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1.
Rev Esp Enferm Dig ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958154

RESUMO

INTRODUCTION: The early diagnosis of achalasia requires a high degree of clinical suspicion, and delays in diagnosis are frequent. High-resolution oesophageal manometry (HRM) is the gold standard for its diagnostic confirmation. There are two HRM systems, perfusion and solid-state, which allow its classification into three subtypes: I, or classical; II, or with pan-oesophageal pressurization; and III, or spastic. OBJECTIVE: To determine the clinical and manometric characteristics of the three subtypes with high-resolution perfusion and solid-state equipment and the time of evolution until diagnosis. METHODS: This was a multicentre, observational, retrospective study of patients from the INTEGRA database of the Spanish Association of Neurogastroenterology and Motility who were diagnosed with primary achalasia confirmed by HRM, who fell under the Chicago Classification v3.0, and who had not been treated. RESULTS: The study included 110 patients (subtype I, N = 14; subtype II, N = 73; subtype III, N = 23). The HRM equipment was perfusion for 49 and solid-state for 61. The mean age was 61.8 ± 14 years (age range 44-81), the age was lower in subtype II, and the sex distribution was similar. The time of clinical evolution until diagnosis was > 12 months (51.6%), subtype II being the one that was diagnosed earlier and the most often (66.3%). Dysphagia was the most frequent symptom (90.5%). According to the comparative analysis by high-resolution perfusion and solid-state oesophageal manometry equipment, the baseline pressure of the lower oesophageal sphincter was higher in the solid-state oesophagus, but the difference was not statistically significant. The median integrated relaxation pressure at 4 seconds (IRP4) was similar (21 mmHg) between the perfusion and solid-state measurements. We describe the ranges of IRP4 in achalasia patients with both systems and confirm the possibility of achalasia even when IRP4 is within the normal range. CONCLUSIONS: Achalasia in our environment has a significant diagnostic delay. No significant differences were observed in the oesophagogastric junction between the two groups diagnosed with perfusion and solid-state equipment.

2.
Dis Colon Rectum ; 66(12): e1186-e1194, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37556018

RESUMO

BACKGROUND: People living with HIV have an increased risk of anal cancer. OBJECTIVE: To estimate anal cancer incidence and related risk factors in a national cohort of HIV-infected patients. DESIGN: Prospective multicenter cohort study. SETTINGS: Multicenter study including patients from the Spanish HIV Research Network. PATIENTS: We collected data from 16,274 HIV-infected treatment-naive adults recruited from January 2004 to November 2020. MAIN OUTCOMES MEASURES: The primary outcome measures of this study were the incidence and prevalence of anal carcinoma. The secondary outcome measures included the associations between baseline and time-dependent covariables and the primary end point. RESULTS: Twenty-six cases of anal cancer were diagnosed, 22 of which were incident cases resulting in a cumulative incidence of 22.29 of 100,000 person-years, which was stable during the study period. At the end of the study, 20 of the 43 centers had screening programs for high-grade anal dysplasia. Patients with anal cancer were males (26/26; 100% vs 13,833/16,248; 85.1%), were mostly men who have sex with men (23/26; 88.5% vs 10,017/16,248; 61.6%), had a median age of 43 years (interquartile range, 35-51), were more frequently previously diagnosed with an AIDS-defining illness (9/26; 34.6% vs 2429/16,248; 15%), and had lower nadir CD4 cell counts (115 vs 303 µL). About a third (34.6%, 9/26) were younger than 35 years. In multivariable analysis, men who have sex with men and patients with previous AIDS-defining illness had an 8.3-fold (95% CI, 1.9-36.3) and 2.7-fold (95% CI, 1.1-6.6) increased HR for developing anal cancer, respectively. Patients with higher CD4 cell counts during the follow-up showed a 28% lower risk per each additional 100 CD4 cell/µL (95% CI, 41%-22%). LIMITATIONS: Lack of information on some potential risk factors, screening, and treatment of high-grade anal dysplasia were not uniformly initiated across centers during the study period. CONCLUSIONS: Although the overall incidence in our study was low, there was a significant number of patients younger than 35 years with anal cancer. In addition to age, other factors, such as men who have sex with men and patients with severe immunosuppression (current or past), should be prioritized for anal cancer screening. INCIDENCIA DEL CNCER DE ANO Y LOS FACTORES DE RIESGO RELACIONADOS CON PACIENTES INFECTADOS POR VIH INCLUIDOS EN LA COHORTE PROSPECTIVA NACIONAL ESPAOLA CORIS: ANTECEDENTES:Las personas portadoras del virus de la inmunodeficiencia humana tienen un mayor riesgo de cáncer anal.OBJETIVO:Nosotros queremos estimar la incidencia de cáncer anal y los factores de riesgo relacionados en una cohorte nacional española de pacientes infectados por VIH.DISEÑO:Estudio de cohortes de tipo multicéntrico y prospectivo.ÁMBITO:Se incluyeron pacientes de la Red Española de Investigación en VIH.PACIENTES:Recolectamos los datos de 16,274 adultos infectados por el VIH que nunca habían recibido tratamiento, reclutados desde enero de 2004 hasta noviembre de 2020.MEDIDAS DE RESULTADO PRINCIPALES:Las medidas de resultado primarias de este estudio fueron la incidencia y la prevalencia del carcinoma anal. Las medidas de resultado secundarias incluyeron las asociaciones entre las covariables basales y dependientes del tiempo y el criterio principal de valoración.RESULTADOS:Se diagnosticaron 26 casos de cáncer anal, de los cuales 22 fueron casos incidentales resultando con una incidencia acumulada de 22,29/100.000 personas-año que se mantuvo estable durante el período de estudio.Al final de nuestro estudio, 20 de los 43 centros referentes tenían programas de detección de displasia anal de alto grado. Los pacientes con cáncer anal eran hombres (26/26; 100% vs 13 833/16 248; 85,1%), en su mayoría hombres que mantenían sexo con otros hombres (23/26; 88,5% vs 10 017/16 248; 61,6%), la mediana de edad fue de 43 años (IQR: 3 -51), 34,6% (9/26) < 35 años, previa y frecuentemente diagnosticados con una enfermedad definitoria de SIDA (9/26; 34,6% vs 2429/16248; 15%) y que tenían un punto opuesto mucho más bajo en el recuentos de células CD4 (115 µL frente a 303 µL).En el análisis multivariable, los hombres que tenían relaciones sexuales con otros hombres y los pacientes con enfermedades definitorias de sida anteriores, tenían un aumento de 8,3 veces (IC del 95%: 1,9 a 36,3) y de 2,7 veces (IC del 95%: 1,1 a 6,6) en el cociente de riesgos instantáneos para desarrollar cáncer anal, respectivamente. Los pacientes con recuentos de células CD4 más altos durante el seguimiento mostraron un riesgo 28 % menor por cada 100 células CD4/µl adicionales (95% IC: 41%- 22%).LIMITACIONES:La falta de información sobre algunos factores potenciales de riesgo, la detección y el tratamiento de la displasia anal de alto grado no se iniciaron uniformemente en todos los centros durante el período de estudio.CONCLUSIONES:Si bien la incidencia general en nuestro estudio fue baja, hubo un número significativo de pacientes de <35 años con cáncer anal. Además de la edad, otros factores como los hombres que tienen sexo con hombres y los pacientes con inmunosupresión severa (actual o pasada) deben priorizarse para la detección del cáncer anal. ( Traducción-Dr. Xavier Delgadillo ).


Assuntos
Síndrome da Imunodeficiência Adquirida , Neoplasias do Ânus , Carcinoma , Minorias Sexuais e de Gênero , Adulto , Masculino , Humanos , Feminino , Incidência , Estudos de Coortes , Homossexualidade Masculina , Estudos Prospectivos , Neoplasias do Ânus/epidemiologia , Fatores de Risco , Estudos Retrospectivos
3.
Int J Mol Sci ; 22(8)2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33917098

RESUMO

Mammalian mitochondrial ribosomes (mitoribosomes) synthesize a small subset of proteins, which are essential components of the oxidative phosphorylation machinery. Therefore, their function is of fundamental importance to cellular metabolism. The assembly of mitoribosomes is a complex process that progresses through numerous maturation and protein-binding events coordinated by the actions of several assembly factors. Dysregulation of mitoribosome production is increasingly recognized as a contributor to metabolic and neurodegenerative diseases. In recent years, mutations in multiple components of the mitoribosome assembly machinery have been associated with a range of human pathologies, highlighting their importance to cell function and health. Here, we provide a review of our current understanding of mitoribosome biogenesis, highlighting the key factors involved in this process and the growing number of mutations in genes encoding mitoribosomal RNAs, proteins, and assembly factors that lead to human disease.


Assuntos
Suscetibilidade a Doenças , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Ribossomos Mitocondriais/metabolismo , Biomarcadores , Regulação da Expressão Gênica , Humanos , Proteínas Mitocondriais/química , Proteínas Mitocondriais/genética , Mutação , Fosforilação Oxidativa , Ligação Proteica , Processamento de Proteína Pós-Traducional , Proteínas Ribossômicas/química , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo
4.
Environ Microbiol ; 18(10): 3403-3424, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26913973

RESUMO

By the time the complete genome sequence of the soil bacterium Pseudomonas putida KT2440 was published in 2002 (Nelson et al., ) this bacterium was considered a potential agent for environmental bioremediation of industrial waste and a good colonizer of the rhizosphere. However, neither the annotation tools available at that time nor the scarcely available omics data-let alone metabolic modeling and other nowadays common systems biology approaches-allowed them to anticipate the astonishing capacities that are encoded in the genetic complement of this unique microorganism. In this work we have adopted a suite of state-of-the-art genomic analysis tools to revisit the functional and metabolic information encoded in the chromosomal sequence of strain KT2440. We identified 242 new protein-coding genes and re-annotated the functions of 1548 genes, which are linked to almost 4900 PubMed references. Catabolic pathways for 92 compounds (carbon, nitrogen and phosphorus sources) that could not be accommodated by the previously constructed metabolic models were also predicted. The resulting examination not only accounts for some of the known stress tolerance traits known in P. putida but also recognizes the capacity of this bacterium to perform difficult redox reactions, thereby multiplying its value as a platform microorganism for industrial biotechnology.


Assuntos
Genoma Bacteriano , Pseudomonas putida/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Carbono/metabolismo , Genômica , Nitrogênio/metabolismo , Pseudomonas putida/metabolismo
5.
Hum Mutat ; 35(12): 1476-84, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25219341

RESUMO

Mitochondrial DNA (mtDNA) is replicated throughout life in postmitotic cells, resulting in higher levels of somatic mutation than in nuclear genes. However, controversy remains as to the importance of low-level mtDNA somatic mutants in cancerous and normal human tissues. To capture somatic mtDNA mutations for functional analysis, we generated synaptosome cybrids from synaptic endings isolated from fresh hippocampus and cortex brain biopsies. We analyzed the whole mtDNA genome from 120 cybrid clones derived from four individual donors by chemical cleavage of mismatch and Sanger sequencing, scanning around two million base pairs. Seventeen different somatic point mutations were identified, including eight coding region mutations, four of which result in frameshifts. Examination of one cybrid clone with a novel m.2949_2953delCTATT mutation in MT-RNR2 (which encodes mitochondrial 16S rRNA) revealed a severe disruption of mtDNA-encoded protein translation. We also performed functional studies on a homoplasmic nonsense mutation in MT-ND1, previously reported in oncocytomas, and show that both ATP generation and the stability of oxidative phosphorylation complex I are disrupted. As the mtDNA remains locked against direct genetic manipulation, we demonstrate that the synaptosome cybrid approach can capture biologically relevant mtDNA mutants in vitro to study effects on mitochondrial respiratory chain function.


Assuntos
Encéfalo/metabolismo , DNA Mitocondrial/genética , Fosforilação Oxidativa , Mutação Puntual , Sinaptossomos/metabolismo , Trifosfato de Adenosina/biossíntese , Sequência de Aminoácidos , Humanos , Dados de Sequência Molecular
6.
Enferm Infecc Microbiol Clin ; 32(6): 359-62, 2014.
Artigo em Espanhol | MEDLINE | ID: mdl-24054972

RESUMO

INTRODUCTION: An increase in cases of pertussis, mainly in young infants, has been reported in the last few years. The clinical presentation of this disease is very similar to that produced by respiratory syncytial virus (RSV), which makes the diagnosis difficult. OBJECTIVE: To compare the clinical and epidemiological characteristics between Bordetella pertussis and RSV infections in infants admitted to hospital. MATERIAL AND METHODS: An analytical matched case-control study was conducted during the period 2008-2011. Cases were defined as infants admitted with pertussis confirmed by PCR in nasopharyngeal aspirate. Each case was matched by age, sex and date of admission to two controls defined as patients with RSV infection detected by immunochromatography in nasal aspirate. Demographic, clinical, laboratory data were compared. RESULTS: Seventy eight patients (26 cases of pertussis and 52 controls RSV+) were included. Sociodemographic characteristics were similar in both groups. Cases had more days of symptoms prior to admission, longer hospital stays, and increased frequency of epidemic family environment. Apnoea and cyanosis were more frequent. Cases of pertussis were more likely to have apnoea, cyanosis, and lymphocytosis while RSV infections had more frequent fever, vomiting and respiratory distress. CONCLUSIONS: The clinical presentations of pertussis and RSV infection are similar, but there are some characteristics that can help to distinguish between them.


Assuntos
Infecções por Vírus Respiratório Sincicial/diagnóstico , Infecções por Vírus Respiratório Sincicial/epidemiologia , Coqueluche/diagnóstico , Coqueluche/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Lactente , Masculino , Admissão do Paciente , Estudos Retrospectivos
7.
Mol Microbiol ; 85(6): 1057-71, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22834929

RESUMO

Clustered regularly interspaced short palindromic repeats (CRISPR) confer immunity against mobile genetic elements (MGEs) in prokaryotes. Streptococcus agalactiae, a leading cause of neonatal infections contains in its genome two CRISPR/Cas systems. We show that type 1-C CRISPR2 is present in few strains but type 2-A CRISPR1 is ubiquitous. Comparative sequence analysis of the CRISPR1 spacer content of 351 S. agalactiae strains revealed that it is extremely diverse due to the acquisition of new spacers, spacer duplications and spacer deletions that witness the dynamics of this system. The spacer content profile mirrors the S. agalactiae population structure. Transfer of a conjugative transposon targeted by CRISPR1 selected for spacer rearrangements, suggesting that deletions and duplications pre-exist in the population. The comparison of protospacers located within MGE or the core genome and protospacer-associated motif-shuffling demonstrated that the GG motif is sufficient to discriminate self and non-self and for spacer selection and integration. Strikingly more than 40% of the 949 different CRISPR1 spacers identified target MGEs found in S. agalactiae genomes. We thus propose that the S. agalactiae type II-A CRISPR1/Cas system modulates the cohabitation of the species with its mobilome, as such contributing to the diversity of MGEs in the population.


Assuntos
DNA Bacteriano/genética , Sequências Repetitivas Dispersas , Recombinação Genética , Sequências Repetitivas de Ácido Nucleico , Streptococcus agalactiae/genética , Conjugação Genética , Elementos de DNA Transponíveis , Transferência Genética Horizontal , Variação Genética , Dados de Sequência Molecular , Análise de Sequência de DNA
8.
Front Pharmacol ; 14: 1132530, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37063300

RESUMO

Introduction: Bloodstream infections (BSI) are a major cause of mortality all over the world. Inappropriate empirical antimicrobial treatment (i-EAT) impact on mortality has been largely reported. However, information on related factors for the election of i-EAT in the treatment of BSI in adults is lacking. The aim of the study was the identification of risk-factors associated with the use of i-EAT in BSI. Methods: A retrospective, observational cohort study, from a prospective database was conducted in a 400-bed acute-care teaching hospital including all BSI episodes in adult patients between January and December 2018. The main outcome variable was EAT appropriation. Multivariate analysis using logistic regression was performed. Results: 599 BSI episodes were included, 146 (24%) received i-EAT. Male gender, nosocomial and healthcare-associated acquisition of infection, a high Charlson Comorbidity Index (CCI) score and the isolation of multidrug resistant (MDR) microorganisms were more frequent in the i-EAT group. Adequation to local guidelines' recommendations on EAT resulted in 91% of appropriate empirical antimicrobial treatment (a-EAT). Patients receiving i-EAT presented higher mortality rates at day 14 and 30 when compared to patients with a-EAT (14% vs. 6%, p = 0.002 and 22% vs. 9%, p < 0.001 respectively). In the multivariate analysis, a CCI score ≥3 (OR 1.90 (95% CI 1.16-3.12) p = 0.01) and the isolation of a multidrug resistant (MDR) microorganism (OR 3.79 (95% CI 2.28-6.30), p < 0.001) were found as independent risk factors for i-EAT. In contrast, female gender (OR 0.59 (95% CI 0.35-0.98), p = 0.04), a correct identification of clinical syndrome prior to antibiotics administration (OR 0.26 (95% CI 0.16-0.44), p < 0.001) and adherence to local guidelines (OR 0.22 (95% CI 0.13-0.38), p < 0.001) were identified as protective factors against i-EAT. Conclusion: One quarter of BSI episodes received i-EAT. Some of the i-EAT related factors were unmodifiable (male gender, CCI score ≥3 and isolation of a MDR microorganism) but others (incorrect identification of clinical syndrome before starting EAT or the use of local guidelines for EAT) could be addressed to optimize the use of antimicrobials.

9.
J Infect Prev ; 24(4): 182-186, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37333870

RESUMO

Background: Cancer has been associated with an increased risk of in-hospital mortality in CDI patients. However, data on delayed mortality in cancer patients with CDI are scarce. Aim/Objective: The aim of the present study was to compare outcomes between oncological patients and the general population with Clostridioides difficile infection (CDI) after 90 days of follow-up. Methods: A multicenter prospective cohort study was conducted in 28 hospitals participating in the VINCat program. Cases were all consecutive adult patients who met the case definition of CDI. Sociodemographic, clinical, and epidemiological variables and evolution at discharge and after 90 days were recorded for each case. Findings/results: The mortality rate was higher in oncological patients (OR = 1.70, 95% CI: 1.08-2.67). In addition, oncological patients receiving chemotherapy (CT) presented higher recurrence rates (18.5% vs 9.8%, p = 0.049). Among oncological patients treated with metronidazole, those with active CT showed a higher rate of recurrence (35.3% vs 8.0% p = 0.04). Discussion: Oncological patients presented a higher risk of poor outcomes after CDI. Their early and late mortality rates were higher than in the general population, and in parallel, those undergoing chemotherapy (especially those receiving metronidazole) had higher rates of recurrence.

10.
Glob Health Action ; 16(1): 2242670, 2023 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-37643136

RESUMO

BACKGROUND: COVID-19 vaccination is a global priority. Latin American countries have some of the highest COVID-19 death rates worldwide with vaccination hampered by a variety of reasons, including mis- and disinformation, vaccine hesitancy, and vaccine supply constraints. Addressing vaccine hesitancy through effective messages has been found to help increase vaccine uptake. Participatory processes could be used to co-design health messages for this purpose. OBJECTIVE: This article describes the methodology used to co-design evidence-based audio messages to be deployed in a cohort of individuals through an interactive voice response (IVR) mobile phone survey intervention, aimed towards increasing vaccination uptake in an adult population in Colombia. METHODS: Participants of the COVID-19 vaccination message co-design process included a sample of the general population of the country, representatives of the funder organisation, and research team members. The co-design process consisted of four phases: (1) formative quantitative and qualitative research, (2) message drafting based on the results of the formative research, (3) message content evaluation, and (4) evaluation of the voices to deliver the audio messages; and was informed by reflexive meetings. RESULTS: Three categories of evidence-based audio messages were co-designed, each corresponding to an arm of the mHealth intervention: (1) factual messages, (2) narrative messages, and (3) mixed messages. An additional fourth arm with no message was proposed for control. The iterative co-design process ended with a total of 14 audio messages recorded to be deployed via the intervention. CONCLUSIONS: Co-developing health messages in response to health emergencies is possible. Adopting more context-relevant, participatory, people-centred, and reflexive multidisciplinary approaches could help develop solutions that are more responsive to the needs of populations and public health priorities. Investing resources in message co-design is deemed to have a greater potential for influencing behaviours and improving health outcomes.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Adulto , Humanos , Vacinas contra COVID-19/uso terapêutico , Colômbia , COVID-19/prevenção & controle , Prioridades em Saúde , Estudos Interdisciplinares
11.
PLoS Genet ; 5(11): e1000721, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19911043

RESUMO

Bacterial endosymbionts of insects play a central role in upgrading the diet of their hosts. In certain cases, such as aphids and tsetse flies, endosymbionts complement the metabolic capacity of hosts living on nutrient-deficient diets, while the bacteria harbored by omnivorous carpenter ants are involved in nitrogen recycling. In this study, we describe the genome sequence and inferred metabolism of Blattabacterium strain Bge, the primary Flavobacteria endosymbiont of the omnivorous German cockroach Blattella germanica. Through comparative genomics with other insect endosymbionts and free-living Flavobacteria we reveal that Blattabacterium strain Bge shares the same distribution of functional gene categories only with Blochmannia strains, the primary Gamma-Proteobacteria endosymbiont of carpenter ants. This is a remarkable example of evolutionary convergence during the symbiotic process, involving very distant phylogenetic bacterial taxa within hosts feeding on similar diets. Despite this similarity, different nitrogen economy strategies have emerged in each case. Both bacterial endosymbionts code for urease but display different metabolic functions: Blochmannia strains produce ammonia from dietary urea and then use it as a source of nitrogen, whereas Blattabacterium strain Bge codes for the complete urea cycle that, in combination with urease, produces ammonia as an end product. Not only does the cockroach endosymbiont play an essential role in nutrient supply to the host, but also in the catabolic use of amino acids and nitrogen excretion, as strongly suggested by the stoichiometric analysis of the inferred metabolic network. Here, we explain the metabolic reasons underlying the enigmatic return of cockroaches to the ancestral ammonotelic state.


Assuntos
Bacteroidetes/genética , Baratas/microbiologia , Evolução Molecular , Nitrogênio/metabolismo , Simbiose/genética , Aminoácidos/metabolismo , Amônia/metabolismo , Animais , Formigas/microbiologia , Enterobacteriaceae/genética , Genoma Bacteriano , Genômica/métodos , Interações Hospedeiro-Patógeno/genética , Redes e Vias Metabólicas , Filogenia
12.
Future Microbiol ; 17: 1445-1453, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36314417

RESUMO

Background: The 2016 cumulative incidence of Clostridioides difficile infection (CDI) in Spain was reported by the European Center for Disease Control to be above the mean of other European countries. The aim of this multicenter prospective observational cohort study was to examine the risk factors that determine 90-day CDI recurrence in Catalonia, Spain. Methods: The study included 558 consecutive adults admitted to hospital who had a symptomatic, first positive CDI diagnosis. Sociodemographic, clinical and epidemiological variables were recorded. The primary outcome was 90-day CDI recurrence. Results: In this Catalan population, having received more than one course of antibiotics in the 30 days prior to CDI diagnosis (odds ratio: 2.459; 95% CI: 1.195-5.060; p = 0.015) and active chemotherapy (odds ratio: 4.859; 95% CI: 1.495-15.792; p = 0.009) are significant predictors of 90-day CDI recurrence. Conclusion: The identification of independent risk factors of 90-day CDI recurrence will enable the optimization of preventive measures in at-risk populations.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Humanos , Adulto , Estudos Prospectivos , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/tratamento farmacológico , Antibacterianos/uso terapêutico , Fatores de Risco , Hospitais , Recidiva , Estudos Retrospectivos
13.
Nat Commun ; 13(1): 4233, 2022 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-35882847

RESUMO

There are currently no treatments for geographic atrophy, the advanced form of age-related macular degeneration. Hence, innovative studies are needed to model this condition and prevent or delay its progression. Induced pluripotent stem cells generated from patients with geographic atrophy and healthy individuals were differentiated to retinal pigment epithelium. Integrating transcriptional profiles of 127,659 retinal pigment epithelium cells generated from 43 individuals with geographic atrophy and 36 controls with genotype data, we identify 445 expression quantitative trait loci in cis that are asssociated with disease status and specific to retinal pigment epithelium subpopulations. Transcriptomics and proteomics approaches identify molecular pathways significantly upregulated in geographic atrophy, including in mitochondrial functions, metabolic pathways and extracellular cellular matrix reorganization. Five significant protein quantitative trait loci that regulate protein expression in the retinal pigment epithelium and in geographic atrophy are identified - two of which share variants with cis- expression quantitative trait loci, including proteins involved in mitochondrial biology and neurodegeneration. Investigation of mitochondrial metabolism confirms mitochondrial dysfunction as a core constitutive difference of the retinal pigment epithelium from patients with geographic atrophy. This study uncovers important differences in retinal pigment epithelium homeostasis associated with geographic atrophy.


Assuntos
Atrofia Geográfica , Degeneração Macular , Humanos , Degeneração Macular/genética , Proteômica , Epitélio Pigmentado da Retina , Transcriptoma/genética
14.
BMC Bioinformatics ; 10: 391, 2009 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-19943962

RESUMO

BACKGROUND: ESTs or variable sequence reads can be available in prokaryotic studies well before a complete genome is known. Use cases include (i) transcriptome studies or (ii) single cell sequencing of bacteria. Without suitable software their further analysis and mapping would have to await finalization of the corresponding genome. RESULTS: The tool JANE rapidly maps ESTs or variable sequence reads in prokaryotic sequencing and transcriptome efforts to related template genomes. It provides an easy-to-use graphics interface for information retrieval and a toolkit for EST or nucleotide sequence function prediction. Furthermore, we developed for rapid mapping an enhanced sequence alignment algorithm which reassembles and evaluates high scoring pairs provided from the BLAST algorithm. Rapid assembly on and replacement of the template genome by sequence reads or mapped ESTs is achieved. This is illustrated (i) by data from Staphylococci as well as from a Blattabacteria sequencing effort, (ii) mapping single cell sequencing reads is shown for poribacteria to sister phylum representative Rhodopirellula Baltica SH1. The algorithm has been implemented in a web-server accessible at http://jane.bioapps.biozentrum.uni-wuerzburg.de. CONCLUSION: Rapid prokaryotic EST mapping or mapping of sequence reads is achieved applying JANE even without knowing the cognate genome sequence.


Assuntos
Biologia Computacional/métodos , Etiquetas de Sequências Expressas , Genoma , Análise de Sequência de DNA/métodos , Software , Sequência de Bases , Bases de Dados Genéticas , Internet , Interface Usuário-Computador
16.
An Pediatr (Engl Ed) ; 90(5): 272-279, 2019 May.
Artigo em Espanhol | MEDLINE | ID: mdl-29871841

RESUMO

INTRODUCTION: The health-related quality of life (HRQoL) questionnaire is important in order to assess the effects of therapeutic intervention. The aim of this study is to analyse HRQoL, comparing cases of attention deficit hyperactivity disorder (ADHD) treated with methylphenidate (ADHD-T), untreated cases (ADHD-N), and controls. MATERIAL AND METHODS: The study included a sample of 228 participants between 8 and 14 years old (114 controls, 57 ADHD-T, and 57 ADHD-N). Consecutive sampling was used in ADHD according to DSM-IV criteria (ADHD Rating Scales IV), and random sampling of controls matched by gender and age. The evaluation of HRQoL was made by using KIDSCREEN-52 parent version. RESULTS: The intensity of ADHD symptoms is significantly lower in ADHD-T than in ADHD-N. There is a moderate significant correlation between greater intensity of ADHD symptoms and worse HRQoL. ADHD cases have significantly worse HRQoL than controls on psychic well-being, mood, relationship with parents and friends, school environment, and social acceptance. The cases of ADHD-T have significantly better HRQoL than ADHD-N in the school dimension, but do not differ significantly in other dimensions of KIDSCREEN-52. CONCLUSIONS: It would be advisable that the treatment of ADHD integrates multi-dimensional therapeutic models that improve the basic symptoms of the disorder, as well as the HRQoL.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Metilfenidato/uso terapêutico , Qualidade de Vida , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Inquéritos e Questionários , Resultado do Tratamento
17.
Environ Microbiol ; 10(12): 3417-22, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19025557

RESUMO

Blattabacteria are intracellular endosymbionts of cockroaches and primitive termites that belong to the class Flavobacteria and live only in specialized cells in the abdominal fat body of their hosts. In the present study we determined genome sizes as well as genome copy numbers for the endosymbionts of three cockroach species, Blattella germanica, Periplaneta americana and Blatta orientalis. The sole presence of blattabacteria in the fat body was demonstrated by rRNA-targeting techniques. The genome sizes of the three blattabacteria were determined by pulsed field gel electrophoresis. The resulting total genome sizes for the three symbionts were all approximately 650 +/- 15 kb. Comparison of the genome sizes with those of free-living Bacteroidetes shows extended reduction, as occurs in other obligatory insect endosymbionts. Genome copy numbers were determined based on cell counts and determination of DNA amounts via quantitative PCR. Values between 10.2 and 18.3 and between 323 and 353 were found for the symbionts of P. americana and B. orientalis respectively. Polyploidy in intracellular bacteria may play a significant role in the genome reduction process.


Assuntos
Bacteroidetes/genética , Blattellidae/microbiologia , Baratas/microbiologia , Genoma Bacteriano , Periplaneta/microbiologia , Animais , DNA Bacteriano/genética , Eletroforese em Gel de Campo Pulsado , Corpo Adiposo/microbiologia , Hibridização In Situ
18.
Gac Sanit ; 32 Suppl 1: 32-40, 2018 10.
Artigo em Espanhol | MEDLINE | ID: mdl-30274747

RESUMO

Participation is a process that requires the involvement of the policy makers, managers, technicians and staff of the institutions, and of citizens, as well as intersectoral and interdisciplinary action. To generate transformative changes, an infrastructure that encourages participation and planned action is required, and that recognises all the actors in the process. It takes time and commitment to ensure continuity through the joint production of actions, hence the importance of consolidating participatory projects that continue beyond political changes making public services sustainable. Training, the appropriate use of participation tools and a horizontal policy of delegated power are essential to ensure participation. Surveys, sociograms, flowcharts, health assets mapping, participatory budgets and participatory evaluation matrices are some of the tools that can be chosen, depending on the type of subjects addressed, the time and resources available, the characteristics of the participating population and territory, as well as determining the use that will be made of the information generated for the next phase. Participation tools are useful for citizens and professionals to analyze, understand, debate and decide collectively how to improve living conditions and environments. Over the past decade, social networks in the virtual environment have generated new trends in mass participation, which are self-managed by citizens.


Assuntos
Participação da Comunidade/métodos , Humanos , Modelos Organizacionais , Relatório de Pesquisa , Sociedades Médicas , Espanha
19.
Psicothema ; 29(1): 103-110, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28126067

RESUMO

BACKGROUND: The aim of this research is to analyze Attention Deficit Hyperactivity Disorder Rating Scales IV (ADHD RS-IV) criteria validity and its clinical usefulness for the assessment of Attention Deficit Hyperactivity Disorder (ADHD) as a function of assessment method and age. METHODOLOGY: A sample was obtained from an epidemiological study (n = 1095, 6-16 years). Clinical cases of ADHD (ADHD-CL) were selected by dimensional ADHD RS-IV and later by clinical interview (DSM-IV). ADHD-CL cases were compared with four categorical results of ADHD RS-IV provided by parents (CATPA), teachers (CATPR), either parents or teachers (CATPAOPR) and both parents and teachers (CATPA&PR). Criterion validity and clinical usefulness of the answer modalities to ADHD RS-IV were studied. RESULTS: ADHD-CL rate was 6.9% in childhood, 6.2% in preadolescence and 6.9% in adolescence. Alternative methods to the clinical interview led to increased numbers of ADHD cases in all age groups analyzed, in the following sequence: CATPAOPR> CATPRO> CATPA> CATPA&PR> ADHD-CL. CATPA&PR was the procedure with the greatest validity, specificity and clinical usefulness in all three age groups, particularly in the childhood. CONCLUSIONS: Isolated use of ADHD RS-IV leads to an increase in ADHD cases compared to clinical interview, and varies depending on the procedure used.


Assuntos
Fatores Etários , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Escalas de Graduação Psiquiátrica , Avaliação de Sintomas/métodos , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Criança , Escolaridade , Feminino , Humanos , Entrevista Psicológica , Masculino , Pais , Prevalência , Estudos de Amostragem , Ensino
20.
Rev. cuba. med ; 61(2): e2583, abr.-jun. 2022. tab, graf
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1408990

RESUMO

Introducción: Al día de hoy no se ha alcanzado un consenso sobre el mejor enfoque para realizar el tamizaje y la detección precoz del Cáncer de Próstata (CaP), en la población. No obstante, hay programas que recomiendan la utilización de la prueba de antígeno prostático específico rápida para la detección de CaP sin un análisis de correlación frente a la prueba sérica. Objetivo: Identificar la correlación entre las pruebas de antígeno prostático específico rápida y sérica, en la población mexicana. Métodos: Se realizó un estudio descriptivo, transversal y retrospectivo, bajo un muestreo no probabilístico por conveniencia. En el período comprendido entre el 25 de mayo al 13 de julio de 2017. Se calcularon los coeficientes de correlación punto biserial (r pb ) y phi (r phi ). Resultados: Se incluyeron 1 635 registros, principalmente de la Ciudad de México y del Estado de México (n= 1 398; 85,5 por ciento, IC95 por ciento 81-89,9). La edad promedio fue de 51 años (DE= 7,68). El valor promedio de antígeno prostático sérico fue de 1,49 ng/mL (DE= 1,91). La proporción de hombres con una prueba rápida positiva (n=60; 3,7 por ciento; IC95 por ciento 2,9-4,6) fue menor (p= 0,0415) en comparación con la proporción de pacientes con una prueba sérica ≥ 4 ng/mL (n=85; 5,2 por ciento; IC95 por ciento 4,1-6,3). El número de casos dobles negativos fue de 1 530 (93,6 por ciento; IC95 por ciento 92,3-94,6) y de dobles positivos fue de 40 (2,4 por ciento; IC95 por ciento1,7-3,2). Los coeficientes de correlación punto biserial y phi mostraron una correlación baja entre la prueba rápida y la prueba sérica de antígeno prostático (rpb= 0,469; p < 0,001; r2= 0,2199 y r ph i= 0,540; p < 0,001; r2= 0,2916). Conclusiones: La prueba de antígeno prostático específico rápida es una herramienta conveniente para los programas de detección de alteración prostática en unidades médicas del primer nivel de atención, donde la prueba sérica no se puede realizar, al ser una prueba con una baja sensibilidad y con un bajo coeficiente de correlación respecto de la prueba de antígeno prostático específico sérica, esto es un punto importante que debe considerarse al diseñar programas de detección oportuna de cáncer de próstata(AU)


Introduction: To date, no consensus has been reached on the best approach for screening and early detection of Prostate Cancer (PCa) in the population. However, there are programs recommending the use of the rapid prostate-specific antigen test for the detection of PCa without a correlation analysis versus the serum test. Objective: To identify the correlation between rapid and serum prostate specific antigen tests in the Mexican population. Methods: A descriptive, cross-sectional and retrospective study was carried out, under a non-probabilistic convenience sampling from May 25 to July 13, 2017. The correlation coefficients of point biserial (rpb) and phi (rphi) were calculated. Results: One thousand six hundred thirty five (1,635) records were included, mainly from Mexico City and the State of Mexico (n= 1,398; 85.5 percent, 95 percent CI 81-89.9). The average age was 51 years (SD= 7.68). The mean value of serum prostate antigen was 1.49 ng/ml (SD= 1.91). The proportion of men with positive rapid test (n=60; 3.7 percent; 95 percent CI 2.9-4.6) was lower (p= 0.0415) compared to the proportion of patients with a serum test ≥ 4 ng/ml (n= 85; 5.2 percent; 95 percent CI 4.1-6.3). The number of double negative cases was 1,530 (93.6 percent; CI95 percent 92.3-94.6) and of double positives was 40 (2.4 percent; CI95 percent 1.7-3.2). The point biserial and phi correlation coefficients showed low correlation between the rapid test and the serum prostate antigen test (rpb= 0.469; p < 0.001; r2= 0.2199 and rphi= 0.540; p < 0.001; r2= 0. 2916). Conclusions: The rapid prostate-specific antigen test is a convenient tool for prostatic alteration detection programs in primary care medical units, where the serum test cannot be performed, however, as it is a test with low sensitivity and with low correlation coefficient with respect to serum prostate-specific antigen testing, this is an important point to consider when designing prostate cancer early detection programs(AU)


Assuntos
Humanos , Masculino , Neoplasias da Próstata/diagnóstico , Programas de Rastreamento , Antígeno Prostático Específico , Epidemiologia Descritiva , Estudos Transversais , Estudos Retrospectivos , México
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