvement of the SVM classification performance.

Separating physiological from pathological effects of drugs tested for retinal toxicity in animal models

Abstract Purpose Drugs tested for retinal toxicity in animal models frequently induce physiological effects with or without pathological effects. The physiological effects may be interpreted to reflect toxic action. Here, different experimental approaches and modes of data analysis are described to separate physiological from pathological effects of drugs on retinal function and structure in laboratory animals. Methods The flash electroretinogram (ERG) and the visual evoked potential (VEP) were used to assess respectively the functional integrity of the distal and proximal parts of the retina following intravitreal administration of drugs. Histology at the light microscopic level and immunocytochemistry were used to evaluate structural damage and to localize the site/s of action of the drugs. Results The ERG responses and the VEP were recorded at different time intervals after intravitreal injection of different drugs in order to assess short‐term and long‐term retinal effects. In some cases severe functional deficit was identified, but it was transient in nature, and partial or even complete recovery was observed during a follow‐up period of at least 4 weeks. Different modes of data analysis were applied in order to separate physiological effects from pathological ones. Conclusion Drugs, used in the ophthalmic clinic, can be retinotoxic and induce permanent retinal damage, or may exert transient changes that can reflect drug interference with the normal physiological function of the retina. Data are analyzed to separate these possibilities in order to allow accurate assessment of drug toxicity. Furthermore, drugs exerting transient physiological effects can be used to study the normal mechanisms of visual information processing in the retina.

Editorial: Issues for DSM-V: I) Including Biological Variables To Objectively Comfort the Clinical Diagnosis of Borderline Personality Disorder and II) Proposing a New Subcategory To Be Included in the Criteria Sets for Further Study

Borderline personality disorder (BPD) is a serious chronic condition which may lead to a poor quality of life and carries a considerable risk of comorbidity and suicide. The syndrome has been acknowledged and investigated in psychiatry for at least seventy years. The DSM-IV gives a panel of nine symptoms and manifestations for its diagnosis, but not taking into account neurobiological and objective issues. The issue of whether BPD should be considered as a discrete condition, as the edge of a dimensional state ranging from ‘almost normal’ personalities to clearly pathological ones or as a hybrid of traits and symptomatic behaviors (McGlashan, 2005) seems to be important to correctly diagnose our patients and is a corner stone in the Research Agenda for DSM-V. The pathophysiology of BPD is very important because this is the progress which will probably lead to the development of effective treatments. Several investigators have shown some laboratory and objective clinical fi ndings in BPD as normality in endocrinological dynamic tests (De La Fuente et al., 2002), alterations in sleep-EEG parameters (De la Fuente et al., 2004), disturbed regional brain glucose metabolism (De la Fuente et al., 1997), abnormal scalp EEGs (De la Fuente et al., 1998) and an extremely high prevalence of neurologic soft signs (De la Fuente et al., 2006). These facts probably refl ect common underlying non focal nervous system failure and hypothalamic-pituitary-adrenal axis normality in BPD. However, these fi ndings are not pathognomonic of the condition and BPD is diagnosed according to DSM-IV when a patient shows at least fi ve symptoms out of a list of nine. First & Zimmerman (2006) propose that biological variables can aid to identify the patients as compared to the criteria used now to defi ne them. For this the objective signs and facts found in BPD could be included as diagnostic criteria in the DSM-V. Scalp wake EEG, the clinical exploration for neurologic soft signs, sleep EEG recordings and the two endocrine tests, dexamethasone suppression and TRH stimulation, which are cheap, not invasive and have shown to be linked to the diagnosis of BPD could be incorporated in a diagnostic weighting construct with these variables as additional score items. This would have at least three advantages over the present criteria: fi rstly, a part of the diagnosis of BPD would become objective, secondly, having these parameters would attach physiopathological information to the diagnosis and thirdly, the laboratory information and objective

Transition from physiological to pathophysiological indices as exemplified by amyloidosis in periodic disease, non-insulin-dependent diabetes mellitus, and Alzheimer’s disease

Theoretical studies on amyloidosis have been performed. The results promote understanding of primary causes and molecular mechanisms of the formation of pathological protein and permits tracing the transitions from physiological indices to pathological ones in periodic disease (PD), non-insulin-dependent diabetes mellitus (NIDDM), and Alzheimer’s disease (AD). Blockage of the biochemical target by a biologically active substance (drug) at the initial stage of disease makes it possible to avoid formation of pathology. The concept of a “situational physiological skip” is introduced. A new class of drugs (situational controllers of metabolism) that affect transitions from the normal state to pathology in initial periods of disease can be developed. The rational way of finding the prototype of a new drug with a new mechanism of action is computer-aided the developmenrt of a drug on the basis of the spatial structure the target protein. The development of inner structure of proteins related to pathology should be based on distinct grouping of patients according to their genotypes and phenotypes.

Coxa magna quantification using MRI in Legg-Calve-Perthes disease

Background: The idiopathic avascular necrosis of the femoral epiphysis characterizes the Legg-Calve-Perthes disease in pediatric osteoarticular pathologies. The coxa magna, more frequently observed, corresponds to an enlargement and deformation of the femoral head. The volume extension induces a subluxation of the hip, which is a bad prognosis for the healthy function of the joint. Methods: The aim of the study was to quantify the coxa magna in Legg-Calve-Perthes disease using magnetic resonance imaging. Twenty-five patients with unilateral Legg-Calve-Perthes disease were included in the clinical protocol and the volume properties of cartilaginous epiphyseal head were quantified using custom-made image processing software. Findings: Difference in cartilage volume between healthy hips and pathological ones were significant. Excepting one patient, we observed a statistically significant volume increase for the pathological hip, the mean value being +13%. Interpretation: Our results confirmed the effective three-dimensional properties of the coxa magna, which is clearly associated to a negative prognosis for the future of the joint. To our knowledge, the volume quantification of coxa magna has not been established before. The non-radiant MRI associated to three-dimensional investigation could potentially improve the clinical follow up of children to adapt the non-invasive treatment and to plan the surgery if necessary.

Collagen Turnover in Normal and Degenerate Human Intervertebral Discs as Determined by the Racemization of Aspartic Acid

Knowledge of rates of protein turnover is important for a quantitative understanding of tissue synthesis and catabolism. In this work, we have used the racemization of aspartic acid as a marker for the turnover of collagen obtained from healthy and pathological human intervertebral disc matrices. We measured the ratio of the d- and l-isomers in collagen extracted from these tissues as a function of age between 16 and 77 years. For collagen taken from healthy discs, the fractional increase of d-Asp was found to be 6.74 x 10(-4)/year; for degenerate discs, the corresponding rate was 5.18 x 10(-4)/year. Using the racemization rate found previously for the stable population of collagen molecules in dentin, we found that the rate of collagen turnover (k(T)) in discs is not constant but rather a decreasing function of age. The average turnover rate in normal disc between the ages of 20 and 40 is 0.00728 +/- 0.00275/year, and that between the ages of 50 and 80 is 0.00323 +/- 0.000947/year, which correspond to average half-lives of 95 and 215 years, respectively. Turnover of collagen from degenerate discs may be more rapid than that found for normal discs; however, statistical analysis leaves this point uncertain. The finding of a similar correlation between the accumulation of d-Asp and that of pentosidine for three normal collagenous tissues further supports the idea that the accumulation of pentosidine in a particular tissue can, along with the racemization of aspartic acid, be used as a reliable measure of protein turnover.

Motor cortical network oscillations driven by voltage‐ and ligand‐gated currents

Motor cortical network oscillations driven by voltage‐ and ligand‐gated currents

The Assessment of Spirituality and Religiousness in Schizophrenia

To assess religious coping in schizophrenia, we developed and tested a clinical grid, as no validated questionnaire exists for this population. One hundred fifteen outpatients were interviewed. Results obtained by 2 clinicians were compared. Religion was central in the lives of 45% of patients, 60% used religion extensively to cope with their illness. Religion is a multifaceted construct. Principal component analysis elicited 4 factors: subjective dimension, collective dimension, synergy with psychiatric treatment, and ease of talking about religion with psychiatrist. Different associations were found between these factors and psychopathology, substance abuse, and psychosocial adaptation. The high prevalence of spirituality and religious coping clearly indicates the necessity of addressing spirituality in patient care. Our clinical grid is suitable for this purpose. It proved its applicability to a broad diversity of religious beliefs, even pathological ones. Interjudge reliability and construct validity were high and specific training is not required.

Significant Decrease in Tropoelastin Gene Expression in Fibroblasts from a Japanese Costello Syndrome Patient with Impaired Elastogenesis and Enhanced Proliferation

Costello syndrome is a connective tissue disorder associated with sparse, thin, and fragmented elastic fibers in tissues. In this study we demonstrated a significant decrease in the expression of tropoelastin mRNA in fibroblasts derived from a Japanese Costello syndrome patient with impaired elastogenesis and enhanced proliferation. In contrast, there were no changes in expression of the Harvey ras (HRAS), fibrillin-1, fibulin-5, microfibril-associated glycoprotein-1 (MAGP-1), lysyl oxidase (LOX), or 67-kDa non-integrin elastin-binding protein (EBP) gene. The proliferative activity of the Costello fibroblasts was about 4-fold higher than that of the normal and pathological control ones. However, no mutations were detected in the coding region of HRAS mRNA. Transduction of the bovine tropoelastin (bTE) gene with the lentiviral vector restored the elastic fiber formation and decreased the growth rate in the Costello fibroblasts. These results strongly suggest that the defect of human tropoelastin (hTE) gene expression should induce the impaired elastogenesis and enhanced proliferation of Costello fibroblasts, and that a primary cause other than the HRAS gene mutation should contribute to the pathogenesis in the present Costello case.