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Objective: To study the prevalence of common dyslipidemia among overweight and obese children between 2-18 years in a tribal region. Methods: This cross-sectional study was carried out in 151 overweight and obese children aged 2-18 years, who visited the pediatric outpatient department of a tertiary care hospital in Jharkhand between 1 August and 30 November, 2022. Dyslipidemia was defined as anyone of the following: a total cholesterol level of 240 mg/dL, a triglyceride level of 150 mg/dL, a low-density lipoprotein cholesterol level (LDL-C) of 140 mg/dL, a high-density lipoprotein cholesterol level (HDL-C) of 40 mg/dL, or the use of a lipid-lowering drug [8]. Overweight and obesity were defined as per World Health Organization criteria. Result: The prevalence of dyslipidemia was 63.6%. The most common type of dyslipidemia was low HDL-C + high TG levels found in 32.5% (n=49) children. The most prevalent pattern of dyslipidemia in overweight children was low HDL-C (19, 32.3%); and in obese children low HDL-C and high TG levels (39, 42.3%). Conclusion: The prevalence rate of dyslipidemia was high among overweight and obese children in this region. There was a positive association between dyslipidemia and body mass index.
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Purpose: The objective of this study was to identify the association between fetal hemoglobin (HbF) concentration, blood transfusion, and retinopathy of prematurity (ROP) in preterm infants. Methods: This was an observational, prospective study. A total of 410 preterm infants born with <36 weeks gestational age and <2.0 kg birth weight in a tertiary care center of central India for a period of 1 year were included in this study. Clinical data were obtained from case notes. HbF of infants was measured in the blood sample using high?performance liquid chromatography at the first visit and after 1 month follow?up and was analyzed statistically. Dilated fundus examination was done as per ROP screening guidelines, and ROP was classified as per the International Classification of Retinopathy of Prematurity (ICROP), 2021. The study subjects were divided into two groups based on the status of ROP. The relationship among HbF, blood transfusion, and ROP was evaluated in both the groups. The relationship between other clinical characteristics and various neonatal risk factors was also studied between the groups. Results: A total of 410 preterm infants were included in this study, of which 110 infants had ROP (26.8%). Blood transfusion was found to be significantly associated with the development of ROP. Higher fraction of HbF (%) was associated with a lower prevalence of ROP. HbF was also inversely related with the severity of ROP. Conclusion: Replacing HbF by adult hemoglobin during blood transfusion may promote the development of ROP. Conversely, maintaining a higher percentage of HbF may be a protective factor against ROP.
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Humans , Female , Pregnancy , Brugada Syndrome/complications , Anesthesia, Obstetrical , Anesthesia, Spinal , Bupivacaine , Cesarean Section , Anesthetics, LocalABSTRACT
As part of U-40 activities, chapters have traditionally held sessions of lectures and hands-on as the Basic Lecture Course (BLC) to improve the basic skills and knowledge of young cardiovascular surgeons. Because of the COVID-19 epidemic, we have shifted our activities from onsite to online. This column focuses on “management of postoperative delirium and pain” in the lecture of “Postoperative Management in Cardiovascular Surgery” given by the Chubu Chapter in 2020. We summarize the lecture and report the results of a questionnaire survey of the U-40 members.
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Prevention, early diagnosis, and early treatment of skeletal-related events (SREs) are important in the treatment of potential or current cases of bone metastasis. In August 2020, our hospital established the bone metastasis team and the bone metastasis board (BMB) started actively engaging in activities aimed at improving the outcome of bone metastasis. We retrospectively examined whether a combined modality therapy started in the diagnosis of bone metastases could prevent the onset of SREs and whether it could prolong survival and improve activities of daily living. The 75 advanced cancer patients who underwent BMB at our hospital from August 1, 2020 to July 31, 2022 were divided into two groups according to when BMB performed before and after SREs for comparative analysis. Numerical Rating Scale improved, however Performance Status did not improve in both groups, and there was no difference in survival between the both groups (15.3 vs. 9.0 months, HR: 0.74, 95%; CI: 0.42–1.29, p=0.29). In conclusion, patients who suffered from SREs from the time of bone metastasis diagnosis were treated early. However, the incidence of SREs after BMB in our hospital was 22.6%, and it is necessary to actively work to prevent SREs in the future.
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SUMMARY: The superior vena cava is usually located only on the right side, but persistence of the left superior vena cavais observed in about 0.3 to 0.5 % of adults. A routine dissection of the cadaver of a 91-year-old Japanese female, whose cause of death was sepsis due to cholecystitis, was performed at Nagasaki University and revealed a double-sided superior vena cava. On the right side, the superior vena cava opened to the right atrium, while on the left, it opened into the extended coronary sinus. Veins in the left head, neck and upper limb regions joined to form the persistent left superior vena cava, with eventual drainage into the expanded coronary vein. An anastomosing branch occurred between each superior vena cava, and two thymic veins opened to the anastomosing branch. The azygos vein in the azygos venous system opened into the right superior vena cava, whereas a hemi-azygos vein opened into the azygos vein. The accessory hemi-azygos vein also opened into the azygos vein and opened cranially into the left superior vena cava. The left supreme intercostal vein also opened into the left superior vena cava. Several studies have reported a persistent left superior vena cava and the various considerations for its occurrence. Here, we propose a new hypothesis for the embryonic development of the persistent left superior vena cava with the thymic vein. This hypothesis essentially states that the left brachiocephalic vein fails to mature due to inadequate venous return from the thymic vein during the embryonic period, and the left superior vena cava then remains to maintain venous return from the left head, neck and upper limb. We also discuss the clinical significance of the persistent left superior vena cava.
RESUMEN: Usualmente la vena cava superior se localiza solo en el lado derecho, sin embargo en aproximadamente 0,3 a 0,5 % de los adultos se observa la persistencia de la vena cava superior izquierda. En la Universidad de Nagasaki se realizó una disección de rutina del cadáver de una mujer japonesa de 91 años, cuya causa de muerte fue sepsis debido a una colecistitis. El cuerpo presentaba una vena cava superior doble. En el lado derecho, la vena cava superior llegaba al atrio derecho, mientras que en el lado izquierdo drenaba al seno coronario. Las venas de las regiones de la cabeza, el cuello y del miembro superior izquierdo formaban la vena cava superior izquierda persistente, con drenaje hacia la vena coronaria. Se observó una rama anastomótica entre cada vena cava superior y dos venas tímicas drenaban a la rama anastomótica. La vena ácigos drenaba a la vena cava superior derecha, mientras que una vena hemiácigos drenaba a la vena ácigos. La vena hemiácigos accesoria también drnaba en la vena ácigos y cranealmente lo hacia la vena cava superior izquierda. La vena intercostal suprema izquierda drenaba en la vena cava superior izquierda. Varios estudios han informado una vena cava superior izquierda persistente y las diversas consideraciones para su aparición. Aquí, proponemos una nueva hipótesis para el desarrollo embrionario de la vena cava superior izquierda persistente con la vena tímica, que esencialmente establece que la vena braquiocefálica izquierda no se dearrolla debido a un retorno venoso inadecuado de la vena tímica durante el período embrionario, y se mantiene la vena cava superior izquierda para el retorno venoso de la cabeza, el cuello y el miembro superior izquierdo. Además se informa de la importancia clínica de la persistencia de la vena cava superior izquierda.
Subject(s)
Humans , Female , Aged, 80 and over , Anatomic Variation , Persistent Left Superior Vena Cava/pathology , Azygos Vein , CadaverABSTRACT
Objective : Parkinson’s disease (PD) is a disease treated by polytherapy. This time, the authors report the role of pharmacists in one of the few Parkinson’s disease facilities in Japan (https://sunwels.jp/pdhouse/; abbreviated as PD House), which was born from the voices of PD patients. Methods : The backgrounds of 52 patients admitted to the PD House and prescriptions for them were analyzed to mainly clarify: the percentages of patients aged 75 or over and those using 7 or more prescribed drugs; and frequently used drugs to be carefully administered to the elderly. The approaches provided by pharmacists through interprofessional collaboration were also analyzed. Results : The percentages of patients aged 75 or over and those receiving benefits for individuals requiring care were 71.2 and 92.3%, respectively. Those using 7 or more prescribed drugs accounted for 75.0%. In multidisciplinary collaboration, pharmacists were involved in not only pharmacotherapy but also nutritional evaluation of patients with severe nutritional disorders, proposal of appropriate nutritional therapy, understanding of swallowing function, and appropriate medication teaching. Conclusion : The actual situation of PD patients, where they used multiple drugs, and their backgrounds suggest that interprofessional collaboration is indispensable for PD treatment, and the roles of pharmacists were shown to be important.
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We provided inpatient rehabilitation treatment and return-to-school guidance to a junior high school student with medulloblastoma and pervasive developmental disorder (autism spectrum disorder). Here we describe the rehabilitation treatment for patients with physical and developmental disabilities. A 13-year-old boy who was diagnosed with pervasive developmental disorder at 4 years of age was able to perform activities of daily living independently and attend junior high school. However, he was admitted to our hospital with new-onset ataxia. Magnetic resonance imaging revealed a cerebellar tumor. After total tumor excision was performed, pathological analysis revealed medulloblastoma, which was treated initially with radiation therapy and then chemotherapy for 1 year. Rehabilitation was initiated 2 days post-surgery. We evaluated his communication abilities. He showed stereotypical behavior owing to the autism spectrum disorder；therefore, we performed low-intensity repetitive exercises. The functional independence measure score at discharge was 67/126 (motor 44/91, cognitive 23/35). We taught his teachers how to properly assist him, and he successfully returned to school post-discharge. Although this was a case in which the child had multiple disabilities, ataxia caused by the medulloblastoma aggravated his developmental disability. Thus, understanding the characteristics of communication and its strengths was vital in determining a treatment plan that enabled his return to school.
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Objective: To evaluate the efficacy of fan therapy for the relief of dyspnea in patients with chronic progressive disease. Methods: A systematic electronic database search of all available articles published before October 23, 2019 was conducted using Ichushi-Web of the Japan Medical Abstract Society databases, CENTRAL, EMBASE, and MEDLINE. In addition, a hand-search for updates was performed using PubMed on June 30, 2020 and December 7, 2021. The inclusion criteria were: 1) any RCTs comparing the effect of fan therapy with any other intervention, and 2) patients aged ≥18 years. Exclusion criteria were: 1) duplicate references, and 2) conference presentations. Results: We identified 110 studies, of which 10 met our criteria for inclusion. Finally, five studies were used in the meta-analysis. Fan therapy significantly improved dyspnea in patients with chronic progressive disease compared to control groups with a standardized mean difference of −1.43 (95% confidence interval: −2.70 to −0.17, I2=94%, p<0.0001). Conclusion: Fan therapy was found to be effective in reducing dyspnea in chronic progressive disease.
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We provided inpatient rehabilitation treatment and return-to-school guidance to a junior high school student with medulloblastoma and pervasive developmental disorder (autism spectrum disorder). Here we describe the rehabilitation treatment for patients with physical and developmental disabilities. A 13-year-old boy who was diagnosed with pervasive developmental disorder at 4 years of age was able to perform activities of daily living independently and attend junior high school. However, he was admitted to our hospital with new-onset ataxia. Magnetic resonance imaging revealed a cerebellar tumor. After total tumor excision was performed, pathological analysis revealed medulloblastoma, which was treated initially with radiation therapy and then chemotherapy for 1 year. Rehabilitation was initiated 2 days post-surgery. We evaluated his communication abilities. He showed stereotypical behavior owing to the autism spectrum disorder；therefore, we performed low-intensity repetitive exercises. The functional independence measure score at discharge was 67/126 (motor 44/91, cognitive 23/35). We taught his teachers how to properly assist him, and he successfully returned to school post-discharge. Although this was a case in which the child had multiple disabilities, ataxia caused by the medulloblastoma aggravated his developmental disability. Thus, understanding the characteristics of communication and its strengths was vital in determining a treatment plan that enabled his return to school.
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The importance of off the job training in surgical education are widely recognized. The Japanese Board of Cardiovascular Surgery has required a board candidate to do at least 30 hours of off the job training from 2017. U-40 Basic Lecture Course are held annually for young cardiovascular surgeon to learn about basic surgical skills. U-40 Advanced Lecture Course was started to provide opportunity to have more advanced hands-on lecture for young cardiovascular surgeon. However, after the COVID-19 pandemic, the opportunity to hold hands-on seminars are highly limited. In such circumstances, we held a hybrid hands-on seminar. We report details about the hybrid hands-on seminar.
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Abstract Objective Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a member of the carcinoembryonic antigen family. Although its expression has been found in chronic oral inflammatory epithelium, this study aimed to know whether CEACAM1 in oral keratinocytes participates in host immune response against Candida albicans . Methodology We investigated CEACAM1 expression in oral keratinocytes induced by C. albicans as well as by Candida cell wall component β-glucan particles (β-GPs). Furthermore, the effects of CEACAM1 on β-GPs-induced heme oxygenase-1 (HO-1) expression and its related signals were examined. Results Fluorescence staining showed CEACAM1 expression in oral keratinocytes (RT7) cells, whereas quantitative reverse transcription (RT)-PCR indicated that both live and heat-killed C. albicans increased CEACAM1 mRNA expression in RT7 cells. Examinations using quantitative RT-PCR and western blotting indicated that CEACAM1 expression was also increased by β-GPs derived from C. albicans . Specific siRNA for CEACAM1 decreased HO-1 expression induced by β-GPs from C. albicans as well as the budding yeast microorganism Saccharomyces cerevisiae . Moreover, knockdown of CEACAM1 decreased β-GPs-induced ROS activity in the early phase and translocation of Nrf2 into the nucleus. Conclusion CEACAM1 in oral keratinocytes may have a critical role in regulation of HO-1 for host immune defense during Candida infection.
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Abstract Objectives To analyze the efficiency of a multigenic targeted massively parallel sequencing panel related to endocrine disorders for molecular diagnosis of patients assisted in a tertiary hospital involved in the training of medical faculty. Material and methods Retrospective analysis of the clinical diagnosis and genotype obtained from 272 patients in the Endocrine unit of a tertiary hospital was performed using a custom panel designed with 653 genes, most of them already associated with the phenotype (OMIM) and some candidate genes that englobes developmental, metabolic and adrenal diseases. The enriched DNA libraries were sequenced in NextSeq 500. Variants found were then classified according to ACMG/AMP criteria, with Varsome and InterVar. Results Three runs were performed; the mean coverage depth of the targeted regions in panel sequencing data was 249×, with at least 96.3% of the sequenced bases being covered more than 20-fold. The authors identified 66 LP/P variants (24%) and 27 VUS (10%). Considering the solved cases, 49 have developmental diseases, 12 have metabolic and 5 have adrenal diseases. Conclusion The application of a multigenic panel aids the training of medical faculty in an academic hospital by showing the picture of the molecular pathways behind each disorder. This may be particularly helpful in developmental disease cases. A precise genetic etiology provides an improvement in understanding the disease, guides decisions about prevention or treatment, and allows genetic counseling.
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Abstract Objective: Although oral fibroblasts are thought to have the potential to enhance host defenses against Candida albicans , it is unknown whether they are able to recognize Candida cell components to increase the expression of antifungal peptides, such as defensin factors, against Candida infection. Methodology: We performed expression profiles of defensin genes induced by heat-killed C. albicans in oral immortalized fibroblasts (GT1) using cDNA microarray analysis. From those results, quantitative RT-PCR was used to examine the effects of Candida β-glucan-containing particles (β-GPs) on β-Defensin 118 (DEFB 118) expression in oral mucosal cells. Furthermore, the antifungal activities of recombinant DEFB 118 against C. albicans and C. glabrata were investigated using fungicidal assays. Results: Microarray analysis showed that DEFB118, β-Defensin 129 (DEFB129), and α-Defensin 1 (DEFA1) genes were induced by heat-killed C. albicans and that their mRNA expressions were also significantly increased by live as well as heat-killed C. albicans . Next, we focused on DEFB118, and found that GT1, primary fibroblasts, and RT7 (oral immortalized keratinocytes) constitutively expressed DEFB118 mRNA expression in RT-PCR. Furthermore, C. albicans β-GPs significantly increased the expression of DEFB118 mRNA in GT1 and primary fibroblasts. Although DEFB118 mRNA expression in RT7 was significantly induced by both live and heat-killed C. albicans, C. albicans β-GPs failed to have an effect on that expression. Finally, recombinant DEFB118 significantly decreased the survival of both strains of C. albicans in a dose-dependent manner, whereas no effects were seen for both C. glabrata strains. Conclusion: DEFB118, induced by C. albicans β-GPs from oral fibroblasts, may play an important role in oral immune responses against C. albicans infection.
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Sepsis causes long-term disability, such as immune dysfunction, neuropsychological disorders, persistent inflammation, catabolism, and immunosuppression, leading to a high risk of death in survivors, although the contributing factors of mortality are unknown. The purpose of this experimental study in rats was to examine renal (rSNA) and splanchnic (sSNA) sympathetic nerve activity, as well as baroreflex sensitivity, in acute and chronic post-sepsis periods. The rats were divided into two groups: control group with naïve Wistar rats and sepsis group with 2-mL intravenous inoculation of Escherichia coli at 108 CFU/mL. Basal mean arterial pressure, heart rate, rSNA, sSNA, and baroreflex sensitivity were evaluated in all groups at the acute (6 h) and chronic periods (1 and 3 months). Basal rSNA and sSNA were significantly reduced in the surviving rats, as was their baroreflex sensitivity, for both pressor and hypotensive responses, and this effect lasted for up to 3 months. A single episode of sepsis in rats was enough to induce long-term alterations in renal and splanchnic sympathetic vasomotor nerve activity, representing a possible systemic event that needs to be elucidated. These findings showed that post-sepsis impairment of sympathetic vasomotor response may be one of the critical components in the inability of sepsis survivors to respond effectively to new etiological illness factors, thereby increasing their risk of post-sepsis morbidity.
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Dry solid matter (rutin content: 51.6 mg/g; quercetin content: 72.2 mg/g) extracted from Tartary buckwheat boiled noodles using 70% methanol as the solvent was found to have α-glucosidase inhibitory activity. As for fractions fractionated by silica gel column chromatography, the fractions rich in quercetin and rutin showed remarkable α-glucosidase inhibitory activity. Tartary buckwheat boiled noodles used as samples in this study contained quercetin produced from rutin by the action of rutinase, suggesting that both rutin and quercetin contained were involved in the α-glucosidase inhibitory activity of the dry solid extract. Changes in postprandial blood glucose levels were compared for boiled noodles made from two types of buckwheat (i.e., Tartary buckwheat and common buckwheat), revealing that blood glucose elevation after eating Tartary buckwheat boiled noodles was suppressed. The blood glucose level 40 minutes after eating Tartary buckwheat boiled noodles was significantly low (p<0.05). It can be concluded that this might be caused by the α-glucosidase inhibitory activity of rutin (270.0 mg) and quercetin (330.5 mg), which correspond to a total amount of 935 mg of rutin equivalents, in the gastrointestinal tract. As a result, the digestion of carbohydrates contained in the samples consumed and their absorption by the intestine might be inhibited, resulting in the suppression of increases in blood glucose levels. The presence of a certain amount of quercetin was considered to be key to the suppression of blood glucose elevation. It is important to control rapid postprandial blood glucose increases to prevent diabetes from developing or becoming serious. This study suggests the potential for Tartary buckwheat boiled noodles to contribute to diabetes prevention.
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Most cases of partial anomalous pulmonary venous return are associated with atrial septal defect. We however report a surgical case of partial anomalous pulmonary venous return that was diagnosed in an adult without atrial septal defect. The patient was a 44-year-old man who presented with hemoptysis. Computed tomography revealed an absent left pulmonary artery. We performed bronchial artery embolization. Partial anomalous pulmonary venous return (Qp/Qs 3.33) in which the right pulmonary vein returned to the superior vena cava and moderate aortic regurgitation were diagnosed by computed tomography and transthoracic echocardiography ; this was an indication for surgery. Approximately 2 months after the emergency hospitalization due to hemoptysis, we performed a modified Warden procedure and aortic valve replacement. Postoperative computed tomography showed good reconstruction of the superior vena cava and right upper pulmonary vein. He was discharged on postoperative day 38.
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BACKGROUND@#It has been pointed out that prolonged television (TV) viewing is one of the sedentary behaviors that is harmful to health; however, the association between socioeconomic status (SES) and prolonged TV viewing time has not been sufficiently investigated in Japan.@*METHODS@#The study population are the participants of NIPPON DATA2010, which is a prospective cohort study of the National Health and Nutrition Survey 2010 in Japan. They were residents in 300 randomly selected areas across Japan. This study included 2752 adults. SES was classified according to the employment status, educational attainment, living status, and equivalent household expenditure (EHE). Prolonged TV viewing time was defined as more than or equal to 4 h of TV viewing per day. Multivariable logistic regression analyses were conducted to examine the association of SES with prolonged TV viewing time.@*RESULTS@#The mean TV viewing time was 2.92 h in all participants. Of 2752 participants, 809 (29.4%) prolonged TV viewing, and the mean TV viewing time of them was 5.61 h. The mean TV viewing time in participants without prolonged TV viewing time was 1.81 h. The mean TV viewing time was prolonged as age classes increased and significantly longer in aged ≥60 years. Prolonged TV viewing time was associated with not working for all age classes and sexes. Only among women, education attainment and living status were also associated with prolonged TV viewing time. For education attainment, the lower the received years of education, the higher odds ratios (OR) of prolonged TV viewing time. For living status, in women aged <60 years, living with others had a significantly higher OR compared to living with spouse. On the other hand, in women aged ≥60 years, living alone had a significantly higher OR. EHE did not have any significant associations with prolonged TV viewing time.@*CONCLUSIONS@#In a general Japanese population, it should be noted that the association between SES and prolonged TV viewing time differed by age and sex. Particularly, it must draw attention to the prolonged TV viewing in elderly. The intervention in order to shorten TV viewing time needs to consider these attributes.
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Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Young Adult , Educational Status , Japan , Prospective Studies , Sedentary Behavior , Sex Factors , Social Class , Socioeconomic Factors , Television/statistics & numerical dataABSTRACT
RESUMO Objetivo: Avaliar sensibilidade do volume corneano, asfericidade e índice D para o diagnóstico precoce de ceratocone. Métodos: Estudo transversal analítico, realizado entre dezembro de 2018 e outubro de 2020, no qual foram analisados os prontuários de 39 pacientes (78 olhos) diagnosticados com ceratocone por um único subespecialista em córnea, por meio dos critérios de Belin/Ambrosio Enhanced Ectasia. Os dados coletados foram: asfericidade anterior, asfericidade posterior, índice D e suas frações (Da, Db, Dt, Dp e Df). Os dados foram digitados e manipulados em Excel, para posterior tratamento utilizando o programa Statistical Package for Social Science do Windows, versão 21.0. As variáveis categóricas foram apresentadas como valor absoluto e percentual. Variáveis contínuas foram apresentadas como média ± desvio-padrão e mediana (intervalo de confiança de 95%). Resultados: Foram analisados 78 olhos, com idade média de 28,2±5,8 anos e porcentagem entre o sexo feminino e masculino de 59,0% e 41,0%, respectivamente. O índice D apresentou estreita relação com sua fração Db nos casos iniciais de ceratocone, enquanto a fração Dt apresentou tal relação de forma reduzida. Conclusão: A correlação entre o índice D e sua fração Db sugere alterações precoces na elevação corneana posterior, colaborando para o diagnóstico de ceratocone subclínico.
ABSTRACT Objective: To assess sensitivity of corneal volume, corneal asphericity, and D index in early diagnosis of keratoconus. Methods: A cross-sectional analytical study, carried out between December 2018 and October 2020, which analyzed the medical records of 39 patients (78 eyes) diagnosed as keratoconus by a single corneal specialist, using the criteria of Belin-Ambrosio Enhanced Ectasia Display. The collected data were anterior asphericity, posterior asphericity, D index and its parameters (Da, Db, Dt, Dp and Df). The data were entered and handled in Excel, for later data treatment using the software Statistical Package for Social Science, version 21.0, for Windows. The categorical variables were presented as absolute value and percentages. The continuous variables were presented as mean±standard deviation, and median (95% of confidence interval). Results: We analyzed 78 eyes, mean age of 28.2±5.8 years, 59.0% of sample were female, and 41.0%, male. The D index showed a close relation to its Db parameter in the cases of keratoconus at early stage, while Dt parameter showed a reduced relation. Conclusion: The correlation between the D index and its Db parameter suggests early changes in the posterior corneal elevation, contributing to early diagnosis of subclinical keratoconus.
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Humans , Male , Female , Adult , Tomography/methods , Corneal Topography , Keratoconus/physiopathology , Keratoconus/diagnostic imaging , Epidemiology, Descriptive , Cross-Sectional Studies , Early DiagnosisABSTRACT
OBJECTIVES: Single nucleotide variants (SNVs) are the most common type of genetic variation among humans. High-throughput sequencing methods have recently characterized millions of SNVs in several thousand individuals from various populations, most of which are benign polymorphisms. Identifying rare disease-causing SNVs remains challenging, and often requires functional in vitro studies. Prioritizing the most likely pathogenic SNVs is of utmost importance, and several computational methods have been developed for this purpose. However, these methods are based on different assumptions, and often produce discordant results. The aim of the present study was to evaluate the performance of 11 widely used pathogenicity prediction tools, which are freely available for identifying known pathogenic SNVs: Fathmn, Mutation Assessor, Protein Analysis Through Evolutionary Relationships (Phanter), Sorting Intolerant From Tolerant (SIFT), Mutation Taster, Polymorphism Phenotyping v2 (Polyphen-2), Align Grantham Variation Grantham Deviation (Align-GVGD), CAAD, Provean, SNPs&GO, and MutPred. METHODS: We analyzed 40 functionally proven pathogenic SNVs in four different genes associated with differences in sex development (DSD): 17β-hydroxysteroid dehydrogenase 3 (HSD17B3), steroidogenic factor 1 (NR5A1), androgen receptor (AR), and luteinizing hormone/chorionic gonadotropin receptor (LHCGR). To evaluate the false discovery rate of each tool, we analyzed 36 frequent (MAF>0.01) benign SNVs found in the same four DSD genes. The quality of the predictions was analyzed using six parameters: accuracy, precision, negative predictive value (NPV), sensitivity, specificity, and Matthews correlation coefficient (MCC). Overall performance was assessed using a receiver operating characteristic (ROC) curve. RESULTS: Our study found that none of the tools were 100% precise in identifying pathogenic SNVs. The highest specificity, precision, and accuracy were observed for Mutation Assessor, MutPred, SNP, and GO. They also presented the best statistical results based on the ROC curve statistical analysis. Of the 11 tools evaluated, 6 (Mutation Assessor, Phanter, SIFT, Mutation Taster, Polyphen-2, and CAAD) exhibited sensitivity >0.90, but they exhibited lower specificity (0.42-0.67). Performance, based on MCC, ranged from poor (Fathmn=0.04) to reasonably good (MutPred=0.66). CONCLUSION: Computational algorithms are important tools for SNV analysis, but their correlation with functional studies not consistent. In the present analysis, the best performing tools (based on accuracy, precision, and specificity) were Mutation Assessor, MutPred, and SNPs&GO, which presented the best concordance with functional studies.