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Just as reference genome sequences revolutionized human genetics, reference maps of interactome networks will be critical to fully understand genotype-phenotype relationships. Here, we describe a systematic map of ?14,000 high-quality human binary protein-protein interactions. At equal quality, this map is ?30% larger than what is available from small-scale studies published in the literature in the last few decades. While currently available information is highly biased and only covers a relatively small portion of the proteome, our systematic map appears strikingly more homogeneous, revealing a "broader" human interactome network than currently appreciated. The map also uncovers significant interconnectivity between known and candidate cancer gene products, providing unbiased evidence for an expanded functional cancer landscape, while demonstrating how high-quality interactome models will help "connect the dots" of the genomic revolution.
Assuntos
Mapas de Interação de Proteínas , Proteoma/metabolismo , Animais , Bases de Dados de Proteínas , Estudo de Associação Genômica Ampla , Humanos , Camundongos , Neoplasias/metabolismoRESUMO
OBJECTIVES: To identify factors associated with poor prognoses in newborns with a prenatal diagnosis of gastroschisis in eight hospitals in Bogota, Colombia, from 2011 to 2022. METHODS: A multi-center retrospective case-control study was conducted on newborns with gastroschisis in eight hospitals in Bogota, Colombia. Poor prognosis was defined as the presence of sepsis, intestinal complications, or death. RESULTS: The study included 101 patients. Preterm newborns under 32 weeks had a poor neonatal prognosis (OR 6.78 95â¯% CI 0.75-319). Oligohydramnios (OR 4.95 95â¯% CI 1.15-21.32) and staged closure with silo (OR 3.48; 95â¯% CI 1.10-10.96) were risk factors for neonatal death, and intra-abdominal bowel dilation of 20-25â¯mm was a factor for the development of intestinal complications (OR 3.22 95â¯% CI 1.26-8.23). CONCLUSIONS: Intra-abdominal bowel dilation between 20 and 25â¯mm was associated with intestinal complications, while oligohydramnios was associated with the risk of perinatal death, requiring increased antenatal surveillance of fetal wellbeing. Management with primary reduction when technically feasible is recommended in these infants, considering that the use of silos was associated with higher mortality.
Assuntos
Gastrosquise , Humanos , Recém-Nascido , Colômbia/epidemiologia , Gastrosquise/diagnóstico , Gastrosquise/diagnóstico por imagem , Gastrosquise/epidemiologia , Gastrosquise/mortalidade , Feminino , Estudos Retrospectivos , Gravidez , Estudos de Casos e Controles , Prognóstico , Masculino , Fatores de Risco , Oligo-Hidrâmnio/epidemiologia , Oligo-Hidrâmnio/diagnóstico , Ultrassonografia Pré-Natal , Adulto , Recém-Nascido PrematuroRESUMO
During and after the pandemic caused by the SARS-CoV-2 virus, the use of personal care products and disinfectants increased in universities worldwide. Among these, quaternary ammonium-based products stand out; these compounds and their intermediates caused substantial changes in the chemical composition of the wastewater produced by these institutions. For this reason, improvements and environmentally sustainable biological alternatives were introduced in the existing treatment systems so that these institutions could continue their research and teaching activities. For this reason, the objective of this study was to develop an improved culture medium to cultivate ammonium oxidising bacteria (AOB) to increase the biomass and use them in the treatment of wastewater produced in a faculty of sciences in Bogotá, D.C., Colombia. A Plackett Burman Experimental Design (PBED) and growth curves served for oligotrophic culture medium, and production conditions improved for the AOB. Finally, these bacteria were used with total heterotrophic bacteria (THB) for wastewater treatment in a pilot plant. Modification of base ammonium broth and culture conditions (6607 mg L-1 of (NH4)2SO4, 84 mg L-1 CaCO3, 40 mg L-1 MgSO4·7H2O, 40 mg L-1 CaCl2·2H2O and 200 mg L-1 KH2PO4, 10% (w/v) inoculum, no copper addition, pH 7.0 ± 0.2, 200 r.p.m., 30 days) favoured the growth of Nitrosomonas europea, Nitrosococcus oceani, and Nitrosospira multiformis with values of 8.23 ± 1.9, 7.56 ± 0.7 and 4.2 ± 0.4 Log10 CFU mL-1, respectively. NO2- production was 0.396 ± 0.0264, 0.247 ± 0.013 and 0.185 ± 0.003 mg L-1 for Nitrosomonas europea, Nitrosococcus oceani and Nitrosospira multiformis. After the 5-day wastewater treatment (WW) by co-inoculating the three studied bacteria in the wastewater (with their self-microorganisms), the concentrations of AOB and THB were 5.92 and 9.3 Log10 CFU mL-1, respectively. These values were related to the oxidative decrease of Chemical Oxygen Demand (COD), (39.5 mg L-1), Ammonium ion (NH4+), (6.5 mg L-1) Nitrite (NO2-), (2.0 mg L-1) and Nitrate (NO3-), (1.5 mg L-1), respectively in the five days of treatment. It was concluded, with the improvement of a culture medium and production conditions for three AOB through biotechnological strategies at the laboratory scale, being a promising alternative to bio-augment of the biomass of the studied bacteria under controlled conditions that allow the aerobic removal of COD and nitrogen cycle intermediates present in the studied wastewater. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03961-4.
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Background: The quality of recovery is an important component in the evaluation of perioperative care. To measure this, the Quality of Recovery-15 (QoR-15) scale has been validated previously. The aim of this study was to culturally, linguistically, and psychometrically adapt this scale to the Colombian Spanish language. Methods: After linguistic adaptation, a validation study of the psychometric properties was carried out. These included validity, reliability, and responsiveness. The scale was administered after the administration of general anaesthesia. Validity was determined by correlating with the general recovery VAS, surgical risk, surgical duration, and length of hospital stay. Structural validity was assessed using factor analysis. Test-retest and internal consistency were used to measure reliability. Results: Interviews were conducted with 161 adults. A positive correlation was found between the Spanish version of the QoR-15 scale (QoR-15C) and VAS scores (r=0.51), and a negative correlation between the QoR-15C score and the duration of surgery (r=-0.47) and hospital stay (r=-0.62). The reliability of the scale was adequate. Cronbach's alpha was 0.74, and Lin's correlation concordance coefficient was 0.99. Confirmatory factor analysis indicated that the scale in the Colombian Spanish version does not have a single domain, whilst exploratory factor analysis indicated that the scale may measure an additional factor. Conclusions: The QoR-15C scale for assessing the quality of recovery after general anaesthesia showed psychometric properties comparable with those of the English scale. This allows the scale to be considered for use in research and clinical practice.
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Background: Mild secretion defects are the most frequent and challenging blood platelet disorders to diagnose. Most δ-granule secretion tests lack validation, are not quantitative, or have unreliable response to weak platelet agonists. Objectives: To compare platelet serotonin secretion by HPLC-electrochemical detection technique (HPLC-ECD) with the reference isotopic test (3H-5-HT), evaluating its performance in clinical laboratories. Methods: The assay validation followed STARD-2015 recommendations. HPLC-ECD measured the nonsecreted serotonin remaining in platelet pellets after aggregation, comparing it with the reference 3H-5-HT assay. We studied subjects with inherited and aspirin-induced blood platelet disorders and assessed the HPLC-ECD operation for routine clinical diagnosis. Results: Calibration curves were linear (R2 = 0.997), with SD for residuals of 3.91% and analytical sensitivity of 5ng/mL. Intra- and interassay imprecision bias ranged between -8.5% and 2.1% and -9% and 3.1%, respectively. Serotonin recovery and stability were >95%, and the variability range of measurements was -5.5% to 4.6%. Statistical differences detected between tests were biologically irrelevant, with bias of 1.48% (SD, 8.43) and CI agreement of -18% to 15%. Both assays distinctly detected platelet secretion induced by 10 µM epinephrine and 4 µmM adenosine diphosphate. However, HPLC-ECD is quantitative and more sensitive to low serotonin content in blood platelets. Reference cutoffs for each agonist were determined in 87 subjects. Initially, the HPLC-ECD requires relatively expensive equipment and trained operators but has remarkably cheap running costs and a turn-around time of 24-36 hours. We have used this diagnostic tool routinely for >8 years. Conclusion: HPLC-ECD assay for platelet serotonin secretion is highly accurate, has advantages over the reference 3H-5-HT test, and is suitable as a clinical laboratory technique.
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Genes and gene products do not function in isolation but within highly interconnected 'interactome' networks, modeled as graphs of nodes and edges representing macromolecules and interactions between them, respectively. We propose to investigate genotype-phenotype associations by methodical use of alleles that lack single interactions, while retaining all others, in contrast to genetic approaches designed to eliminate gene products completely. We describe an integrated strategy based on the reverse yeast two-hybrid system to isolate and characterize such edge-specific, or 'edgetic', alleles. We established a proof of concept with CED-9, a Caenorhabditis elegans BCL2 ortholog. Using ced-9 edgetic alleles, we uncovered a new potential functional link between apoptosis and a centrosomal protein. This approach is amenable to higher throughput and is particularly applicable to interactome network analysis in organisms for which transgenesis is straightforward.
Assuntos
Proteínas de Caenorhabditis elegans/genética , Mapeamento de Interação de Proteínas/métodos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Alelos , Sequência de Aminoácidos , Animais , Sítios de Ligação , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/fisiologia , Proteínas de Ligação ao Cálcio/genética , Genes de Helmintos , Genótipo , Modelos Moleculares , Fenótipo , Proteínas Repressoras/fisiologia , Técnicas do Sistema de Duplo-HíbridoRESUMO
We analyzed the natural killer cell immunoglobulin-like receptor (KIR) genes and immunoglobulin allotypes in the development of type 2 diabetes (T2D) based on body mass index (BMI) measurements (obese vs. non-obese) in Puerto Rican Americans. Genetic interactions between the KIR haplotype A homozygotes (HAH) and its fraction containing two inhibitory receptors 2DL3 and 2DL1 and the activating receptor 2DS4 with immunoglobulin allotypes were studied. We found a significant association between the HAH and T2D (p=0.002; OR=7.97) and its interaction with the immunoglobulin allotype z: GM f/f (-) (p=<0.0001; OR, not determined) only in non-obese individuals. This association were due to the interactions between the 2DL3/2DL3, 2DL1/2DL1, and 2DS4 fragment with GM f/f (-) in T2D patients (p=0.0017; OR=3.45). Analysis based on BMI demonstrated associations in both obese (p=0.037; OR=2.43; 95% CI=0.97-6.31) and non-obese individuals (p=<0.0001; OR=8.38; 95% CI=2.49-29.31). By contrast, the interaction of the GM allotype f/f (-) with the HAH fragment was associated with T2D only in non-obese individuals (p=<0.0001; OR=18.2; 95% CI=3.71-113.4). As expected, interaction of both HAH and its fragment with HLA-C group's ligands were significant. We used informative short tandem repeats (STRs) that distinguish major populations to determine genetic admixture and found that there was no genetic stratification in our cohort. Our findings are consistent with the possibility of an autoimmune and/or innateimmune component in the pathogenesis of T2D: NK receptors with chronic inflammation in obese and genetic interactions with G1M allotype in T2D non-obese possibly mediating autoimmunity.
Assuntos
Diabetes Mellitus Tipo 2/genética , Alótipos de Imunoglobulina/genética , Alótipos Gm de Imunoglobulina/genética , Obesidade/genética , Receptores KIR/genética , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/etnologia , Feminino , Haplótipos , Hispânico ou Latino/genética , Homozigoto , Humanos , Células Matadoras Naturais/imunologia , Masculino , Pessoa de Meia-Idade , Proteínas Monoméricas de Ligação ao GTP , Porto Rico/etnologia , Receptores KIR/análise , Estados UnidosRESUMO
Natural killer cells are important in innate defense against viral infections. The interplay between stimulatory and inhibitory natural killer cell receptors and their corresponding human leukocyte antigen ligands are known to influence the outcome of acute Hepatitis C virus infection. Frequencies of NK receptor genes (8 inhibitory, 6 activating and 2 pseudogenes) and HLA class II alleles (DRB1, DQB1) were analyzed in 160 Puerto-Rican American drug users with Hepatitis C virus infection; 121 had chronic viremia (CV) and 39 were spontaneous clearance (SC). We further ruled out genetic stratification using short tandem repeats. Interaction between KIR gene receptor 2DL3/2DL3 and its ligand, C1/C1 of HLA-Cw alleles and spontaneous clearance was confirmed (p=0.03, OR=3.05). We also found a new interaction between the KIR receptor gene 2DL3 with HLA-DRB1*1201 (p=0.0001, OR=22) associated with SC, and an association of HLA DQB1*0501 (p=0.05, OR=0.30) with CV. Our findings suggested a role for MHC class II alleles in Hepatitis C virus peptide presentation to T cells together with NK ligand interaction involving pathways that will be useful for the development of immunotherapeutic interventions.
Assuntos
Genes MHC da Classe II , Antígenos HLA-C/genética , Hepacivirus/imunologia , Antígenos da Hepatite C/imunologia , Hepatite C Crônica/imunologia , Receptores KIR/genética , Adulto , Alelos , Feminino , Frequência do Gene , Hepatite C Crônica/complicações , Hepatite C Crônica/genética , Hepatite C Crônica/virologia , Humanos , Células Matadoras Naturais/imunologia , Masculino , Receptores KIR/imunologia , Receptores KIR/metabolismo , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/imunologia , Linfócitos T/imunologia , ViremiaRESUMO
The presence of cells or tissues from two individuals, chimeras, or the presence of cells and tissues that include the gonads, tetragametic chimerism can be detected by the analysis of cytogenetics and analysis of polymorphic genetic markers, using patterns of pedigree inheritance. These methodologies include determination of sex chromosomes, major histocompatibility complex (MHC) polymorphisms and panels of short tandem repeats (STRs) that include mitochondrial DNA markers. Studies routinely involve cases of temporal chimerism in blood transfusion, or following allotransplantation to measure the outcome of the organ, lymphopoietic tissues or bone marrow grafts. Demonstration of persistent chimerism is usually discovered in cases of inter-sexuality due to fusion of fraternal twins or in cases of fusion of embryos with demonstrable allogeneic monoclonality of blood which, excluded maternity or paternity when blood alone is used as the source of DNA. In single pregnancies it is possible to produce two kinds of microchimerism: feto-maternal and materno-fetal, but in cases of fraternal twin pregnancies it is possible to identify three different kinds which are related to cases of vanishing twins that can be identified during pregnancy by imaging procedures; (1) hematopoietic, (2) gonadal, and (3) freemartins when the twins have different sex and the individual born is a female with either gonadal or both gonadal and hematopoietic tissues. Fraternal twin pregnancies can also produce fusion of embryos. Such cases could be of different sex presenting with inter-sexuality or in same sex twins. One of such cases, the best studied, showed evidence of chimerism and tetragametism. In this regard, the case was studied because of disputed maternity of two of her three children. All tissues studied, except for the blood, demonstrated four genetic components but only two in her blood of four possible showed allogeneic monoclonality consistent with the interpretation that her blood originated from one hematopoietic stem cell. Also, microchimerism, due to traffic of cells via materno-fetal or feto-maternal has been prompted by reports of their potential association with the development of autoimmune disorders including systemic lupus erythematosus (SLE) and systemic sclerosis, and in allotransplantation. In addition, their relevance of chimerism in the positive and negative selection of T cells in the thymus has not been addressed. T lymphocytes play a central role in controlling the acquired immune response and furthermore serve as crucial effector cells through antigen specific cytotoxic activity and the production of soluble mediators. Central tolerance is established by the repertoire selection of immature T lymphocytes in the thymus, avoiding the generation of autoreactive T cells. Expression of chimeric antigens in the thymus could modify the generation of specific T cell clones in chimeric subjects and these mechanisms could be important in the induction of central tolerance against foreign antigens important in allo-transplantation. In this review, we discuss the genetics of chimerism and tetragametism and its potential role in thymic selection and the relevance in allotransplantation and autoimmune disorders.
Assuntos
Autoimunidade , Quimerismo , Tolerância Imunológica , Animais , Bovinos , Quimerismo/embriologia , DNA Mitocondrial/análise , Feminino , Freemartinismo/diagnóstico , Freemartinismo/genética , Marcadores Genéticos/genética , Células Germinativas/citologia , Hematopoese , Humanos , Masculino , Transplante Homólogo/imunologiaRESUMO
BACKGROUND: The definition of human MHC class I haplotypes through association of HLA-A, HLA-Cw and HLA-B has been used to analyze ethnicity, population migrations and disease association. RESULTS: Here, we present HLA-E allele haplotype association and population linkage disequilibrium (LD) analysis within the ~1.3 Mb bounded by HLA-B/Cw and HLA-A to increase the resolution of identified class I haplotypes. Through local breakdown of LD, we inferred ancestral recombination points both upstream and downstream of HLA-E contributing to alternative block structures within previously identified haplotypes. Through single nucleotide polymorphism (SNP) analysis of the MHC region, we also confirmed the essential genetic fixity, previously inferred by MHC allele analysis, of three conserved extended haplotypes (CEHs), and we demonstrated that commercially-available SNP analysis can be used in the MHC to help define CEHs and CEH fragments. CONCLUSION: We conclude that to generate high-resolution maps for relating MHC haplotypes to disease susceptibility, both SNP and MHC allele analysis must be conducted as complementary techniques.
Assuntos
Genes MHC Classe I , Variação Genética , Antígenos HLA/genética , Antígenos de Histocompatibilidade Classe I/genética , Alelos , Linhagem Celular , Mapeamento Cromossômico , Cromossomos Humanos Par 6 , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Humanos , Desequilíbrio de Ligação , Polimorfismo de Nucleotídeo Único , Antígenos HLA-ERESUMO
RESUMEN Objetivo: Explorar y describir dimensiones que afectan la adherencia terapéutica en personas mayores con hipertensión o diabetes tipo 2 en Araucanía, Chile. Metodología: Investigación cualitativa, etnográfica y descriptiva, que se aborda con análisis de contenido según Bardin. Corresponde a una primera fase de un estudio exploratorio, en la que se realizan dos grupos focales, con participación de 12 personas mayores de 70 años con hipertensión, diabetes tipo 2 o ambas. Resultados: Se describen trece categorías emergentes, tres in vivo (ser carga para otras personas, obtención de ayuda a partir del celular y vida empobrecida) y diez teóricas (edadismo, aislamiento y soledad, cultura popular para control de la patología, estructura familiar matriarcal, modelo biomédico arraigado, infravaloración del equipo no médico, paradoja de las expectativas no cumplidas, importancia de la participación social, el autocuidado, adherencia incompleta y fragmentada y riesgo de descompensación). Conclusión: La categoría ageísmo, aislamiento y soledad subyace a un mayor riesgo cardiovascular, por la dificultad que tienen las personas que sufren soledad para adherirse al tratamiento. La relación de ayuda se describe débilmente, prevaleciendo el paternalismo biomédico. Se requiere fortalecer estrategias participativas en el programa cardiovascular y actividades a partir de las necesidades de personas mayores.
ABSTRACT Aim: To explore and describe the dimensions that affect the therapeutic adherence of elderly patients with high blood pressure and/or type 2 diabetes in Araucanía, Chile. Methods: This was a qualitative, ethnographic, and descriptive research that addressed its content analysis following Bardin. It corresponds to the first phase of an exploratory study in which two focus groups are carried out; the participants were 12 people over 70 years of age with hypertension and/or type 2 diabetes. Results: Thirteen emerging categories are described: three are in vivo (being a burden for others, getting help using the cellphone, and impoverished life), and ten are theoretical (ageism, isolation and loneliness, popular culture to control the pathology, matriarchal family structure, deep-rooted biomedical model, underestimation of the non-medical team, unfulfilled expectations paradox, importance of social participation, self-care, incomplete and fragmented adherence, and risk of decompensation). Conclusion: The ageism, isolation and loneliness categories present a greater cardiovascular risk due to the difficulty that people who suffer loneliness have to adhere to the treatment. The aid relationship is weakly described, and the biomedical paternalism prevails. It is necessary to strengthen participatory strategies in the cardiovascular program, and activities based on the needs of the elderly.
RESUMO Objetivo: Explorar e descrever as dimensões que afetam a adesão terapêutica em idosos hipertensos e diabéticos tipo 2, Araucanía, Chile. Metodologia: Pesquisa qualitativa etnográfica, descritiva, abordada com a análise de conteúdo segundo Bardin. Corresponde à primeira fase de um estudo exploratório, no qual são realizados dois grupos focais, com a participação de 12 pessoas com mais de 70 anos com hipertensão, diabetes tipo 2 ou ambos. Resultados: Treze categorias emergentes são descritas, três in vivo; ser um fardo para os outros, obtendo ajuda do celular e da vida empobrecida, e dez teóricos; ageismo, isolamento e solidão, cultura popular para o controle da patologia, estrutura familiar matriarcal, modelo biomédico arraigado, subestimação da equipe não médica, paradoxo das expectativas não atendidas, importância da participação social, autocuidado, adesão incompleta e fragmentada e descompensação de risco. Conclusão: A categoria idade, isolamento e solidão está subjacente a um maior risco cardiovascular, devido à dificuldade que as pessoas que sofrem de solidão têm para aderir ao tratamento. A relação de ajuda é mal descrita, prevalecendo o paternalismo biomédico. É necessário fortalecer estratégias participativas no programa cardiovascular e atividades baseadas nas necessidades dos idosos.
Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus , Etarismo , Cooperação e Adesão ao Tratamento , HipertensãoRESUMO
Objetivo: Explorar y describir dimensiones que afectan la adherencia terapéutica en personas mayores con hipertensión o diabetes tipo 2 en Araucanía, Chile. Metodología: Investigación cualitativa, etnográfica y descriptiva, que se aborda con análisis de contenido según Bardin. Corresponde a una primera fase de un estudio exploratorio, en la que se realizan dos grupos focales, con participación de 12 personas mayores de 70 años con hipertensión, diabetes tipo 2 o ambas. Resultados: Se describen trece categorías emergentes, tres in vivo (ser carga para otras personas, obtención de ayuda a partir del celular y vida empobrecida) y diez teóricas (edadismo, aislamiento y soledad, cultura popular para control de la patología, estructura familiar matriarcal, modelo biomédico arraigado, infravaloración del equipo no médico, paradoja de las expectativas no cumplidas, importancia de la participación social, el autocuidado, adherencia incompleta y fragmentada y riesgo de descompensación). Conclusión: La categoría ageísmo, aislamiento y soledad subyace a un mayor riesgo cardiovascular, por la dificultad que tienen las personas que sufren soledad para adherirse al tratamiento. La relación de ayuda se describe débilmente, prevaleciendo el paternalismo biomédico. Se requiere fortalecer estrategias participativas en el programa cardiovascular y actividades a partir de las necesidades de personas mayores.
Aim: To explore and describe the dimensions that affect the therapeutic adherence of elderly patients with high blood pressure and/or type 2 diabetes in Araucanía, Chile. Methods: This was a qualitative, ethnographic, and descriptive research that addressed its content analysis following Bardin. It corresponds to the first phase of an exploratory study in which two focus groups are carried out; the participants were 12 people over 70 years of age with hypertension and/or type 2 diabetes. Results: Thirteen emerging categories are described: three are in vivo (being a burden for others, getting help using the cellphone, and impoverished life), and ten are theoretical (ageism, isolation and loneliness, popular culture to control the pathology, matriarchal family structure, deep-rooted biomedical model, underestimation of the non-medical team, unfulfilled expectations paradox, importance of social participation, self-care, incomplete and fragmented adherence, and risk of decompensation). Conclusion: The ageism, isolation and loneliness categories present a greater cardiovascular risk due to the difficulty that people who suffer loneliness have to adhere to the treatment. The aid relationship is weakly described, and the biomedical paternalism prevails. It is necessary to strengthen participatory strategies in the cardiovascular program, and activities based on the needs of the elderly.
Objetivo: Explorar e descrever as dimensões que afetam a adesão terapêutica em idosos hipertensos e diabéticos tipo 2, Araucanía, Chile. Metodologia: Pesquisa qualitativa etnográfica, descritiva, abordada com a análise de conteúdo segundo Bardin. Corresponde à primeira fase de um estudo exploratório, no qual são realizados dois grupos focais, com a participação de 12 pessoas com mais de 70 anos com hipertensão, diabetes tipo 2 ou ambos. Resultados: Treze categorias emergentes são descritas, três in vivo; ser um fardo para os outros, obtendo ajuda do celular e da vida empobrecida, e dez teóricos; ageismo, isolamento e solidão, cultura popular para o controle da patologia, estrutura familiar matriarcal, modelo biomédico arraigado, subestimação da equipe não médica, paradoxo das expectativas não atendidas, importância da participação social, autocuidado, adesão incompleta e fragmentada e descompensação de risco. Conclusão: A categoria idade, isolamento e solidão está subjacente a um maior risco cardiovascular, devido à dificuldade que as pessoas que sofrem de solidão têm para aderir ao tratamento. A relação de ajuda é mal descrita, prevalecendo o paternalismo biomédico. É necessário fortalecer estratégias participativas no programa cardiovascular e atividades baseadas nas necessidades dos idosos.
RESUMO
The susceptibility to type 2 diabetes (T2D) involves genetic factors. We studied the distribution of KIR and MHC class I ligands phenotype and genotype frequencies, as well as immunoglobulin KM and GM allotype frequencies in a group of patients (N = 95) with T2D and ethnically matched healthy controls (N = 74) with Puerto Rican ethnic background. We found a slight increase of the 2DL3/2DL3 homozygous genotype in T2D. Moreover, the association between 2DL3/2DL3 genotype was significant in the presence of 2DS4 (pC = 0.01). Also, we observed an epistatic effect of the interaction of 2DL3/2DL3, 2DS4 with allele z of G1M in T2D (pC = 0.004, OR = 3.60, 95% CI, 1.62-8.10). This genetic interaction between KIR and G1M allotypes, associated with T2D, was also significant by multiple logistic regression analysis (p < 0.0001, OR = 4.90, 95% CI, 2.12-11.3). We did not detect population stratification using unlinked short tandem repeat (STR) markers, demonstrating that the patients and controls were ethnically matched. Hence, we have demonstrated in this study an epistatic interaction between KIR genes and the G1M allotype that influences the susceptibility to T2D in Puerto Rican Americans. Our findings are important for understanding the autoimmune or innate immune inflammatory-mediated mechanisms involved in the pathogenesis of T2D.
Assuntos
Proteínas de Transporte/genética , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Alótipos de Imunoglobulina/metabolismo , Proteínas Monoméricas de Ligação ao GTP/genética , Diabetes Mellitus Tipo 2/etnologia , Epistasia Genética , Feminino , Frequência do Gene , Genótipo , Hispânico ou Latino/etnologia , Humanos , Alótipos de Imunoglobulina/genética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Estados UnidosRESUMO
PURPOSE: Cardiac rehabilitation (CR) in patients with chronic heart failure (CHF) has met with resistance from third-party payers in low- and middle-income countries because of lack of evidence regarding its cost-effectiveness. We aimed to provide information to help better inform this decision-making process. METHODS: Costs associated with a 12-week exercise-based rehabilitation program in Colombia for patients with CHF were estimated. We collected data on all medical resources used in ambulatory care and data on hospital costs incurred for treating patients with uncompensated CHF. A literature search to establish the hospitalization rates because of uncompensated CHF, death because of CHF, and potential decreases in these data because of the utilization of CR was conducted. We modeled incremental costs and effectiveness over a period of 5 years from the perspective of the third-party payer. RESULTS: All costs were converted from Colombian pesos to US dollars. For an exercise-based CR program of 12-week duration (36 sessions), costs ranged from US$265 to US$369 per patient. Monthly costs associated with ambulatory care of CHF averaged US$128 ± US$321 per patient, and hospitalization costs were US$3621 ± US$5 444 per event. Yearly hospitalization incidence rates with and without CR were 0.154 and 0.216, respectively. The incremental cost of CR would be US$998 per additional quality-adjusted life-year. Sensitivity analysis did not significantly change these results. CONCLUSIONS: Cardiac rehabilitation in patients with CHF in settings such as Colombia can be a cost-effective strategy, with minimal incremental costs and better quality of life, mainly because of decreased rates of hospitalization.
Assuntos
Assistência Ambulatorial/economia , Terapia por Exercício/economia , Insuficiência Cardíaca/economia , Insuficiência Cardíaca/reabilitação , Hospitalização/economia , Doença Crônica , Colômbia , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Hospitalização/estatística & dados numéricos , Humanos , Modelos Econômicos , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de VidaRESUMO
Plants generate effective responses to infection by recognizing both conserved and variable pathogen-encoded molecules. Pathogens deploy virulence effector proteins into host cells, where they interact physically with host proteins to modulate defense. We generated an interaction network of plant-pathogen effectors from two pathogens spanning the eukaryote-eubacteria divergence, three classes of Arabidopsis immune system proteins, and ~8000 other Arabidopsis proteins. We noted convergence of effectors onto highly interconnected host proteins and indirect, rather than direct, connections between effectors and plant immune receptors. We demonstrated plant immune system functions for 15 of 17 tested host proteins that interact with effectors from both pathogens. Thus, pathogens from different kingdoms deploy independently evolved virulence proteins that interact with a limited set of highly connected cellular hubs to facilitate their diverse life-cycle strategies.
Assuntos
Arabidopsis/imunologia , Arabidopsis/metabolismo , Interações Hospedeiro-Patógeno , Doenças das Plantas/imunologia , Imunidade Vegetal , Receptores Imunológicos/metabolismo , Fatores de Virulência/metabolismo , Arabidopsis/genética , Arabidopsis/microbiologia , Proteínas de Bactérias/metabolismo , Evolução Molecular , Genes de Plantas , Imunidade Inata , Oomicetos/patogenicidade , Mapeamento de Interação de Proteínas , Pseudomonas syringae/patogenicidadeRESUMO
The most common test to identify latent tuberculosis is the tuberculin skin test that detects T cell responses of delayed type hypersensitivity type IV. Since it produces false negative reactions in active tuberculosis or in high-risk persons exposed to tuberculosis patients as shown in this report, we studied antibody profiles to explain the anergy of such responses in high-risk individuals without active infection. Our results showed that humoral immunity against tuberculin, regardless of the result of the tuberculin skin test is important for protection from active tuberculosis and that the presence of high antibody titers is a more reliable indicator of infection latency suggesting that latency can be based on the levels of antibodies together with in vitro proliferation of peripheral blood mononuclear cells in the presence of the purified protein derivative. Importantly, anti-tuberculin IgG antibody levels mediate the anergy described herein, which could also prevent reactivation of disease in high-risk individuals with high antibody titers. Such anti-tuberculin IgG antibodies were also found associated with blocking and/or stimulation of in vitro cultures of PBMC with tuberculin. In this regard, future studies need to establish if immune responses to Mycobacterium tuberculosis can generate a broad spectrum of reactions either toward Th1 responses favoring stimulation by cytokines or by antibodies and those toward diminished responses by Th2 cytokines or blocking by antibodies; possibly involving mechanisms of antibody dependent protection from Mtb by different subclasses of IgG.
Assuntos
Anergia Clonal/imunologia , Hipersensibilidade Tardia/imunologia , Imunidade Humoral/imunologia , Mycobacterium tuberculosis/imunologia , Exposição Ocupacional/efeitos adversos , Recursos Humanos em Hospital , Teste Tuberculínico , Tuberculose/imunologia , Adulto , Idoso , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Proliferação de Células/efeitos dos fármacos , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Células Th1/imunologia , Células Th2/imunologia , Tuberculose/sangueRESUMO
Purified protein derivative (PPD) or tuberculin skin testing is used to identify infected individuals with Mycobacterium tuberculosis (Mtb) and to assess cell-mediated immunity to Mtb. In the present study, we compared PBMC cultures in the presence of tuberculin or Candida antigens using cytokine bead arrays and RNA microarrays. Measurements of different cytokines and chemokines in supernatants of PMBC cultures in the presence of PPD showed increased levels of interferon (IFN)-gamma in active tuberculosis infection (ATBI) and latent TB infected (LTBI) compared to controls, and increased levels of TNF-alpha in ATBI compared with LTBI. Also, we found increase of IL-6 in cultures of PPD positive and controls but not in the cultures with Candida. We also report the molecular signature of tuberculosis infection, in ATBI patients, the following genes were found to be up-regulated and absent in LTBI individuals: two kinases (JAK3 and p38MAPK), four interleukins (IL-7, IL-2, IL-6, and IFNbeta1), a chemokine (HCC-4) a chemokine receptor (CxCR5), two interleukin receptors (IL-1R2 and IL-18R1), and three additional ones (TRAF5, Smad2, CIITA, and NOS2A). By contrast, IL-17 and IGFBP3 were significantly up-regulated in LTBI. And, STAT4, GATA3, Fra-1, and ICOS were down-regulated in ATBI but absent in LTBI. Conversely, TLR-10, IL-15, DORA, and IKK-beta were down-regulated in LTBI but not in ATBI. Interestingly, the majority of the up-regulated genes found in ATBI were found in cultures stimulated with tuberculin (PPD) or Candida antigens, suggesting that these pathogens stimulate similar immunological pathways. We believe that the molecular signature distinguishing active from latent tuberculosis infection may require using cytokine bead arrays along with RNA microarrays testing cell cultures at different times following in vitro proliferation assays using several bacterial antigens and PPD.
Assuntos
Candida/imunologia , Tuberculose Latente/imunologia , Leucócitos Mononucleares/metabolismo , Mycobacterium tuberculosis/imunologia , Tuberculose Pulmonar/imunologia , Antígenos de Bactérias/imunologia , Candida/patogenicidade , Candidíase/sangue , Candidíase/diagnóstico , Candidíase/imunologia , Candidíase/patologia , Proliferação de Células , Células Cultivadas , Citocinas/biossíntese , Citocinas/genética , Citocinas/metabolismo , Diagnóstico Diferencial , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Janus Quinase 3/genética , Janus Quinase 3/imunologia , Janus Quinase 3/metabolismo , Tuberculose Latente/sangue , Tuberculose Latente/diagnóstico , Tuberculose Latente/patologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/patologia , Análise em Microsséries , Mycobacterium tuberculosis/patogenicidade , Transdução de Sinais , Fatores de Transcrição/imunologia , Tuberculina/imunologia , Teste Tuberculínico , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/patologia , Virulência , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Intravenous drug use has become the principal route of hepatitis C virus (HCV) transmission due to the sharing of infected needles. In this study, we analyzed the distribution of HLA-KIR genotypes among 160 Puerto Rican intravenous drug users (IDUs) with HCV infection and 92 HCV-negative Puerto Rican IDUs. We found a significant association between the presence of different combinations of KIR inhibitory receptor genes (KIR2DL2 and/or KIR2DL3, pC=0.01, OR=0.07; KIR2DL2 and/or KIR2DL3+KIR2DS4, pC=0.01, OR=0.39) and HLA-C1 homozygous genotypes (HLA-C1+KIR2DS4, pC=0.02, OR=0.43; HLA-C1+KIR2DL2+KIR2DS4, pC=0.02, OR=0.40) together with the activating receptor KIR2DS4 (HLA-C1+KIR2DS4+KIR2DL3 and/or KIR2DL2, pC=0.004, OR=0.38) with protection from HCV infection. Our findings in HCV-infected and non-infected IDUs suggest an important role for KIRs (KIR2DL2 and KIR2DL3) with group HLA-C1 molecules, in the presence of activating KIR2DS4, in protection from HCV infection. These results support the hypothesis that activator signaling, mediated by KIR2DS4, plays a determinant role in the regulation of NK cell antiviral-activity.
Assuntos
Antígenos HLA/genética , Hepatite C/genética , Receptores KIR/genética , Abuso de Substâncias por Via Intravenosa/genética , Análise por Conglomerados , Frequência do Gene , Genótipo , Antígenos HLA-C/genética , Hepatite C/virologia , Humanos , Receptores KIR2DL2/genética , Receptores KIR2DL3/genética , Abuso de Substâncias por Via Intravenosa/virologiaRESUMO
HIV infection and its outcome is complex because there is great heterogeneity not only in clinical presentation, incomplete clinical information of markers of immunodeficiency and in measurements of viral loads. Also, there many gene variants that control not only viral replication but immune responses to the virus; it has been difficult to study the role of the many AIDS restricting genes (ARGs) because their influence vary depending on the ethnicity of the populations studies and because the cost to follow infected individuals for many years. Nevertheless, at least genes of the major histocompatibility locus (MHC) such as HLA alleles have been informative to classify infected individuals following HIV infection; progression to AIDS and long-term-non-progressors (LTNP). For example, progressors could be defined as up to 5 years, up to 11 years or as we describe in this report up to 15 years from infection, and LTNP could be individuals with normal CD4+ T cell counts for more than 15 years with or without high viral loads. In this review, we emphasized that in the studies of ARGs the HLA alleles are important in LTNP; HLA-B alleles influencing the advantage to pathogens to produce immune defense mediated by CD8+ T cells (cognate immunuity). Our main point we make in this report is that contrary to recent reports claiming that this dominant effect was unlikely due to differences in NK activation through ligands such as HLA-Bw4 motif, we believe that cognate immunity as well as innate immunity conferred by NK cells are involved. The main problem is that HLA-Bw4 alleles can be classified according the aminoacid in position 80. Isoleucine determines LTNP, which is a ligand for 3DS1. Such alleles did not include HLA-B*44. B*13 and B*27 which have threonine at that position. The authors have not considered the fact that in addition to the NK immunoglobulin receptors, NK receptors can be of the lectin like such as NKG2A/HLA-E to influence the HIV infection outcome. HLA-Bw4 as well as HLA-Bw6 alleles can be classified into those with threonine or methionine in the second position of their leader peptides. These leader peptides are ligands for NKG2A in which methionine influences the inhibitory role of NKG2A for killing infected targets. Functional studies have not been done as well as studies of these receptors in infected individuals. However, analyses of the leader peptides of HLA-B alleles in published reports, suggested that threonine in the second position can explain the importance of HLA-B*57, B*13, B*44 as well as certain Bw6 alleles in LNTP. In addition, we analyzed the San Francisco database that was reported and found that the association of HLA-B alleles with LNTP or with progressors can be due to the presence of threonine or methionine in their second position. Therefore, studies of outcome of HIV infection should include not only mechanisms of cognate immunity mediated by peptides and CD8+ T cells but also, NK receptors of two types, NKG2A as well as 3DSI. We propose that the SCID mouse should be used to understand mechanisms mediated by many of the ARGs especially the importance of thymus derived cells as well as NK receptor interactions with their ligands in this experimental animal transplanted with human stem cells, thymus or NK cells obtained from individuals of known HLA genotypes.
RESUMO
Objetivo. Diseñar un medio de cultivo complejo para la producción de biomasa y fosfatasas ácidas a partir de bacterias solubilizadoras de fosfatos aisladas de suelo. Materiales y métodos. A partir de muestras de suelo de cultivos de palma de aceite se realizaron los aislamientos y la selección de bacterias fosfato solubilizadoras (BFS) en agar SMRS1, las cuales fueron sometidas a pruebas de antagonismo con el fin de verificar su aptitud para la formación de co-cultivos. Posteriormente, se realizó un diseño experimental Box-Behnken para evaluar el efecto de cada uno de los componentes del medio de cultivo sobre la producción de biomasa y enzimas fosfatasas a escala de laboratorio. Finalmente se realizaron curvas de crecimiento y de producción de enzima para determinar los tiempos de producción. Resultados. Se obtuvieron 5 bacterias fosfato solubilizadoras, de las cuales 3 fueron seleccionadas con base en el índice de solubilización; dichas cepas, de morfología bacilar Gram negativa, fueron identificadas como A, B y C, cuyos índices de solubilización correspondieron a 2,03, 2,12 y 2,83, respectivamente. De acuerdo con los análisis de ANOVA para el diseño experimental de Box Behnken, el factor que tuvo efecto significativo sobre la actividad fosfatasa (p<0,01), fue el hidrolizado de levadura, y el formulado que generó la mayor concentración de biomasa y actividad fosfatasa (p<0,01) fue el que contenía 10, 15 y 2,5 gL-1 de roca fosfórica sacarosa e hidrolizado de levadura, respectivamente, obteniendo valores máximos de biomasa y actividad fosfatasa de 11,8 unidades logarítmicas de UFC y 12,9 unidades fosfatasa con incubación por 24 horas a 100 rpm. Conclusión. Se determinó que el medio con formulación 10gL-1 de roca fosfórica, 2,5gL-1 de hidrolizado de levadura y 15gL-1 de sacarosa comercial, fue ideal para la producción de biomasa y enzimas fosfatasas a partir de las cepas evaluadas. Así mismo, se comprobó que el hidrolizado de levadura fue el único factor significativamente influyente en la producción de enzimas fosfatasas.
Objective. To design a complex culture media for the production of biomass and acid phosphatases from phosphate-solubilizing bacteria isolated from soil. Materials and methods. Phosphate-solubilizing bacteria were isolated from oil palm crop soil samples and selected on SMRS1 agar, which were then assessed with antagonism tests to verify their aptitude to form a co-culture. A Box-Behnken experimental design was applied to evaluate the effect of each one of the culture media components on the production of biomass and phosphatase enzymes at a laboratory scale. Finally, microbial growth and enzyme production curves were carried out in order to determine their production times. Results. Five phosphate-solubilizing bacterial strains were isolated and three of them were selected based on their solubilization indices. These Gram negative strains with bacillus morphology were identified as A, B and C; their solubilization indices were 2.03, 2.12, and 2.83, respectively. According to the ANOVA analyses for the Box-Behnken design, the only factor which had a significant effect on the phosphatase activity (p<0.01) was hydrolyzed yeast, and the formulation that generated the highest biomass concentration and phosphatase activity (p<0.01) contained 10, 15 and 2.5 gL-1 of phosphoric rock, sucrose and hydrolyzed yeast, respectively. After 24 hours of incubation at 100 rpm, the highest values of biomass and phosphatase activity were obtained: 11.8 logarithmic units of CFU and 12.9 phosphatase units. Conclusion. We determined that the culture media based on phosphoric rock 10 gL-1, hydrolyzed yeast 2.5 gL-1 and commercial sucrose 15 gL-1 was ideal for the production of biomass and phosphatases by the strains evaluated; likewise, we proved that the hydrolyzed yeast was the only factor significantly influential for the production of phosphatases.
Objetivo. Desenhar um meio de cultura complexo para a produção de biomassa e fosfatase ácida a partir de bactérias solubilizadoras de fosfato isoladas do solo. Materiais e métodos. De amostras de solo de plantações de dendezeiros foram isoladas e selecionadas bactérias solubilizadoras de fosfato (BFS) em ágar SMRS1, que foram testadas em provas de antagonismo para verificar sua capacidade de formar co-culturas. Subsequentemente, foi realizado um desenho experimental do tipo Box-Behnken para avaliar o efeito de cada um dos componentes do meio de cultura na produção de biomassa e de enzimas fosfatase a escala de laboratório. Finalmente foram realizadas curvas de crescimento e de produção da enzima para determinar os tempos de produção. Resultados. Foram obtidas 5 bactérias solubilizadoras de fosfato, das quais 3 foram selecionadas com base no índice de solubilização, tais cepas, de morfologia bacilar Gram negativas, foram identificadas como A, B e C, cujos índices de solubilização corresponderam a 2,03, 2 12 e 2,83, respectivamente. De acordo com a análise ANOVA para o desenho experimental do tipo Box Behnken, o fator que teve efeito significativo na atividade da fosfatase (p <0,01), foi o hidrolisado de levedura, e o formulado que gerou a maior concentração de biomassa e atividade da fosfatase (p <0,01) foi aquel que contive 10, 15 e 2,5 gL-1 de rocha fosfato sacarose e hidrolisado de levedura, respectivamente, obtendo-se valores máximos de biomassa e atividade de fosfatase de 11,8 unidades log de UFC e 12,9 unidades de fosfatase com incubação durante 24 horas a 100 rpm. Conclusão. Foi determinado que o meio com formulação 10gL-1 de rocha fosfórica, 2,5 gL-1 de hidrolisado de levedura e 15gL-1 de sacarose comercial, foi ideal para a produção de biomassa e enzimas fosfatase a partir das cepas avaliadas. Da mesma forma, verificou-se que o hidrolisado de levedura foi o único fator significativo influente na produção de enzimas fosfatase.