18 resultados para Controle de doenças transmissíveis
em Universidade Federal do Rio Grande do Norte(UFRN)
Resumo:
Investigar a qualidade de vida de pacientes com coinfecção HIV/ tuberculose e apreender as mudanças impostas para viver simultaneamente com estas doenças transmissíveis. Métodos: Pesquisa com abordagem qualiquantitativa, realizada em ambulatório especializado em Fortaleza, Brasil, entre 2009 e 2010, com 34 coinfectados. Para coleta de dados foi utilizada uma escala de qualidade de vida, denominada HAT-QoL que possui 42 itens e questões abertas para possibilitar perceber as mudanças em face das doenças. Resultados: A maioria dos participantes tinha tuberculose na forma pulmonar, eram homens, com pouca escolaridade. A qualidade de vida mostrou-se prejudicada nos domínios relacionados às questões econômicas, sexuais e de sigilo. Ainda, foi evidenciado, que a coinfecção impõe mudanças no cotidiano que corroboram e ampliam o comprometimento da qualidade de vida. Conclusão: Vivenciar a coinfecção, mesmo com terapêutica adequada, produz alterações na vida dos infectados, cujas repercussões podem ser amenizadas com intervenções que promovam a saúde
Resumo:
Proteinases are enzymes distributed widely founded in several organisms and perform many different functions, from maintaining homeostasis to the worsening of some diseases such as cancer, autoimmune diseases and infections. The proteins responsible of controlling the action of these enzymes are the inhibitors, that are classified based on their target proteases and are founded since simple organisms, such as bacteria, to higher organisms, such as larger plants and mammals. Plant proteinase inhibitors act by reducing or inactivating the activity of target proteases, thus, these proteins have been studied as potential tools in the treatment of diseases related to protease activities. In this context, an inhibitor of chymotrypsin from Erythrina velutina, called EvCI was previously purified and it was observed that this protein plays in vitro anticoagulant activity and anti-inflammatory activity in in vivo model. Aiming to reduce the environmental impact caused by the purification EvCI in high amounts and to facilitate the process of obtaining this protein, the recombinant chymotrypsin inhibitor from Eryhrina velutina was produced after cloning and expression in Escherichia coli. The bacteria were grown in LB medium and after induction of the expression this material was subjected to procedures for cell lysis and the product was applied on Nickel-affinity column. The proteins adsorbed were digested by thrombin and applied on Chymotrypsin-Sepharose affinity column, obtaining the purified inhibitor, named recEvCI. After electrophoresis, the recombinant inhibitor showed an approximately molecular mass of 17 kDa, and reduced the chymotrypsin and elastase activities in vitro. The recombinant inhibitor was sequenced and was found similar amino acids residues when compared to other inhibitors deposited in the database, with some modifications. recEvCI showed high stability under pH variations and reducing conditions, maintaining its activity around 80%. This protein increased the blood coagulation time in vitro by acting on the intrinsic pathway and did not show cytotoxicity against strains of mouse 3T3 fibroblasts and RAW 264.7 macrophages. recEvCI showed microbicide activity related to release of nitric oxide and consequently the activation of macrophages, futhermore having proinflammatory effects assessed by increased release of TNF-α. These results indicate that recEvCI can be biotechnologically used as a new tool in the control of coagulation-related diseases as well as can be an activating agent of the immune system in immunosuppressed individuals
Resumo:
According to demographic estimates, by the year 2025 Brazil will be the sixth country in the world in number of elderly. For this reason, it is a purpose of public policies to help people to reach that age being healthier. The current health care model of health surveillance through the Family Health Strategy (EFS, in portuguese) is configured as a gateway into the care of the elderly in the Unified Health System (SUS, in portuguese). It is also an area of development of practices to promote health, prevention and control of chronic nondegenerative diseases. The aim of this study was to analyze the health care of the elderly provided by ESF professionals for the achievement of a full care. The study is descriptive case study with a quantitative approach, performed in the city of Santo Antônio/RN. The population included all health professionals, who are FHS members of the city that agreed to participate of the survey, a total of 80 professionals. Data were collected using a structured questionnaire, having mostly closed questions and divided into two parts: one containing sociodemographic information of health professionals and vocational training and the other, the activities carried on by the professionals in senior care, being analyzed from a database tabulated in a spreadsheet and discussed according to the descriptive statistics in tables, graphs and charts using frequencies, medians and values of central tendency. It was verified a predominance of professionals who finished highschool, mostly female, aged from 30 to 34 years old, with training completed in the last 10 years, without being graduated in the field of geriatrics or gerontology and mostly without training in gerontology. Family members and caregivers were the components of the social support network most identified by the professionals (66.3%).The elderly access to the Family Health Basic Unit was considered by83.8% of professionals as the most important factor that interferes in the activities of health care of the elderly. Considering the inclusion of the family in care: 98.8% of professionals consider the family as one of the goals of care, but 82.5% assist the family to know their role and participate in the care of the elderly, emphasizing that no professional makes use of tools for evaluating the functionality of the family. Regarding the actions taken to assist the elderly, 91.25% have home visits program to the elderly, 88.75% use the host program; 77.5% know the habits of life, cultural, ethical and religious values of the elderly, their families and their community ;51.25% complement the activities through intersectoral actions, 50%participate in groups of living with the elderly; 33.75% keeps track and maintain updated the health information of the elderly; 11.25% of the professionals perform the Single Therapy Planning (PTS, in portuguese) and few implement the actions to promote health according to PTS; there is a deficit in the number of professional categories in the identification and monitoring of the frail older people in their households. It is concluded that the health care of the elderly developed by ESF professionals differs among the professional categories. It was identified weaknesses in the promotion of an active and healthy aging and also in the establishment of an integrated and full care of the elderly. It is recommended the adoption of permanent educational activities by the City Management, initially for ESF professionals in the the perspective of the guidelines of the National Policy of Health Care for the Elderly and later to the other professionals that are part of the health care network of the elderly, at all levels of care in the city for the development of strategies and practices that promote the improvement of the quality of healthcare for the elderly, expecting concrete and effective results in terms of promoting health within Brazilian reality
Resumo:
This dissertation considered the development of two papers, both related to mortality in Brazil. In the first article, "The context of mortality according to the three broad groups of causes of death in Brazilian capitals, 2000 and 2010", the objective was to analyze the mortality rate according to the three major groups of causes of death in Brazilian capitals. In the second article, "Typology and characteristics of mortality from external causes in the municipalities in the Northeast of Brazil, 2000 and 2010", it was built up a typology for the Northeastern municipalities taking into account information on mortality from external causes and a set of indicators related to socioeconomic, demographic, and infrastructure aspects of such municipalities, both articles for the years 2000 and 2010. Thus, we used data from the Mortality Information System of the Ministry of Health. Furthermore, it was used information from the Demographic Census for those years. The variables relating to socioeconomic and demographic conditions used in this study were those available on the home page of the United Nations Program for Development. The variables relating to socioeconomic and demographic conditions used in this study were those available on the home page of the United Nations Program for Development. Was used in Article 1 the pro-rata distribution method to accomplish the redistribution of ill-defined causes. Moreover, made use of the technique of cluster analysis with the aim of grouping the capital that had proportions of deaths from ill-defined causes similar to each other. Already in Section 2, we used the technique of Empirical Bayesian estimation; spatial statistics technique; and finally, the Grade of Membership method to find types of municipalities from information on mortality from external causes associated with socioeconomic, demographic and infrastructure variables. As the main results, it stands out in Article 1, in relation to data quality, we observed the formation of four groups of similar capital between themselves, as the proportion of illdefined causes. Regarding the behavior of mortality, according to the three major groups of causes of death, it was noted both for 2000 and for 2010 the prevalence of deaths from noncommunicable diseases for both sexes, although the reduction was identified rates in some of the capitals. Communicable diseases stood out as the second cause of death among women. Also, we found that deaths due to external causes are responsible for the second cause of death among men, as well as presenting an increase among women. As for the Article 2, stands out, in general, not just an extension of mortality from external causes in the municipalities, as well as an enlargement of the configurator stain existence of external cause deaths for the whole area of Northeast. Regarding the typology of municipalities, three vi extreme profiles were buit: the profile 1, which comprises municipalities with high rates of mortality from external causes and the best social indicators; the profile 2, that was composed of municipalities that are characterized by having low mortality rates from external causes and the lowest social indicators; and the profile 3, that brings together municipalities with intermediate mortality rates and median values considered in relation to social indicators. Although we have not seen changes in the characteristics of the profiles, we observed an increase in the proportion of municipalities that belong to the extreme profile 3, taking into account the mixed profiles.
Resumo:
Investigar a qualidade de vida de pacientes com coinfecção HIV/ tuberculose e apreender as mudanças impostas para viver simultaneamente com estas doenças transmissíveis. Métodos: Pesquisa com abordagem qualiquantitativa, realizada em ambulatório especializado em Fortaleza, Brasil, entre 2009 e 2010, com 34 coinfectados. Para coleta de dados foi utilizada uma escala de qualidade de vida, denominada HAT-QoL que possui 42 itens e questões abertas para possibilitar perceber as mudanças em face das doenças. Resultados: A maioria dos participantes tinha tuberculose na forma pulmonar, eram homens, com pouca escolaridade. A qualidade de vida mostrou-se prejudicada nos domínios relacionados às questões econômicas, sexuais e de sigilo. Ainda, foi evidenciado, que a coinfecção impõe mudanças no cotidiano que corroboram e ampliam o comprometimento da qualidade de vida. Conclusão: Vivenciar a coinfecção, mesmo com terapêutica adequada, produz alterações na vida dos infectados, cujas repercussões podem ser amenizadas com intervenções que promovam a saúde
Resumo:
Proteinases are enzymes distributed widely founded in several organisms and perform many different functions, from maintaining homeostasis to the worsening of some diseases such as cancer, autoimmune diseases and infections. The proteins responsible of controlling the action of these enzymes are the inhibitors, that are classified based on their target proteases and are founded since simple organisms, such as bacteria, to higher organisms, such as larger plants and mammals. Plant proteinase inhibitors act by reducing or inactivating the activity of target proteases, thus, these proteins have been studied as potential tools in the treatment of diseases related to protease activities. In this context, an inhibitor of chymotrypsin from Erythrina velutina, called EvCI was previously purified and it was observed that this protein plays in vitro anticoagulant activity and anti-inflammatory activity in in vivo model. Aiming to reduce the environmental impact caused by the purification EvCI in high amounts and to facilitate the process of obtaining this protein, the recombinant chymotrypsin inhibitor from Eryhrina velutina was produced after cloning and expression in Escherichia coli. The bacteria were grown in LB medium and after induction of the expression this material was subjected to procedures for cell lysis and the product was applied on Nickel-affinity column. The proteins adsorbed were digested by thrombin and applied on Chymotrypsin-Sepharose affinity column, obtaining the purified inhibitor, named recEvCI. After electrophoresis, the recombinant inhibitor showed an approximately molecular mass of 17 kDa, and reduced the chymotrypsin and elastase activities in vitro. The recombinant inhibitor was sequenced and was found similar amino acids residues when compared to other inhibitors deposited in the database, with some modifications. recEvCI showed high stability under pH variations and reducing conditions, maintaining its activity around 80%. This protein increased the blood coagulation time in vitro by acting on the intrinsic pathway and did not show cytotoxicity against strains of mouse 3T3 fibroblasts and RAW 264.7 macrophages. recEvCI showed microbicide activity related to release of nitric oxide and consequently the activation of macrophages, futhermore having proinflammatory effects assessed by increased release of TNF-α. These results indicate that recEvCI can be biotechnologically used as a new tool in the control of coagulation-related diseases as well as can be an activating agent of the immune system in immunosuppressed individuals
Resumo:
Dengue, amongst the virus illnesses one can get by vectorial transmission, is the one that causes more impact in the morbidity and mortality of world s population. The resistance to the insecticides has caused difficulties to control of vector insect (Aedes aegypti) and has stimulated a search for vegetables with larvicidal activity. The biodiversity of Caatinga is barely known and it is potential of use even less. Some plants of this biome are commercialized in free fairs northeast of Brazil, because of its phytotherapics properties. The vegetables in this study had been selected by means of a questionnaire applied between grass salesmen and natives of the Serido region from Rio Grande do Norte state; culicids eggs had been acquired with traps and placed in container with water for the larva birth. Thirty larvae had been used in each group (a group control and five experimental groups), with four repetitions four times. The vegetables had been submitted to the processes of decoction, infusion and maceration in the standard concentration of 100g of the vegetable of study in 1l of H2O and analyzed after ½, 1, 2, 4, 8, 12, 24 and 48 hours for verification of the average lethal dose (LD50) from the groups with thirty larva. The LD50 was analyzed in different concentrations (50g/l, 100g/l, 150g/l, 200g/l e 300g/l) of Aspidosperma pyrifolium Mart. 48 extracts of rind, leaf and stem of the seven vegetal species: Aspidosperma pyrifolium Mart., Mimosa verrucosa Benth, Mimosa hostilis (Mart.) Benth., Myracrodruon urundeuva Allemão, Ximenia americana L, Bumelia sartorum Mart Zizyphus joazeiro Mart, had been analyzed. The extracts proceeding from the three methods were submitted to the freezedrying, to evaluate and to quantify substances extracted in each process. The results had shown that Aspidosperma pyrifolium Mart. and Myracrodruon urundeuva Allemão are the species that are more distinguished as larvicidal after 24 hours of experiment, in all used processes of extraction in the assays. The Zizyphus joazeiro Mart species has not shown larvicidal activity in none of the assays. In relation to the extraction method, the decoction was the most efficient method in the mortality tax of the A. aegypti larvae
Resumo:
Heart transplantation (HT) represents one of the greatest advances in medicine over the last decades. It is indicated for patients with severe heart disease unresponsive to clinical treatment and conventional surgery, poor short-term prognosis and a 1- year mortality rate over 40%. HT has improved survival worldwide (80% in the first year, 70% in five years and 60% in ten years). However, the procedure has been associated with weight change and increased risk of secondary conditions such as diabetes, hypertension, dyslipidemia and obesity due to immunosuppressive therapy following transplantation. The objective of this study was to determine the impact of weight change on the metabolic stability of HT patients. The study was retrospective with data collected from the records of 82 adult patients (83% male; average age 45.06±12.04 years) submitted to HT between October 1997 and December 2005 at a transplantation service in Ceará (Brazil). The selected outcome variables (biopathological profile, weight and body mass index―BMI) were related to biochemical and metabolic change. The results were expressed in terms of frequency, measures of central tendency, Student s t test and Pearson s correlation coefficients. The analysis showed that following HT the average global BMI increased from 23.77±3.68kg/m2 to 25.48±3.92kg/m2 in the first year and to 28.38±4.97kg/m2 in the fifth. Overweight/obese patients (BMI ≥ 25 kg/m2) had higher average levels of glucose, total cholesterol, low-density lipoprotein and triglycerides than patients with eutrophy/malnutrition (BMI < 25 kg/m2). In conclusion, overweight/obese patients were likely to present higher average levels of glucose, triglycerides, total cholesterol and fractions than patients with eutrophy/malnutrition, indicating a direct and significant relation between nutritional status and weight change in the metabolic profile of HT patients
Resumo:
Resolutions of the Board of numbers 359 and 360, of December 23, 2003, relating to Nutrition Labelling for Packaged Foods, establish quality standards and provide the education activities for health consumption, since one of the factors that enable the selection of healthier foods are the food labels as an important part in nutrition education. This is a descriptive study with a cross-sectional design. To calculate sample size, it was considered a margin of error of 20%, confidence level of 95% and prevalence of 52.5% for verifying nutritional information in a pilot study conducted in 2007. A total of 145 subjects were interviewed, resulting in 371 consumers in Natal, Rio Grande do Norte, Brazil, in order to determine prevalence of consulting nutritional information contained on food labels as a nutritional guideline for consumers and its association with sociodemographic variables as well as identify the intervention measures suggested by intervieweds so that this information can be better used to select healthy foods. Twenty-five of the 69 supermarkets belonging to the Supermarket Association of Rio Grande do Norte (ASSURN) were randomly selected. Data collection relied on interviews and extensive direct observation, using a semi-structured form composed of eight closed questions, some of which were multiple choice, and ten open questions. The chi-square test was performed for statistical analysis, using Statistical Package for Social Sciences (SPSS) 15.0 software. Label information most consulted was: expiry date (91.6%); product brand (49.4%); nutritional information (47.0%); zero trans fat (32.9%); zero sugar content (12.8%); zero fat content (3.0%); rich in fibers (2.7%); whether light or diet (30.4%); list of ingredients (16.8%); whether the product contained gluten or not (4.1%). When asked about the importance of nutritional information, 96.8% of the subjects responded important or very important ; of these 46.6% and 3.8% reported partially or totally understanding the information presented. It was found that 41.6% of the consumers consulted nutritional information for dietary reasons related to nontransmissible chronic diseases and 35.7% to be able to choose healthier foods. The data show a significant association between motivation to choose healthier foods and higher family income and schooling (p<0.0001). The intervention measures mentioned to make nutritional information better understood and used were: information and orientation about nutritional information, provided by qualified professionals in the supermarkets, the commercial establishment or the product manufacturer (73.9%) and media disclosure about the nature, importance and purpose of nutritional information (42.9%). In despite of communication noises the consumers use the nutrition claim for the nutritional guidance, showing association with some demographic variables. However, they desire the implementation of intervention measures that can be contextualized in the political construction of nutrition education to promote healthy food choices
Resumo:
Universidade Federal do Rio Grande do Norte
Resumo:
The changes incurred in the financial system with the introduction of new technologies and new forms of administration of banks has caused impact on the health of workers. These changes, which passed in the process of work, generate a combined share of the risk factors that result in numerous injuries and illnesses among banks, notably between the operators of banks tellers. The Work-Related Musculoskeletal Disordes - WRMD represent a group of occupational diseases always present among these workers. Because of its high incidence and the amount of financial resour envolved to manage the problem has been the object of constant study. This paper aims to analyze the bank teller activity; search the occurrence of WRMD in the activity, identifying the factors determining the occurrence of WRMD in the activity and determine the real number of touchs on a keyboard made by the operator and propose solutions that influence the reduction of illness in the workplace of the bank teller. Methodological tools of ergonomics are used to provide a broad knowledge of aspects of work that have been studied and influential in the generation of occupational diseases studied. It was found that activity put workers to serious risk of occupational diseases. As the main contributory factors and determinants for this illness: the requirements and control the numbers daily endorsements; evaluation system based on performance targets for productivity; management system at time of service to customers; work with stressful factors (broken box); excess of time worked; furniture of workstations with ergonomic inadequacies and policy for the prevention of occupational diseases inefficient. They have also noted cases of illness for DORT workers without fulfilling the legal requirement of the issuance of the communication of labour accident and without the removal of the employee of the workplace
Resumo:
The presence of fixed orthodontics appliances interfere on sanitation, allowing periodontal diseases to appear, despite the fact patients keep on visiting the dentist every month. This research aims to determine a protocol for the mechanical control of the dental biofilm performed by the professional. A protocol that was able to maintain the periodontal health of the patients under orthodontic treatment with fixed appliances, and in order to do so, it used a non-controlled, randomized and blind clinical essay. The sample involved 40 adolescents who were under the installation of fixed orthodontics appliances and it was divided in three groups, as follows: monthly controlled group (group 1) composed of 11 patients, the quarterly controlled group (group 2) with 16 patients and the semestrial controlled group (group 3) with 13 patients. For data collection, an interview and clinical exams with probing depth measurement, quantity of keratinized mucosa, Gingival Index and the Plaque Index were used. On the initial exam all patients received brushing guidelines as well as the professional control of dental biofilm, with periodontal scaler, Robinson s brush and prophylactic paste. However, Group 1 returned every month for control procedures; Group 2 every three months and Group 3 after six months. The intervention had a six-month duration (for all the three groups), when all the exams were repeated by another examiner who did not know which group each patient was inserted in. Finally, the research concluded that despite the fact there is no statistically significant difference among the three groups, clinically the patients from the monthly group presented a better response to professional control, with less accumulation of dental biofilm and less rate of gingival inflammation. Thus, the mechanical control of the dental biofilm performed by the professional could not avoid gingival increase, characterized by the raise of probing depth measurement, neither the quantity of keratinized mucosa
Resumo:
The search which it aim was to analyze the Periodontal Disease as a risk factor for the development of the Stable Angina Pectoris. For that, 120 patients (52 blokes and 68 wenches ), ages ranging from 40 to 65 years old, and attended to the Hemodinamic´s Sector of the Natal Hospital Center, showing the historic of Angina Pectoris to accomplishment of cinecoronariografhy. Before the accomplishment of this exam, the patients were submitted to interview, to investigate the possible risk factors for the Cardiovascular diseases , and it was followed of clinical periodontal examination to evaluate the presence of Periodontal Disease. After the cinecoronariography, the patients who presented diagnosis of important arterial obstruction (above 70%) were enrolled to the case grup. However the individuals with arteries free of obstruction, or obstrution below 30%, were considered without historic of Cardiovascular disease and therefore enrolled for the control grup. The groups were paired by the variables age and gender. From the analysis of the results, a did not observed statisticment the significant association between the presence of the Periodontal Disease, probing depth, periodontal attachment level, severity and extension index of the Periodontal Disease, besides the visible plaque index (VPI) an gingival bleeding index (GBI) regarding to the existence of Stable Angina Pectoris. Nevertheless , it was identified statisticment the significant association between the sistemic arterial hypertension , seric level of total cholesterol, LDL, HDL and triglycerides, showing all of them, classic risk factors appointed by the literature. Therefore, it was conclued that Periodontal Disease did not represent association with the StableAngina Pectoris at least among the studied population
Resumo:
the institutionalized elderly presents for being more fragile a lot of body balance s changes, which can induce falls and health frailty. One of the consequences of it is the appearance of dizziness, vestibular or not. This study aims to identify the risk factors related to dizziness in institutionalized elderly, with and without vestibular disorders, in the city of Natal-RN. Method: a case-control study realized in 12 regulated by Health Surveillance Long Term Care Institutions for the elderly in Natal-RN. Elected seniors with good cognitive level and able to walk, totaling 115 individuals, and of these, 102 were selected according to the presence of dizziness in the last year (n = 51) and their controls (n = 51), paired by sex and age. The 51 elderly patients with dizziness were divided into 3 groups case: case one, for elderly with dizziness and without vestibulopathy (n=38); case two, for elderly with dizziness and vestibulopathy (n=13) and case three, for all the seniors with dizziness, or added to the case 1 case 2 (n=51). The 51 seniors who served as controls were also divided into three groups, according to the number of individuals of each case: control 1, n = 38, control 2, n = 13 control and 3 (sum of 1 control with control 2), n = 51. As possible risk factors were analyzed variables related to characteristics of the institution, to the habits of life of older people and those concerned with the health of the elderly. For statistical analysis, we used the chi-square or Fisher exact test for a significance level of 5% and calculating the association magnitude between variables by measuring the Odds Ratio. Results: as risk factors for dizziness without vestibular disorders were found the presence of hypertension and cardiovascular disease, as well as the presence of three or more disorders for elderly and use of gastric protector drugs. For the elderly group from case two were found no associated risk factor. For elderly patients with dizziness in the case group three, we observed the same risk factors found for the elderly in the case group one, plus the presence of osteoarthritis pathology, which was also significant for this group. Conclusion: dizziness in institutionalized elderly is associated with systemic common diseases in this age group and the vestibulopathy presents itself as pathology on an isolated way, not being possible, with our data, associate it with non-risk factors
Resumo:
The development of complex diseases such as preeclampsia are determined by both environmental and genetic factors, but there is also interaction among these factors. Preeclampsia is a pregnancy-specific disorder characterized by de-novo hypertension and proteinuria after 20th week of gestation. There is a broad spectrum of clinical presentations related to hypertensive disorders of pregnancy (HDP) that can range from mild preeclampsia to eclampsia (seizures) or HELLP syndrome (Hemolysis, Elevation of Liver enzymes, Low Platelets). Those clinical outcomes might be linked to different pathological mechanisms. Our work aims to identify factors (i.e. genes and environmental) associated with the HDP’s clinical spectrum. Using a case-control approach, we selected a total of 1498 pregnant women for epidemiological and genetic studies, encompassing 755 normotensive (control); 518 preeclampsia; 84 eclampsia; and 141 HELLP. Women were genotyped for 18 SNPs across 5 candidate genes (FLT1, ACVR2A, ERAP1, ERAP2 and LNPEP). For the environmental factors, we found maternal age, parity status and pre-gestational body mass index as important risk factors associated with disease. Genes were associated in a phenotype-specific manner: ACVR2A with early preeclampsia (rs1424954, p=0.002); FLT1 with HELLP syndrome (rs9513095, p=0.003); and ERAP1 with eclampsia (rs30187, p=0.03). Our results suggest that different genetic mechanisms along with specific environmental factors might determine the clinical spectrum of HDP. In addition, phenotype refinement seems to be an essential step in the search for complex disease genes