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OBJECTIVE: To assess the cost-effectiveness of benralizumab (benra) vs. mepolizumab (mepo) and dupilumab (dupi) for the treatment of patients with severe uncontrolled asthma from the Spanish Health System perspective. METHODS: Exacerbations avoided, quality-adjusted life years (QALYs) gained and costs in a 5-year period were estimated with a Markov model for a cohort of 1,000 patients in which, based on published evidence, 31% of the patients received biologics + oral corticosteroids (OCS) and 69% received only biologics. Efficacy data (exacerbation reduction and OCS elimination) were derived from a matching-adjusted indirect comparison. Published EQ-5D utilities per health state (biologic alone, biologic + OCS, standard of care + OCS, exacerbations, and post-exacerbations) were used for QALY estimation. Utility decrements associated with exacerbation management [-0.1 (OCS or emergency visits), -0.2 (hospitalization)] derived from the literature were applied. Costs (, 2022) included drug acquisition (ex-factory price), administration and disease management. An expert panel (2 pneumologists and 1 pharmacist) validated all inputs. RESULTS: Benra was more effective (52.21 QALYs) than mepo (51.39 QALYs) and dupi (51.30 QALYs). Benra avoided more exacerbations (2.87 exacerbations) compared to mepo (4.70 exacerbations) and dupi (5.11 exacerbations) for the 5-year horizon. Total costs/patient were 56,093.77 (benra), 59,280.45 (mepo) and 62,991.76 (dupi), resulting in benra dominating (more QALYs with lower costs) vs. mepo and dupi. CONCLUSIONS: Benralizumab can be considered as a dominant treatment alternative vs. other biologic drugs for the treatment of uncontrolled severe eosinophilic asthma patients in Spain.
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Antiasmáticos , Asma , Produtos Biológicos , Eosinofilia Pulmonar , Humanos , Análise Custo-Benefício , Espanha , Eosinofilia Pulmonar/tratamento farmacológico , Corticosteroides/uso terapêutico , Produtos Biológicos/uso terapêuticoRESUMO
Gene expression involving RNA polymerase II is regulated by the concerted interplay between mRNA synthesis and degradation, crosstalk in which mRNA decay machinery and transcription machinery respectively impact transcription and mRNA stability. Rpb4, and likely dimer Rpb4/7, seem the central components of the RNA pol II governing these processes. In this work we unravel the molecular mechanisms participated by Rpb4 that mediate the posttranscriptional events regulating mRNA imprinting and stability. By RIP-Seq, we analysed genome-wide the association of Rpb4 with mRNAs and demonstrated that it targeted a large population of more than 1400 transcripts. A group of these mRNAs was also the target of the RNA binding protein, Puf3. We demonstrated that Rpb4 and Puf3 physically, genetically, and functionally interact and also affect mRNA stability, and likely the imprinting, of a common group of mRNAs. Furthermore, the Rpb4 and Puf3 association with mRNAs depends on one another. We also demonstrated, for the first time, that Puf3 associates with chromatin in an Rpb4-dependent manner. Our data also suggest that Rpb4 could be a key element of the RNA pol II that coordinates mRNA synthesis, imprinting and stability in cooperation with RBPs.
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Impressão Genômica , RNA Polimerase II/genética , Processamento Pós-Transcricional do RNA , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Sítios de Ligação , Cromatina/química , Cromatina/metabolismo , Regulação Fúngica da Expressão Gênica , Anotação de Sequência Molecular , Ligação Proteica , RNA Polimerase II/metabolismo , Estabilidade de RNA , RNA Mensageiro/classificação , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Transcrição GênicaRESUMO
Signal transducer and activator of transcription (STAT) proteins are critical for the regulation of numerous biological processes. In cattle, microarray analyses identified STAT1 as a differentially expressed gene in the endometrium during the peri-implantation period. To gain new insights about STAT1 during the oestrous cycle and early pregnancy, we investigated STAT1 transcript and protein expression, as well as its biological activity in bovine tissue and cells of endometrial origin. Pregnancy increased STAT1 expression on Day 16, and protein and phosphorylation levels on Day 20. In cyclic and pregnant females, STAT1 was located in endometrial cells but not in the luminal epithelium at Day 20 of pregnancy. The expression of STAT1 during the oestrous cycle was not affected by progesterone supplementation. In vivo and in vitro, interferon-tau (IFNT) stimulated STAT1 mRNA expression, protein tyrosine phosphorylation and nuclear translocation. Using chromatin immunoprecipitation in IFNT-stimulated endometrial cells, we demonstrated an increase of STAT1 binding on interferon regulatory factor 1 (IRF1), cytokine-inducible SH2-containing protein (CISH), suppressor of cytokine signaling 1 and 3 (SOCS1, SOCS3) gene promoters consistent with the induction of their transcripts. Our data provide novel molecular insights into the biological functions of STAT1 in the various cells composing the endometrium during maternal pregnancy recognition and implantation.
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Endométrio/metabolismo , Interferon Tipo I/metabolismo , Proteínas da Gravidez/metabolismo , Fator de Transcrição STAT1/metabolismo , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Transporte Ativo do Núcleo Celular , Animais , Sítios de Ligação , Bovinos , Células Cultivadas , Implantação do Embrião , Ciclo Estral/genética , Ciclo Estral/metabolismo , Feminino , Regulação da Expressão Gênica , Idade Gestacional , Inseminação Artificial/veterinária , Fosforilação , Gravidez , Cultura Primária de Células , Regiões Promotoras Genéticas , Fator de Transcrição STAT1/genética , Transdução de Sinais , Proteínas Supressoras da Sinalização de Citocina/genética , Fatores de TempoRESUMO
Several interleukin 6 gene (IL6) polymorphisms are implicated in susceptibility to rheumatoid arthritis (RA). It has not yet been established with certainty if these polymorphisms are associated with the severe radiographic damage observed in some RA patients, particularly those with the development of joint bone ankylosis (JBA). The objective of the present study was to evaluate the association between severe radiographic damage in hands and the -174G/C and -572G/C IL6 polymorphisms in Mexican Mestizo people with RA. Mestizo adults with RA and long disease duration (>5 years) were classified into two groups according to the radiographic damage in their hands: a) severe radiographic damage (JBA and/or joint bone subluxations) and b) mild or moderate radiographic damage. We compared the differences in genotype and allele frequencies of -174G/C and -572G/C IL6 polymorphisms (genotyped using polymerase chain reaction-restriction fragment length polymorphism) between these two groups. Our findings indicated that the -174G/C polymorphism of IL6 is associated with severe joint radiographic damage [maximum likelihood odds ratios (MLE_OR): 8.03; 95%CI 1.22-187.06; P = 0.03], whereas the -572G/C polymorphism of IL6 exhibited no such association (MLE_OR: 1.5; 95%CI 0.52-4.5; P = 0.44). Higher anti-cyclic citrullinated peptide antibody levels were associated with more severe joint radiographic damage (P = 0.04). We conclude that there is a relevant association between the -174G/C IL6 polymorphism and severe radiographic damage. Future studies in other populations are required to confirm our findings.
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Artrite Reumatoide/genética , Traumatismos da Mão/genética , Mãos/efeitos da radiação , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único , Adulto , Artrite Reumatoide/complicações , Artrite Reumatoide/etnologia , Feminino , Predisposição Genética para Doença , Traumatismos da Mão/etnologia , Traumatismos da Mão/etiologia , Humanos , Masculino , México/etnologia , Pessoa de Meia-IdadeAssuntos
Asma/epidemiologia , Ansiedade/epidemiologia , Bronquiectasia/epidemiologia , Comorbidade , Consenso , Técnica Delphi , Progressão da Doença , Dispneia/epidemiologia , Feminino , Refluxo Gastroesofágico/epidemiologia , Humanos , Pólipos Nasais/epidemiologia , Obesidade/epidemiologia , Gravidez , Fumar/epidemiologia , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: There is a lack of information about the genotype frequencies of IL-6 -174G/C and -572G/C polymorphisms in Mexicans with rheumatoid arthritis (RA). Therefore, the aim of this study was to evaluate the association of the IL-6 -174G/C and -572G/C polymorphisms in Mexican mestizo with RA. METHODS: We included 137 patients with RA and 102 healthy controls. Patients were assessed for clinical characteristics. IL-6 -174G/C and -572G/C polymorphisms were genotyped using PCR-RFLP analysis. Allele and genotype frequencies and the Hardy-Weinberg equilibrium were computed. Odds ratios (ORs) were computed to identify the risk for RA associated with the presence of GG genotype in comparison with the GC or CC genotypes. RESULTS: The genotype -174GG occurred at a higher frequency in cases and controls (77.4% versus 78.4%, P = 0.845). We found similar results for the genotype -572GG (54% in patients versus 60.8% in controls, P = 0.295). CONCLUSIONS: This is the first study to evaluate the association of -174G/C and -572G/C polymorphisms of the IL-6 gene with RA in Mexican mestizo patients. These two polymorphisms were not associated with RA in the studied sample. Additional studies are required to evaluate if these IL-6 polymorphisms have relevance to the development of more severe disease.
Assuntos
Artrite Reumatoide/genética , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Adulto , Alelos , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Interleucina-6/sangue , Masculino , México , Pessoa de Meia-IdadeRESUMO
Reversal Error (RE) is a common error in algebra problem solving. This error occurs when students recognize the information in the statement but make mistakes when translating some sentences from natural language to algebraic language, reversing the relationship between two variables in comparison word problems. Structural Magnetic Resonance Image (sMRI) data were collected with the purpose of identifying brain anatomical regions related to the RE phenomenon. The aim of the research was to investigate the brain anatomy differences between participants who failed more than 50% of the answers on the task (N=15) and those who responded correctly 100% of the time (N=18). sMRI analysis revealed differences between the two groups, and details about these data can be found in Ventura-Campos et al. (2022) [1]. This data set contains the sMRI (raw data, pre-processed images), and an excel file with personal information such as age and gender, the scanner with which their sMRI were collected, and the group to which each of the 33 subjects belonged.
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BACKGROUND: Two out of three wrist fractures seen in the emergency are displaced but most can be treated conservatively after closed reduction. Patient-reported pain during closed reduction of distal radius fractures varies widely and the best method to decrease the perceived pain has not been well established. The purpose of this study was to assess the pain during closed reduction of distal radius fractures after using the hematoma block as method of anaesthesia. PATIENTS AND METHODS: Cross-sectional clinical study including all patients who presented an acute fracture of the distal radius requiring closed reduction and immobilization during a six-month period in two University Hospitals. Demographic data, fracture classification, perceived pain using a visual analog scale at different times of reduction and complications were registered. RESULTS: Ninety-four consecutive patients were included. Mean age was 61 years. Mean pain score at initial assessment was 6 points. After the hematoma block, the perceived pain during the reduction manoeuvre improved to 5.1 points at the wrist, but increased to 7.3 points at the fingers. Pain decreased to 4.9 points during cast placement and reached 1.4 point after sling placement. The reported pain was higher in women at all times. There were no significant differences according to the according to the type of fracture. No neurological or skin complications were observed. CONCLUSIONS: The hematoma block is only a mild effective method to reduce the wrist pain during closed reduction of distal radius fractures. This technique decreases slightly the perceived pain in the wrist and does not reduce the pain in the fingers. Other reduction methods or other analgesic techniques may be more effective options. LEVEL OF EVIDENCE: Therapeutic study. Cross-sectional study - Level IV.
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BACKGROUND: Two out of three wrist fractures seen in an emergency department are displaced but most can be treated conservatively after closed reduction. Patient-reported pain during closed reduction of distal radius fractures varies widely and the best method to decrease the perceived pain has not been well established. The purpose of this study was to assess pain during closed reduction of distal radius fractures after using haematoma block as method of anaesthesia. PATIENTS AND METHODS: Cross-sectional clinical study including all patients who presented an acute fracture of the distal radius requiring closed reduction and immobilisation during a six-month period in two University Hospitals. Demographic data, fracture classification, perceived pain using a visual analogue scale at different times of reduction and complications were registered. RESULTS: Ninety-four consecutive patients were included. Mean age was 61 years. Mean pain score at initial assessment was 6 points. After the haematoma block, the perceived pain during the reduction manoeuvre improved to 5.1 points at the wrist, but increased to 7.3 points at the fingers. Pain decreased to 4.9 points during cast placement and reached 1.4 point after sling placement. The reported pain was higher in women at all times. There were no significant differences according to the according to the type of fracture. No neurological or skin complications were observed. CONCLUSIONS: Haematoma block is only a mildly effective method to reduce wrist pain during closed reduction of distal radius fractures. This technique slightly decreases the perceived pain in the wrist and does not reduce the pain in the fingers. Other reduction methods or other analgesic techniques may be more effective options. LEVEL OF EVIDENCE: Therapeutic study. Cross-sectional study - Level IV.
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During the last decade, the veterinary anesthetics have gained popularity as recreational drugs. The aim of this study was to document the use of "anestecia de caballo" (xylazine) and its consequences among drug users in Puerto Rico. The study combined a cross-sectional survey with 89 drug users and two focus groups conducted in Mayagüez with frontline drug treatment providers. Drug users were recruited from communities of the San Juan metropolitan area using a variety of ethnographic and outreach strategies. A short questionnaire developed for the study collected information on sociodemographics, xylazine use, and its consequences. The two focus groups were conducted to discuss the details related to xylazine use, its consequences, and utilization awareness. The sample comprised 63 males (70.8%) and 26 females with a mean age of 37.2 years. The mean number of years of drug use was 14.3, with a mean frequency of drug use of 5.9 times daily. More than 65% reported speedball as the principal drug of use. The prevalence of xylazine use was 80.7%. More than 42% of the sample used xylazine in a mixture with speedball. The main route of administration of xylazine was injection but 14% reported the use of xylazine by inhalation. More than 35% of the sample reported skin lesions and 21.1% reported at least one overdose episode. Multiple logistic regression analysis revealed that males (OR = 3.47, CI = 1.10-12.00) and those who reported speedball as their main drug of use (OR = 9.34, CI = 2.51-34.70) were significantly more likely to be xylazine users. Focus groups revealed that drug users claimed to recognize the presence of xylaxine in a mixture of speedball based on its effects, taste, the color of the drug (dark brown), and its odor. In conclusion, the use of xylazine among drug users in Puerto Rico seems to be an emerging trend with potentially serious health consequences.
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Hipnóticos e Sedativos , Abuso de Substâncias por Via Intravenosa/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Xilazina , Administração por Inalação , Adulto , Cocaína/administração & dosagem , Estudos Transversais , Combinação de Medicamentos , Feminino , Grupos Focais , Heroína/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Porto Rico/epidemiologia , Úlcera Cutânea/etiologia , Inquéritos e Questionários , Adulto JovemRESUMO
This study was designed to extend research on motor skill development in autism spectrum disorder using a dual-task skill. Nine autistic and 18 non-autistic youths walked without grasping or while reaching to grasp a small or large object. Step extremity ratio, percent time in double support, and normalized speed were quantified. We hypothesized that gait would differ between autistic and non-autistic youth and that differences would be moderated by the phase (approach and grasp) and the complexity of the task (walking and grasping versus walking alone). Although gait parameters were similar during the walking-only trials, the combined task resulted in slower speed and shorter steps in autistic youth, particularly during the grasp phase. These findings, while in a small sample, offer preliminary evidence that autistic youth who show typical gait during simple assessments of motor ability may have difficulties in more complex tasks that require the coordination of movements.
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Transtorno do Espectro Autista , Adolescente , Marcha , Força da Mão , Humanos , Desempenho Psicomotor , CaminhadaRESUMO
BACKGROUND: Lung retransplantation (LR) is a valid choice with a significant risk of perioperative morbidity and mortality in selected patients with graft dysfunction after lung transplantation. Our goal is to analyse our experience in LR in terms of survival and lung function. METHODS: Retrospective study of patients undergoing LR (1990-2019). VARIABLES: recipients and procedure, early mortality, survival and lung function in patients with CLAD. Quantitative variables (mean±SD); qualitative (%). Student's t test or χ2 was used. Survival was estimated using Kaplan-Meier, compared with Log Rank. A p < 0.05 was established as significant. RESULTS: Of 784 transplanted patients, 25 patients (mean age 38.41-16.3 years, 12 men and 13 women) were LR; (CLAD (n = 19), pulmonary infarction (n = 2), airway complications (n = 2), graft dysfunction (n = 1), hyperacute rejection (n = 1), mean time to retransplantation: 5.41 ± 3.87 years in CLAD and 21.2 ± 21.4 days in non-CLAD. The 90-day mortality was 52% and 36.8% in the second period (p = 0.007), being higher in patients who required preoperative ECMO (80 vs. 20%, p = 0.04). The 1- and 5-year survival was 53.9% and 37.7%, respectively (p = 0.016). Survival of the CLAD group was greater (p = 0.08). Pre LR ECMO decreased survival (p = 0.032). After LR, FEV1 improved an average of 0.98 ± 0.13L (25.6 ± 18.8%) (p = 0.001). CONCLUSIONS: LR is a high mortality procedure that requires careful selection of patients with better results in patients with CLAD. The lung function of patients with CLAD improved significantly.
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Transplante de Pulmão , Feminino , Rejeição de Enxerto , Humanos , Pulmão , Masculino , Encaminhamento e Consulta , Testes de Função Respiratória , Estudos Retrospectivos , Fatores de RiscoRESUMO
Chitosan (CHI) is a natural biopolymer with antimicrobial, anti-inflammatory, antioxidant and digestive modulatory effects, which can be used in the ruminant diet to replace antibiotics. The aim of this study was to evaluate the effects of CHI on lamb growth traits, nutrients digestibility, muscle and fatty deposition, meat fatty acid (FA) profile, meat quality traits and serum metabolome. Thirty 30-month-old male lambs, half Suffolk and half Dorper, with an average BW of 21.65 ± 0.86 kg, were fed in a feedlot system for a total of 70 days. The lambs were separated into two groups according to the diet: the control (CON) group which received the basal diet and the CHI group which received the basal diet with the addition of CHI as 2 g/kg of DM in the diet. Lambs supplemented with CHI had a greater (P < 0.05) final BW, DM intake, final body metabolic weight (P < 0.05) and lower residual feed intake than the CON group. Animals fed CHI had a greater (P < 0.05) starch digestibility at 14 and 28 days, average daily gain at 14, 42 and 56 days, greater feed efficiency at 28 days and feed conversation at 14 and 42 days in feedlot. Most of the carcass traits were not affected (P > 0.05) by the treatment; however, the CHI supplementation improved (P < 0.05) dressing and longissimus muscle area. The treatments had no effect (P > 0.05) on the meat colour and other quality measurements. Meat from the CHI-fed lambs had a greater concentration (P < 0.05) of oleic-cis-9 acid, linoleic acid, linolenic-trans-6 acid, arachidonic acid and eicosapentaenoic acid. According to the variable importance in projection score, the most important metabolites to differentiate between the CON and the CHI group were hippurate, acetate, hypoxanthine, arginine, malonate, creatine, choline, myo-inositol, 2-oxoglutarate, alanine, glycerol, carnosine, histidine, glutamate and 3-hydroxyisobutyrate. Similarly, fold change (FC) analysis highlighted succinate (FC = 1.53), arginine (FC = 1.51), hippurate (FC = 0.68), myo-inositol (FC = 1.48), hypoxanthine (FC = 1.45), acetate (FC = 0.73) and malonate (FC = 1.35) as metabolites significantly different between groups. In conclusion, the present data showed that CHI changes the muscle metabolism improving muscle mass deposition, the lamb's performance and carcass dressing. In addition, CHI led to an alteration in the FA metabolism, changes in the meat FA profile and improvements in meat quality.
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Quitosana , Ração Animal/análise , Animais , Composição Corporal , Dieta/veterinária , Masculino , Carne , Ovinos , Carneiro DomésticoRESUMO
The BW has been largely used as a selection criterion in genetic selection programmes; however, increases in BW can affect animal metabolism and metabolites. The knowledge of how genetic potential for growth affects the metabolites can give a footprint of growth metabolism. This research aimed to evaluate the effect of genetic potential for post-weaning growth (GG) on performance, carcass traits and serum metabolome of non-castrated Nellore males during the finishing phase. Forty-eight Nellore non-castrated males, with divergent potential for post-weaning growth, were selected and divided into two groups: high potential for post-weaning growth (HG; n = 24) and low potential for post-weaning growth (LG; n = 24). Animals were kept and fed for 90 days where performance and ultrasound carcass traits were evaluated. Blood samples were collected at the beginning and end of feeding period to analyse serum metabolites concentration. The hot carcass weight and dressing percentage were recorded at slaughter. The feedlot performance and carcass traits were not affected by genetic potential. The HG animals had a lower glucose (P = 0.039), glutamate (P = 0.038), glutamine (P = 0.004), greater betaine (P = 0.039) and pyruvate (P = 0.039) compared to the LG group at the beginning of feedlot. In addition, higher creatine phosphate concentrations were observed at the beginning of feeding period, compared to final, for both groups (P = 0.039). In conclusion, the genetic potential for post-weaning growth does not affect performance and carcass traits during the finishing period. Differences in metabolite concentrations can be better found at the beginning of feedlot, providing a footprint of growth metabolism, but similar metabolite concentration at the end of finishing period.
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Bovinos/fisiologia , Metabolômica , Carne Vermelha/análise , Animais , Composição Corporal/genética , Bovinos/sangue , Bovinos/genética , Bovinos/crescimento & desenvolvimento , Dieta/veterinária , Masculino , Fenótipo , DesmameRESUMO
Chronic renal disease patients under chronic dialysis (CRDD) have a multifactorial immunological deterioration with an increased risk of Candida infections. Incidence of Candida infections is increasing. Choice of suitable antifungal agents is limited due to the resistance of some species to several antifungals. Aim of the present study was to identify the distribution and antifungal susceptibility patterns of oral isolated Candida species from infected and colonized patients, as well as to investigate the risk factors for oral infection in patients on dialysis. Cross-sectional study, approved by the institutional bioethics committees was performed in CRDD patients. Demographic, clinic data, and oral mucosa samples were obtained. Infection diagnosis was established clinically and confirmed with exfoliative cytology, each sample was plated on CHROMagar Candida and incubated at 36°C for 2 days. Yeast species were identified by carbohydrate assimilation ID 32C AUX system and the apiweb database. For the antifungal susceptibility test, the M44 A-3 method (CLSI) using fluconazole (FCZ), miconazole (MCZ), nystatin (NYS), and voriconazole (VCZ). Study included 119 participants, the main cause of CRD was nephropathy due to DM2 (58%), and three-fourths of the patients were under hemodialysis. Candida prevalence was 56.3% of 67 colonized or infected patients, 88 isolates were obtained. Principal identified species were C. albicans (51.1%), C. glabrata (25%), and C. tropicalis (14.8%). C. glabrata showed a reduced response to FCZ in 50% of isolates and C. albicans had a reduced response in 16% of the isolates. Antifungal agent with the least efficacious response or with the lowest susceptibility in the isolates of these patients was MCZ, followed by VCZ and FCZ, whereas NYS induced the best antifungal response.
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Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candidíase Bucal/microbiologia , Boca/microbiologia , Insuficiência Renal Crônica/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Candida/classificação , Candidíase Bucal/complicações , Candidíase Bucal/diagnóstico , Candidíase Bucal/epidemiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/microbiologia , Diabetes Mellitus Tipo 2/terapia , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/microbiologia , Nefropatias Diabéticas/terapia , Farmacorresistência Fúngica/efeitos dos fármacos , Feminino , Humanos , Masculino , México/epidemiologia , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Diálise Renal/efeitos adversos , Diálise Renal/estatística & dados numéricos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Adulto JovemRESUMO
AIM: To assess gingival overgrowth prevalence and severity in a group of kidney transplant (KT) patients, and analyze the effect of immunosuppressor drugs Cyclosporin A (CsA), Tacrolimus (Tac), Sirolimus (Siro), Azathioprine (Aza) and Mofetil Mycophenolate on this complication. METHODS: Gingival overgrowth presence and severity was classified, and the impact of immunosuppressor drugs, age, oral hygiene, verapamil and nifedipine on this condition was analyzed by multiple logistic regression. RESULTS: 172 KT pts. were examined; 137 used CsA, 25 Tac, 6 Sirolimus, 107 Aza and 56 MMF. Gingival overgrowth prevalence was 59.1% on CsA, 12.0% on Tac, and 16.7% on Sirolimus. CsA odds ratio (OR) 15.2, age <45 OR 5.6, and poor oral hygiene OR 3.2, increased, and Aza OR 0.05 and MMF OR 0.03, decreased GO prevalence. CONCLUSIONS: Aza and MMF effect was a significant protection against GO prevalence in this group of KT patients.
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Azatioprina/efeitos adversos , Ciclosporina/efeitos adversos , Hipertrofia Gengival/induzido quimicamente , Imunossupressores/efeitos adversos , Transplante de Rim , Ácido Micofenólico/análogos & derivados , Adulto , Estudos Transversais , Feminino , Hipertrofia Gengival/epidemiologia , Humanos , Masculino , Ácido Micofenólico/efeitos adversos , Índice de Gravidade de DoençaRESUMO
Rabbit hemorrhagic disease (RHD) is a highly infectious disease in European rabbits (Oryctolagus cuniculus), caused by a virus belonging to the genus Lagovirus (RHDV; family Caliciviridae). In 2010, a new genotype of RHDV (RHDV2 or RHDVb, currently designated GI.2) emerged in France, affecting both domestic rabbits, even those vaccinated for the classical RHDV genotypes (currently designated GI.1) and wild rabbits. GI.2 was subsequently identified in other European countries. The aim of the present study was to monitor the GI.2 epidemic in wild rabbits in Andalusia (southern Spain) during the period 2013-2017. At the beginning of summer 2013, high mortalities were detected in wild rabbit populations in southern Spain. A total of 96 affected hunting or protected areas were surveyed. The first outbreak was observed on June 2013. The number of outbreaks sharply increased in 2013 and 2014, with a decreasing trend being observed during the following years. The spatial distribution of GI.2 was not homogeneous, since most of the detected outbreaks were concentrated in the western part of Andalusia. The outbreaks peaked in winter and spring and have been detected in the last five consecutive years, which suggests endemic circulation of GI.2 in wild rabbit populations in Spain. A total of 190 dead rabbits from 87 of the 96 areas surveyed were collected during the study period. Mortality affected rabbits of different age classes, including kittens. RT-PCR confirmed the presence of GI.2 RNA in the livers of 185 of the 190 (97.4%) rabbits. Phylogenetic analysis performed on eleven samples collected in different provinces of Andalusia between 2013 and 2017, showed high nucleotide identity with GI.2 strains Spain, France and Portugal. The results constitute an important step in understanding of the emergence and spread of GI.2 in this country and will provide valuable information for the development of surveillance programs in Europe.
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Animais Selvagens , Infecções por Caliciviridae/veterinária , Epidemias/veterinária , Vírus da Doença Hemorrágica de Coelhos , Coelhos/virologia , Animais , Infecções por Caliciviridae/epidemiologia , Infecções por Caliciviridae/virologia , Doenças Transmissíveis Emergentes/veterinária , Doenças Transmissíveis Emergentes/virologia , Filogenia , RNA Viral/genética , RNA Viral/isolamento & purificação , Espanha/epidemiologiaRESUMO
Substitutions on the P(1) cyclobutyl side chain of SCH 503034 were studied by introduction of hydroxyl and fluoro substituents. Additionally, effects of fluoro substitution on other P1 moieties were evaluated.
Assuntos
Prolina/análogos & derivados , Inibidores de Serina Proteinase/síntese química , Inibidores de Serina Proteinase/farmacologia , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/química , Área Sob a Curva , Química Farmacêutica/métodos , Desenho de Fármacos , Flúor/química , Hepatite C/tratamento farmacológico , Humanos , Concentração Inibidora 50 , Cinética , Modelos Químicos , Conformação Molecular , Prolina/síntese química , Prolina/farmacologia , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: Our objective is to contribute an updated view on a condition as rare as oat-cell carcinoma of the esophagus by reviewing the literature and reporting two recent patients seen in our department. MATERIAL AND METHOD: A retrospective study with a review of all medical records of patients seen in our ward and diagnosed with esophageal neoplasm for 6 years (January 2000 to December 2006). RESULTS: 249 cases of esophageal neoplasms were found, of them 106 were of squamous ancestry (42.6%), 141 were adenocarcinomas (56.6%), and 2 were oat-cell carcinomas (0.8%). Only in 45 (18%) was surgical resection feasible, 23 underwent palliative surgery (endoprostheses, gastrostomies, and jejunostomies not included) (9.3%), and the rest (181 cases, 72.7%) received derivative surgery or no surgery at all. CONCLUSIONS: We can affirm that this neoplasm is highly aggressive, displaying in practically all cases dissemination to other sites; this is a rare cancer that mainly affects men and whose clinical picture is similar to that of other malignancies involving the esophagus.