The Identified Skeletal Collection of the School of Legal Medicine: a contemporary osteological collection housed in Universidad Complutense de Madrid, Spain.

ABSTRA: Osteological collections are an important resource for the development of methods to assist in the study of skeletal remains in archeological and/or forensic contexts. The aim is to describe the current characteristics of the Identified Skeletal Collection of the School of Legal Medicine and its historical context. The Identified Skeletal Collection of the School of Legal Medicine of the Complutense University of Madrid consists of 138 male and 95 female individuals, born between 1880 and 1980 and deceased between 1970 and 2009. The minimum age of the sample is perinatal and the maximum age is 97 years. The collection is an essential tool for forensic research, given that its population characteristics can be extrapolated to those of present-day Spain. Access to this collection offers unique teaching opportunities as well as provides the information necessary to develop various lines of research.

Intermittent fasting disrupts hippocampal-dependent memory and norepinephrine content in aged male and female mice.

Intermittent fasting (IMF) is associated with many health benefits in animals and humans. Yet, little is known if an IMF diet affects mood and cognitive processing. We have previously identified that IMF in diet-induced obese males increases norepinephrine and dopamine content in the hypothalamus and increases arcuate neuropeptide Y (NPY) gene expression more than in ad libitum control males. This suggests that IMF may improve cognition through activation of the hindbrain norepinephrine neuronal network and reverse the age-dependent decline in NPY expression. Less is known about the association between anxiety and IMF. Although, in humans, IMF during Ramadan may alleviate anxiety. Here, we address the impact of IMF on anxiety-like behavior using the open field test, hippocampal-dependent memory using the Y-maze and spatial object recognition, and hippocampal-independent memory using novel object recognition in middle-aged male and female (12 mo) and aged male and female (18 mo) mice. Using ELISA, we determined norepinephrine (NE) content in the dorsal hippocampus (DH) and prefrontal cortex (PFC). We also investigated gene expression in the arcuate nucleus (ARC), the lateral hypothalamus (LH), and the locus coeruleus (LC). In IMF-treated females at both ages, we observed an improvement in spatial navigation although an impairment in spatial object orientation. IMF-treated females (12 mo) had a reduction and IMF-treated males (12 mo) displayed an improvement in novel object recognition memory. IMF-treated females (18 mo) exhibited anxiolytic-like behavior and increased locomotion. In the DH, IMF-treated males (12 mo) had a greater amount of NE content and IMF-treated males (18 mo) had a reduction. In the ARC, IMF-treated males (12 mo) exhibited an increase in Agrp and Npy and a decrease in Adr1a. In the ARC, IMF-treated males (18 mo) exhibited an increase in Npy and a decrease in Adr1a; females had a trending decrease in Cart. In the LH at 12 months, IMF-treated males had a decrease in Npy5r, Adr1a, and Adr1b; both males and females had a reduction in Npy1r. In the LH, IMF-treated females (18 mo) had a decrease in Hcrt. In the LC at both ages, mice largely exhibited sex effects. Our findings indicate that IMF produces alterations in mood, cognition, DH NE content, and ARC, LH, and LC gene expression depending on sex and age.

Deletion of Growth Hormone Secretagogue Receptor in Kisspeptin Neurons in Female Mice Blocks Diet-Induced Obesity.

The gut peptide, ghrelin, mediates energy homeostasis and reproduction by acting through its receptor, growth hormone secretagogue receptor (GHSR), expressed in hypothalamic neurons in the arcuate (ARC). We have shown 17ß-estradiol (E2) increases Ghsr expression in Kisspeptin/Neurokinin B/Dynorphin (KNDy) neurons, enhancing sensitivity to ghrelin. We hypothesized that E2-induced Ghsr expression augments KNDy sensitivity in a fasting state by elevating ghrelin to disrupt energy expenditure in females. We produced a Kiss1-GHSR knockout to determine the role of GHSR in ARC KNDy neurons. We found that changes in ARC gene expression with estradiol benzoate (EB) treatment were abrogated by the deletion of GHSR and ghrelin abolished these differences. We also observed changes in metabolism and fasting glucose levels. Additionally, knockouts were resistant to body weight gain on a high fat diet (HFD). Behaviorally, we found that knockouts on HFD exhibited reduced anxiety-like behavior. Furthermore, knockouts did not refeed to the same extent as controls after a 24 h fast. Finally, in response to cold stress, knockout females had elevated metabolic parameters compared to controls. These data indicate GHSR in Kiss1 neurons modulate ARC gene expression, metabolism, glucose homeostasis, behavior, and thermoregulation, illustrating a novel mechanism for E2 and ghrelin to control Kiss1 neurons.

Impact of immunoprophylaxis with palivizumab on respiratory syncytial virus infection in preterm infants less than 35 weeks in Colombian hospitals.

OBJECTIVE: To evaluate the impact of immunoprophylaxis with palivizumab in preterm infants less than 35 weeks in terms of hospitalization rate, intensive care unit requirement, and mortality. METHODS: A prospective cohort study was conducted at six Colombian hospitals. Preterm infants less than 35 weeks who received at least one dose of palivizumab during the first 6 months of life were included. The primary outcome was the hospitalization rate related to respiratory syncytial virus (RSV) infection. RESULTS: A total of 222 newborns participated in the study; 204 (91.8%) completed the 6-month follow-up, and three died during the study. 88.7% received a second dose of palivizumab, 79.7% a third, 34.7% a fourth, and 25.2% a fifth. The nonadjusted incidence rate of RSV infection was 2.4%, and the overall RSV-positive hospitalization rate was 1.9%. The proportion of patients that required Neonatal Intensive Care Unit (NICU) and mechanical ventilation in relation to RSV infection was 1.4%. Discharge with home oxygen, pulmonary dysplasia, and being younger than 6 months were significantly associated with respiratory infection. Furthermore, exposition to cigarette smoke was the only factor associated with increased risk of hospitalization. The group that required hospitalization received fewer doses of palivizumab (p = 0.049). No discontinuation of treatment due to adverse events were reported. No death was judged to be related to palivizumab. CONCLUSION: The hospitalization rate and the need for NICU admission were lower than those reported in the literature. In this real-life setting, palivizumab appears to be effective in preventing serious cases of RSV infection.

Ontogeny of morphological variations in the vertebral column: Prevalence and bony variability in young Spanish children.

Pre- and postnatal development and variability in discrete vertebral traits have been poorly described in embryonic studies. Numerous authors have reported that these variations are observable only from adolescence; scientific publications on the vertebrae of fetuses and infants are scarce. Thus, the aims of this study were to (1) describe the ontogeny and variability of anatomical variations in the vertebral column of a Spanish infant population and (2) analyze the frequency and relationship between sex, age, and intertrait variables. A total of 4728 vertebrae from 197 skeletons were studied. The age at death ranged from 22 intrauterine weeks to 8 years. Twenty morphological traits related to vertebral column development were analyzed. A descriptive statistical analysis was performed, and the chi-square test was used to measure the relationship between sex, age, and intertrait variables. We observed that 88.32% of skeletons expressed discrete traits along the spine. In fetuses, the double transverse foramen and unclosed transverse process of the axis were the most prevalent traits. In infants older than one year, the appearance of the L5 cleft neural arch, unclosed transverse process of the atlas, and craniocaudal shifts were frequent. A significant result was found between sex and the unclosed transverse process in the axis. The intertrait relationship was significant for all traits that shared the same embryonic structure. Morphological variations became visible following the appearance of ossification centers during the pre- and postnatal periods, and their etiology was associated with embryonic development.

Sternal human variability and population affinity: Frequency of discrete traits and their relationship with sex and age.

Sternal morphological variations differ among populations and are influenced by the interaction between inheritance, development, and environment. There are currently no studies that include all variability from a morphogenesis approach following a homogeneous definition. The aims of this study were (a) to develop a standardized method for the anatomical study of the sternum; (b) to analyze the prevalence of the morphological variations and their relationship between sex and age; (c) to compare the results with other populations. The sterna of 155 skeletons from a Spanish population were studied. The age at the time of death was 17 to 97 years. We analyzed two metric and 22 sternal morphological variations described in the literature and designed an illustrated atlas. The atlas was validated using the intraclass correlation coefficient (ICC). A descriptive statistical analysis was conducted to measure the prevalence and relationship between sex and age. To analyze the interpopulation variability, we compared our results with those from other authors. The atlas with definitions and reference images improves the observation and detection of all morphological variations of the sternum (ICC = 0.90). The dependence between the morphological traits and sex was significant for the variations in the sternal angle, the number of esternebra, and the development of the xiphoid process. No significant differences were found between age group and morphological traits. The expression of the sternal morphological variation and sex are population-specific. The results will help standardize future studies and provide valuable information on the variability of the sternal morphological variation.

Measuring dimensional and morphological heat alterations of dismemberment-related toolmarks with an optical roughness metre.

This experimental study provides a further understanding of the post-burning nature of sharp force trauma. The main objective is to analyse the distortion that fire may inflict on the length, width, roughness, and floor shape morphology of toolmarks induced by four different implements. To this end, four fresh juvenile pig long bones were cut with a bread knife, a serrated knife, a butcher machete, and a saw. A total of 120 toolmarks were induced and the bone samples were thus burnt in a chamber furnace. The lesions were analysed with a 3D optical surface roughness metre before and after the burning process. Afterwards, descriptive statistics and correlation tests (Student's t-test and analysis of variance) were performed. The results show that fire exposure can distort the signatures of sharp force trauma, but they remain recognisable and identifiable. The length decreased in size and the roughness increased in a consistent manner. The width did not vary for the saw, serrated knife, or machete toolmarks, while the bread knife lesions slightly shrunk. The floor shape morphology varied after burning, and this change became more noticeable for the three knives. It was also observed that the metrics of the serrated knife and machete cut marks showed no significant variations. Our results demonstrate that there is a variation in the toolmark characteristics after burning. This distortion is dependent on multiple factors that influence their dimensional and morphological changes, and the preservation of class features is directly reliant upon the weapon employed, the trauma caused, and the burning process conditions.

A disproportionate impact of G9a methyltransferase deficiency on the X chromosome.

G9a is a histone methyltransferase responsible for the dimethylation of histone H3 at lysine 9 (H3K9me2). G9a plays key roles in transcriptional silencing of developmentally regulated genes, but its role in X-chromosome inactivation (XCI) has been under debate. Here, we uncover a female-specific function of G9a and demonstrate that deleting G9a has a disproportionate impact on the X chromosome relative to the rest of the genome. G9a deficiency causes a failure of XCI and female-specific hypersensitivity to drug inhibition of H3K9me2. We show that G9a interacts with Tsix and Xist RNAs, and that competitive inhibition of the G9a-RNA interaction recapitulates the XCI defect. During XCI, Xist recruits G9a to silence X-linked genes on the future inactive X. In parallel on the future Xa, Tsix recruits G9a to silence Xist in cis Thus, RNA tethers G9a for allele-specific targeting of the H3K9me2 modification and the G9a-RNA interaction is essential for XCI.

Cut or burnt? - Categorizing morphological characteristics of heat-induced fractures and sharp force trauma.

Distinguishing trauma from heat-induced fractures is a challenge faced by forensic anthropologists and pathologists during medicolegal investigations in which fire has been used by the perpetrators to destroy evidence. This paper aims to validate the provided identification features to distinguish between fire induced alterations and sharp force trauma. A total of 80 cremated adult individuals were used in this paper: 3 recently deceased embalmed cadavers from Cementerio Sur de Madrid for the sharp force trauma experiment in which 55 pre-burning injuries were inflicted using a machete and a serrated knife in different anatomical regions. And 77 cremated individuals from the Forensic Anthropology and Odontology Laboratory osteological collection. Five cremated long bones from this collection were selected, and 10 cuts were manually inflicted using a serrated knife to analyse post-burning trauma. Heat-induced changes and trauma morphologic characteristics were thus documented and analysed. The examination and documentation of morphological traits enabled the production of a heat-induced changes visual guide and a flow-chart. Two intraclass correlation tests were performed to validate the capacity of the observer to distinguish between fire related alterations and toolmarks. The results obtained in the statistical analysis indicate that, even if the toolmarks are visible and recognizable upon macroscopic observation by the observers, some features, such as the step and the transverse fractures can be mistaken with inflicted trauma. The use of the proposed features coupled with careful anthropological examination is recommended and has been found functional for participants with no prior knowledge in the analysis of cremated remains.

Through fire and flames: post-burning survival and detection of dismemberment-related toolmarks in cremated cadavers.

During a homicide investigation in which fire has been used to reduce the size of the cadaver and conceal the evidence of injuries, the identification of perimortem trauma presents a challenge, in particular in cases when the perpetrator has dismembered the body followed by burning the remains. It is therefore important to understand the effects which heat causes on fresh bone. The aim of this paper is to perform a pilot study on the survival ratio of toolmarks in different anatomical regions associated with dismemberment, and a descriptive analysis of the variables that may potentially influence the post-burning survival and detection. To achieve this, three donated embalmed cadavers were used to simulate a case in which an attempted dismemberment and burning had occurred. Fifty-five pre-burning injuries were manually induced: 30 using a machete to inflict chopping trauma, and 25 with a serrated bread knife to inflict sharp force trauma, on the thigh, knee, ankle and wrist. The cadavers were cremated in a furnace at Madrid's Cementerio Sur and the burnt remains were analysed at the Laboratorio de Antropología y Odontología Forense of the Universidad Complutense de Madrid. Not all pre-burning injuries inflicted were visible after the cremation process; only 13% were detected in this experiment. Toolmarks can be masked, modified, destroyed or overlooked from the outset of the procedure due to several factors which influence the post-burning survival and detection of toolmarks and contribute to conceal the evidence of trauma. Additional research should be done to study further variables which affect the post-burning visibility of sharp force trauma.

B2 and ALU retrotransposons are self-cleaving ribozymes whose activity is enhanced by EZH2.

Transposable elements make up half of the mammalian genome. One of the most abundant is the short interspersed nuclear element (SINE). Among their million copies, B2 accounts for ∼350,000 in the mouse genome and has garnered special interest because of emerging roles in epigenetic regulation. Our recent work demonstrated that B2 RNA binds stress genes to retard transcription elongation. Although epigenetically silenced, B2s become massively up-regulated during thermal and other types of stress. Specifically, an interaction between B2 RNA and the Polycomb protein, EZH2, results in cleavage of B2 RNA, release of B2 RNA from chromatin, and activation of thermal stress genes. Although an established RNA-binding protein and histone methyltransferase, EZH2 is not known to be a nuclease. Here, we provide evidence for the surprising conclusion that B2 is a self-cleaving ribozyme. Ribozyme activity depends on Mg+2 and monovalent cations but is resistant to protease treatment. However, contact with EZH2 accelerates cleavage rate by >100-fold, suggesting that EZH2 promotes a cleavage-competent RNA conformation. B2 modification-interference analysis demonstrates that phosphorothioate changes at A and C nucleotides can substitute for EZH2. B2 nucleotides 45 to 55 and 100 to 101 are essential for activity. Finally, another family of SINEs, the human ALU element, also produces a self-cleaving RNA and is cleaved during T-cell activation as well as thermal and endoplasmic reticulum (ER) stress. Thus, B2/ALU SINEs may be classified as "epigenetic ribozymes" that function as transcriptional switches during stress. Given their high copy numbers, B2 and ALU may represent the predominant ribozyme activity in mammalian cells.

Gold-Catalyzed Hydrophenoxylation of Propargylic Alcohols and Amines: Synthesis of Phenyl Enol Ethers.

A practical method for the synthesis of phenyl enol ethers is reported. The combination of a gold(I) catalyst and potassium carbonate selectively mediates the addition of phenols to propargylic alcohols/amines in a chemo-, regio-, and stereoselective fashion in high yield. The resulting enol ethers are formed exclusively with a Z-configuration and can be obtained from a wide array of phenols and propargylic alcohols or amines with the reaction showing excellent functional group tolerance.

TERRA RNA Antagonizes ATRX and Protects Telomeres.

Through an integration of genomic and proteomic approaches to advance understanding of long noncoding RNAs, we investigate the function of the telomeric transcript, TERRA. By identifying thousands of TERRA target sites in the mouse genome, we demonstrate that TERRA can bind both in cis to telomeres and in trans to genic targets. We then define a large network of interacting proteins, including epigenetic factors, telomeric proteins, and the RNA helicase, ATRX. TERRA and ATRX share hundreds of target genes and are functionally antagonistic at these loci: whereas TERRA activates, ATRX represses gene expression. At telomeres, TERRA competes with telomeric DNA for ATRX binding, suppresses ATRX localization, and ensures telomeric stability. Depleting TERRA increases telomerase activity and induces telomeric pathologies, including formation of telomere-induced DNA damage foci and loss or duplication of telomeric sequences. We conclude that TERRA functions as an epigenomic modulator in trans and as an essential regulator of telomeres in cis.

Destabilization of B2 RNA by EZH2 Activates the Stress Response.

More than 98% of the mammalian genome is noncoding, and interspersed transposable elements account for ∼50% of noncoding space. Here, we demonstrate that a specific interaction between the polycomb protein EZH2 and RNA made from B2 SINE retrotransposons controls stress-responsive genes in mouse cells. In the heat-shock model, B2 RNA binds stress genes and suppresses their transcription. Upon stress, EZH2 is recruited and triggers cleavage of B2 RNA. B2 degradation in turn upregulates stress genes. Evidence indicates that B2 RNA operates as a "speed bump" against advancement of RNA polymerase II, and temperature stress releases the brakes on transcriptional elongation. These data attribute a new function to EZH2 that is independent of its histone methyltransferase activity and reconcile how EZH2 can be associated with both gene repression and activation. Our study reveals that EZH2 and B2 together control activation of a large network of genes involved in thermal stress.

Functional Proteomic Analysis of Repressive Histone Methyltransferase Complexes Reveals ZNF518B as a G9A Regulator.

Cell-type specific gene silencing by histone H3 lysine 27 and lysine 9 methyltransferase complexes PRC2 and G9A-GLP is crucial both during development and to maintain cell identity. Although studying their interaction partners has yielded valuable insight into their functions, how these factors are regulated on a network level remains incompletely understood. Here, we present a new approach that combines quantitative interaction proteomics with global chromatin profiling to functionally characterize repressive chromatin modifying protein complexes in embryonic stem cells. We define binding stoichiometries of 9 new and 12 known interaction partners of PRC2 and 10 known and 29 new interaction partners of G9A-GLP, respectively. We demonstrate that PRC2 and G9A-GLP interact physically and share several interaction partners, including the zinc finger proteins ZNF518A and ZNF518B. Using global chromatin profiling by targeted mass spectrometry, we discover that even sub-stoichiometric binding partners such as ZNF518B can positively regulate global H3K9me2 levels. Biochemical analysis reveals that ZNF518B directly interacts with EZH2 and G9A. Our systematic analysis suggests that ZNF518B may mediate the structural association between PRC2 and G9A-GLP histone methyltransferases and additionally regulates the activity of G9A-GLP.

Toward a consensus on the binding specificity and promiscuity of PRC2 for RNA.

Polycomb repressive complex-2 (PRC2) is a histone methyltransferase required for epigenetic silencing during development and cancer. Early works suggested binding specificity of PRC2 to certain long non-coding RNAs for recruitment to chromatin. More recent studies provided evidence both in favor and against this idea. Here, we bridge the two existing models of PRC2-RNA interaction. RepA RNA is a good binding partner for PRC2, while multiple non-relevant RNAs, including bacterial mRNAs, also bind PRC2; Kds depend to some extent on the experimental conditions. Human and mouse PRC2 have broadly similar RNA-binding properties in vitro. Examination of evidence supporting an existing model for site-specific recruitment of PRC2 by a well-defined RNA motif in cells reveals that results are PRC2 independent. We conclude that promiscuous and specific RNA-binding activities of PRC2 in vitro are not mutually exclusive, and that binding specificity in vivo remains to be demonstrated.

Locus-specific targeting to the X chromosome revealed by the RNA interactome of CTCF.

CTCF is a master regulator that plays important roles in genome architecture and gene expression. How CTCF is recruited in a locus-specific manner is not fully understood. Evidence from epigenetic processes, such as X chromosome inactivation (XCI), indicates that CTCF associates functionally with RNA. Using genome-wide approaches to investigate the relationship between its RNA interactome and epigenomic landscape, here we report that CTCF binds thousands of transcripts in mouse embryonic stem cells, many in close proximity to CTCF's genomic binding sites. CTCF is a specific and high-affinity RNA-binding protein (Kd < 1 nM). During XCI, CTCF differentially binds the active and inactive X chromosomes and interacts directly with Tsix, Xite, and Xist RNAs. Tsix and Xite RNAs target CTCF to the X inactivation center, thereby inducing homologous X chromosome pairing. Our work elucidates one mechanism by which CTCF is recruited in a locus-specific manner and implicates CTCF-RNA interactions in long-range chromosomal interactions.

Evaluación de la aplicación de las guías de hipertensión y diabetes en un programa de crónicos / Hypertension and diabetes guidelines evaluation and application in a chronic disease program / Avaliação da implementação das guias de hipertensão e diabetes em um programa de pacientes crônicos

Introducción: La Hipertensión arterial (HTA) y la Diabetes Mellitus (DM) hacen parte de las enfermedades crónicas no trasmisibles (ECNT) y ocupan las primeras causas de morbimortalidad a nivel mundial y nacional. Por tal razón es importante el control de estas enfermedades para prevenir la progresión de las coomorbilidades, con un impacto directo en la calidad de vida y en los costos de atención del paciente, por esto es importante evaluar la correcta aplicación de las guías de HTA y DM en los programas de prevención y control de las ECNT. Metodología: Se realizó un estudio descriptivo transversal por medio de un muestreo aleatorio estratificado. Para evaluar el control de los pacientes según la aplicación de las guías de Hipertensión y Diabetes en una población de usuarios inscritos en los programas de promoción y prevención de una Entidad Adaptada al Sistema, en la ciudad de Bogotá. Resultados: Se obtuvo una población de 425 pacientes hipertensos y de 279 diabéticos con un nivel de confianza de 95% y una precisión del 80%. Se encontró en el programa de hipertensos un cumplimiento de la guía del 67,8% y un control de la enfermedad del 60%. De los pacientes diabéticos evaluados se encontró un cumplimiento de la guía del 62,8% y un control de la patología menor al 1% y un aceptable control del 51%. Conclusión: Con el porcentaje de cumplimiento encontrado en la aplicación de las guías se está logrando un control en el programa de hipertensión de acuerdo a lo esperado, sin embargo en el programa de pacientes diabéticos se encuentra un bajo control. Por tal razón es imperativo mejorar la aplicación de las guías de manejo de estas patologías y así impactar en el control de la enfermedad y la calidad de vida de los pacientes.

Introduction: The hypertension and Mellitus diabetes are two of the highly risky diseases that are not contagious and are the first causes of mortality in an international and national level. For this reason is important to control these diseases to prevent the progression of the illnesses, with a direct impact in the life style and in the costs of the services for the patients, because of this is important to evaluate the right use of the HTA and DM guides in the prevention and control programs of the ECNT. Methodology: A transversal descriptive study was run by a random stratified sampling. To evaluate the control of the patients according to the application of the HTA and DM guides in a group of users of the promotion and prevention programs of a medical services institution in Bogota. Results: A group of 425 Hypertension patients and 279 diabetic patients was obtain; with a trusting level of 95% and a precision level of 80%. In the hypertension program was found a fulfillment of the guide of 67.75% and a 60% of the disease control. About the diabetic patients that were evaluated was found a fulfillment of the guide of 62.75%, less of 1% pathology control and an acceptable control of 51%. Conclusions: With the application guide percentage is being achieved the control in the hypertension program according to what was expected, but in the program of diabetic patients was found an underachieve. For this reason a better application of the guides is needed for the control of these diseases and because of this an impact in the illness control and life style of the patients.

Introdução: A hipertensão arterial (HTA) e a Diabetes mellitus (DM) fazem parte das doenças crônicas não transmissíveis (DCNT), sendo causas primarias de morbimortalidade no nível mundial e nacional. Além disso, é importante o controle destas doenças com o fim de prevenir a progressão das comorbilidades, com um impacto direito na qualidade de vida e nos custos da atenção dos doentes. Pelo anterior, é importante avaliar a correta implementação das Guias de HTA e DM nos programas de prevenção e controle das DCNT. Metodologia: Foi feito um estudo descritivo, transversal, aleatório estratificado, com o fim de avaliar o controle dos pacientes crônicos segundo a implementação das Guias de HTA e DM em uma população de usuários inscritos nos programas de promoção e prevenção de uma entidade adaptada ao sistema, na cidade de Bogotá. Resultados: Obteve-se uma população de 425 pacientes com HTA e de 279 com DM, com um nível de confiança de 95% e uma precisão de 80%. A implementação da Guia foi de 67,8% nos pacientes com HTA, com 60% de controle da doença. Nos pacientes com DM, a implementação da guia foi de 62,8%, controle da doença menor de 1% e controle aceitável de 51%. Conclusão: Segundo a porcentagem obtida da implementação das Guias, está-se logrando um controle no programa de HTA, embora no programa de pacientes com DM existe um baixo controle. É por isso que é importante melhorar a implementação das guias destas doenças, com o fim de impactar no controle da doença mesma e a qualidade de vida dos pacientes.

ATRX directs binding of PRC2 to Xist RNA and Polycomb targets.

X chromosome inactivation (XCI) depends on the long noncoding RNA Xist and its recruitment of Polycomb Repressive Complex 2 (PRC2). PRC2 is also targeted to other sites throughout the genome to effect transcriptional repression. Using XCI as a model, we apply an unbiased proteomics approach to isolate Xist and PRC2 regulators and identified ATRX. ATRX unexpectedly functions as a high-affinity RNA-binding protein that directly interacts with RepA/Xist RNA to promote loading of PRC2 in vivo. Without ATRX, PRC2 cannot load onto Xist RNA nor spread in cis along the X chromosome. Moreover, epigenomic profiling reveals that genome-wide targeting of PRC2 depends on ATRX, as loss of ATRX leads to spatial redistribution of PRC2 and derepression of Polycomb responsive genes. Thus, ATRX is a required specificity determinant for PRC2 targeting and function.