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1.
Biochem Soc Trans ; 52(1): 455-464, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38372373

RESUMO

Transcription represents a central aspect of gene expression with RNA polymerase machineries (RNA Pol) driving the synthesis of RNA from DNA template molecules. In eukaryotes, a total of three RNA Pol enzymes generate the plethora of RNA species and RNA Pol II is the one transcribing all protein-coding genes. A high number of cis- and trans-acting factors orchestrates RNA Pol II-mediated transcription by influencing the chromatin recruitment, activation, elongation, and/or termination steps. The levels of DNA accessibility, defining open-euchromatin versus close-heterochromatin, delimits RNA Pol II activity as well as the encounter with other factors acting on chromatin such as the DNA replication or DNA repair machineries. The stage of the cell cycle highly influences RNA Pol II activity with mitosis representing the major challenge. In fact, there is a massive inhibition of transcription during the mitotic entry coupled with chromatin dissociation of most of the components of the transcriptional machinery. Mitosis, as a consequence, highly compromises the transcriptional memory and the perpetuation of cellular identity. Once mitosis ends, transcription levels immediately recover to define the cell fate and to safeguard the proper progression of daughter cells through the cell cycle. In this review, we evaluate our current understanding of the transcriptional repression associated with mitosis with a special focus on the molecular mechanisms involved, on the potential function behind the general repression, and on the transmission of the transcriptional machinery into the daughter cells. We finally discuss the contribution that errors in the inheritance of the transcriptional machinery across mitosis might play in stem cell aging.


Assuntos
Mitose , RNA Polimerase II , RNA Polimerase II/metabolismo , Transcrição Gênica , Cromatina , DNA , RNA
2.
Acta Neurochir (Wien) ; 166(1): 86, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363400

RESUMO

BACKGROUND: Pituitary adenomas (PA) are neoplasms of pituitary adenohypophyseal cell lineage, which are the third most common cause of brain tumors among adults. Due to hormone secretion, PAs are closely related to metabolic syndrome (MetS). However, the relationship between these two entities has been scarcely studied to date. PURPOSE: This paper aims to evaluate changes in the metabolic status of patients with PA before and after surgical treatment and to look for differences in metabolic outcomes among patients according to the adenoma type and the surgery success rate. METHODS: We assessed patients with PA who went through transsphenoidal surgery for its treatment, documenting metabolic parameters before and after surgery, analyzed whole sample changes, and then stratified them according to adenoma type (nonfunctioning, somatotroph, lactotroph, and corticotroph), and surgery success (total resection, near-total resection, partial resection, subtotal resection). RESULTS: A total of 214 patients were enrolled for this study. The prevalence of MetS with AACE criteria went from 51.52% before surgery to 28.99% after surgery (P < 0.001). Hyperglycemia (HG) was the most beneficial component; it went from 56% pre-surgery to 40.51% post-surgery (P = 0.03). The total resection group had the best improvement, with a significant decrease of prevalence in MetS from 83 to 16% (P < 0.001), and every component, except hypoalphalipoproteinemia (HA): obesity went from 96 to 67% (P < 0.001), arterial hypertension (AH) 59 to 24% (P < 0.001), HG 74 to 23% (P < 0.001), and hypertriglyceridemia (HTG) from 81 to 54% (P < 0.001). According to MetS prevalence, there was no difference in the improvement according to PA type. CONCLUSION: Surgical treatment in patients with PA is associated with MetS improvement.


Assuntos
Adenoma , Síndrome Metabólica , Neoplasias Hipofisárias , Adulto , Humanos , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/patologia , Síndrome Metabólica/cirurgia , Síndrome Metabólica/etiologia , Procedimentos Neurocirúrgicos/efeitos adversos , Adenoma/cirurgia , Adenoma/patologia , Seio Esfenoidal/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
3.
J Autoimmun ; 135: 102990, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36621176

RESUMO

OBJECTIVES: To characterize the splicing machinery (SM) of leukocytes from primary antiphospholipid syndrome (APS), systemic lupus erythematosus (SLE) and antiphospholipid syndrome with lupus (APS + SLE) patients, and to assess its clinical involvement. METHODS: Monocytes, lymphocytes and neutrophils from 80 patients (22 APS, 35 SLE and 23 APS + SLE) and 50 HD were purified, and 45 selected SM components were evaluated by qPCR-microfluidic array. Relationship with clinical features and underlying regulatory mechanisms were assessed. RESULTS: APS, SLE and APS + SLE leukocytes displayed significant and specific alterations in SM-components (SMC), associated with clinical features [autoimmune profiles, disease activity, lupus nephritis (LN), and CV-risk markers]. A remarkable relationship among dysregulated SMC in monocytes and the presence of LN in SLE was highlighted, revealing a novel pathological mechanism, which was further explored. Immunohistology analysis of renal biopsies highlighted the pathological role of the myeloid compartment in LN. Transcriptomic analysis of monocytes from SLE-LN(+) vs SLE-LN(-) identified 271 genes differentially expressed, mainly involved in inflammation and IFN-signaling. Levels of IFN-related genes correlated with those of SMC in SLE-LN(+). These results were validated in two external SLE-LN(+) datasets of whole-blood and kidney biopsies. In vitro, SLE-LN(+)-serum promoted a concomitant dysregulation of both, the IFN signature and several SMC, further reversed by JAKinibs treatment. Interestingly, IFNs, key inflammatory cytokines in SLE pathology, also altered SMC. Lastly, the over/down-expression of selected SMC in SLE-monocytes reduced the release of inflammatory cytokines and their adhesion capacity. CONCLUSION: Overall, we have identified, for the first time, a specific alteration of SMC in leukocytes from APS, SLE and APS + SLE patients that would be responsible for the development of distinctive clinical profiles.


Assuntos
Síndrome Antifosfolipídica , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Inflamação , Citocinas
4.
Int J Neurosci ; : 1-10, 2023 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-37060337

RESUMO

BACKGROUND: Pituitary adenomas are benign tumors located in the anterior hypophysis. Its appearance is associated with the development of parameters related to metabolic syndrome; therefore, surgical treatment could reduce associated morbimortality. METHODS: Pre- and post-surgical MRI, using the Hardy-Wilson and Knosp classification, and clinical data according to the American Association of Clinical Endocrinology (AACE) criteria for metabolic syndrome: all the patients were followed-up until 208.57 days were reviewed on 217 consecutive patients with pituitary surgery. RESULTS: Seventy-four patients were included in this study. There was a significant reduction in tumor size in mm3 [average pre- and post-surgery respectively: 12,362 mm3 (±12,397); 3,910 mm3 (±7,160)], (p < 0.0001). This was confirmed by the Hardy-Wilson and Knosp classification, where most patients went from grade IV C (33.7%) to grade 0 (12.1%), IA (20.2%), IIB (21.36%), and IIC (16.2%); as well as from grade 4 (24.3%) to grade 0 (45.9%), respectively. After surgery, there were statistically significant reductions in total serum levels of glucose [average pre- and post-surgery, respectively: 116 mg/dL (±26.9); 90 mg/dL (±10.2)], (p < 0.001), triglycerides [average pre- and post-surgery, 240 mg/dL (±102); 171 mg/dL (±60.5)], (p = 0.001); and HDL-c [average pre- and post-surgery, respectively: 39 mg/dL (±11.8); 44.6 mg/dL (±8.4)], (p = 0.029). The other parameters remained unchanged. CONCLUSION: This is the first study to demonstrate the relationship between the presence of pituitary adenoma and significative changes in serum glucose, triglycerides and c-HDL related to metabolic syndrome.

5.
Curr Psychol ; 42(9): 7466-7474, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34305365

RESUMO

Loneliness is a common social phenomenon across countries with negative effects in health. Thus, the measurement of loneliness is of paramount importance. The Three-Item Loneliness Scale (TILS) was designed to be used in large-population surveys as a quick measure of loneliness. The aim of this study is to provide a Spanish validation of the TILS. A representative sample of the Spanish population (N = 1951) was used. We analysed the psychometric properties, factor structure, and distribution demographics characteristics of the Spanish TILS. Analyses showed differences regarding age, gender, educational level, employment status, household composition and annual gross income in line with previous literature. The confirmatory factor analysis revealed a unifactorial structure, with significant moderate correlations between the TILS and depression, anxiety, paranoia and well-being, and mild significant correlations with belongingness and mistrust. The internal consistency of the Spanish TILS was good (α = 0.82). Our study indicates that the TILS is a valid and reliable measure of loneliness in the Spanish population. Loneliness is a modern epidemic and a precursor of mental and health problems that reduced the quality of life. Therefore, it is important to have reliable measures of this phenomenon.

6.
Ann Oncol ; 30(6): 927-933, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30903140

RESUMO

BACKGROUND: HER2-positive (+) breast cancers, defined by HER2 overexpression and/or amplification, are often addicted to HER2 to maintain their malignant phenotype. Yet, some HER2+ tumors do not benefit from anti-HER2 therapy. We hypothesize that HER2 amplification levels and PI3K pathway activation are key determinants of response to HER2-targeted treatments without chemotherapy. PATIENTS AND METHODS: Baseline HER2+ tumors from patients treated with neoadjuvant lapatinib plus trastuzumab [with endocrine therapy for estrogen receptor (ER)+ tumors] in TBCRC006 (NCT00548184) were evaluated in a central laboratory for HER2 amplification by fluorescence in situ hybridization (FISH) (n = 56). HER2 copy number (CN) and FISH ratios, and PI3K pathway status, defined by PIK3CA mutations or PTEN levels by immunohistochemistry were available for 41 tumors. Results were correlated with pathologic complete response (pCR; no residual invasive tumor in breast). RESULTS: Thirteen of the 56 patients (23%) achieved pCR. None of the 11 patients with HER2 ratio <4 and/or CN <10 achieved pCR, whereas 13/45 patients (29%) with HER2 ratio ≥4 and/or CN ≥10 attained pCR (P = 0.0513). Of the 18 patients with tumors expressing high PTEN or wild-type (WT) PIK3CA (intact PI3K pathway), 7 (39%) achieved pCR, compared with 1/23 (4%) with PI3K pathway alterations (P = 0.0133). Seven of the 16 patients (44%) with HER2 ratio ≥4 and intact PI3K pathway achieved pCR, whereas only 1/25 (4%) patients not meeting these criteria achieved pCR (P = 0.0031). CONCLUSIONS: Our findings suggest that there is a clinical subtype in breast cancer with high HER2 amplification and intact PI3K pathway that is especially sensitive to HER2-targeted therapies without chemotherapy. A combination of HER2 FISH ratio and PI3K pathway status warrants validation to identify patients who may be treated with HER2-targeted therapy without chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Receptor ErbB-2/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Classe I de Fosfatidilinositol 3-Quinases/genética , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Feminino , Seguimentos , Amplificação de Genes , Humanos , Hibridização in Situ Fluorescente , Lapatinib/administração & dosagem , Terapia Neoadjuvante , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Prognóstico , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/genética , Indução de Remissão , Trastuzumab/administração & dosagem
7.
J Intern Med ; 284(1): 61-77, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29532531

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) patients are at increased risk of insulin resistance (IR); however, the specific mechanisms mediating this association are currently unknown. OBJECTIVE: To investigate whether the inflammatory activity associated with RA accounts for the observed defective glucose metabolism and lipid metabolism in these patients. METHODS: We followed two main strategies: (i) extensive metabolic profiling of a RA cohort of 100 patients and 50 healthy control subjects and (ii) mechanistic studies carried out in both a collagen-induced arthritis mouse model and 3T3-L1 adipocytes treated with conditioned serum from RA patients. RESULTS: Following the exclusion of obese and diabetic subjects, data from RA patients demonstrated a strong link between the degree of systemic inflammation and the development of IR. These results were strengthened by the observation that induction of arthritis in mice resulted in a global inflammatory state characterized by defective carbohydrate and lipid metabolism in different tissues. Adipose tissue was most susceptible to the RA-induced metabolic alterations. These metabolic effects were confirmed in adipocytes treated with serum from RA patients. CONCLUSIONS: Our results show that the metabolic disturbances associated with RA depend on the degree of inflammation and identify inflammation of adipose tissue as the initial target leading to IR and the associated molecular disorders of carbohydrate and lipid homeostasis. Thus, we anticipate that therapeutic strategies based on tighter control of inflammation and flares could provide promising approaches to normalize and/or prevent metabolic alterations associated with RA.


Assuntos
Artrite Reumatoide/sangue , Glicemia/metabolismo , Inflamação/sangue , Lipídeos/sangue , Células 3T3-L1 , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Adulto , Idoso , Animais , Artrite Experimental/sangue , Estudos de Casos e Controles , Doença Crônica , Estudos de Coortes , Feminino , Humanos , Resistência à Insulina/fisiologia , Masculino , Camundongos , Pessoa de Meia-Idade
8.
J Cell Biochem ; 118(12): 4468-4478, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28464260

RESUMO

Extracellular nucleotides and nucleosides have emerged as important elements regulating tissue homeostasis. Acting through specific receptors, have the ability to control gene expression patterns to direct cellular fate. We observed that SKOV-3 cells express the ectonucleotidases: ectonucleotide pyrophosphatase 1 (ENPP1), ecto-5'-nucleotidase (NT5E), and liver alkaline phosphatase (ALPL). Strikingly, in pulse and chase experiments supplemented with ATP, SKOV-3 cells exhibited low catabolic efficiency in the conversion of ADP into AMP, but they were efficient in converting AMP into adenosine. Since these cells release ATP, we proposed that the conversion of ADP into AMP is a regulatory node associated with the migratory ability and the mesenchymal characteristics shown by SKOV-3 cells under basal conditions. The landscape of gene expression profiles of SKOV-3 cell cultures treated with apyrase or adenosine demonstrated similarities (e.g., decrease FGF16 transcript) and differences (e.g., the negative regulation of Wnt 2, and 10B by adenosine). Thus, in SKOV-3 we analyzed the migratory ability and the expression of epithelium to mesenchymal transition (EMT) markers in response to apyrase. Apyrase-treatment favored the epithelial-like phenotype, as revealed by the re-location of E-cadherin to the cell to cell junctions. Pharmacological approaches strongly suggested that the effect of Apyrase involved the accumulation of extracellular adenosine; this notion was strengthened when the incubation of the SKOV-3 cell with α,ß-methylene ADP (CD73 inhibitor) or adenosine deaminase was sufficient to abolish the effect of apyrase on cell migration. Overall, adenosine signaling is a fine tune mechanism in the control of cell phenotype in cancer. J. Cell. Biochem. 118: 4468-4478, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Movimento Celular/efeitos dos fármacos , Neoplasias Ovarianas/metabolismo , Purinas/farmacologia , Apirase/metabolismo , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Humanos , Proteínas de Neoplasias/metabolismo , Purinas/metabolismo
9.
Appl Microbiol Biotechnol ; 101(22): 8279-8291, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28990140

RESUMO

The production of acetone, butanol and ethanol by fermentation of renewable biomass has potential to become a valuable industrial process. Mechanisms of solvent production and sporulation involve some common regulators in some ABE-producing clostridia, although details of the links between the pathways are not clear. In this study, we compare a wild-type (WT) Clostridium beijerinckii NRRL B-598 with its mutant strain OESpo0A, in which the gene encoding Spo0A, an important regulator of both sporulation and solventogenesis, is overexpressed in terms of solvent and acid production. We also compare morphologies during growth on two different media: TYA broth, where the WT culture sporulates, and RCM, where the WT culture does not. In addition, RT-qPCR-based analysis of expression profiles of spo0A, spoIIE, sigG, spoVD, ald and buk1 genes involved in sporulation or solvent production in these strains, were compared. The OESpo0A mutant did not produce spores and butanol titre was lower compared to the WT, but increased amounts of butyric acid and ethanol were produced. The gene spo0A had high levels of expression in the WT under non-sporulating culture conditions while other selected genes for sporulation factors were downregulated significantly. Similar observations were obtained for OESpo0A where spo0A overexpression and downregulation of other sporulation genes were demonstrated. Higher expression of spo0A led to higher expression of buk1 and ald, which could confirm the role of spo0A in activation of the solventogenic pathway, although solvent production was not affected significantly in the WT and was weakened in the OESpo0A mutant.


Assuntos
Acetona/metabolismo , Proteínas de Bactérias/genética , Clostridium beijerinckii/genética , Solventes/metabolismo , Esporos Bacterianos/crescimento & desenvolvimento , Butanóis/metabolismo , Clostridium beijerinckii/metabolismo , Etanol/metabolismo , Fermentação , Regulação Bacteriana da Expressão Gênica , Mutação , Reação em Cadeia da Polimerase , Fatores de Transcrição/genética
11.
Med Oral Patol Oral Cir Bucal ; 22(4): e425-e431, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28578367

RESUMO

BACKGROUND: The validity of the surveys on self-reported smoking status is often questioned because smokers underestimate cigarette use and deny the habit. It has been suggested that self-report should be accompanied by cotinine test. This report evaluates the usefulness of serum cotinine test to assess the association between smoking and periodontal status in a study with a large sample population to be used in studies with other serum markers in epidemiologic and periodontal medicine researches. MATERIAL AND METHODS: 578 patients who were part of a multicenter study on blood biomarkers were evaluated about smoking and its relation to periodontal disease. Severity of periodontal disease was determinate using clinical attachment loss (CAL). Smoking was assessed by a questionnaire and a blood sample drawn for serum cotinine determination. RESULTS: The optimal cut-off point for serum cotinine was 10 ng/ml. Serum cotinine showed greater association with severity of CAL than self-report for mild-moderate CAL [OR 2.03 (CI95% 1.16-3.53) vs. OR 1.08 (CI95% 0.62-1.87) ] advanced periodontitis [OR 2.36 (CI95% 1.30- 4.31) vs. OR 2.06 (CI95% 0.97-4.38) ] and extension of CAL > 3 mm [ OR 1.78 (CI95% 1.16-1.71) vs. 1.37 (CI95% 0.89-2.11)]. When the two tests were evaluated together were not shown to be better than serum cotinine test. CONCLUSIONS: Self-reported smoking and serum cotinine test ≥ 10ng/ml are accurate ,complementary and more reliable methods to assess the patient's smoking status and could be used in studies evaluating serum samples in large population and multicenter studies. CLINICAL RELEVANCE: The serum cotinine level is more reliable to make associations with the patient's periodontal status than self-report questionnaire and could be used in multicenter and periodontal medicine studies.


Assuntos
Cotinina/sangue , Doenças Periodontais/sangue , Fumar/sangue , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Periodontais/complicações , Reprodutibilidade dos Testes , Autorrelato
12.
J Med Primatol ; 45(2): 92-102, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26956694

RESUMO

BACKGROUND: Synapses loss during aging is associated to neurophysiologic alterations that impair organism's health span, thus making the study and prevention of sensory decline relevant for healthy aging and welfare. Therefore the aim of this study was to obtain normative data related to the electrophysiological responses of the different neurosensory components in the visual, auditory and somatosensory pathways in healthy geriatric rhesus monkeys in captivity. METHODS: Twenty-four rhesus monkeys were divided in two groups: (i) Geriatric monkeys, 20-30 years of age, and (ii) Young monkeys, 7 years of age. Evoked potentials were obtained from the visual, auditory and somatosensory pathways. RESULTS: Regardless the sensory pathways evaluated, a significant delay in nerve conduction was observed in the geriatric group in comparison to the young group. CONCLUSIONS: Evoked potentials allowed identifying changes generated during aging in rhesus monkeys and normative data for this species were obtained.


Assuntos
Envelhecimento/fisiologia , Vias Auditivas/fisiologia , Macaca mulatta/fisiologia , Distúrbios Somatossensoriais/veterinária , Vias Visuais/fisiologia , Animais , Condutividade Elétrica , Potenciais Evocados Auditivos do Tronco Encefálico , Potenciais Somatossensoriais Evocados , Potenciais Evocados Visuais , Feminino , Masculino , Condução Nervosa/fisiologia , Distúrbios Somatossensoriais/fisiopatologia , Nervo Tibial/fisiologia
13.
Appl Microbiol Biotechnol ; 100(12): 5427-36, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26852409

RESUMO

Random mutagenesis and genome shuffling was applied to improve solvent tolerance and isopropanol/butanol/ethanol (IBE) production in the strictly anaerobic bacteria Clostridium beijerinckii DSM 6423. Following chemical mutagenesis with N-methyl-N-nitro-N-nitrosoguanidine (NTG), screening of putatively improved strains was done by submitting the mutants to toxic levels of inhibitory chemicals or by screening for their tolerance to isopropanol (>35 g/L). Suicide substrates, such as ethyl or methyl bromobutyrate or alcohol dehydrogenase inhibitors like allyl alcohol, were tested and, finally, 36 mutants were isolated. The fermentation profiles of these NTG mutant strains were characterized, and the best performing mutants were used for consecutive rounds of genome shuffling. Screening of strains with further enhancement in isopropanol tolerance at each recursive shuffling step was then used to spot additionally improved strains. Three highly tolerant strains were finally isolated and able to withstand up to 50 g/L isopropanol on plates. Even if increased tolerance to the desired end product was not always accompanied by higher production capabilities, some shuffled strains showed increased solvent titers compared to the parental strains and the original C. beijerinckii DSM 6423. This study confirms the efficiency of genome shuffling to generate improved strains toward a desired phenotype such as alcohol tolerance. This tool also offers the possibility of obtaining improved strains of Clostridium species for which targeted genetic engineering approaches have not been described yet.


Assuntos
2-Propanol/farmacologia , Clostridium beijerinckii/efeitos dos fármacos , Clostridium beijerinckii/genética , Clostridium beijerinckii/metabolismo , Embaralhamento de DNA , Mutagênese , 2-Propanol/isolamento & purificação , Reatores Biológicos , Clostridium beijerinckii/isolamento & purificação , Tolerância a Medicamentos , Fermentação , Engenharia Genética/métodos , Solventes
14.
Rheumatol Int ; 36(2): 231-41, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26494567

RESUMO

Biological drugs have proven efficacy and effectiveness in treatment of rheumatoid arthritis (RA), although none has been shown to be superior. Few studies have evaluated the cost-effectiveness of biological drugs in real-life clinical conditions. The objective of this study was to compare the cost-effectiveness of infliximab, etanercept and adalimumab in achieving clinical remission (DAS28 < 2.6) when used as initial biological therapy. Patients were diagnosed with RA who began treatment with infliximab, etanercept or adalimumab in the Reina Sofia Hospital (Cordoba, Spain) between January 1, 2007, and December 31, 2012. Effectiveness was measured as the percentage of patients who achieved clinical remission after 2 years. The cost analysis considered the use of direct health resources (perspective of the healthcare system). Cost-effectiveness was calculated by dividing the total mean cost of each treatment by the percentage of patients who achieved remission. One hundred and thirty patients were included: 55 with infliximab, 44 with adalimumab and 31 with etanercept. After 2 years, 45.2 % of patients with adalimumab achieved clinical remission, versus 29.1 % with infliximab (p = 0.133) and 22.7 % with etanercept (p = 0.040), with no differences between etanercept and infliximab (p = 0.475). The average total cost at 2 years was €29,858, €25,329 and €23,309 for adalimumab, infliximab and etanercept, respectively, while the mean cost (95 %CI) to achieve remission was €66,057 (48,038­84,076), €87,040 (78,496­95,584) and €102,683 (94,559­110,807), respectively. Adalimumab was more efficient than etanercept (p < 0.001) and infliximab (p = 0.026), with no differences between etanercept and infliximab (p = 0.086). Adalimumab was the most cost-effective treatment in achieving clinical remission in real-life clinical conditions in RA patients during the study period.


Assuntos
Adalimumab/economia , Adalimumab/uso terapêutico , Antirreumáticos/economia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/economia , Custos de Medicamentos , Etanercepte/economia , Etanercepte/uso terapêutico , Infliximab/economia , Infliximab/uso terapêutico , Adalimumab/efeitos adversos , Adulto , Idoso , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Redução de Custos , Análise Custo-Benefício , Etanercepte/efeitos adversos , Feminino , Humanos , Infliximab/efeitos adversos , Masculino , Pessoa de Meia-Idade , Modelos Econômicos , Sistema de Registros , Indução de Remissão , Espanha , Fatores de Tempo , Resultado do Tratamento
15.
Rheumatol Int ; 36(12): 1627-1632, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27778067

RESUMO

To analyse the cost-effectiveness, in daily clinical practice, of the strategy of treating to the target of clinical remission (CR) in patients with established rheumatoid arthritis (RA), after 2 years of treatment with biological therapy. Adult patients with established RA were treated with biological therapy and followed up for 2 years by a multidisciplinary team responsible for their clinical management. Treatment effectiveness was evaluated by the DAS28 score. The direct costs incurred during this period were quantified from the perspective of the healthcare system. We calculated the cost-effectiveness of obtaining a DAS28 < 2.6, considered as CR. The study included 144 RA patients treated with biological therapies. After 2 years of treatment, 32.6% of patients achieved CR. The mean cost of achieving CR at 2 years was 79,681 ± 38,880 euros. The strategy of treatment to the target of CR is considered the most effective, but in actual clinical practice in patients with established RA, it has a high cost.


Assuntos
Antirreumáticos/economia , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/economia , Análise Custo-Benefício , Adulto , Antirreumáticos/uso terapêutico , Artrite Reumatoide/economia , Produtos Biológicos/uso terapêutico , Bases de Dados Factuais , Feminino , Custos de Cuidados de Saúde , Humanos , Masculino , Metotrexato/economia , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Indução de Remissão , Índice de Gravidade de Doença , Sulfassalazina/economia , Sulfassalazina/uso terapêutico , Resultado do Tratamento
16.
BMC Musculoskelet Disord ; 17(1): 382, 2016 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-27596243

RESUMO

BACKGROUND: Several measurements are often used in daily clinical practice in the assessment of Ankylosing Spondylitis (AS) patients. The Assessment in SpondyloArthiritis International Society (ASAS) recommend in its core set: chest expansion modified Schöber test, Occiput to wall distance, lateral lumbar flexion, cervical rotation and The Bath Ankylosing Spondylitis Metrology Index (BASMI). BASMI also includes five measurements, some of them recommended by ASAS. Three versions of BASMI have been published with different scales and intervals for each component of the index. Though studies about reliability of these measurements are needed. The aim of this study was to analyze inter-rater reliability of recommended spinal mobility measures in AS. METHODS: We examined reproducibility of spinal mobility measurements on 33 AS patients performed by two experienced rheumatologists in the same day. Descriptive statistics, Intraclass Correlation Coefficients (ICC), and Smallest Detectable Difference (SDD) using the Bland-Altman criteria were obtained for all the measurements. RESULTS: Chest expansion showed the lowest value of ICC (0.66) and occiput-wall the highest (0.97). SDD was 2.43 units for BASMI2 and 1.27 units for BASMI10. CONCLUSIONS: Reliability according to ICC was moderate to high in all measurements. BASMI10, instead BASMI2, must be used: measurements used to calculate are the same but there is better reliability. Inter-rater variation, expressed as SDD, must be taken in account: smaller improvements do not demonstrate the efficacy of treatment because they can be due to experimental error and not to the treatment itself.


Assuntos
Espondilite Anquilosante/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Exame Físico/métodos , Espondilite Anquilosante/fisiopatologia
17.
Rev Sci Tech ; 35(3): 845-862, 2016 Dec.
Artigo em Espanhol, Inglês | MEDLINE | ID: mdl-28332645

RESUMO

The risk of zoonoses spreading from birds to humans is lower, quantitatively speaking, than the risk of transmission between other host groups, because the two taxonomic groups share fewer pathogens. Nevertheless, birds have a number of epidemiological characteristics that make them extremely important hosts in the transmission and maintenance of zoonoses, including their susceptibility to pathogens that are extremely hazardous to humans (such as highly pathogenic avian influenza virus, West Nile virus and Chlamydia psittaci) and their ability to travel long distances, especially in the case of migratory birds. The fact that the human diet includes poultry products (meat, eggs and their by-products) also means that most human cases of foodborne zoonoses are infections of avian origin. Lastly, close contact between humans and pet birds or urban birds leads to interactions of public health concern. This article sets out to describe the main factors that determine the role of birds in the epidemiology of zoonotic infections.


Le risque que les oiseaux transmettent des zoonoses à l'homme est moins élevé, au plan quantitatif, qu'entre hôtes d'autres catégories, car le nombre d'agents pathogènes affectant à la fois ces deux groupes taxonomiques est moindre. Cependant, certaines particularités épidémiologiques des oiseaux leur font jouer un rôle d'hôtes importants dans la persistance et la transmission de zoonoses : d'une part, leur sensibilité à des agents pathogènes dangereux pour l'homme (par exemple, le virus de l'influenza aviaire hautement pathogène, le virus de West Nile, Chlamydia psittaci) et, d'autre part, leur capacité à se déplacer sur de longues distances, notamment dans le cas des oiseaux migrateurs. En outre, les produits avicoles faisant partie des denrées alimentaires consommées par l'homme (viande de volaille, oeufs et produits dérivés), la majorité des cas de zoonoses d'origine alimentaire diagnostiqués chez l'homme sont d'origine aviaire. Enfin, les contacts étroits entre les humains et leurs oiseaux de compagnie ou avec des oiseaux des villes entraînent des interactions qui sont à prendre en compte en santé publique. Les auteurs décrivent les principales caractéristiques épidémiologiques des oiseaux jugées déterminantes par rapport aux infections zoonotiques.


El riesgo de transmisión de zoonosis de aves a humanos es menor, cuantitativamente hablando, que el que tiene lugar entre otros grupos de hospedadores, debido a que estos dos grupos taxonómicos comparten un menor número de agentes patógenos. No obstante, algunas particularidades epidemiológicas de las aves las convierten en hospedadores de gran importancia en el mantenimiento y la transmisión de zoonosis, como su capacidad de contraer infecciones por agentes patógenos peligrosos para los humanos (como el virus de la influenza aviar altamente patógena, el virus del Nilo Occidental o Chlamydia psittaci, entre otros) así como su gran capacidad de desplazamiento, especialmente en el caso de las aves migratorias. Además, el hecho de que la alimentación humana incluya productos avícolas (carne y huevos y productos derivados) hace que la mayoría de casos de zoonosis de origen alimentario diagnosticados en humanos sean infecciones de origen aviar. Por último, el estrecho contacto entre humanos y mascotas aviares o aves urbanas conlleva interacciones de interés para la salud pública. Este trabajo pretende describir los principales determinantes epidemiológicos de las aves en relación con las infecciones zoonósicas.


Assuntos
Zoonoses/epidemiologia , Zoonoses/transmissão , Migração Animal , Animais , Animais Selvagens , Aves , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/transmissão , Dieta , Doenças Transmitidas por Alimentos/epidemiologia , Humanos , Animais de Estimação , Produtos Avícolas , Fatores de Risco
18.
Appl Microbiol Biotechnol ; 99(4): 1885-95, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25388943

RESUMO

The wine sector is actively seeking strategies and technologies that facilitate the production of wines with lower alcohol content. One of the simplest approaches to achieve this aim would be the use of wine yeast strains which are less efficient at transforming grape sugars into ethanol; however, commercial wine yeasts have very similar ethanol yields. We recently demonstrated that Metschnikowia pulcherrima AWRI1149 was able to produce wine with reduced alcohol concentration when used in sequential inoculation with a wine strain of Saccharomyces cerevisiae. Here, different inoculation regimes were explored to study the effect of yeast population dynamics and potential yeast interactions on the metabolism of M. pulcherrima AWRI1149 during fermentation of non-sterile Shiraz must. Of all inoculation regimes tested, only ferments inoculated with M. pulcherrima AWRI1149 showed reduced ethanol concentration. Population dynamics revealed the presence of several indigenous yeast species and one of these, Saccharomyces uvarum (AWRI 2846), was able to produce wine with reduced ethanol concentration in sterile conditions. Both strains however, were inhibited when a combination of three non-Saccharomyces strains, Hanseniaspora uvarum AWRI863, Pichia kluyveri AWRI1896 and Torulaspora delbrueckii AWRI2845 were inoculated into must, indicating that the microbial community composition might impact on the growth of M. pulcherrima AWRI1149 and S. uvarum AWRI 2846. Our results indicate that mixed cultures of M. pulcherrima AWRI1149 and S. uvarum AWRI2846 enable an additional reduction of wine ethanol concentration compared to the same must fermented with either strain alone. This work thus provides a foundation to develop inoculation regimes for the successful application of non-cerevisiae yeast to the production of wines with reduced alcohol.


Assuntos
Álcoois/metabolismo , Metschnikowia/crescimento & desenvolvimento , Metschnikowia/metabolismo , Interações Microbianas , Saccharomyces/crescimento & desenvolvimento , Saccharomyces/metabolismo , Vinho/microbiologia , Fermentação , Metschnikowia/fisiologia , Dinâmica Populacional , Saccharomyces/fisiologia
19.
Ir Vet J ; 68(1): 21, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26351565

RESUMO

BACKGROUND: Laboratory diagnostic techniques able to detect Mycoplasma agalactiae are essential in contagious agalactia in dairy goats. This study was designed: 1) to determine the detection limits of PCR and culture in goat milk samples, 2) to examine the effects of experimental conditions including the DNA extraction method, PCR technique and storage conditions (fresh versus frozen stored milk samples) on these methods and 3), to establish agreement between PCR and culture techniques using milk samples from goats with mastitis in commercial dairy herds. The study was conducted both on artificially inoculated and field samples. RESULTS: Our findings indicate that culture is able to detect M. agalactiae in goat milk at lower concentrations than PCR. Qualitative detection of M.agalactiae by culture and PCR was not affected by sample freezing, though the DNA extraction method used significantly affected the results of the different PCR protocols. When clinical samples were used, both techniques showed good agreement. CONCLUSIONS: The results from this study indicate that both culture and PCR are able to detect M. agalactiae in clinical goat mastitis samples. However, in bulk tank milk samples with presumably lower M. agalactiae concentrations, culture is recommended within the first 24 h of sample collection due to its lower limit of detection. To improve the diagnostic sensitivity of PCR in milk samples, there is a need to increase the efficiency of extracting DNA from milk samples using protocols including a previous step of enzymatic digestion.

20.
Appl Environ Microbiol ; 80(5): 1670-8, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24375129

RESUMO

Over recent decades, the average ethanol concentration of wine has increased, largely due to consumer preference for wine styles associated with increased grape maturity; sugar content increases with grape maturity, and this translates into increased alcohol content in wine. However, high ethanol content impacts wine sensory properties, reducing the perceived complexity of flavors and aromas. In addition, for health and economic reasons, the wine sector is actively seeking technologies to facilitate the production of wines with lower ethanol content. Nonconventional yeast species, in particular, non-Saccharomyces yeasts, have shown potential for producing wines with lower alcohol content. These yeast species, which are largely associated with grapes preharvest, are present in the early stages of fermentation but, in general, are not capable of completing alcoholic fermentation. We have evaluated 50 different non-Saccharomyces isolates belonging to 24 different genera for their capacity to produce wine with a lower ethanol concentration when used in sequential inoculation regimes with a Saccharomyces cerevisiae wine strain. A sequential inoculation of Metschnikowia pulcherrima AWRI1149 followed by an S. cerevisiae wine strain was best able to produce wine with an ethanol concentration lower than that achieved with the single-inoculum, wine yeast control. Sequential fermentations utilizing AWRI1149 produced wines with 0.9% (vol/vol) and 1.6% (vol/vol) (corresponding to 7.1 g/liter and 12.6 g/liter, respectively) lower ethanol concentrations in Chardonnay and Shiraz wines, respectively. In Chardonnay wine, the total concentration of esters and higher alcohols was higher for wines generated from sequential inoculations, whereas the total concentration of volatile acids was significantly lower. In sequentially inoculated Shiraz wines, the total concentration of higher alcohols was higher and the total concentration of volatile acids was reduced compared with those in control S. cerevisiae wines, whereas the total concentrations of esters were not significantly different.


Assuntos
Álcoois/metabolismo , Metschnikowia/metabolismo , Saccharomyces/metabolismo , Vinho/microbiologia , Biotransformação
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