Computer Assisted Diagnosis and Treatment Planning of Femoroacetabular Impingement (FAI)

Femoroacetabular impingement (FAI) is a dynamic conflict of the hip defined by a pathological, early abutment of the proximal femur onto the acetabulum or pelvis. In the past two decades, FAI has received increasing focus in both research and clinical practice as a cause of hip pain and prearthrotic deformity. Anatomical abnormalities such as an aspherical femoral head (cam-type FAI), a focal or general overgrowth of the acetabulum (pincer-type FAI), a high riding greater or lesser trochanter (extra-articular FAI), or abnormal torsion of the femur have been identified as underlying pathomorphologies. Open and arthroscopic treatment options are available to correct the deformity and to allow impingement-free range of motion. In routine practice, diagnosis and treatment planning of FAI is based on clinical examination and conventional imaging modalities such as standard radiography, magnetic resonance arthrography (MRA), and computed tomography (CT). Modern software tools allow three-dimensional analysis of the hip joint by extracting pelvic landmarks from two-dimensional antero-posterior pelvic radiographs. An object-oriented cross-platform program (Hip2Norm) has been developed and validated to standardize pelvic rotation and tilt on conventional AP pelvis radiographs. It has been shown that Hip2Norm is an accurate, consistent, reliable and reproducible tool for the correction of selected hip parameters on conventional radiographs. In contrast to conventional imaging modalities, which provide only static visualization, novel computer assisted tools have been developed to allow the dynamic analysis of FAI pathomechanics. In this context, a validated, CT-based software package (HipMotion) has been introduced. HipMotion is based on polygonal three-dimensional models of the patient’s pelvis and femur. The software includes simulation methods for range of motion, collision detection and accurate mapping of impingement areas. A preoperative treatment plan can be created by performing a virtual resection of any mapped impingement zones both on the femoral head-neck junction, as well as the acetabular rim using the same three-dimensional models. The following book chapter provides a summarized description of current computer-assisted tools for the diagnosis and treatment planning of FAI highlighting the possibility for both static and dynamic evaluation, reliability and reproducibility, and its applicability to routine clinical use.

Focal Epilepsy: MR Imaging of Nonhemodynamic Field Effects by Using a Phase-cycled Stimulus-induced Rotary Saturation Approach with Spin-Lock Preparation.

Purpose To investigate whether nonhemodynamic resonant saturation effects can be detected in patients with focal epilepsy by using a phase-cycled stimulus-induced rotary saturation (PC-SIRS) approach with spin-lock (SL) preparation and whether they colocalize with the seizure onset zone and surface interictal epileptiform discharges (IED). Materials and Methods The study was approved by the local ethics committee, and all subjects gave written informed consent. Eight patients with focal epilepsy undergoing presurgical surface and intracranial electroencephalography (EEG) underwent magnetic resonance (MR) imaging at 3 T with a whole-brain PC-SIRS imaging sequence with alternating SL-on and SL-off and two-dimensional echo-planar readout. The power of the SL radiofrequency pulse was set to 120 Hz to sensitize the sequence to high gamma oscillations present in epileptogenic tissue. Phase cycling was applied to capture distributed current orientations. Voxel-wise subtraction of SL-off from SL-on images enabled the separation of T2* effects from rotary saturation effects. The topography of PC-SIRS effects was compared with the seizure onset zone at intracranial EEG and with surface IED-related potentials. Bayesian statistics were used to test whether prior PC-SIRS information could improve IED source reconstruction. Results Nonhemodynamic resonant saturation effects ipsilateral to the seizure onset zone were detected in six of eight patients (concordance rate, 0.75; 95% confidence interval: 0.40, 0.94) by means of the PC-SIRS technique. They were concordant with IED surface negativity in seven of eight patients (0.88; 95% confidence interval: 0.51, 1.00). Including PC-SIRS as prior information improved the evidence of the standard EEG source models compared with the use of uninformed reconstructions (exceedance probability, 0.77 vs 0.12; Wilcoxon test of model evidence, P < .05). Nonhemodynamic resonant saturation effects resolved in patients with favorable postsurgical outcomes, but persisted in patients with postsurgical seizure recurrence. Conclusion Nonhemodynamic resonant saturation effects are detectable during interictal periods with the PC-SIRS approach in patients with epilepsy. The method may be useful for MR imaging-based detection of neuronal currents in a clinical environment. (©) RSNA, 2016 Online supplemental material is available for this article.

Neighbourhood abundance and small-tree survival in a lowland Bornean rainforest

Conspecific effects of neighbours on small-tree survival may have a role in tree population dynamics and community composition of tropical forests. This notion was tested with data from two 4-ha plots in lowland forest at Danum, Sabah (Borneo), for a 21-year interval (censuses at 1986, 1996, 2001, 2007). Species with ≥45 focal trees 10 to <100 cm stem girth per plot in 1986 were selected. Logistic regressions fitted mean focal tree size and mean inverse-distance-weighted basal area abundance of neighbours (within 20 m), for the periods over which each focus tree was alive. Coefficients of variation of neighbourhood basal area abundance, both spatially and temporally, quantified the changing environment of each focus tree. Fits were critically and individually evaluated, with corrections for spatial autocorrelation. Conspecific effects at Danum was generally very weak or non-existent: species’ mortality rates varied also across plots. The main reasons appear to be that (1) species were not dense enough to interact despite frequent although weak spatial aggregation, and their neighbourhoods were highly differing in species composition; and (2) these neighbourhoods were highly variable temporally, meaning that focus trees experienced stochastically fluctuating neighbourhood environments. Only one species, Dimorphocalyx muricatus, showed strong conspecific effects (varying between plots) which can be explained by its distinct ecology. This understorey species is highly aggregated on ridges and is drought-tolerant. That this functionally and habitat-specialized species, has implied intraspecific density-dependent feedback in its dynamics is a remarkable indication of the overall processes maintaining stability of the Danum forest.

Modification of aviary design reduces incidence of falls, collisions and keel bone damage in laying hens

Non-cage housing systems for laying hens such as aviaries provide greater freedom to perform species-specific behavior and thus are thought to improve welfare of the birds; however, aviaries are associated with a high prevalence of keel bone damage (fractures and deviations), which is a major welfare problem in commercial laying hens. Potential causes of keel bone damage are falls and collisions with internal housing structures that occur as birds move between tiers or perches in the aviary. The aim of this study was to investigate the scope for reducing keel bone damage by reducing falls and collisions through modifications of aviary design. Birds were kept in 20 pens in a laying hen house (225 hens per pen) that were assigned to four different treatments (n = 5 pens per treatment group) including (1) control pens and pens modified by the addition of (2) perches, (3) platforms and (4) ramps. Video recordings at 19, 22, 29, 36 and 43 weeks of age were used to analyze controlled movements and falls (including details on occurrence of collision, cause of fall, height of fall and behavior after fall) during the transitional dusk and subsequent dark phase. Palpation assessments (focusing on fractures and deviations) using 20 focal hens per pen were conducted at 18, 20, 23, 30, 37, 44, 52 and 60 weeks of age. In comparison to the control group, we found 44% more controlled movements in the ramp (P = 0.003) and 47% more controlled movements in the platform treatments (P = 0.014) as well as 45% fewer falls (P = 0.006) and 59% fewer collisions (P < 0.001) in the ramp treatment. There were no significant differences between the control and perch treatments. Also, at 60 weeks of age, 23% fewer fractured keel bones were found in the ramp compared with the control treatment (P = 0.0053). After slaughter at 66 weeks of age, no difference in keel bone damage was found between treatment groups and the prevalence of fractures increased to an average of 86%. As a potential mechanism to explain the differences in locomotion, we suggest that ramps facilitated movement in the vertical plane by providing a continuous path between the tiers and thus supported more natural behavior (i.e. walking and running) of the birds. As a consequence of reducing events that potentially damage keel bones, the installation of ramps may have reduced the prevalence of keel fractures for a major portion of the flock cycle. We conclude that aviary design and installation of specific internal housing structures (i.e. ramps and platforms) have considerable potential to reduce keel bone damage of laying hens in aviary systems.

Temporal analysis of PI-3kinase and MAPK signal transduction during skeletal muscle overload

Skeletal muscles can adapt to increased mechanical forces (or loading) by increasing the size and strength of the muscle. Knowledge of the molecular mechanisms by which muscle responds to increased loading may lead to the discovery of novel treatment strategies for muscle wasting and frailty. The objective of this research was to examine the temporal associations between the activation of specific signaling pathway intermediates and their potential upstream regulator(s) in response to increased muscle loading. Previous work has demonstrated that focal adhesion kinase (FAK) activity is increased in overloaded hypertrophying skeletal muscle. Thus FAK is a candidate for transducing the loading stimulus in skeletal muscle, potentially by activating phosphatidylinositol 3-kinase (PI3K) and members of the mitogen-activated protein kinase (MAPK) family. However, it was unknown if muscle overload would result in activation of PI3K or the MAPKs. Thus, this work seeks to characterized the temporal response of (1) MAPK phosphorylation (including Erk 2, p38 MAPK and JNK), (2) PI3K activity, and (3) FAK tyrosine phosphorylation in response to 24 hours of compensatory overload in the rat soleus and plantaris muscles. In both muscles, overload resulted in transient Increases in the phosphorylation state of Erk2 and JNK, which peaked within the first hour of overload and returned to baseline thereafter. In contrast, p38 MAPK phosphorylation remained elevated throughout the entire 24-hour overload period. Moreover, overload increased PI3K activity only, in the plantaris and only at 12 hours. Moreover, 24 hours of overload induced a significant increase in total protein content in the plantaris but not the soleus. Thus an increase in total muscle protein content within the 24-hour loading period was observed only in muscle exhibiting increased PI3K activity. Surprisingly, FAK tyrosine phosphorylation was not increased during the overload period in either muscle, indicating that PI3K activation and increased MAPK phosphorylation were independent of increased FAK tyrosine phosphorylation. In summary, increased PI3K activity and sustained elevation of p38 MAPK phosphorylation were associated with muscle overload, identifying these pathways as potential mediators of the early hypertrophic response to skeletal muscle overload. This suggests that stimuli or mechanisms that activate these pathways may reduce/minimize muscle wasting and frailty. ^

Improving Health Literacy in Connecticut: A Prescription for Healthy Lives and Communities

The Practicum Project is a supervised service-learning experience that integrates curriculum with hands-on experience in a public health setting. All 2nd year students are expected to work collaboratively in assessing the extent, causes and public health responses to a selected public health problem confronting citizens of Connecticut. The focal topic for the 2006 Project was Health Literacy in Connecticut. During this past spring, 17 students of our program, working alongside and in partnership with more than 75 community-based stakeholders across Connecticut, completed over 1800 hours of service-learning in pursuit of answers to 3 questions: Can the present and future burden of health literacy be estimated for Connecticut? What is the current capacity of Connecticut’s health and social service system to halt the crisis we confront today? Can new policy and regulatory strategies be put forth to reduce the severity and scope of the problem? This occasion and the accompanying report mark the completion of their project and acknowledge the considerable contributions that many have made to the success of this educational experience. Through those combined efforts, students gained experience and skill addressing one of the most significant public health issues of our time; also, they gained insight into the breadth and capacity of our public health system and established invaluable relationships with public health practitioners, agencies and institutions around the state. Their report documents a rich campus-community partnership to advance public health goals.

Development and validation of the Neuro Symptom Inventory in the primary brain tumor patient population

Symptoms has been shown to predict quality of life, treatment course and survival in solid tumor patients. Currently, no instrument exists that measures both cancer-related symptoms and the neurologic symptoms that are unique to persons with primary brain tumors (PBT). The aim of this study was to develop and validate an instrument to measure symptoms in patients who have PBT. A conceptual analysis of symptoms and symptom theories led to defining the symptoms experience as the perception of the frequency, intensity, distress, and meaning that occurs as symptoms are produced, perceived, and expressed. The M.D. Anderson Symptom Inventory (MDASI) measures both symptoms and how they interfere with daily functioning in patients with cancer, which is similar to the situational meaning defined in the analysis. A list of symptoms pertinent to the PBT population was added to the core MDASI and reviewed by a group of experts for validity. As a result, 18 items were added to the core MDASI (the MDASI-BT) for the next phase of instrument development, establishing validity and reliability through a descriptive, cross-sectional approach with PBT patients. Data were collected with a patient completed demographic data sheet, an investigator completed clinician checklist, and the MDASI-BT. Analysis evaluated the reliability and validity of the MDASI-BT in PBT patients. Data were obtained from 201 patients. The number of items was reduced to 22 by evaluation of symptom severity as well as cluster analysis. Regression analysis showed more than half (56%) of the variability in symptom severity was explained by the brain tumor module items. Factor analysis confirmed that the 22 item MDASI-BT measured six underlying constructs: (a) affective; (b) cognitive; (c) focal neurologic deficits; (d) constitutional symptoms; (e) treatment-related symptoms; and (f) gastrointestinal symptoms. The MDASI-BT was sensitive to disease severity and if the patient was hospitalized. The MDASI-BT is the first instrument to measure symptoms in PBT patients that has demonstrated reliability and validity. It is the first step in a program of research to evaluate the occurrence of symptoms and plan and evaluate interventions for PBT patients. ^

Long-term hyperexcitability of sensory and motor axons in Aplysia californica: Induction by axotomy, serotonin, and transient depolarization

Neuropathic pain is a debilitating neurological disorder that may appear after peripheral nerve trauma and is characterized by persistent, intractable pain. The well-studied phenomenon of long-term hyperexcitability (LTH), in which sensory somata become hyperexcitable following peripheral nerve injury may be important for both chronic pain and long-lasting memory formation, since similar cellular alterations take place after both injury and learning. Though axons have previously been considered simple conducting cables, spontaneous afferent signals develop from some neuromas that form at severed nerve tips, indicating intrinsic changes in sensory axonal excitability may contribute to this intractable pain. Here we show that nerve transection, exposure to serotonin, and transient depolarization induce long-lasting sensory axonal hyperexcitability that is localized to the treated nerve segment and requires local translation of new proteins. Long-lasting functional plasticity may be a general property of axons, since both injured and transiently depolarized motor axons display LTH as well. Axonal hyperexcitability may represent an adaptive mechanism to overcome conduction failure after peripheral injury, but also displays key features shared with cellular analogues of memory including: site-specific changes in neuronal function, dependence on transient, focal depolarization for induction, and requirement for synthesis of new proteins for expression of long-lasting effects. The finding of axonal hyperexcitability after nerve injury sheds new light on the clinical problem of chronic neuropathic pain, and provides more support for the hypothesis that mechanisms of long-term memory storage evolved from primitive adaptive responses to injury. ^

Maternal nutrition and oral health factors in early childhood caries

Background. Early Childhood Caries (ECC) is the most common chronic infectious disease of childhood worldwide. Seven of ten American children have one or more decayed or filled primary teeth by age five. ECC prevalence is especially high in lower socio-economic ethnic populations. Commonly recognized as a diet-induced disease, focal etiological factors include cariogenic bacteria, fermentable carbohydrates, and a susceptible newly erupted tooth. Sequencing of breast and/or bottle feeding and introduction of beikost come at a time when children's defense mechanisms and, perhaps maternal direction of children's dietary patterns, are not yet fully developed or mature. To date, most research has examined biological factors, while maternal factors, especially psychosocial ones, have received scant attention. Objective. To examine the association of psychosocial factors in terms of maternal nutrition and oral health knowledge, attitudes, and beliefs, as well as social support and self-efficacy (KABS2) in a population of socio-economically disadvantaged infants and young children. A secondary aim was to describe ECC prevalence in this population. Methods. This study examined cross-sectionally the relationship between selected maternal psychosocial variables and ECC in a convenience sample of Mexican-American women and very young children participating in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) in San Antonio, Texas. Mothers were surveyed by use of a criteria- and content-valid, reliable questionnaire, and dental examinations were conducted on 191 children, aged 5 to 47 months old. Results. Thirty-nine percent of the children had ECC. As assessed on a 30-question scale, women in whose children were diagnosed with ECC were found to demonstrate lower Knowledge ( p=0.03), Attitudes (p=0.02), Beliefs (p=0.04), and Social Support (p<0.01) scores, compared to women whose children were found to be caries-free. No differences in Self-Efficacy scores were found between the groups. Conclusions. These data indicate that current etiological model depicting relevant factors associated with ECC in Mexican-American infants and children of low socio-economic status should be broadened to include consideration of maternal psychosocial factors such as nutrition and oral health knowledge, attitudes, beliefs, and social support, and that these factors should be considered when planning educational approaches to reduce the occurrence of ECC. ^

Platelets and Anti-Angiogenic Resistance in Ovarian Carcinoma

Background: Resistance to targeted anti-angiogenic therapy is a growing clinical concern given the disappointing clinical impact of anti-angiogenic. Platelets represent a component of the tumor microenvironment that are implicated in metastasis and represent a significant reservoir of angiogenic regulators. Thrombocytosis has been shown to be caused by malignancy and associated with adverse clinical outcomes, however the causal connections between these associations remain to be identified. Materials and Methods: Following IRB approval, patient data were collected on patients from four U.S. centers and platelet levels through and after therapy were considered as indicators of recurrence of disease. In vitro effects of platelets on cancer cell proliferation, apoptosis, and migration were examined. RNA interference was used to query signaling pathways mediating these effects. The necessity of platelet activation for in vitro effect was analyzed. In vivo orthotopic models were used to query the impact of thrombocytosis and thrombocytopenia on the efficacy of cytotoxic chemotherapy, the effect of aspirin on thrombocytosis and cancer, and platelet effect on anti-angiogenic therapy. Results: Platelets were found to increase at the time of diagnosis of ovarian cancer recurrence in a pattern comparable to CA-125. Platelet co-culture increased proliferation, increased migration, and decreased apoptosis in all cell lines tested. RNA interference implicated platelet derived growth factor alpha (PDGFRA) and transforming growth factor beta-receptor 1 (TGFBR1) signaling. Biodistribution studies suggested minimal platelet sequestration of taxanes. Blockade of platelet activation blocked in vitro effects. In vivo, thrombocytosis blocked chemotherapeutic efficacy, thrombocytopenia increased chemotherapeutic efficacy, and aspirin therapy partially blocked the effects of thrombocytosis. In vivo, withdrawal of anti-angiogenic therapy caused loss of therapeutic benefit with evidence of accelerated disease growth. This effect was blocked by use of a small-molecule inhibitor of Focal Adhesion Kinase. Anti-angiogenic therapy was also associated with increased platelet infiltration into tumor that was not seen to the same degree in the control or FAK-inhibitor-treated mice. Conclusions: Platelets are active participants in the growth and metastasis of tumor, both directly and via facilitation of angiogenesis. Blocking platelets, blocking platelet activation, and blocking platelet trafficking into tumor are novel therapeutic avenues supported by this data. Copyright © 2012 Justin Neal Bottsford-Miller, all rights reserved.

EFFECTS OF THE ACTA2 R258C MUTATION ON VASCULAR SMOOTH MUSCLE CELL PHENOTYPE AND PROPERTIES

Thoracic Aortic Aneurysms and Dissections (TAAD) are the fifteenth leading cause of death in the United States. About 15% of TAAD patients have family history of the disease. The most commonly mutated gene in these families is ACTA2, encoding smooth muscle-specific α-actin. ACTA2 missense mutations predispose individuals both to TAAD and to vascular occlusive disease of small, muscular arteries. Mice carrying an Acta2 R258C mutant transgene with a wildtype Acta2 promoter were generated and bred with Acta2-/- mice to decrease the wildtype: mutant Acta2 ratio. Acta2+/+ R258C TGmice have decreased aortic contractility without aortic disease. Acta2+/- R258C TG mice, however, have significant aortic dilatations by 12 weeks of age and a hyperproliferative response to injury. We characterized smooth muscle cells (SMCs) from bothmouse models under the hypothesis that mutant α-actin has a dominant negative effect, leading to impaired contractile filament formation/stability, improper focal adhesion maturation and increased proliferation. Explanted aortic SMCs from Acta2+/+ R258C TG mice are differentiated - they form intact filaments, express higher levels of contractile markers compared to wildtype SMCs and have predominantly nuclear Myocardin-Related Transcription Factor A (MRTF-A) localization. However, ultracentrifugation assays showed large unpolymerized actin fractions, suggesting that the filaments are brittle. In contrast, Acta2+/- R258C TG SMCs are less well-differentiated, with pools of unpolymerized actin, more cytoplasmic MRTF-A and decreased contractile protein expression compared to wildtype cells. Ultracentrifugation assays after treating Acta2+/- R258C TGSMCs with phalloidin showed actin filament fractions, indicating that mutant α-actin can polymerize into filaments. Both Acta2+/+ R258C TGand Acta2+/- R258C TGSMCs have larger and more peripheral focal adhesions compared to wildtype SMCs. Rac1 was more activated in Acta2+/+ R258C TGSMCs; both Rac1 and RhoA were less activated in Acta2+/- R258C TG SMCs, and FAK was more activated in both transgenic SMC lines compared to wildtype. Proliferation in both cell lines was significantly increased compared to wildtype cells and could be partially attenuated by inhibition of FAK or PDGFRβ. These data support a dominant negative effect of the Acta2 R258C mutation on the SMC phenotype, with increasing phenotypic severity when wildtype: mutant α-actin levels are decreased.

Improving disclosure of medical errors: Including patients and family members in the disclosure process

Over the last decade, adverse events and medical errors have become a main focus of interest for the standards of quality and safety in the U.S. healthcare system (Weinstein & Henderson, 2009). Particularly when a medical error occurs, the disclosure of medical errors and its practices have become a focal point of the healthcare process. Patients and family members who have experienced a medical error might be able to provide knowledge and insight on how to improve the disclose process. However, patient and family member are not typically involved in the disclosure process, thus their experiences go unnoticed. ^ The purpose of this research was to explore how best to include patients and family members in the disclosure process regarding a medical error. The research consisted of 28 qualitative interviews from three stakeholder groups: Hospital Administrators, Clinical Service Providers, and Patients and Family Members. They were asked for their ideas and suggestions on how best to include patients and family members in the disclosure process. Framework Analysis was used to analyze this data and find prevalent themes based on the primary research question. A secondary aim was to index categories created based on the interviews that were collected. Data was used from the Texas Disclosure and Compensation Study with Dr. Eric Thomas as the Principal Investigator. Full acknowledgement of access to this data is given to Dr. Thomas. ^ The themes from the research revealed that each stakeholder group was interested and open to including patients and family members in the disclosure process and that the disclosure process should not be a "one-way" avenue. The themes gave many suggestions regarding how to best include patients and family members in the disclosure process of a medical error. Secondary aims revealed several ways to assess the ideas and suggestion given by the stakeholders. Overall, acceptability of getting the perspective of patients and family members was the most common theme. Comparison of each stakeholder group revealed that including patients and family members would be beneficial to improving hospital disclosure practices. ^ Conclusions included a list of recommendations and measureable appropriate strategies that could provide hospital with key stakeholders insights on how to improve their disclosure process. Sharing patients and family members experience with healthcare providers can encourage a shift in culture where patients are valued and active in participating in hospital practices. To my knowledge, this research is the very first of its kind and moves the disclosure process conversation forward in a patient-family member inclusion direction that will assist in improving disclosure practices. Future research should implement and evaluate the success of the various inclusion strategies.^

Characterization of the interaction between local cerebral metabolic rate for glucose and acid -base index in ischemic rat brain employing a double-isotope methodology

The association between increases in cerebral glucose metabolism and the development of acidosis is largely inferential, based on reports linking hyperglycemia with poor neurological outcome, lactate accumulation, and the severity of acidosis. We measured local cerebral metabolic rate for glucose (lCMRglc) and an index of brain pH--the acid-base index (ABI)--concurrently and characterized their interaction in a model of focal cerebral ischemia in rats in a double-label autoradiographic study, using ($\sp{14}$C) 2-deoxyglucose and ($\sp{14}$C) dimethyloxazolidinedione. Computer-assisted digitization and analysis permitted the simultaneous quantification of the two variables on a pixel-by-pixel basis in the same brain slices. Hemispheres ipsilateral to tamponade-induced middle cerebral occlusion showed areas of normal, depressed and elevated glucose metabolic rate (as defined by an interhemispheric asymmetry index) after two hours of ischemia. Regions of normal glucose metabolic rate showed normal ABI (pH $\pm$ SD = 6.97 $\pm$ 0.09), regions of depressed lCMRglc showed severe acidosis (6.69 $\pm$ 0.14), and regions of elevated lCMRglc showed moderate acidosis (6.88 $\pm$ 0.10), all significantly different at the.00125 level as shown by analysis of variance. Moderate acidosis in regions of increased lCMRglc suggests that anaerobic glycolysis causes excess protons to be generated by the uncoupling of ATP synthesis and hydrolysis. ^

Expression of p53, {\it * ras\/} and PCNA in human colonic neoplasms: Possible biomarkers of malignant potential

Colorectal cancer is a leading cause of cancer mortality and early detection can significantly improve the clinical outcome. Most colorectal cancers arise from benign neoplastic lesions recognized as adenomas. Only a small percentage of all adenomas will become malignant. Thus, there is a need to identify specific markers of malignant potential. Studies at the molecular level have demonstrated an accumulation of genetic alterations, some hereditary but for the most occurring in somatic cells. The most common are the activation of ras, an oncogene involved in signal transduction, and the inactivation of p53, a tumor suppressor gene implicated in cell cycle regulation. In this study, 38 carcinomas, 95 adenomas and 20 benign polyps were analyzed by immunohistochemistry for the abnormal expression of p53 and ras proteins. An index of cellular proliferation was also measured by labeling with PCNA. A general overexpression of p53 was immunodetected in 66% of the carcinomas, while 26% of adenomas displayed scattered individual positive cells or a focal high concentration of positive cells. This later was more associated with severe dysplasia. Ras protein was detected in 37% of carcinomas and 32% of adenomas mostly throughout the tissue. p53 immunodetection was more frequent in adenomas originating in colons with synchronous carcinomas, particularly in patients with familial adenomatous polyposis and it may be a useful marker in these cases. Difference in the frequency of p53 and ras alterationbs was related to the location of the neoplasm. Immunodetection of p53 protein was correlated to the presence of a mutation in p53 gene at exon 7 and 5 in 4/6 carcinomas studied and 2 villous adenomas. Thus, we characterized in adenomas the abnormal expression of two proteins encoded by the most commonly altered genes in colorectal cancer. p53 alteration appears to be more specifically associated with transition to malignancy than ras. By using immunohistochemistry, a technique that keeps the architecture of the tissue intact, it was possible to correlate these alterations to histopathological characteristics that were associated with higher risks for transformation: villous content, dysplasia and size of adenoma. ^

Crises of social significances: adolescents and their projects for future work

This is a report on data raised through research, which has already finished, about Identification references in adolescents . Objetives : To analyze and reflect upon the collected data, adolescents' representations about the work field and their projects for future work. To conceptualize about the crises of social significances which produce and order sense and, therefore, organize our perceptions of work through social discourses and practices which have an impact on the subjectivity of adolescents and young adults. Methodology: Brief presentation of the concepts which frame the qualitative research in this area. Reading and analysis of fragments from adolescents' accounts, obtained in focal groups at different state secondary schools. Conclusions: The adolescents researched portray a self-image full of uncertainty and skepticism as regards their future possibilities. The impact produced by the fall of work as an ideal of doing and being is made evident in their accounts. Only some of them link their future project with an invested and valuable activity, even if this is not associated with economic safety and wellbeing. Others present themselves as incapable to modify the state of things, which offers a field connected with consumerist values and with the idea that "you are worth what you have (in material things)".