Emotional Value of Fear Memory and the Role of the Ventral Hippocampus in Systems Consolidation.

Recent studies have explored the circuitry involving the ventral hippocampus (vHPC), the amygdala, and the prefrontal cortex, a pathway mainly activated to store contextual information efficiently. Lesions in the vHPC impair remote memory, but not in the short term. However, how the vHPC is affected by distinct memory strength or its role in systems consolidation has not yet been elucidated. Here, we investigated how distinct training intensities, with strong or weak contextual fear conditioning, affect activation of the dorsal hippocampus (dHPC) and the vHPC. We found that the time course of memory consolidation differs in fear memories of different training intensities in both the dHPC and vHPC. Our results also indicate that memory generalization happens alongside greater activation of the vHPC, and these processes occur faster with stronger fear memories. The vHPC is required for the expression of remote fear memory and may control contextual fear generalization, a view corroborated by the fact that inactivation of the vHPC suppresses generalized fear expression, making memory more precise again. Systems consolidation occurs concomitantly with greater activation of the vHPC, which is accelerated in stronger fear memories. These findings lead us to propose that greater activation of the vHPC could be used as a marker for memory generalization.

Differential gene co-expression network analyses reveal novel molecules associated with transcriptional dysregulation of key biological processes in osteoarthritis knee cartilage.

Objectives: To compare co-expression networks of normal and osteoarthritis knee cartilage to uncover molecules associated with the transcriptional misregulation compromising biological processes (BPs) critical for cartilage homeostasis. Design: Normal and osteoarthritis human knee cartilage RNA-seq GSE114007 dataset was obtained from the Gene Expression Omnibus database. Partial Correlation and Information Theory (PCIT) algorithm was used to build co-expression networks containing all nodes connecting to at least one differentially expressed gene (DEG) in normal and osteoarthritis networks. Hub and hub centrality genes were used to perform functional enrichment analysis. Enriched BPs known to be associated with both healthy and diseased cartilage were compared in depth. Results: Differential co-expression network analyses allowed the identification of DDX43 and USP42 as exclusively co-expressed with DEGs in normal and osteoarthritis networks, respectively. The top hub and hub centrality genes of these networks were HIST1H3A and SNHG12 (normal) and TAF9B and OTUD1 (osteoarthritis). Enrichment analysis revealed several shared BPs between the contrasting groups, which are well-known in osteoarthritis pathogenesis. Protein-protein interaction network analysis for these BPs showed a global down-regulation of transcription factors in osteoarthritis. Specific transcription factors were identified as pleiotropic mediators in articular cartilage maintenance since they take part in several BPs. In addition, chromatin organisation and modification proteins were found relevant for osteoarthritis development. Conclusion: Differential gene co-expression analysis allowed the identification of novel and high priority therapeutic candidate genes that may drive modifications in the transcriptional "status" of cartilage in osteoarthritis.

Reactivation enables memory updating, precision-keeping and strengthening: exploring the possible biological roles of reconsolidation.

Although much has been learned regarding the molecular and cellular mechanisms of memory reconsolidation, its actual biological function remains unclear. In this work we investigate the possibility that three different mnemonic processes - updating, precision-keeping and trace strengthening - are mediated by reconsolidation in contextual fear conditioning. Reconsolidation involves the activation of calcium channels for the destabilization during the reactivation. Our results show that when memory is reactivated in a situation that does not match the original information, content is modified, i.e., "updated". However, when the contextual condition matches the original one, memory reactivation contributes either to its strengthening or to the maintenance of its precision content over time. Since the L-type voltage-gated calcium channel antagonist nimodipine blocked these effects, we suggest that reconsolidation is the mechanism supporting these processes.

A conceptual and disease model framework for osteoporotic kyphosis.

UNLABELLED: This paper presents a multi-method research project to develop a conceptual framework for measuring outcomes in studies of osteoporotic kyphosis. The research involved literature research and qualitative interviews among clinicians who treat patients with kyphosis and among patients with the condition. INTRODUCTION: Kyphosis due to at least one vertebral compression fracture is prevalent among osteoporotic patients, resulting in well-documented symptoms and impact on functioning and well-being. A three-part study led to development of a conceptual measurement framework for comprehensive assessment of symptoms, impact, and treatment benefit for kyphosis. METHODS: A literature-based disease model (DM) was developed and tested with physicians (n = 10) and patients (n = 10), and FDA guidelines were used to develop a final disease model and a conceptual framework. RESULTS: The DM included signs, symptoms, causes/triggers, exacerbations, and functional status associated with kyphosis. The DM was largely confirmed, but physicians and patients added several concepts related to impact on functioning, and some concepts were not confirmed and removed from the DM. CONCLUSIONS: This study confirms the need for more comprehensive assessment of health outcomes in kyphosis, as most current studies omit key concepts.

Balloon kyphoplasty compared to vertebroplasty and nonsurgical management in patients hospitalised with acute osteoporotic vertebral compression fracture: a UK cost-effectiveness analysis.

UNLABELLED: The purpose of the study was to estimate the cost-effectiveness of balloon kyphoplasty compared to nonsurgical management and vertebroplasty for the treatment of hospitalised osteoporotic vertebral compression fractures in the UK. A cost-effectiveness model was constructed and used for analysis. Balloon kyphoplasty may be cost-effective compared to relevant alternatives. INTRODUCTION: The objective of this study was to estimate the cost-effectiveness of balloon kyphoplasty (BKP) for the treatment of patients hospitalised with acute osteoporotic vertebral compression fracture (OVCF) compared to percutaneous vertebroplasty (PVP) and nonsurgical management (NSM) in the UK. METHODS: A Markov simulation model was developed to evaluate treatment with BKP, NSM and PVP in patients with symptomatic OVCF. Data on health-related quality of life (HRQoL) with acute OVCF were derived from the FREE and VERTOS II randomised clinical trials (RCTs) and normalised to the NSM arm in the FREE trial. Estimated differences in mortality among the treatments and costs for NSM were obtained from the literature whereas procedure costs for BKP and PVP were obtained from three National Health Service hospitals. It was assumed that BKP and PVP reduced hospital length of stay by 6 days compared to NSM. RESULTS: The incremental cost-effectiveness ratio was estimated at Great Britain Pound Sterling (GBP) 2,706 per quality-adjusted life year (QALY) and GBP 15,982 per QALY compared to NSM and PVP, respectively. Sensitivity analysis showed that the cost-effectiveness of BKP vs. NSM was robust when mortality and HRQoL benefits with BKP were varied. The cost-effectiveness of BKP compared to PVP was particularly sensitive to changes in the mortality benefit. CONCLUSION: BKP may be a cost-effective strategy for the treatment of patients hospitalised with acute OVCF in the UK compared to NSM and PVP. Additional RCT data on the benefits of BKP and PVP compared to simulated sham surgery and further data on the mortality benefits with BKP compared to NSM and PVP would reduce uncertainty.

Opposite action of hippocampal CB1 receptors in memory reconsolidation and extinction.

Retrieval of a consolidated memory triggers a number of processes which depend, among other factors, on the duration of the reactivation session: reconsolidation requires a brief reactivation session, and extinction, a prolonged one. The scope of this study is to explore the potential role of the hippocampal endocannabinoid system on reconsolidation and extinction processes. Bilateral infusion of the CB1 cannabinoid receptor antagonist, N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) into the CA1 region of the dorsal hippocampus of Wistar rats after memory reactivation facilitated the reconsolidation of the contextual fear conditioning memory. The inhibition of protein synthesis with DRB in the same brain region blocked memory reconsolidation. Both effects were persistent, lasting up to 7 days after the first retrieval experience. In contrast, the local infusion of anandamide blocked memory reconsolidation, an effect that was antagonized by the combined administration of anandamide with a subthreshold dose of a CB1 antagonist, supporting a CB1-mediated role of the hippocampal endocannabinoid system in the modulation of the memory reconsolidation. Local infusion of AM251 into CA1 blocked memory extinction whereas the administration of anandamide facilitated it; however, when combined with a subthreshold concentration of the CB1 antagonist, anandamide did not affect the extinction process. The clear-cut, opposite effects observed in each situation suggest a possible role of the hippocampal endocannabinoid system as a switching mechanism deciding which processes will take place, either maintaining the original memory (reconsolidation) or promoting a new learning (extinction).

Percepção da qualidade de vida de indivíduos com doença de parkinson através do PDQ-39 / Perception of quality of life in individuals with Parkinson's disease using the PDQ-39

A Doença de Parkinson (DP) é uma doença crônica e degenerativa do sistema nervoso central que afeta principalmente pessoas acima de 50 anos. Estudos que avaliaram a qualidade de vida (QV) em parkinsonianos revelaram significativo impacto negativo da doença nesses indivíduos. O Parkinson Disease Questionnaire39 (PDQ-39) tem sido indicado como instrumento mais apropriado para avaliação da QV do indivíduo com DP. OBJETIVO: Avaliar a percepção da QV de indivíduos com DP do Ambulatório de Distúrbios do Movimento da Instituição, através do PDQ-39. MÉTODO: Participaram deste estudo indivíduos com diagnóstico de DP, entre os estágios 1 e 3 da escala de Hoehn & Yahr Modificada e com idade igual ou superior a 40 anos. RESULTADOS: Trinta e três indivíduos com média de idade de 64,65 (±10,44) anos e tempo médio de evolução da doença de 9,27 (±4,40) anos participaram deste estudo. A análise descritiva mostrou que a mediana do escore total no PDQ-39 foi 25 por cento, ocorrendo pior percepção da QV nas dimensões "Atividade de Vida Diária (AVD)" (41,67 por cento) e "Mobilidade" (34,32 por cento). Encontrou-se alta associação entre o escore total e a dimensão "Mobilidade" (r s= 0,82) e moderada associação das dimensões "AVD" (r s= 0,68) e "Comunicação" (r s= 0,53) com o escore total. CONCLUSÕES: As limitações motoras relacionadas à mobilidade, AVDs e comunicação possuem relação significativa com a percepção geral da QV dos indivíduos com DP. Estes achados sugerem que programas de reabilitação que tenham como objetivo a melhora da QV na DP devem enfocar tais limitações.

Parkinson's disease (PD) is a chronic degenerative disease of the central nervous system that affects mainly individuals older than 50 years of age. Studies evaluating quality of life (QOL) in individuals with PD have revealed that this disease has a significant negative impact. The Parkinson's Disease Questionnaire-39 (PDQ-39) has been indicated as one of the most appropriate instrument for evaluating QOL in individuals with PD. OBJECTIVE: To evaluate the perception of QOL in individuals with PD at our Institution's outpatient service for movement disorders, using the PDQ-39. METHOD: Individuals with a diagnosis of PD who were aged 40 years and older and classified in stages 1 to 3 of the Modified Hoehn & Yahr scale were included in this study. RESULTS: Thirty-three individuals of mean age 64.65 ± 10.44 years and mean duration of the disease of 9.27 ± 4.40 years participated in this study. The descriptive analysis showed that the median total score in the PDQ-39 was 25 percent, with worst perceptions of QOL in the dimensions of "Activities of Daily Living" (ADL) (41.67 percent) and "Mobility" (34.32 percent). A high association was found between the total score and the dimension of "Mobility" (r s= 0.82) and a moderate association between the total score and the dimensions of "ADL" (r s= 0.68) and "Communication" (r s = 0.53). CONCLUSIONS: Motor limitations relating to mobility, ADL and communication were significantly related to the general perception of QOL among individuals with PD. These findings suggest that rehabilitation programs aiming to improve QOL among individuals with PD should focus on these limitations.

[Nutritional status recording in hospitalized patient notes]. / Menções sobre o estado nutricional nos registos clínicos de doentes hospitalizados.

The prevalence of disease-related malnutrition (DRM) is described to be of 30-60% on admission to hospital, and of 10% in the community. It has been associated with worse clinical outcomes, namely higher morbidity and mortality as well as higher frequency of health care and its associated costs. The lack of screening and monitoring of nutritional status have been said to be risk factors for the increased prevalence of DRM during hospital stay. The aims of this study were to evaluate the importance given by health care professionals to certain aspects related with nutritional status (weight, food intake) of hospital patients and to see if there were any differences between the under and non undernourished ones. A systematic sample of patients from six hospitals was collected. Pregnancy, paediatric age and critical illness were exclusion criteria as well as incapacity to fulfil nutritional risk screening protocol and length-of-stay less than 24h. Socio-demographic, anthropometric data and clinical notes (e.g. weight, food/nutrient intake) from medical records were collected and Nutritional Risk Screening 2002 protocol was applied. A total of 1152 patients were included in this study. The prevalence of nutritional risk varied between 28.5% and 47.3% while undernutrition classified by anthropometrical parameters was considerably lower (6.3% to 14.9%). Two thirds of the patients had their food intake monitored and registered in medical records but only one third were weighted. Undernourished patients had their food intake more frequently monitored but their weight was less frequently measured, than the well-nourished ones. DRM prevalence amongst hospital patients on admission is significantly high. Clinical notes regarding nutritional status is rather infrequent on medical records. This study showed that urges the need to empower health care providers of the importance of the screening and monitoring of weight and food intake, on admission and during hospital stay.

Temporal expression pattern of myostatin transcripts during chicken embryogenesis

No presente estudo, estimou-se a abundância dos transcritos da miostatina foi estimada durante a embriogênese de galinha por análises de RT-PCR competitiva. Níveis basais de mRNA desse gene foram detectados até o estádio HH15, enquanto acúmulos significativos nesses níveis foram observados apenas no estádio HH24, seguido por redução na abundância desses transcritos a partir do estádio HH26. Tais descobertas preliminares proporcionam informações relevantes sobre a ativação do fator de crescimento miostatina durante o desenvolvimento in ovo de aves.

Osteoblastoma of the mandible: systematic review of the literature and report of a case.

Benign osteoblastoma is a bone tumour that seldom occurs in the facial bones. The objective of this article is to add one more case of this rare lesion to the academic literature and to provide a systematic review of previously published cases. A new case of benign osteoblastoma is presented and clinical, radiographic and microscopic aspects, as well as differential diagnosis, treatment and follow-up are discussed. The importance of the correct diagnosis of this type of lesion is stressed, since it presents a clinical, radiographic and microscopic similarity to other bone lesions, including malignant tumours, which may lead the professional into conducting the case in an improper manner.

Standard-curve competitive RT-PCR quantification of myogenic regulatory factors in chicken embryos.

The reverse transcription-polymerase chain reaction (RT-PCR) is the most sensitive method used to evaluate gene expression. Although many advances have been made since quantitative RT-PCR was first described, few reports deal with the mathematical bases of this technique. The aim of the present study was to develop and standardize a competitive PCR method using standard-curves to quantify transcripts of the myogenic regulatory factors MyoD, Myf-5, Myogenin and MRF4 in chicken embryos. Competitor cDNA molecules were constructed for each gene under study using deletion primers, which were designed to maintain the anchorage sites for the primers used to amplify target cDNAs. Standard-curves were prepared by co-amplification of different amounts of target cDNA with a constant amount of competitor. The content of specific mRNAs in embryo cDNAs was determined after PCR with a known amount of competitor and comparison to standard-curves. Transcripts of the housekeeping -actin gene were measured to normalize the results. As predicted by the model, most of the standard-curves showed a slope close to 1, while intercepts varied depending on the relative efficiency of competitor amplification. The sensitivity of the RT-PCR method permitted the detection of as few as 60 MyoD/Myf-5 molecules per reaction but approximately 600 molecules of MRF4/Myogenin mRNAS were necessary to produce a measurable signal. A coefficient of variation of 6 to 19% was estimated for the different genes analyzed (6 to 9 repetitions). The competitive RT-PCR assay described here is sensitive, precise and allows quantification of up to 9 transcripts from a single cDNA sample.

Standard-curve competitive RT-PCR quantification of myogenic regulatory factors in chicken embryos

The reverse transcription-polymerase chain reaction (RT-PCR) is the most sensitive method used to evaluate gene expression. Although many advances have been made since quantitative RT-PCR was first described, few reports deal with the mathematical bases of this technique. The aim of the present study was to develop and standardize a competitive PCR method using standard-curves to quantify transcripts of the myogenic regulatory factors MyoD, Myf-5, Myogenin and MRF4 in chicken embryos. Competitor cDNA molecules were constructed for each gene under study using deletion primers, which were designed to maintain the anchorage sites for the primers used to amplify target cDNAs. Standard-curves were prepared by co-amplification of different amounts of target cDNA with a constant amount of competitor. The content of specific mRNAs in embryo cDNAs was determined after PCR with a known amount of competitor and comparison to standard-curves. Transcripts of the housekeeping á-actin gene were measured to normalize the results. As predicted by the model, most of the standard-curves showed a slope close to 1, while intercepts varied depending on the relative efficiency of competitor amplification. The sensitivity of the RT-PCR method permitted the detection of as few as 60 MyoD/Myf-5 molecules per reaction but approximately 600 molecules of MRF4/Myogenin mRNAS were necessary to produce a measurable signal. A coefficient of variation of 6 to 19 percent was estimated for the different genes analyzed (6 to 9 repetitions). The competitive RT-PCR assay described here is sensitive, precise and allows quantification of up to 9 transcripts from a single cDNA sample.

Influence of the neural tube/notochord complex on MyoD expression and cellular proliferation in chicken embryos.

Important advances have been made in understanding the genetic processes that control skeletal muscle formation. Studies conducted on quails detected a delay in the myogenic program of animals selected for high growth rates. These studies have led to the hypothesis that a delay in myogenesis would allow somitic cells to proliferate longer and consequently increase the number of embryonic myoblasts. To test this hypothesis, recently segmented somites and part of the unsegmented paraxial mesoderm were separated from the neural tube/notochord complex in HH12 chicken embryos. In situ hybridization and competitive RT-PCR revealed that MyoD transcripts, which are responsible for myoblast determination, were absent in somites separated from neural tube/notochord (1.06 and 0.06 10(-3) attomol MyoD/1 attomol beta-actin for control and separated somites, respectively; P<0.01). However, reapproximation of these structures allowed MyoD to be expressed in somites. Cellular proliferation was analyzed by immunohistochemical detection of incorporated BrdU, a thymidine analogue. A smaller but not significant (P = 0.27) number of proliferating cells was observed in somites that had been separated from neural tube/notochord (27 and 18 for control and separated somites, respectively). These results confirm the influence of the axial structures on MyoD activation but do not support the hypothesis that in the absence of MyoD transcripts the cellular proliferation would be maintained for a longer period of time.

Influence of the neural tube/notochord complex on MyoD expression and cellular proliferation in chicken embryos

Important advances have been made in understanding the genetic processes that control skeletal muscle formation. Studies conducted on quails detected a delay in the myogenic program of animals selected for high growth rates. These studies have led to the hypothesis that a delay in myogenesis would allow somitic cells to proliferate longer and consequently increase the number of embryonic myoblasts. To test this hypothesis, recently segmented somites and part of the unsegmented paraxial mesoderm were separated from the neural tube/notochord complex in HH12 chicken embryos. In situ hybridization and competitive RT-PCR revealed that MyoD transcripts, which are responsible for myoblast determination, were absent in somites separated from neural tube/notochord (1.06 and 0.06 10-3 attomol MyoD/1 attomol á-actin for control and separated somites, respectively; P<0.01). However, reapproximation of these structures allowed MyoD to be expressed in somites. Cellular proliferation was analyzed by immunohistochemical detection of incorporated BrdU, a thymidine analogue. A smaller but not significant (P = 0.27) number of proliferating cells was observed in somites that had been separated from neural tube/notochord (27 and 18 for control and separated somites, respectively). These results confirm the influence of the axial structures on MyoD activation but do not support the hypothesis that in the absence of MyoD transcripts the cellular proliferation would be maintained for a longer period of time

Identification of enhancer-like elements in the ribosomal intergenic spacer of Odontophrynus americanus 2n and 4n (Amphibia, Anura).

Repetitive elements are found in the ribosomal intergenic spacer (IGS) of most organisms. A particularly complex pattern of internal repetition occurs in the IGSs of O. americanus 2n and 4n, which are composed of several types of BamHI subrepeats (B-SRs). The most repetitive one is approximately 87 bp long, and is highly represented in the IGS variants of these amphibians. Sequence analyses of six diploid and two tetraploid B-SRs show 87% and 86% homology, respectively, and related secondary structure predictions. The comparison of the 2n and 4n B-SR sequences aligned with the 81 bp enhancer of Xenopus laevis reveals 36% homology. Furthermore, other B-SR features like size, number, and secondary structures resemble those of Xenopus enhancers, suggesting that B-SRs may function as regulators of O. americanus rDNA transcription. The present data also corroborate the close evolutionary relationship between 2n and 4n O. americanus species.

[Comparative study of Agfa-Gavaert, Kodak Ultra-Speed and Kodak Ektaspeed dental radiographic films, processed in Sillib solution]. / Estudo comparativo entre os filmes radiográficos dentais Agfa-Gevaert, Kodak Ultra-Speed e Kodak Ektaspeed, processados na solução Sillib.

The films were compared through their characteristic curves obtained in experimental conditions and processed in Sillib's developers. Radiographies of a phanton, obtained in standard conditions of exposure and development, were analysed by dentists and technicians for judgement. It was possible to conclude that as long as the recommendations of films and developers manufactures are followed, the results are acceptable for dental clinical work, when these films were processed in Sillib's solution (20 degrees C/2 min). The judges preferred those which received two times the recommended exposure.

[Radiographic study of the applicability of three anatomical landmarks in transcranial radiography of the temporomandibular joint]. / Estudo radiográfico da aplicabilidade de três pontos de reparo anatômicos nas radiografias transcranianas da articulação temporomandibular.

The variability of the angles formed between the long axis of the right and left condyles and the midsagittal plane, as well as the applicability of three anatomic landmarks--zigoma, gonion and base of the mandible, for transcranian radiographs of the TMJ were studied. The radiographic method used in this study was the HIRTZ axial projection. The results of the measurements showed a great variation in the angle formed by the long axis of the condyles and the midsagittal plane, from 48 degrees-79 degrees (x = 63.73 degrees) for the right side, from 50 degrees-80 degrees (x = 67.43 degrees) for the left side. It was also observed that the use of the three anatomic landmarks must not be generalized, being more precisely indicated for tapering head and face.