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Antinuclear antibodies (ANA) are important diagnostic markers in many autoimmune rheumatological diseases. The indirect immunofluorescence assay applied on human epithelial cells generates images that are used in the detection of ANA. The classification of these images for different ANA patterns requires human experts. It is time-consuming and subjective as different experts may label the same image differently. Therefore, there is an interest in machine learning-based automatic classification of ANA patterns. In our study, to build an application for the automatic classification of ANA patterns, we construct a dataset and learn a deep neural network with a transfer learning approach. We show that even in the existence of a limited number of labeled data, high accuracies can be achieved on the unseen test samples. Our study shows that deep learning-based software can be built for this task to save expert time.
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Background/aim: Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting mostly small joints, such as hand and foot joints symmetrically with irreversible joint destruction. In this study, the relationship between CD39 expression and the treatment response of RA patients was examined to investigate its potential as a biomarker that demonstrates treatment response. Materials and methods: This study included 77 RA patients and 40 healthy controls (HC). The RA patients were divided into 2 groups based on their response to RA treatment, those with a good response to methotrexate (MTX) monotherapy and those with an inadequate response based on the American College of Rheumatology and the European League Against Rheumatism response criteria. Various immunological parameters and Disease Activity Score in 28 Joints (DAS28) were examined between the groups using the Student's t-test. Results: The monocytic myeloid-derived suppressor cell (M-MDSC) percentage was higher in the RA patient group versus the HC group. The CD39 expression in the T lymphocytes were higher in patients that responded well to the MTX compared to those showing inadequate response. Additionally, s negative correlation was found between the DAS28 and CD39 in the T cells. Conclusion: The results showed that the improvement in treatment response to the therapy in RA patients could be because of the enhancement in the CD39/adenosine (ADO) pathway. Therefore, therapies targeting the CD39/ADO pathway in T cells may improve RA treatments.
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Antirreumáticos , Apirase , Artrite Reumatoide , Metotrexato , Humanos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Metotrexato/uso terapêutico , Feminino , Masculino , Apirase/metabolismo , Pessoa de Meia-Idade , Antirreumáticos/uso terapêutico , Antirreumáticos/farmacologia , Adulto , Biomarcadores/sangue , Resultado do Tratamento , Antígenos CD/metabolismo , Estudos de Casos e Controles , Idoso , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismoRESUMO
Background/Aims: To investigate the presence of seronegative celiac disease in patients with isolated refractory dyspepsia and gastroesophageal reflux disease (GERD)-related complaints. Methods: This was a single-center, prospective study performed at a tertiary care referral hospital. Among 968 consecutive patients, 129 seronegative patients with tissue damage consistent with Marsh IIIa classification or above were included. The patients were divided into two groups: dyspepsia (n=78) and GERD (n=51). Biopsies were taken from the duodenum regardless of endoscopic appearance, and patients with Marsh IIIa or above damage were advised to consume a gluten-free diet. The Glasgow Dyspepsia Severity (GDS) score, Reflux Symptom Index (RSI), and Biagi score were calculated at baseline and every 3 months. Control endoscopy was performed every 6 months during follow-up. Results: The median follow-up time was 19.9 months (range, 6 to 24 months) in the dyspepsia group and 19.2 months (range, 6 to 24 months) in the GERD group. All the patients were positive for the HLA-DQ2 and DQ8 haplotypes. The differences between the mean GDS scores (14.3±2.1 vs 1.1±0.2, respectively, p<0.05), RSI scores (6.3±0.8 vs 0.7±0.1, respectively, p<0.05), and Biagi scores (3.1±0.4 vs 0.7±0.3 in the dyspepsia group and 2.5±0.4 vs 0.5±0.2 in GERD group) before and after implementation of the gluten-free diet were statistically significant. The decreases in the scores were consistent with improvements in the histological findings. There was no significant correlation between endoscopic appearance and histological examination results (p=0.487). Conclusions: Seronegative celiac disease may be considered in this group of patients. Even if a patient is seronegative and has normal endoscopic findings, duodenal biopsy should be considered.
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Doença Celíaca , Dispepsia , Refluxo Gastroesofágico , Doença Celíaca/diagnóstico , Dieta Livre de Glúten , Dispepsia/etiologia , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/diagnóstico , Humanos , Estudos ProspectivosRESUMO
OBJECTIVE: Anemia in patients with chronic kidney disease (CKD) is the result of reduced erythropoietin, disturbed erythropoiesis and decreased lifespan of circulating erythrocytes. Excessive eryptosis or premature suicidal erythrocyte death is characterized by cell shrinkage and phosphatidylserine externalization. This study aimed to explore accelerated eryptosis and accompanying biochemical alterations in CKD patients. PATIENTS AND METHODS: A total of 106 CKD patients (59 predialysis [PreD] patients, 26 haemodialysis [HD] patients and 21 peritoneal dialysis [PD] patients) and a control group composed of 29 healthy volunteers were included in this study. Data on superoxide dismutase (SOD) activity (U/mL), annexin-V binding (mean fluorescent intensity, MFI) and intracellular calcium ([Ca2+]i; MFI) as well as the hematologic and biochemical parameters were recorded. RESULTS: The [Ca2+]i levels were 3.05 ± 1.66 MFI, 2.24 ± 0.99 MFI, 2.38 ± 0.87 MFI and 1.71 ± 0.46 MFI in the PreD, HD, PD and control groups, respectively. Other than significantly higher [Ca2+]i levels in the PreD group than in the control group (p < 0.001), no significant difference was noted between study groups in terms of [Ca2+]i. Annexin-V binding was 1.05 ± 0.99 MFI in PreD group, 1.15 ± 0.56 MFI in HD group, 1.06 ± 0.87 MFI in PD group, and 0.88 ± 0.86 MFI in controls. Annexin-V binding was significantly higher in PreD, HD and PD groups compared with the control group (p < 0.001 for each). SOD activity was 0.07 ± 0.07 in the PreD group, 0.13 ± 0.08 in the HD group, 0.14 ± 0.07 in the PD group, and 0.03 ± 0.01 in the control group. SOD activity in both HD and PD groups were significantly higher than control and PreD groups (p < 0.001 for each). Lower albumin, higher ferritin, and higher parathormon levels were found to be correlated with eryptosis biomarkers. Patients treated vs. non-treated with calcium channel blockers had significantly lower annexin-V binding levels (p = 0.013). Patients treated vs. non-treated with erythropoietin (EPO) had elevated annexin-V binding level (p < 0.001) and lower [Ca2+]i (p = 0.014). CONCLUSION: In conclusion, our findings revealed the presence accelerated eryptosis, as a potential contributing factor to development of anemia, in patients with CKD stages 3-5D. Inflamation and parathormon can also accelerate eryptosis. Favorable effect of CCB and EPO on eryptosis needs to be confirmed in larger scale studies.
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Anemia , Eriptose , Eritropoetina , Insuficiência Renal Crônica , Albuminas/metabolismo , Albuminas/farmacologia , Anexina A5/metabolismo , Anexina A5/farmacologia , Cálcio , Bloqueadores dos Canais de Cálcio/farmacologia , Eritropoetina/uso terapêutico , Ferritinas , Humanos , Fosfatidilserinas/metabolismo , Fosfatidilserinas/farmacologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Superóxido Dismutase/metabolismoRESUMO
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. For unresectable HCC, transarterial radioembolization (TARE) with Yttrium-90 is a widely used treatment. The aim of this study was to investigate whether monocytic myeloid-derived suppressor cells (M-MDSC) and CD39+ T cells can be non-invasive predictive biomarkers of radiological response and prognosis in patients with HCC treated with TARE. This study was conducted on 39 patients with HCC who were treated with TARE between August 2018 and December 2019 and the control group consisted of 23 healthy volunteers. CD4+, CD8+, CD39+ T cells, Natural killer (NK) cells, myeloid cells (MC) and M-MDSC parameters are examined in the course of TARE treatment with student t test and Kaplan-Meier method. There were statistically significant differences in M-MDSC, CD39+ T cells and MC values between healthy controls and HCC patients. A statistically significant difference was found in M-MDSC and CD4+ T cells values in the HCC patient group who responded to the treatment compared to those who did not. Survival analysis found that patients with lower frequencies (under 3.81%) of M-MDSC showed more prominent differences of overall survival (OS) compared to patients with all high groups. We found that M-MDSC in the peripheral blood might be a useful non-invasive biomarker to predict OS. We have shown for the first time that M-MDSC is correlated with treatment response in HCC patients treated with TARE. Additionally, we have found that the percentage of CD39+ T cells is high in HCC patients and these cells are positively correlated with M-MDSC.
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Carcinoma Hepatocelular/imunologia , Antígenos HLA-DR/imunologia , Receptores de Lipopolissacarídeos/imunologia , Neoplasias Hepáticas/imunologia , Células Supressoras Mieloides/imunologia , Linfócitos T/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/terapia , Estudos de Casos e Controles , Embolização Terapêutica/métodos , Feminino , Humanos , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Células Mieloides/imunologia , Células Mieloides/efeitos da radiação , Células Supressoras Mieloides/efeitos da radiação , Prognóstico , Estudos Prospectivos , Análise de Sobrevida , Linfócitos T/metabolismo , Linfócitos T/efeitos da radiação , Radioisótopos de Ítrio/uso terapêuticoRESUMO
BACKGROUND: Predominantly antibody deficiencies (PADs) are the most prevalent primary immunodeficiencies that are caused by genetic disorders and result in impairment of the immune system. Therefore, PAD diagnosis has been extensively studied, yet their B-cell defects and underlying genetic alterations remain largely unknown. The aim of this study is to determine the immunological differences in PAD patients categorized by patients showing different complications such as splenomegaly, bronchiectasis, and chronic diarrhea. METHODS: A total of 45 participants, consisting of 27 patients diagnosed with PAD and 18 healthy control individuals were included in this study. The relationship between B cell subgroups in PAD patients and control groups are investigated. Additionally, the association between B cell subgroups and complications such as splenomegaly, bronchiectasis, and chronic diarrhea in PAD patients are studied. RESULTS: In this study, we found an association between splenomegaly and various B cell subgroups such as naive B cells, CD21low B cells, and SW memory B cells. In the correlation analysis, we found a negative correlation between naive B cells and splenomegaly. Additionally, to the best of our knowledge, this study is the first to show a statistically significant association between memory B cells and chronic diarrhea as well as between transitional B cells and bronchiectasis. CONCLUSIONS: This study provides biomarkers to predict PAD patients' clinical progression or disease complications.
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Bronquiectasia , Linfócitos B , Biomarcadores , Bronquiectasia/diagnóstico , HumanosRESUMO
BACKGROUND: There is growing evidence indicating that children are less affected from COVID-19. Some authors speculate that childhood vaccinations may provide some cross-protection against COVID-19. In this study, our aim was to compare the circulating antibody titers for multiple childhood vaccine antigens, as an indicator of the state of immune memory between patients with COVID-19 and healthy controls, with a specific aim to identify the association between disease severity and antibody titrations which may indicate a protective function related to vaccine or disease induced memory. METHODS: This study is a case-control study including 53 patients with COVID-19 and 40 healthy volunteers. COVID-19 severity was divided into three groups: asymptomatic, mild and severe. We measured the same set of antibody titers for vaccine antigens, and a set of biochemical and infection markers, in both the case and control groups. RESULTS: Rubella (p = 0.003), pneumococcus (p = 0.002), and Bordetella pertussis (p < 0.0001) titers were found to be significantly lower in the case group than the control group. There was a significant decline in pneumococcus titers with severity of disease (p = 0.021) and a significant association with disease severity for Bordetella pertussis titers (p = 0.014) among COVID patients. Levels of AST, procalcitonin, ferritin and D-dimer significantly increased with the disease severity. DISCUSSION: Our study supports the hypothesis that pre-existing immune memory, as monitored using circulating antibodies, acquired from childhood vaccinations, or past infections confer some protection against COVID-19. Randomized controlled studies are needed to support a definitive conclusion.
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Acinetobacter baumannii is a multi-drug resistant (MDR) gram-negative pathogen leading to nosocomial infections. Hospital-acquired infections due to A.baumannii occur especially in patients hospitalized in intensive care units. Important infections related to this bacterium are pneumonia, bacteremia, endocarditis, skin and soft tissue, urinary tract infections and meningitis. Human transmission is usually through the hospital environment or through medical personnel. A.baumannii isolates increases their virulence not only being multiple resistance to antibiotics but as well as the ability to form biofilm. The biofilm formation of A.baumannii isolates were mostly related with genes encoding curli fiber (csgA), the chaperone-usher fimbria (csuE) and the outer membrane (ompA). The aim of this study was to demonstrate biofilm production and virulence genes in MDR invasive A.baumannii isolates. MDR and similarity status previously known invasive A.baumannii (n= 156) isolates were included in the study. Biofilm production was determined by quantitative microplate biofilm method. Virulence genes csgA, csuE, fimH, ompA and blaPER-1 were investigated by polymerase chain reaction (PCR). It was determined that 60.3% (94/156) of all the isolates formed biofilm. Of these 94 isolates, 17 were weak, 33 were medium and 44 were strong. The mean biomass forming capacity of the isolates was found to be 2.23 ± 0.0033. Among the isolates included in the study (n= 156) the frequency of csgA, csuE, ompA, fimH and blaPER-1 genes were 71.2%, 32.1%, 21.8%, 7.1% and 3.2% respectively. The frequency of csgA, ompA, bap, csuE, fimH virulence genes were found to be 41.5%, 24.5%, 20.2% and 5.3% among biofilm positive isolates respectively. Biofilm-forming isolates were most commonly found in pulsotype II 19.1% (18/94), pulsotype IX 17.0% (16/94) and pulsotype VI 12.8% (12/94). In this study, when the distribution of virulence genes were compAred with the isolates that have weak, medium and strong biofilm, all of the studied genes were found to be more abundant in isolates with strong and medium positive biofilm production. This has shown that excluding fimH gene, csgA, csuE and ompA genes have contributed to the biofilm formation in invasive A.baumannii isolates, respectively.
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Infecções por Acinetobacter , Acinetobacter baumannii , Biofilmes , Farmacorresistência Bacteriana Múltipla , Virulência , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/genética , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Humanos , Virulência/genéticaRESUMO
PURPOSE: The aim of the study was to determine aqueous humor and serum levels of brain-derived neurotrophic factor (BDNF) in diabetic patients with and without retinopathy. METHODS: The study included diabetic patients with or without retinopathy, who had an indication for cataract surgery. The study groups were diabetic patients without retinopathy (Group 2), with nonproliferative diabetic retinopathy (Group 3), and with proliferative retinopathy (Group 4). To quantitatively determine the amount of BDNF in samples, the RayBio Human BDNF ELISA kit (Norcross, GA), based on an enzyme-labeled immunosorbent assay was used. RESULTS: The median serum BDNF levels were significantly lower in all the study groups than in the control group (P values: 0.038 Group 2, 0.02 Group 3, and 0.002 Group 4). Serum BDNF was lower in Group 4 than in Group 3 (P = 0.030), and in Group 3 than in Group 2 (P = 0.04). The median aqueous humor BDNF levels were significantly decreased in all groups (P values: 0.047 Group 2, 0.021 Group 3, and 0.007 Group 4). There was no significant difference between Groups 2, 3, and 4 (P = 0.214). CONCLUSION: The serum and aqueous humor BDNF levels decreased in patients with diabetes mellitus (DM) before the emergence of clinical signs of retinopathy.
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Humor Aquoso/metabolismo , Fator Neurotrófico Derivado do Encéfalo/sangue , Retinopatia Diabética/sangue , Idoso , Extração de Catarata , Cromatografia Líquida de Alta Pressão , Diabetes Mellitus Tipo 2/sangue , Retinopatia Diabética/classificação , Ensaio de Imunoadsorção Enzimática , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Background/aim: Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation. The study aimed to assess serum 14-3-3eta, anti-CarP, and anti-Sa in seronegative RA (SNRA) patients who were treatment-naïve as well as in healthy subjects. This is the first study in the literature to examine these autoantibodies together in SNRA patients. Materials and methods: Forty-five treatment-naïve SNRA patients and 45 healthy subjects were recruited. Drugs change the levels of autoantibodies; therefore, patients who took any medication had been excluded from our study. Anti-carbamylated protein, anti-Sa, and 14-3-3eta were measured by using three different ELISA kits. Results: Median serum concentration of healthy controls in 14-3-3eta was 0.02 (0.020.27) ng/mL. Median serum concentration of SNRA patients in 14-3-3eta was 1.00 (0.481.28) ng/mL. Data were analyzed with MannWhitney U tests; the P-value was <0.001 in 14-3-3eta. Receiver operating characteristic (ROC) curve analysis showed that 14-3-3eta in SNR compared to healthy controls had a significant (P < 0.001) area under the curve (AUC) of 0.90 (95% confidence interval, 0.830.96). At a cutoff of ≥0.33 ng/mL, the ROC curve yielded a sensitivity of 88.9%, a specificity of 82.2%, a positive predictive value of 83.3%, and a negative predictive value of 88.1%. Conclusion: We found that 14-3-3eta can be used as a diagnostic marker in SNRA.
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Proteínas 14-3-3/sangue , Anticorpos Antiproteína Citrulinada/sangue , Artrite Reumatoide/sangue , Autoanticorpos/sangue , Carbamatos/imunologia , Vimentina/imunologia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes SorológicosRESUMO
BACKGROUND: Multidrug-resistant (MDR) Acinetobacter baumannii infections are considered as emerging nosocomial infections particularly in patients hospitalized in intensive care units (ICUs). Therefore, reliable detection of MDR strains is crucial for management of treatment but also for epidemiological data collections. The purpose of this study was to compare antimicrobial resistance and the clonal distribution of MDR clinical and environmental A. baumannii isolates obtained from the ICUs of 10 different hospitals from five geographical regions of Turkey in the context of the demographic and clinical characteristics of the patients. METHODS: A multicenter-prospective study was conducted in 10 medical centers of Turkey over a 6 month period. A total of 164 clinical and 12 environmental MDR A. baumannii isolates were included in the study. Antimicrobial susceptibility testing was performed for amikacin (AN), ampicillin-sulbactam (SAM), ceftazidime (CAZ), ciprofloxacin (CIP), imipenem (IMP) and colistin (COL) by microdilution method and by antibiotic gradient test for tigecycline (TIG). Pulsed-field gel electrophoresis (PFGE) was performed to determine the clonal relationship between the isolates. The detection of the resistance genes, blaOXA-23, blaOXA-24, blaOXA-51, blaOXA-58, blaIMP, blaNDM, blaKPC, blaOXA-48 and blaPER-1 was carried out using the PCR method. RESULTS: The mortality rate of the 164 patients was 58.5%. The risk factors for mortality included diabetes mellitus, liv1er failure, the use of chemotherapy and previous use of quinolones. Antimicrobial resistance rates for AN, SAM, CAZ, CIP, IMP, COL and TIG were 91.8%, 99.4%, 99.4%, 100%, 99.4%, 1.2% and 1.7% respectively. Colistin showed the highest susceptibility rate. Four isolates did not grow on the culture and were excluded from the analyses. Of 172 isolates, 166 (96.5%) carried blaOXA-23, 5 (2.9%) blaOXA-58 and one isolate (0.6%) was positive for both genes. The frequency of blaPER-1 was found to be 2.9%. None of the isolates had blaIMP, blaKPC, blaNDM and blaOXA-48 genes. PFGE analysis showed 88 pulsotypes. Fifteen isolates were clonally unrelated. One hundred fifty-seven (91.2%) of the isolates were involved in 14 different clusters. CONCLUSIONS: Colistin is still the most effective antibiotic for A. baumannii infections. The gene blaOXA-23 has become the most prevalent carbapenemase in Turkey. The distribution of invasive A. baumannii isolates from different regions of Turkey is not diverse so, infection control measures at medical centers should be revised to decrease the MDR A. baumannii infections across the country. The results of this study are expected to provide an important baseline to assess the future prophylactic and therapeutic options.
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Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/genética , Antibacterianos/farmacologia , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana , Infecções por Acinetobacter/epidemiologia , Acinetobacter baumannii/classificação , Acinetobacter baumannii/isolamento & purificação , Adulto , Idoso , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Colistina/farmacologia , Infecção Hospitalar/epidemiologia , Feminino , Humanos , Imipenem/farmacologia , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Epidemiologia Molecular , Filogenia , Estudos Prospectivos , Turquia/epidemiologia , beta-Lactamases/genética , beta-Lactamases/metabolismoRESUMO
Exophiala is a genus of black fungi isolated worldwide from environmental and clinical specimens. Data on antifungal susceptibility of Exophiala isolates are limited and the methodology on susceptibility testing is not yet standardised. In this study, we investigated in vitro antifungal susceptibilities of environmental Exophiala isolates. A total of 87 Exophiala isolated from dishwashers or railway ties were included. A CLSI M38-A2 microdilution method with modifications was used to determine antifungal susceptibility for fluconazole, voriconazole, posaconazole, itraconazole, amphotericin B and terbinafine. Minimum inhibitory concentration (MIC) values were determined visually at 48 hours, 72 hours and 96 hours. MIC-0 endpoint (complete inhibition of growth) was used for amphotericin B and azoles, except fluconazole, for which MIC-2 endpoint (~50% inhibition compared to growth control) was used. Both MIC-0 and MIC-1 (~80% inhibition compared to growth control) results were analysed for terbinafine to enable comparison with previous studies. Fungal growth was sufficient for determination of MICs at 48 hours for all isolates except two Exophiala dermatitidis strains. At 72 hours, most active antifungal agents according to GM MIC were voriconazole and terbinafine, followed by posaconazole, itraconazole and amphotericin B in rank order of decreasing activity. While amphotericin B displayed adequate in vitro activity despite relatively high MICs, fluconazole showed no meaningful antifungal activity against Exophiala.
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Antifúngicos/farmacologia , Microbiologia Ambiental , Exophiala/efeitos dos fármacos , Exophiala/isolamento & purificação , Testes de Sensibilidade MicrobianaRESUMO
PURPOSE: We aimed to investigate the effect of trabeculectomy on serum brain-derived neurotrophic factor (BDNF) levels. Our secondary goal was to compare serum and aqueous humor (AH) BDNF levels in primary open-angle glaucoma (POAG) and control subjects. METHODS: This prospective, cross-sectional study consists of 20 eyes of with advanced-stage POAG who had trabeculectomy and 19 eyes of age- and sex-matched control healthy subjects who had cataract surgery. Serum and AH samples were obtained preoperatively in trabeculectomy group and control subjects. Serum samples were obtained at the third postoperative month in both groups. RESULTS: The aqueous humor and serum levels of BDNF at the surgery day were found to be strongly positive correlated (r = 0.868; p < 0.001). Serum and AH BDNF levels of POAG cases were significantly lower than control subjects at the surgery day (respectively p = 0.038, p = 0.011). In POAG cases, serum BDNF levels significantly increased at the third month after trabeculectomy while there was not a significant difference in control subjects with cataract surgery (p < 0.001; p = 0.717 respectively). CONCLUSION: Trabeculectomy was found to have a positive effect on serum BDNF levels in POAG cases.
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Fator Neurotrófico Derivado do Encéfalo/metabolismo , Glaucoma de Ângulo Aberto/metabolismo , Pressão Intraocular/fisiologia , Trabeculectomia/métodos , Humor Aquoso/metabolismo , Biomarcadores/metabolismo , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Glaucoma de Ângulo Aberto/fisiopatologia , Glaucoma de Ângulo Aberto/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos ProspectivosRESUMO
Between June 2009 and December 2013, 4105 patients were screened for carbapenem-resistant Klebsiella pneumoniae (CR-Kp) colonization in a tertiary care university hospital. The antimicrobial susceptibility and resistance determinants of 279 (6.8%) CR-Kp isolates from single patients were investigated. Additional analysis was performed to evaluate the characteristics and various risk factors for infection in patients with colonization. Of the 279 isolates, 270 harboured OXA-48-like enzymes, and a single isolate harboured IMP-type carbapenemase. A high proportion of isolates were susceptible to carbapenems - except ertapenem. All isolates were susceptible to amikacin and most (94%) were susceptible to colistin and fosfomycin. There was consistent high-level resistance for all isolates to temocillin, piperacillin-tazobactam, amoxicillin-clavulanate and ticarcillin-clavulanate. When colonized and infected patients were compared, only prior carbapenem administration (P = 0.003), was found to be significantly associated with patients with CR-Kp infection.
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Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Portador Sadio/epidemiologia , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/efeitos dos fármacos , Resistência beta-Lactâmica , Adulto , Idoso , Portador Sadio/microbiologia , Monitoramento Epidemiológico , Feminino , Hospitais Universitários , Humanos , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Centros de Atenção Terciária , Turquia , Adulto Jovem , beta-Lactamases/análiseRESUMO
The aim of this study was to investigate the presence of carbapenem resistance in Enterobacteriaeceae isolates recovered from invasive infections, in Hacettepe University Hospital, Ankara, Turkey, between 2005-2009, by phenotypic and genotypic methods. A total of 210 non-duplicated Escherichia coli (n= 153), Klebsiella pneumoniae (n= 47) and Klebsiella oxytoca (n= 10) isolates which were all determined to be extended-spectrum beta-lactamase (ESBL) positive with the BD Phoenix automated identification and antibiotic susceptibility system (Sparks, USA), were included in the study. The isolates were recovered from patients with bloodstream infections. Susceptibility of the isolates to imipenem, meropenem and ertapenem was detected with microdilution method according to the standards of Clinical and Laboratory Standards Institute (CLSI) minimal inhibitory concentration (MIC) breakpoints. Doripenem susceptibility was detected by the E-test (bioMerieux, Hazelwood, USA). All isolates which were found to be non-susceptible to any of the carbapenem antibiotics tested, were characterized by the phenotypic confirmatory tests and the presence of the resistance genes; blaAmpC, blaCTX-M, blaKPC, blaNDM, blaOXA, blaIMP ve blaVIM were screened by polymerase chain reaction (PCR). Among the 210 ESBL-producing Enterobacteriaceae blood isolates, 23 (11%) were identified as non-susceptible to any of the carbapenems tested. Resistance rates for imipenem, meropenem and ertapenem were 5.7% (n= 12), 1.9% (n= 4) and 2.4% (n= 5), respectively. Doripenem was more active than the other carbapenems, with a resistance rate of 1.0%. Seven of 23 isolates were ESBL negative with cefotaxime/clavulanic acid (CTX/CLA) and ceftazidime/clavulanic acid (CAZ/CLA) combined disk diffusion test, however, six of them were ESBL positive with the addition of boronic acid (BA) to CTX/CLA. Among the three isolates positive for Modifiye Hodge test (MHT) and/or ertapenem-BA tests, blaOXA-48 was detected in one and blaAmpC in the other. Phenotypic pAmpC activity was present in three K.pneumoniae isolates of which one was positive for blaAmpC gene. One K.pneumoniae isolate resistant to all carbapenems with MICs > 256 µg/ml and positive for phenotypic meropenem-BA, MHT, imipenem-EDTA, ceftazidime-CAZ/CLA, cefoxitin-BA production, was found to inhabit blaOXA-48 gene. Five isolates were positive for blaOXA-1 and one for blaOXA-10. Two isolates were positive for blaCTX-M, however blaIMP, blaVIM and blaNDM-1 genes were not detected among the isolates. In conclusion, carbapenem non-susceptibility which was low among the Enterobacteriaceae strains isolated in our center, was mostly attributed to the presence of blaOXA type carbapenemases and no accumulation of blaKPC and blaNDM were detected.