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BACKGROUND: The present study aims to evaluate possible cardiac involvement in juvenile dermatomyositis (JDM) patients by conventional methods and cardiac magnetic resonance imaging (MRI) along with a systematic review of the literature on cardiac features in JDM. METHODS: The study group consisted of JDM patients who underwent cardiac MRI. We conducted a systematic review of the published literature involving JDM patients with cardiac involvement. RESULTS: In the present study, although baseline cardiologic evaluations including electrocardiography and echocardiography were within normal limits, we showed late gadolinium enhancement on cardiac MRI in 3 of 11 JDM patients. In the literature review, we identified 25 articles related to cardiac involvement in JDM. However, none of them, except one case report, included cardiac MRI of JDM patients. CONCLUSION: Cardiac abnormalities have been reported among the less frequent findings in patients with JDM. Cardiovascular complications during the long-term disease course are a leading cause of morbidity and mortality in these patients. Early detection of cardiac involvement by cardiac MRI in patients with JDM and aggressive treatment of them may improve the clinical course of these patients. IMPACT: The myocardium in patients with JDM may be involved by inflammation. Myocardial involvement may be evaluated by using contrast-enhanced cardiac MRI. This is the first study evaluating cardiac involvement by cardiac MRI in JDM patients. MRI may show early cardiac involvement in patients whose baseline cardiologic evaluations are within normal limits. Early detection of cardiac involvement by cardiac MRI may improve the long-term prognosis of patients with JDM.
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OBJECTIVE: Superoxide dismutase 1 (SOD1) is an important antioxidant enzyme whose main function is to neutralise superoxide free radicals in the cytoplasm. Heterozygous variants in SOD1 are responsible for a substantial percentage of familial amyotrophic lateral sclerosis (ALS) cases. Recently, several reports have shown that biallelic loss of SOD1 function results in a novel phenotype called infantile SOD1 deficiency syndrome, which is consistent with a recessive pattern of inheritance and can be distinguished from typical (adult-onset) ALS. METHODS: We documented detailed family histories and clinical data, followed by whole-exome sequencing and family co-segregation analysis through Sanger sequencing. To facilitate comparisons, relevant data from fifteen previously reported patients with SOD1-related neurodevelopmental disorders were included. RESULTS: This study presents a new Turkish family with two affected children exhibiting severe delayed motor development, infancy-onset loss of motor skills, axial hypotonia, tetraspasticity, and impaired cognitive functions. Genetic analysis revealed a novel homozygous frameshift variant in SOD1 (c.248dupG [p.Asp84Argfs*8]), with computational biochemical studies shedding light on the mechanistic aspects of SOD1 dysfunction. CONCLUSIONS: Our findings contribute an affirmative report of a fourth biallelic variant resulting in a severe clinical phenotype, reminiscent of those induced by previously identified homozygous loss-of-function SOD1 variants. This research not only advances our understanding of the pathogenesis of this debilitating neurological syndrome but also aligns with ongoing intensive efforts to comprehend and address SOD1-linked ALS.
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Esclerose Lateral Amiotrófica , Superóxido Dismutase-1 , Criança , Feminino , Humanos , Masculino , Esclerose Lateral Amiotrófica/genética , Sequenciamento do Exoma , Homozigoto , Linhagem , Fenótipo , Superóxido Dismutase-1/genética , Turquia , AdolescenteRESUMO
BACKGROUND: Trichohepatoenteric syndrome (THES) is characterized by neonatal-onset intractable diarrhea. It often requires long-term total parenteral nutrition (TPN). In addition, other characteristic findings of the syndrome include growth retardation, facial dysmorphism, hair abnormalities, various immunological problems and other rare system findings. Two genes and their associated pathogenic variants have been associated with this syndrome: SKIC3 and SKIC2. METHODS AND RESULTS: In this case series, the clinical findings and molecular analysis results of a total of 8 patients from 5 different families who presented with persistent diarrhea and were diagnosed with THES were shared. Pathogenic variants were detected in the SKIC3 gene in 6 of our patients and in the SKIC2 gene in 2 patients. It was planned to compare the clinical findings of our patients with other patients, together with literature data, and to present yet-undefined phenotypic features that may be related to THES. In our case series, in addition to our patients with a novel variant, patient number 2 had a dual phenotype (THES and Spondyloepimetaphyseal dysplasia, sponastrime type) that has not been reported yet. Delay in gross motor skills, mild cognitive impairment, radioulnar synostosis, osteoporosis, nephropathy and cystic lesions (renal and liver) were observed as unreported phenotypic findings. CONCLUSIONS: We are expanding the clinical and molecular repertoire of the syndrome regarding patients diagnosed with THES. We recommend that the NGS (next-generation sequencing) multigene panel should be used as a diagnostic tool in cases with persistent diarrhea.
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Doenças do Cabelo , Fenótipo , Humanos , Feminino , Masculino , Lactente , Doenças do Cabelo/genética , Doenças do Cabelo/diagnóstico , Genótipo , Pré-Escolar , DNA Helicases/genética , Diarreia Infantil/genética , Diarreia Infantil/diagnóstico , Mutação/genética , Diarreia/genética , Diarreia/diagnóstico , Criança , Recém-Nascido , Retardo do Crescimento Fetal , FáciesRESUMO
Mediastinal radiotherapy for childhood cancers, particularly Hodgkin disease, has numerous potential adverse effects, including coronary artery disease, pericarditis, cardiomyopathy, valvular disease, and conduction abnormalities. The prevalence of valvular stenosis is relatively low, and regurgitation is more common. Mediastinal radiotherapy-induced valvular disease develops more than 10 years after radiotherapy. Here, we present a case of a 6-year-old boy with moderate to significant mitral stenosis + moderate mitral regurgitation and mild aortic regurgitation that appeared 1.5 months after radiotherapy and showed a progressive course.
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Doenças das Valvas Cardíacas , Doença de Hodgkin , Estenose da Valva Mitral , Masculino , Humanos , Criança , Doença de Hodgkin/radioterapia , Doença de Hodgkin/etiologia , Doenças das Valvas Cardíacas/etiologia , Estenose da Valva Mitral/etiologia , Mediastino , Constrição Patológica , Radioterapia/efeitos adversosRESUMO
Predicting missing historical or forecasting streamflows for future periods is a challenging task. This paper presents open-source data-driven machine learning models for streamflow prediction. The Random Forests algorithm is employed and the results are compared with other machine learning algorithms. The developed models are applied to the Kizilirmak River, Turkey. First model is built with streamflow of a single station (SS), and the second model is built with streamflows of multiple stations (MS). The SS model uses input parameters derived from one streamflow station. The MS model uses streamflow observations of nearby stations. Both models are tested to estimate missing historical and predict future streamflows. Model prediction performances are measured by root mean squared error (RMSE), Nash-Sutcliffe efficiency (NSE), coefficient of determination (R2), and percent bias (PBIAS). The SS model has an RMSE of 8.54, NSE and R2 of 0.98, and PBIAS of 0.7% for the historical period. The MS model has an RMSE of 17.65, NSE of 0.91, R2 of 0.93, and PBIAS of -13.64% for the future period. The SS model is useful to estimate missing historical streamflows, while the MS model provides better predictions for future periods, with its ability to better catch flow trends.
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Algoritmo Florestas Aleatórias , Rios , Turquia , Algoritmos , PrevisõesRESUMO
BACKGROUND: To evaluate the macular and optic disc vascular changes in vitamin B12 deficiency anemia. METHODS: A total of 24 patients with vitamin B12 deficiency anemia and 24 healthy controls were involved in this study. All participants were evaluated for central macular thickness (CMT), peripapillary retina nerve fiber layer (RNFL) thickness, foveal avascular zone (FAZ) area, macular vessel density (VD) in superficial capillary plexus (SCP) and deep capillary plexus (DCP), choriocapillaris flow area, and optic disc radial peripapillary capillary (RPC) VD using optic coherence tomography (OCT) and optic coherence tomography angiography (OCTA). Metabolic parameters were also noted. RESULTS: Temporal RNFL thickness significantly decreased in the B12 deficiency anemia group (p = 0.04). Choriocapillaris flow area (p = 0.045) and macular vessel density in both SCP (p = 0.022) and DCP (p = 0.018) markedly declined in the study group. Optic disc RPC VD in the B12 deficiency anemia group was lower in all regions compared to that of the control group, but the difference was not statistically significant (p > 0.05). There were significant positive correlations between choriocapillaris flow area, macular VD, vitamin B12, and hemoglobin. CONCLUSION: Retinal vascular alterations were observed in B12 deficiency anemia, and OCTA may be beneficial in the diagnosis and follow-up of ocular complications in these cases.
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Anemia , Deficiência de Vitamina B 12 , Humanos , Angiofluoresceinografia/métodos , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/fisiologia , Tomografia de Coerência Óptica/métodos , Deficiência de Vitamina B 12/complicações , Deficiência de Vitamina B 12/diagnóstico por imagemRESUMO
Inflammation plays a key role in the progression of COVID-19 infection from acute viral disease to organ failure and death. Tocilizumab maintains its current place as a frequently preferred agent in hyperinflammatory syndrome in COVID-19 infection. This study was aimed to evaluate changes in oxygen parameters and inflammatory markers before and after treatment, to define survival rates and complications in the patients who have been followed up in the tertiary intensive care unit of our hospital with the diagnosis of COVID-19 and who have been administered tocilizumab for hyperinflammatory syndrome in the follow-up. This study was planned as a retrospective observational study. A total of 132 patients were included in the study. The patient's data; age, comorbidities, sequential organ failure assessment (SOFA) and acute physiologic assessment and chronic health evaluation II (APACHE II) scores, duration of stay on a mechanical ventilator, duration of stay in the intensive care unit, positivity of real-time polymerase chain reaction (Rt-PCR), the presence of lung tomography findings specific to SARS-CoV-2 pneumonia, survival data, laboratory parameters, lactate mmol/L, partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (PCO2), oxygen saturation % (SpO2) and partial pressure of oxygen/inspired oxygen (PaO2/FiO2) values on hospitalization date, tocilizumab administration date and post-administration days one, three, five, and seven; treatments administered and drug complications were recorded. IBM SPSS Version 25.0 statistical package program was used for statistical analysis. Of the 132 patients, 36 were female and 96 were male (p= 0.972). The mean age was 61.9 ± 1.07 years, the mean APACHE 2 score ± standard deviation (SD) was 14.89 ± 5.22 and mortality was 41.7%. The mean duration on a mechanical ventilator was 9.54 ± 15.63 days and the mean length of stay in the intensive care unit was 20.50 ± 15.48 days. A statistically significant difference was found between the PaO2, SpO2, and the PaO2/FiO2 values on the day of hospitalization and days one, three, five, and seven after tocilizumab administration, and also between the day of tocilizumab administration and days following the administration (p<0.001). There was a significant decrease in ferritin, D-dimer, and C-reactive protein levels, and a significant increase in the lymphocyte count (p<0.05). Elevated transaminases (n= 36), acute renal injury (n= 25), atrial fibrillation (n= 10), pneumothorax (n= 10), and pneumomediastinum (n= 6) were the most common complications during the disease. In our study, a significant improvement was observed in inflammatory parameters and oxygen parameters from the first day after tocilizumab administration. In the first seven days patient mortality was zero with improvement in the P/F ratios. These data supported the opinion that tocilizumab might be an effective treatment option for COVID-19 infection. In addition to the potential benefits of tocilizumab in critical COVID-19 patients, it is essential that the side effects related to the use of the drug be closely monitored, and early identification of and intervention in thromboembolic events increases survival.
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COVID-19 , Síndrome do Desconforto Respiratório , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , COVID-19/terapia , SARS-CoV-2 , Oxigênio , Tratamento Farmacológico da COVID-19 , Unidades de Terapia Intensiva , Resultado do TratamentoRESUMO
BACKGROUND: To examine firefighters (FFs) exposed to high levels of fire smoke and, as a result, to uncover risk factors for dry eye disorder (DED) compared to age-and gender-matched healthy individuals. METHODS: In this cross-sectional study, 51 FFs from the Afyonkarahisar Municipality Fire Department were chosen at random (group 1). A control group (group 2) included 51 age- and gender-matched healthy individuals. The Ocular Surface Disease Index (OSDI) questionnaire was administered after all participants were thoroughly explained the study's objectives and procedures. Then, using a portable hand biomicroscope, an ocular exam was performed on-site. DED was defined as a non-anesthetic Schirmer test result of <10 mm and/or a tear film break-up time (TBUT) of <5 seconds. RESULTS: Groups 1 and 2 had mean ages of 44.82±7.29 and 44.73±7.41 years, respectively (p=0.946). The median work duration in group 1 was 14 years (min-max: 1-27 years). TBUT test revealed a significantly increased DED prevalence in group 1 than group 2 (p=0.046). Despite the non-significant difference (p=0.276), Schirmer test revealed that group 1 had a higher DED prevalence than group 2. The OSDI score revealed that group 1 had more mild, moderate, and severe DED than group 2 (p=0.359). Longer work duration was associated with a higher DED prevalence (p=0.179). CONCLUSIONS: Given the high prevalence of fire smoke-induced DED in FFs, preventive measures such as regular ocular exams, encouraging personal protective equipment usage, and health education programs can assist in avoiding complications and reducing the burden of ocular diseases.
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Síndromes do Olho Seco , Bombeiros , Doenças Profissionais , Adulto , Humanos , Pessoa de Meia-Idade , Estudos Transversais , Síndromes do Olho Seco/etiologia , Síndromes do Olho Seco/complicações , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Lágrimas , Distribuição AleatóriaRESUMO
PURPOSE: To investigate changes in the retinal and optic disc (OD) morphology in prolactinoma patients without optical chiasmal compression and/or visual field defects using optical coherence tomography angiography (OCTA). METHODS: In this cross-sectional imaging study, 16 consecutive prolactinoma patients (group 1, 32 eyes) and 15 age- and gender-matched healthy subjects (group 2, 30 eyes) underwent a thorough neuro-ophthalmological examination, which included testing for the presence of any intracranial compressive lesion that could cause optic neuropathy. Retinal morphological parameters, outer retinal and choriocapillaris flow areas, as well as OD vessel density (VD) and retinal nerve fiber layer (RNFL) thickness in for quadrants were then measured using OCTA. RESULTS: Mean age (p = 0.537) and gender (p = 0.385) of participants in groups 1 and 2 did not differ significantly. The mean BCVA for both groups was 0.00 ± 0.00 logMAR. Microadenomas made up the majority of prolactinomas (87.1 %). All retinal morphological parameters in deep capillary plexus (excluding foveal VD) differed significantly between groups 1 and 2 (whole: p < 0.001, parafoveal: p = 0.021, and perifoveal: p < 0.001). Peripapillary RNFL thickness in temporal (p < 0.001), nasal (p = 0.010), and inferior (p = 0.007) quadrants also differed significantly between the two groups. Foveal deep (r = -0.304, p = 0.035) and choriocapillaris flow (r = -0.511, p = 0.008) were negatively correlated with tumor size at diagnosis. CONCLUSIONS: Significant microvascular morphological changes, particularly in the deep retinal layer, as well as in the peripapillary RNFL thickness, were observed in prolactinoma patients. OCTA appears to be capable of detecting non-manifest circumpapillary and even intra-retinal microvascular changes even when there are no obvious signs of prolactinoma-related ocular complications caused by chiasmal compression.
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Disco Óptico , Neoplasias Hipofisárias , Prolactinoma , Angiografia , Angiofluoresceinografia/métodos , Humanos , Disco Óptico/irrigação sanguínea , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/patologia , Prolactinoma/diagnóstico por imagem , Prolactinoma/patologia , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Tomografia de Coerência Óptica/métodosRESUMO
BACKGROUND: Maturity-onset diabetes of the young (MODY), which is the most common cause of monogenic diabetes, has an autosomal dominant pattern of inheritance and exhibits marked clinical and genetic heterogeneity. The aim of the current study was to investigate molecular defects in patients with clinically suspected MODY using a next-generation sequencing (NGS)-based targeted gene panel. METHODS: Candidate patients with clinical suspicion of MODY and their parents were included in the study. Molecular genetic analyses were performed on genomic DNA by using NGS. A panel of ten MODY-causal genes involving GCK, HNF1A, HNF1B, HNF4A, ABCC8, CEL, INS, KCNJ11, NEUROD1, PDX1 was designed and subsequently implemented to screen 40 patients for genetic variants. RESULTS: Ten different pathogenic or likely pathogenic variants were identified in MODY-suspected patients, with a diagnostic rate of 25%. Three variants of uncertain significance were also detected in the same screen. A novel pathogenic variant in the gene HNF1A (c.505_506delAA [p.Lys169AlafsTer18]) was described for the first time in this report. Intriguingly, we were able to detect variants associated with rare forms of MODY in our study population. CONCLUSIONS: Our results suggest that in heterogenous diseases such as MODY, NGS analysis enables accurate identification of underlying molecular defects in a timely and cost-effective manner. Although MODY accounts for 2-5% of all diabetic cases, molecular genetic diagnosis of MODY is necessary for optimal long-term treatment and prognosis as well as for effective genetic counseling.
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Diabetes Mellitus Tipo 2 , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Mutação/genéticaRESUMO
The coronavirus disease-2019 (COVID-19) pandemic continues to threaten the lives of millions of people. Viral shedding through the respiratory tract is the main risk factor for the transmission of the severe acute respiratory syndrome-2 (SARS-CoV-2) virus from sick individuals to healthy individuals. In this study, we aimed to investigate the viral clearance (VC) time in PCR tests of COVID-19 patients and the possible factors affecting this time. Seventy patients older than 18 years of age whose presence of SARS-CoV-2 virus was proven by real-time polymerase chain reaction (Rt-PCR) in nasopharyngeal swab samples were included in the study. The presence of SARS-CoV-2 RNA was investigated by RT-PCR in nasopharyngeal swab samples at 48-72 hour intervals, five days after the initial diagnosis. Demographic , physical examination, laboratory test, computed tomography (CT) results, concomitant diseases, and duration of VC were recorded. Of the cases, 41 were female and 29 were male. The mean age was 45.8 ± 19.2 years. According to the CT results, in the group with no involvement, local involvement and widespread involvement, the duration of VC was 9.66 ± 5.91 days, 9.99 ± 4.68 days, and 10.94 ± 5.34 days, respectively (p> 0.05). While the duration of VC was determined as 8.93 ± 4.33 days in the group without comorbidity, this period was found to be 12.26 ± 5.69 days (p= 0.025) in the group with the comorbidity. It was determined that the duration of VC was 9.55 ± 6.37 days in women and 9.20 ± 7.22 days in men (p= 0.040). The duration of VC was found to be 10.18 ± 7.1 days in patients over 50 years of age and 8.87 ± 5.15 days under 50 years of age (p= 0.03). A significant correlation was found between the laboratory test lactate dehydrogenase level and VC duration (p= 0.007). However, a significant relationship could not be established between other laboratory test results and the duration of VC. In this retrospective observational study, the relationship between viral clearance duration in Rt-PCR and gender, age, CT results, comorbidities and laboratory results in nasopharyngeal swab samples was investigated and it was determined that the duration of VC was significantly prolonged in case of female gender, being over 50 years old and having a comorbid disease. The results obtained may contribute to predict the isolation times of the patients and to reveal the factors that may affect viral shedding.
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COVID-19 , Adulto , Idoso , COVID-19/diagnóstico , Teste para COVID-19 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nasofaringe , RNA Viral/análise , Reação em Cadeia da Polimerase em Tempo Real , SARS-CoV-2/genéticaRESUMO
Marfan syndrome (MFS) is an autosomal dominant genetic condition that mainly affects connective tissue in many parts of the body. Cardinal manifestations involve the ocular, skeletal, and cardiovascular systems. The diagnosis of MFS relies on the revised Ghent criteria, outlined by international expert opinion to facilitate accurate recognition of this syndrome as well as to improve patient management and counseling. However, it may not always be possible to make a definitive diagnosis according to these criteria in each patient and thus molecular confirmation is necessary in subjects with suspected MFS. This debilitating, if not fatal, disorder is caused by mutations in FBN1, which encodes a major constitutive element of extracellular microfibrils. Here, we present a detailed clinical and molecular analysis of 76 Turkish patients with definitive or suspected MFS diagnosed at our center between 2014 and 2019. We were able to identify a total of 51 different FBN1 variants in our cohort, 31 of which have previously been reported in the relevant scientific literature. The remaining 20 variants have not been documented to date. In one patient, we detected a large deletion including the entire FBN1 gene using the array CGH approach. Currently, there are very few studies on the genotype-phenotype correlation of patients with MFS, and no clear genotype-phenotype maps for MFS have been constructed so far, except for some cases. We believe that our findings will make a rich and peculiar contribution to the elusive genotype-phenotype relationship in MFS, especially in this large and populous ethnic group.
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Fibrilina-1/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Síndrome de Marfan/genética , Adolescente , Criança , Pré-Escolar , Hibridização Genômica Comparativa , Feminino , Humanos , Masculino , Síndrome de Marfan/epidemiologia , Síndrome de Marfan/patologia , Linhagem , Polimorfismo de Nucleotídeo Único/genética , Deleção de Sequência/genética , Turquia/epidemiologiaRESUMO
Evaluating trends in antibiotic resistance is a requisite. The study aimed to analyze the profile of multidrug-resistant organisms (MDROs) among hospitalized patients with bacteremia in intensive care units (ICUs) in a large geographical area. This is a 1-month cross-sectional survey for blood-borne pathogens in 57 ICUs from 24 countries with different income levels: lower-middle-income (LMI), upper-middle-income (UMI), and high-income (HI) countries. Multidrug-resistant (MDR), extensively drug-resistant (XDR), or pan-drug-resistant isolates were searched. Logistic regression analysis determined resistance predictors among MDROs. Community-acquired infections were comparable to hospital-acquired infections particularly in LMI (94/202; 46.5% vs 108/202; 53.5%). Although MDR (65.1%; 502/771) and XDR (4.9%; 38/771) were common, no pan-drug-resistant isolate was recovered. In total, 32.1% of MDR were Klebsiella pneumoniae, and 55.3% of XDR were Acinetobacter baumannii. The highest MDR and XDR rates were in UMI and LMI, respectively, with no XDR revealed from HI. Predictors of MDR acquisition were male gender (OR, 12.11; 95% CI, 3.025-15.585) and the hospital-acquired origin of bacteremia (OR, 2.643; 95%CI, 1.462-3.894), and XDR acquisition was due to bacteremia in UMI (OR, 3.344; 95%CI, 1.189-5.626) and admission to medical-surgical ICUs (OR, 1.481; 95% CI, 1.076-2.037). We confirm the urgent need to expand stewardship activities to community settings especially in LMI, with more paid attention to the drugs with a higher potential for resistance. Empowering microbiology laboratories and reports to direct prescribing decisions should be prioritized. Supporting stewardship in ICUs, the mixed medical-surgical ones in particular, is warranted.
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Bactérias/efeitos dos fármacos , Infecções Bacterianas/microbiologia , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana Múltipla , Unidades de Terapia Intensiva/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Infecções Bacterianas/epidemiologia , Criança , Pré-Escolar , Infecção Hospitalar/epidemiologia , Estudos Transversais , Europa (Continente)/epidemiologia , Feminino , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Adulto JovemRESUMO
Mucolipidosis III gamma (ML III γ) is a slowly progressive disorder that affects multiple parts of the body such as the skeleton, joints, and connective tissue structures. It is caused by pathogenic variants in the GNPTG gene that provides instructions for producing the γ subunit of GlcNAc-1-phosphotransferase. In this study we aim to characterize clinical findings and biological insights on two novel GNPTG variants causing ML III γ phenotypes with varying severity. We report on two siblings with ML III γ bearing the previously undescribed c.477C > G (p.Y159*) nonsense variant in a homozygous state as well as a patient with ML III γ bearing the novel c.110 + 19_111-17del variant in a homozygous state. These variants were revealed by whole-exome sequencing and Sanger sequencing, respectively. Their parents, who are heterozygotes for the same mutation, are healthy. The clinical and radiographic presentation of ML III γ in our patients who had c.477C > G (p.Y159*) variant is consistent with a relatively severe form of the disease, which is further supported by a working three-dimensional model of the GlcNAc-1-phosphotransferase γ subunit. On the other hand, it is seen that our patient who carries the c.110 + 19_111-17del variant has a milder phenotype. Our findings help broaden the spectrum of GNPTG variants causing ML III γ and offer structural and mechanistic insights into loss of GlcNAc-1-phosphotransferase γ subunit function.
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Predisposição Genética para Doença , Mucolipidoses/genética , Transferases (Outros Grupos de Fosfato Substituídos)/genética , Códon sem Sentido/genética , Feminino , Homozigoto , Humanos , Articulações/patologia , Masculino , Mucolipidoses/patologia , Fenótipo , Índice de Gravidade de Doença , Irmãos , Esqueleto/patologia , Sequenciamento do ExomaRESUMO
Elongator is a multi-subunit protein complex bearing six different protein subunits, Elp1 to -6, that are highly conserved among eukaryotes. Elp2 is the second major subunit of Elongator and, together with Elp1 and Elp3, form the catalytic core of this essential complex. Pathogenic variants that affect the structure and function of the Elongator complex may cause neurodevelopmental disorders. Here, we report on a new family with three children affected with a severe form of intellectual disability along with spastic tetraparesis, choreoathetosis, and self injury. Molecular genetic analyses reveal a homozygous missense variant in the ELP2 gene (NM_018255.4 (ELP2): c.1385G > A (p.Arg462Gln)), while in silico studies suggest a loss of electrostatic interactions that may contribute to the overall stability of the encoded protein. We also include a comparison of the patients with ELP2-related neurodevelopmental disorder to those previously reported in the literature. Apart from being affected with intellectual disability, we have extremely limited clinical knowledge about patients harboring ELP2 variants. Besides providing support to the causal role of p.Arg462Gln in ELP2-related neurodevelopmental disorder, we add self-injurious behavior to the clinical phenotypic repertoire of the disease.
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Deficiência Intelectual/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Síndrome de Lesch-Nyhan/genética , Paresia/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Sequência de Aminoácidos , Consanguinidade , Família , Feminino , Expressão Gênica , Homozigoto , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/metabolismo , Deficiência Intelectual/patologia , Peptídeos e Proteínas de Sinalização Intracelular/química , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Síndrome de Lesch-Nyhan/diagnóstico , Síndrome de Lesch-Nyhan/metabolismo , Síndrome de Lesch-Nyhan/patologia , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Paresia/diagnóstico , Paresia/metabolismo , Paresia/patologia , Linhagem , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Eletricidade Estática , Turquia , Sequenciamento do Exoma , Adulto JovemRESUMO
BACKGROUND: Tea, second only to water, is one of the most regularly consumed drinks in the world. Its potentially beneficial effects on general health may be enormously important. Optical coherence tomography angiography (OCTA) now allows clinicians to examine the acute retinal morphological changes caused by black tea consumption. The purpose of this study was to investigate the acute impacts of a Camellia sinensis fermentation end-product (black tea) on retinal microvasculature in healthy individuals using OCTA. RESULTS: In this study, 60 healthy people were divided into two groups: group 1 (n = 30) received black tea (2 mg/250 mL of water) and group 2 (n = 30) received only 250 mL of water. Following consumption, AngioVue Analytics software automatically analyzed the foveal, parafoveal, perifoveal macular superficial and deep vascular plexus densities, foveal avascular zone (FAZ) area, FAZ perimeter and foveal vessel density in a 300 µm wide region around the FAZ (FD-300). Male-to-female ratios were 19:11 and 15:15 in groups 1 and 2, respectively (P = 0.217). Mean age was 33.27 ± 7.92 years in group 1 and 31.00 ± 7.30 years in group 2 (P = 0.254). Changes in foveal, perifoveal and parafoveal macular vessel density between groups 1 and 2 were not statistically significant. In addition, no significant differences regarding FAZ, FAZ perimeter and FD-300 were observed. CONCLUSION: There were no acute effects of black tea on macular microcirculation in healthy individuals. The authors, however, believe that this study could serve as a model for future research on the relationship between regular tea consumption and general ocular physiology. © 2021 Society of Chemical Industry.
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Camellia sinensis/metabolismo , Macula Lutea/irrigação sanguínea , Microvasos/diagnóstico por imagem , Retina/diagnóstico por imagem , Chá/metabolismo , Adulto , Angiografia , Camellia sinensis/química , Feminino , Humanos , Macula Lutea/diagnóstico por imagem , Masculino , Microcirculação , Microvasos/fisiologia , Folhas de Planta/química , Folhas de Planta/metabolismo , Estudos Prospectivos , Retina/fisiologia , Tomografia de Coerência Óptica , Adulto JovemRESUMO
PURPOSE: To investigate changes in macular and panretinal neuroretinal functions by electroretinographic examinations in eyes with diabetic macular edema (DME) treated with intravitreal ranibizumab. MATERIAL AND METHODS: Sixty-four patients with DME were included in this prospective study. Patients were treated with ranibizumab injection according to the PRN regimen for over 12 months. Before treatment, all patients underwent fundus fluorescein angiography, optical coherence tomography (OCT), best-corrected visual acuity (BCVA) assessment, full-field (ff-ERG), and multifocal electroretinography (mf-ERG). In monthly visits, BCVA and OCT were performed. Besides, mf-ERG recordings were obtained at months 3, 6, 9, and 12, and ff-ERG was performed at month 12. RESULTS: Fifty-eight patients completed the study. The mean age was 61.1 ± 8.5 (39-80) years. The mean number of injections was 6.19 ± 1.9. The decimal BCVA improved from 0.30 to 0.45 during the 12-month follow-up (p < 0.05). Macular thickness decreased from 413.5 µm to 329.5 µm (p < 0.05). The mf-ERG recordings in the central macular region showed improvements N1 and P1 amplitudes at months 9 and 12. There was a positive correlation between the baseline central (p < 001; r: - 0.378 and p < 0.05; r:-0.335, respectively), the second ring (p < 0.05; r: - 0.260 and p < 0.05; r: - 0.270, respectively) P1- and N1-wave amplitudes, and the BCVA at month 12. Full-field ERG recordings showed that peripheral neuroretinal responses were maintained or improved at month 12. Statistically significant improvements in BCVA and macular thickness were observed at all follow-up visits. CONCLUSION: Multifocal electroretinographic recording started to improve 6 months after the beginning of intravitreal ranibizumab treatment in eyes with DME. This improvement was significant at months 9 and 12. A significant improvement in ff-ERG was observed at month 12.
Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Idoso , Inibidores da Angiogênese/uso terapêutico , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/tratamento farmacológico , Eletrorretinografia , Humanos , Injeções Intravítreas , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Ranibizumab/uso terapêutico , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular , Acuidade VisualRESUMO
PURPOSE: To evaluate anatomical and neuroretinal functional aspects in patients with diabetic macular edema (DME) after intravitreal anti-vascular endothelial growth factor (VEGF) therapy, in particular aflibercept. MATERIALS AND METHODS: This prospective single-centered interventional study was performed at Afyonkarahisar Health Science University Faculty of Medicine, Department of Ophthalmology, where 32 eyes of 32 patients with DME were investigated. All patients received five intravitreal aflibercept injections on a monthly basis and were followed up for ≥ 6 months. After a comprehensive ophthalmological examination, including the measurements of visual acuity and intraocular pressure, and an antero-posterior segment slit-lamp biomicroscopy before and after full pupil dilation, fundus fluorescein angiography and optical coherence tomography were performed at baseline and during the third and sixth months post-therapy. Microperimetry and multifocal electroretinography were also performed at baseline and during the sixth months. RESULTS: Mean visual acuity increased from 0.73 to 0.57 and 0.33 logarithm of the minimum angle of resolution (logMAR) during the third and sixth months, respectively (p < 0.001). Changes in intraocular pressure were not statistically significant (p = 0.472). There was statistically significantly decreased mean central macular thickness from 390.2 µm to 242.6 and 289.7 µm during the third and sixth months, respectively (p < 0.001). Significantly improved fixation patterns during the sixth month, along with significantly increased macular sensitivity from 8.2 to 14.2 dB (p < 0.001) and significantly decreased local deficit from - 10.3 to 5.5 dB (p < 0.001) were observed. Further, there was a significantly increased N1 amplitude in the first ring and significantly increased P1 amplitude in all rings (p for each parameter < 0.05). There was also significantly decreased N1 wave implicit time in all rings and significantly decreased P1 wave in the second, third, fourth and fifth rings (p for each parameter < 0.05). CONCLUSIONS: Patients with DME showed profound improvement in the retinal neurophysiological function, which was also accompanied by anatomical and ultrastructural integrity recovery after intravitreal aflibercept therapy. In the pathogenesis of DME, the influence of neurodegeneration has been increasingly gaining significant attention. Consequently, the need to assess neurophysiological effects of anti-VEGF therapy using a variety of diagnostic measures like electrophysiological studies and multimodal imaging technologies is undeniably growing.
Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Inibidores da Angiogênese/uso terapêutico , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/tratamento farmacológico , Seguimentos , Humanos , Injeções Intravítreas , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Estudos Prospectivos , Tomografia de Coerência Óptica , Resultado do TratamentoRESUMO
PURPOSE: To analyze the vascular morphology changes after consumption of Ginkgo biloba in healthy volunteers by optical coherence tomography angiography (OCTA). METHODS: Sixty healthy volunteers without systemic and ocular disease were included in this prospective pilot study. After receiving the informed consent of the volunteers, Ginkgo biloba extract (120 mg oral capsule) was administered to sixty volunteers for 4 weeks, once a day in the morning. The main outcome measures were the difference between before and after four-week of consumption in best-corrected visual acuity (BCVA), retinal nerve fiber layer (RNFL) and subfoveal choroidal thickness (sfCT) with optical coherence tomography; whole, foveal, parafoveal and perifoveal regions' superior and deep macular vascular plexus vessel density, foveal avascular zone area (FAZ), FAZ perimeter (PERIM), vessel density in a 300 µm wide region around FAZ (FD-300), choroidal and outer retinal flow area, radial peripapillary capillary (RPC) vascular density of whole, inside the disc, peripapillary and four quadrants with OCTA. RESULTS: The study group consisted of sixty eyes of 32 women and 28 men with a mean age of 20.57 ± 1.16 years. In post-consumption measurements, peripapillary and superior, inferior, temporal quadrant RPC vascular density (%) was statistically significantly higher than pre-consumption measurements (p 0.020, p 0.021, p 0.008 and p 0.014, respectively). No significant difference was observed for BCVA, sfCT, other macular or RPC vascular density and flow area OCTA parameters between measurements. CONCLUSION: Four-week consumption of Ginkgo biloba leads to vascular morphological changes in RPC. Further clinical studies are needed to demonstrate its use and effects/benefits in glaucoma, optic neuropathy and other diseases affecting the optic nerve.
Assuntos
Ginkgo biloba , Tomografia de Coerência Óptica , Adulto , Feminino , Angiofluoresceinografia , Humanos , Masculino , Projetos Piloto , Extratos Vegetais , Estudos Prospectivos , Vasos Retinianos/diagnóstico por imagem , Adulto JovemRESUMO
Background/aim: Increase in publications supporting myocardial involvement in the COVID-19 disease has led to need to gain insight into the the global burden of heart failure after pandemic. We examined the course of myocardial systolic function in patients without elevated troponin levels. Materials and methods: We performed a prospective study. Patients with high troponin levels were excluded from the study in order to definitively exclude complications known to cause permanent left ventricular systolic dysfunction, such as acute coronary syndromes. Two echocardiographic examinations were performed. The first evaluation was performed within the days of hospitalization, if possible, on the day when dyspnea is severe. The second evaluation was performed during the outpatient clinic controls one month after the patient was recovered. Left ventricular ejection fraction (LVEF) was measured using the biplane method of disks (modified Simpson's rule). Results: In the first evaluation, LVEF was found to be significantly lower in the severe illness group than mild/moderate illness group (50 ± 6% and 59 ± 6%; p = 0.03). LVEF decrease (<50%) was found in fifteen patients (43 ± 4%) and detected as global hypokinesia but not segmental. All of these patients were in the severe illness group. In the second evaluation, LVEFs of the fifteen patients with decreased LVEF in the first evaluation were improved and detected in normal limits (first evaluation = 43 ± 4% and second evaluation = 55 ± 2%, p = 0.01). Conclusion: Considering patients without elevated troponin levels during COVID-19 infection, no permanent systolic dysfunction was detected after first month of recovery. We found that transient myocardial dysfunction may develop in the severe illness group with normal troponin levels, LVEF may decrease in the acute phase and improve with the recovery period.