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Alzheimer's Disease (AD) is complicated by pro-oxidant intraneuronal Fe(2+) elevation as well as extracellular Zn(2+) accumulation within amyloid plaque. We found that the AD ß-amyloid protein precursor (APP) possesses ferroxidase activity mediated by a conserved H-ferritin-like active site, which is inhibited specifically by Zn(2+). Like ceruloplasmin, APP catalytically oxidizes Fe(2+), loads Fe(3+) into transferrin, and has a major interaction with ferroportin in HEK293T cells (that lack ceruloplasmin) and in human cortical tissue. Ablation of APP in HEK293T cells and primary neurons induces marked iron retention, whereas increasing APP695 promotes iron export. Unlike normal mice, APP(-/-) mice are vulnerable to dietary iron exposure, which causes Fe(2+) accumulation and oxidative stress in cortical neurons. Paralleling iron accumulation, APP ferroxidase activity in AD postmortem neocortex is inhibited by endogenous Zn(2+), which we demonstrate can originate from Zn(2+)-laden amyloid aggregates and correlates with Aß burden. Abnormal exchange of cortical zinc may link amyloid pathology with neuronal iron accumulation in AD.
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Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/antagonistas & inibidores , Precursor de Proteína beta-Amiloide/metabolismo , Ceruloplasmina/antagonistas & inibidores , Zinco/metabolismo , Doença de Alzheimer/metabolismo , Sequência de Aminoácidos , Precursor de Proteína beta-Amiloide/química , Animais , Linhagem Celular , Ceruloplasmina/química , Ceruloplasmina/metabolismo , Humanos , Ferro/metabolismo , Camundongos , Alinhamento de SequênciaRESUMO
OBJECTIVE: The objective of this randomized controlled trial is to compare the effect of bowel preparation using only oral polyethylene glycol electrolyte (PEG) solution vs. oral polyethylene glycol electrolyte solution (PEG) combined with mechanical sodium phosphate (NaP) enema on the surgical field visualization in patients undergoing robot-assisted laparoscopic gynecologic procedures. METHODS: Participants were randomized to either a single oral PEG solution or an oral PEG solution combined by mechanical NaP enema. The intraoperative visualization of the surgical field, the ease of manipulation of the bowels and overall difficulty level of the surgery were evaluated by the surgeon using a self-administered questionnaire. After the surgery, the patients completed a survey assessing postoperative gastrointestinal discomfort. RESULTS: 114 women were enrolled and randomized to oral PEG solution only group (n=48), and oral PEG plus mechanical NaP enema group (n=66). 42 women in oral PEG only group and 59 oral PEG plus NaP enema group completed the study. There was no difference in intraoperative visualization, or overall difficulty of the operation between the two groups, and bowel manipulation was easier in the oral PEG only group. Also, there was no difference in operating time between the groups. The patients' level of gastrointestinal discomfort after the surgery was not significantly different between the two groups. CONCLUSION: Routine use of mechanical NaP enema before robot-assisted laparoscopic gynecologic surgery is not recommended, because it has no additional benefit regarding intraoperative visualization or the surgical level of difficulty over oral bowel preparation methods.
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BACKGROUND: This study was performed to evaluate etiologies and secular trends in primary amenorrhea in South Korea. METHODS: This retrospective multi-center study analyzed 856 women who were diagnosed with primary amenorrhea between 2000 and 2016. Clinical characteristics were compared according to categories of amenorrhea (hypergonadotropic/hypogonadotropic hypogonadism, eugonadism, disorders of sex development) or specific causes of primary amenorrhea. In addition, we assessed secular trends of etiology and developmental status based on the year of diagnosis. RESULTS: The most frequent etiology was eugonadism (39.8%). Among specific causes, Müllerian agenesis was most common (26.2%), followed by gonadal dysgenesis (22.4%). Women with hypergonadotropic hypogonadism were more likely to have lower height and weight, compared to other categories. In addition, the proportion of cases with iatrogenic or unknown causes increased significantly in hypergonadotropic hypogonadism category, but overall, no significant secular trends were detected according to etiology. The proportion of anovulation including polycystic ovarian syndrome increased with time, but the change did not reach statistical significance. CONCLUSION: The results of this study provide useful clinical insight on the etiology and secular trends of primary amenorrhea. Further large-scale, prospective studies are necessary.
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Transtornos 46, XX do Desenvolvimento Sexual , Hipogonadismo , Transtornos 46, XX do Desenvolvimento Sexual/complicações , Amenorreia/epidemiologia , Amenorreia/etiologia , Feminino , Humanos , Hipogonadismo/complicações , Hipogonadismo/diagnóstico , Hipogonadismo/epidemiologia , Ductos Paramesonéfricos/anormalidades , Estudos ProspectivosRESUMO
BACKGROUND: The incidence and prevalence of endometriosis remain unclear due to diagnostic difficulties. Especially, there has been little information regarding the population-based epidemiology of endometriosis. The purpose of this study is to estimate the prevalence and incidence of endometriosis in Korea based on the health insurance claims data. METHODS: This study is a retrospective cohort study using the Korean National Health Insurance Service-National Sample Cohort, which correspond to approximately 1 million Korean populations from 2002 to 2013. Patients aged 15-54 years were selected, and the prevalence and incidence of endometriosis were estimated by time and age groups. RESULTS: The age-adjusted prevalence rate of endometriosis also increased from 2.12 per 1,000 persons (95% confidence interval [CI], 2.01-2.24) in 2002 to 3.56 per 1,000 persons (95% CI, 3.40-3.71) in 2013. The average adjusted incidence showed no statistically significant increase. However, the age-specific incidence of the 15-19 and 20-24 years age groups increased significantly from 0.24 and 1.29 per 1,000 persons in 2003 to 2.73 and 2.71 per 1,000 persons in 2013 (R2 = 0.93 and 0.77, P < 0.001), while the incidence rate of the age group 40-44 and 45-49 years decreased from 2.36 and 1.72 per 1,000 persons in 2003 to 0.81 and 0.27 per 1,000 persons in 2013 (R2 = 0.83 and 0.89, P < 0.001). CONCLUSION: The prevalence and incidence of endometriosis in Korean women were lower than that of previous reports in high-risk population studies. Furthermore, we found a significant increase in the diagnosis of endometriosis in younger age groups.
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Endometriose , Estudos de Coortes , Endometriose/epidemiologia , Feminino , Humanos , Incidência , Programas Nacionais de Saúde , Prevalência , República da Coreia/epidemiologia , Estudos RetrospectivosRESUMO
BACKGROUND: The look-back period is needed to define baseline population for estimating incidence. However, short look-back period is known to overestimate incidence of diseases misclassifying prevalent cases to incident cases. The purpose of this study is to evaluate the impact of the various length of look-back period on the observed incidences of uterine leiomyoma, endometriosis and adenomyosis, and to estimate true incidences considering the misclassification errors in the longitudinal administrative data in Korea. METHODS: A total of 319,608 women between 15 to 54 years of age in 2002 were selected from Korea National Health Insurance Services (KNHIS) cohort database. In order to minimize misclassification bias incurred when applying various length of look-back period, we used 11 years of claim data to estimate the incidence by equally setting the look-back period to 11 years for each year using prediction model. The association between the year of diagnosis and the number of prevalent cases with the misclassification rates by each look-back period was investigated. Based on the findings, prediction models on the proportion of misclassified incident cases were developed using multiple linear regression. RESULTS: The proportion of misclassified incident cases of uterine leiomyoma, endometriosis and adenomyosis were 32.8, 10.4 and 13.6% respectively for the one-year look-back period in 2003. These numbers decreased to 6.3% in uterine leiomyoma and - 0.8% in both endometriosis and adenomyosis using all available look-back periods (11 years) in 2013. CONCLUSION: This study demonstrates approaches for estimating incidences considering the different proportion of misclassified cases for various length of look-back period. Although the prediction model used for estimation showed strong R-squared values, follow-up studies are required for validation of the study results.
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Endometriose/epidemiologia , Leiomioma/epidemiologia , Adolescente , Adulto , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Adulto JovemRESUMO
The relaxin family peptide receptors have been implicated in numerous physiological processes including energy homeostasis, cardiac function, wound healing, and reproductive function. Two family members, RXFP3 and RXFP4, are class A GPCRs with endogenous peptide ligands (relaxin-3 and insulin-like peptide 5 (INSL5), respectively). Polymorphisms in relaxin-3 and RXFP3 have been associated with obesity, diabetes, and hypercholesterolemia. Moreover, central administration of relaxin-3 in rats has been shown to increase food intake, leading to body weight gain. Reported RXFP3 and RXFP4 ligands have been restricted to peptides (both endogenous and synthetic) as well as a low molecular weight positive allosteric modulator requiring a non-endogenous orthosteric ligand. Described here is the discovery of the first potent low molecular weight dual agonists of RXFP3/4. The scaffold identified is competitive with a chimeric relaxin-3/INSL5 peptide for RXFP3 binding, elicits similar downstream signaling as relaxin-3, and increases food intake in rats following acute central administration. This is the first report of small molecule RXFP3/4 agonism.
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Ingestão de Alimentos/efeitos dos fármacos , Receptores Acoplados a Proteínas G/agonistas , Bibliotecas de Moléculas Pequenas/química , Animais , Células CHO , Cricetinae , Cricetulus , AMP Cíclico/metabolismo , Descoberta de Drogas , Ligantes , Peptídeos/química , Peptídeos/farmacologia , Ratos , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Peptídeos/agonistas , Receptores de Peptídeos/genética , Receptores de Peptídeos/metabolismo , Relaxina/farmacologia , Bibliotecas de Moléculas Pequenas/farmacologiaRESUMO
STUDY OBJECTIVE: To evaluate the safety and effectiveness of hysteroscopic myomectomy after uterine artery embolization (UAE) for the treatment of large-sized submucosal myomas with deep intramural invasion that are difficult to treat with 1-step hysteroscopy. DESIGN: A retrospective cohort study (Canadian Task Force classification II-2). SETTING: An academic university hospital. PATIENTS: Eight premenopausal patients with symptomatic submucosal myomas with intramural invasion. INTERVENTIONS: All of the patients after bilateral UAE underwent subsequent hysteroscopic operation 3 to 15 months after UAE. MEASUREMENTS AND MAIN RESULTS: A total of 8 patients who had a large-sized submucosal myoma with deep myometrial invasion were included. The average volume of the submucosal myomas was 87.7±39.9 cm3 as confirmed by magnetic resonance imaging, and the average patient age was 37.6 years. The mean volume reduction of the submucosal myomas was 83.3±16.4% after UAE, and no immediate complications were observed. One-step hysteroscopic myomectomy after UAE was successfully performed in all patients. Leiomyomas with hyaline degeneration were pathologically confirmed. All women showed improved symptoms, and there was no evidence of recurrence 1 year later. One patient conceived naturally and delivered a full-term baby. CONCLUSION: In premenopausal women with large-sized symptomatic submucosal myomas with deep myometrial invasion, hysteroscopic myomectomy after UAE is very effective and safe.
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Leiomioma/cirurgia , Miométrio/cirurgia , Embolização da Artéria Uterina , Miomectomia Uterina/métodos , Neoplasias Uterinas/cirurgia , Adulto , Feminino , Humanos , Histeroscopia/métodos , Leiomioma/diagnóstico por imagem , Leiomioma/patologia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Miométrio/patologia , Estudos Retrospectivos , Neoplasias Uterinas/diagnóstico por imagem , Neoplasias Uterinas/patologiaRESUMO
Research Question: To evaluate the effect of mistletoe on the cell viability of patients with endometriosis, the expression levels of vascular endothelial growth factor (VEGF) were measured, and the change in the expression level of VEGF following mistletoe treatment was recorded. Design: Forty reproductive-aged women with endometriosis (stage I/II [group 1, n=20], and stage III/IV [group 2, n=20]) were prospectively enrolled. Twenty women who underwent gynaecologic operations for benign conditions were selected as the control group. Both eutopic and ectopic endometrial tissues were obtained from the endometriosis patients. The endometrial tissues were cultured and the stromal cells were separated. The cells were cultured for 24 hours with peritoneal fluid from patients and controls with and without mistletoe supplementation (200 ng/mL), respectively. The MTT assay was used to assess cell viability, and VEGF expression was analysed by Western blotting and ELISA. Results: Using peritoneal fluid from endometriosis patients treated with mistletoe, we found that both eutopic and ectopic endometrial stromal cell viability increased after treatment with peritoneal fluid from patients with early-stage (I and II) endometriosis. After mistletoe treatment, the cell viability was decreased, in both eutopic and ectopic endometrial stromal cells in all stages of endometriosis. These findings were verified consistently by evaluating the expression and concentration of VEGF, a marker of angiogenesis. Conclusions: The present study showed that mistletoe can reduce the cell viability of endometrial stromal cells and the peritoneal fluid-induced elevation of VEGF in eutopic and ectopic endometrial stromal cells obtained from endometriosis patients, especially in the early stage. Mistletoe might have anti-angiogenic activity on endometrial stromal cells and thus is a potential candidate for the treatment of endometriosis.
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Sobrevivência Celular/efeitos dos fármacos , Erva-de-Passarinho/química , Fator A de Crescimento do Endotélio Vascular/metabolismo , Western Blotting , Endometriose/tratamento farmacológico , Endometriose/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , HumanosRESUMO
Background: Uterine artery embolization (UAE) is one of the minimally-invasive alternatives to hysterectomy for treatment of uterine leiomyomas. There are various factors affecting the outcomes of UAE, but these have only been sporadically studied. Study Objective: To identify factors associated with the efficacy of UAE for the treatment of uterine leiomyoma, and to develop a model for the prediction of treatment response of uterine leiomyomas to UAE. Study design: A retrospective cohort study (Canadian Task Force Classification II-2) Patients: One hundred ninety-eight patients with symptomatic uterine leiomyomas. Intervention: UAE Measurements and Main Results: Among 198 leiomyoma patients who were treated with UAE, 104 who underwent pelvic magnetic resonance imaging (MRI) with diffusion-weighted imaging were selected for developing prediction model. Variables that were statistically significant from the univariate analysis were: location of leiomyoma, total number of lesions, sum of leiomyomas diameters, T2 signal intensity of largest leiomyoma, and T2 leiomyoma:muscle ratio. After a logistic regression analysis, leiomyoma location and T2 signal intensity of the largest leiomyoma were found to be statistically significant variables. Using intramural myomas defined as controls, submucosal leiomyomas showed a greater response to UAE with an odds ratio of 7.6904. The odds ratio of T2 signal intensity with an increase in signal intensity of 10 was 1.093. Using these two variables, we developed a prediction model. The AUC in the prediction model was 0.833, and the AUC in the validation set was 0.791. Conclusion: We identified that submucosal leiomyomas and those leiomyomas that show high signal intensity on T2-weighted imaging will exhibit a greater response to UAE. Prediction models are clinically helpful in selecting UAE as an appropriate treatment option for managing uterine leiomyoma.
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Leiomioma/terapia , Modelos Biológicos , Embolização da Artéria Uterina , Neoplasias Uterinas/terapia , Adulto , Feminino , Humanos , Leiomioma/diagnóstico por imagem , Leiomioma/patologia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Seleção de Pacientes , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Uterinas/diagnóstico por imagem , Neoplasias Uterinas/patologia , Útero/irrigação sanguínea , Útero/diagnóstico por imagem , Útero/patologiaRESUMO
Uterine leiomyomas are one of the most common benign gynecologic tumors, but the exact causes are not completely understood. In 2011, through DNA sequencing, MED12 mutation was discovered in approximately 71% of uterine leiomyomas. Several recent studies confirmed the high frequency of MED12 mutation in uterine leiomyoma. Nevertheless, no study has been done on MED12 mutation in the case of patients with multiple leiomyomas in a patient. The purpose of this study was to investigate the frequency of MED12 mutations in uterine leiomyomas of South Korean patients. In addition, we examined MED12 mutation in multiple leiomyomas in the same patients. Uterine leiomyoma tissues were obtained from symptomatic women who underwent hysterectomy or myomectomy for medically indicated reasons. We collected 60 uterine leiomyomas from 41 women. Tumor size ranged from 1 to 12cm. Patients' ages ranged from 25 to 55 years with an average of 38.4 years. Of the 60 tumors, 40 (66.67%) displayed MED12 mutation. Among the 41 patients, 14 patients had multiple leiomyomas and we analyzed those multiple leiomyomas. Three of them had the same mutations. Five of them, each leiomyoma had a different mutation. Two of them did not have mutation. Four of them had both mutation-positive and mutation-negative leiomyomas. In conclusion, we confirmed the high frequency of the MED12 mutation in uterine leiomyomas of South Korean patients. We also identified various MED12 mutation status in patients with multiple leiomyomas. This suggests that in a given patient, different tumors may have arisen from different cell origins and therefore it is supposed that occurrence of multiple leiomyoma in a single patient may not be caused by intrauterine metastasis or dissemination.
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Leiomioma/genética , Complexo Mediador/genética , Mutação , Neoplasias Uterinas/genética , Adulto , Povo Asiático/genética , Feminino , Frequência do Gene , Humanos , Pessoa de Meia-IdadeRESUMO
This cross-sectional study analysed the characteristics of HSDD (hypoactive sexual desire disorder) in Korean women. Two hundred and seventeen women seen for sexual dysfunction were assessed using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Revised (DMS IV-TR) and the Female Sexual Function Index (FSFI). A diagnosis of HSDD was more common in women in their 40 s (56%), who had previously undergone surgery for a feeling of 'wide vagina'. Both too much or too little sexual activity caused HSDD. Longer physical contact and sexual foreplay duration lessened the prevalence of HSDD. We concluded that special attention should be paid to women in their 40 s, particularly those with a history of vaginal surgery as they are at risk of HSDD. Potential treatment options should include couple counselling about the optimal frequency and duration of sexual activity, as well as treatment specific to the disorders identified by the FSFI. Impact statement What is already known on this subject: Many socio-medical factors affect the prevalence of HSDD (Hypoactive sexual desire disorder). Age, cultural factors, relationship status, education, religion, employment, mental distress, depression, medications, menopausal status, multiple psychiatric disorders and a variety of medical conditions impact on sexual function. What do the results of this study add: A history of wide vaginal surgery (perineoplasty, vaginal rogation rejuvenation, or anterior vaginal introitoplasty) affects the incidence of HSDD (and have not been evaluated before). Both too much or too little sexual activity were found to have caused HSDD. A longer physical contact and duration of sexual foreplay lessened the prevalence of HSDD. What are the implications of these findings for clinical practice and/or further research: We concluded that special attention should be paid to women in their 40 s; particularly those with a history of wide vaginal surgery, as they are at risk of HSDD. Potential treatment options should include couple counselling about the optimal frequency and duration of sexual activity, as well as treatment specific to the disorders identified by the FSFI.
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Disfunções Sexuais Psicogênicas/epidemiologia , Adulto , Estudos Transversais , Feminino , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Humanos , Incidência , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Disfunções Sexuais Psicogênicas/etiologiaRESUMO
Effective drug discovery demands the availability of microgram to gram quantities of high-quality protein encoded by novel transcripts. Protein expression vectors designed for large-scale protein production often include one or more specific tags to such transcripts, to simplify the purification of the targeted protein. Optimization of the complex expression and purification process requires the evaluation of multiple expression candidate clones to identify a production-suitable construct in terms of quality and final protein yield. Efficiency of the entire expression screening process is typically assessed by direct visualization of the banding patterns from whole-cell lysates on SDS-PAGE gels, by direct staining and/or immunoblotting, using antibodies against the tag or the protein of interest. These techniques, generally run under denaturing conditions, have proven to be only marginally predictive of the purification yield and authentic folding for native proteins. Small-scale, multiparallel affinity purification followed by SDS-PAGE analysis is more predictive for expression screening; however, this approach is labor intensive and time consuming. Here we describe the development of an alternative expression efficiency assessment technique, designed to evaluate the accessibility of affinity tags expressed with the desired fusion proteins, using acoustic membrane microparticle assay technology on the ViBE protein analysis workstation.
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Imunoensaio/métodos , Proteínas Recombinantes de Fusão/análise , Animais , Clonagem Molecular , Escherichia coli/genética , Histidina , Indicadores e Reagentes/química , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Células Sf9 , SpodopteraRESUMO
STUDY OBJECTIVE: To evaluate the safety and efficacy of transvaginal radiofrequency myolysis (RFM) with or without combined hysteroscopy for treatment of large submucosal leiomyomas with a substantial intramural portion. DESIGN: Retrospective observational study (Canadian Task Force classification III). SETTING: Hospital outpatient department. PATIENTS: Twenty-four patients with large submucosal leiomyomas with a substantial intramural portion. INTERVENTIONS: Transvaginal RFM with or without combined hysteroscopy. MEASUREMENTS AND MAIN RESULTS: Twenty-four patients with large submucosal leiomyomas with a substantial intramural portion were enrolled to undergo stepwise RFM. Additional hysteroscopic myomectomy was performed in 6 patients at 3 to 6 months after RFM. Myoma volumes were measured via 3-dimensional ultrasonography before RFM and at 1, 3, 6, 12, and 24 months postoperatively. Symptom severity was assessed using the Uterine Fibroid Symptom and Quality of Life questionnaire and the Health-Related Quality of Life questionnaire. The total volume reduction rate 24 months postoperatively was 84.2%. Symptom severity and health-related quality of life scores demonstrated substantial improvements at 12 months after RFM. CONCLUSIONS: RFM with or without hysteroscopy is an effective treatment for large myomas with deep intramural positioning, and it seems safe for use in all patients with submucosal myoma-related symptoms.
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Procedimentos Cirúrgicos Ambulatórios , Ablação por Cateter/métodos , Leiomioma/cirurgia , Miomectomia Uterina/métodos , Neoplasias Uterinas/cirurgia , Adulto , Terapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Qualidade de Vida , Estudos Retrospectivos , Inquéritos e Questionários , Resultado do Tratamento , Vagina/cirurgiaRESUMO
Colloidal natural organic matter (NOM) is an important foulant to low-pressure membranes (LPMs) employed in drinking water treatment. Removal of colloidal NOM by magnetic ion exchange (MIEX), coagulation, and integrated MIEX and coagulation was investigated in this study to determine the relationship between colloidal NOM removal and membrane fouling reduction. The results showed that coagulation did not selectively remove colloidal NOM and the optimal coagulant dose was primarily determined by the concentration of humic substances. Comparatively, MIEX pretreatment preferentially removed humic substances and reduced the coagulant dose needed for colloidal NOM removal as a result of coagulation stoichiometry. A matched-pair analysis showed that integrated MIEX and coagulation pretreatment at much lower coagulant doses was as effective as coagulation in reducing membrane fouling. It is concluded that integrated MIEX and coagulation is potentially a viable pretreatment approach to reduce membrane fouling and in general removal of colloidal NOM in feedwater is an effective approach for membrane fouling control and should be considered in the research, development, and application of novel LPM-based treatment processes.
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Membranas Artificiais , Purificação da Água/instrumentação , Purificação da Água/métodos , Troca Iônica , MagnetismoRESUMO
Pacinian corpuscles are sensory nerve-end organs located in the deep dermis and subcutaneous tissue of the palms or soles. Pacinian neuroma is an extremely rare feature, defined as hyperplasia or hypertrophy of Pacinian corpuscles. About half of Pacinian neuromas present with point tenderness. There have been a limited number of cases reported around the world. We observed a 45-year-old woman with an 8-month history of a tender whitish papule on her left thumb tip. Histopathologically, an enlarged hypertrophic Pacinian corpuscle in subcutaneous tissue, surrounded by numerous nerve fibers, was found. Herein, we report a case of Pacinian neuroma presenting as a tender papule on a fingertip that was clearly related to repetitive trauma at that site. This case shows that a meticulous history and histological examination can lead to an exact diagnosis and proper treatment.
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Neuroma/diagnóstico , Neuroma/patologia , Corpúsculos de Pacini/patologia , Polegar/patologia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Fibras Nervosas , Neuroma/etiologia , Tela Subcutânea/patologia , Polegar/inervação , Ferimentos e Lesões/complicações , Ferimentos e Lesões/diagnósticoRESUMO
Alopecia totalis (AT) and alopecia universalis (AU), severe forms of alopecia areata (AA), show distinguishable clinical characteristics from those of patch AA. In this study, we investigated the clinical characteristics of AT/AU according to the onset age. Based on the onset age around adolescence (< or ≥ 13 yr), 108 patients were classified in an early-onset group and the other 179 patients in a late-onset group. We found that more patients in the early-onset group had a family history of AA, nail dystrophy, and history of atopic dermatitis than those in the late-onset group. These clinical differences were more prominent in patients with AU than in those with AT. In addition, significantly more patients with concomitant medical disorders, especially allergic diseases were found in the early-onset group (45.8%) than in the late-onset group (31.2%). All treatment modalities failed to show any association with the present hair condition of patients. In the early-onset group, patients with AU or a family history of AA showed worse prognosis, whereas this trend was not observed in the late-onset group. Systemic evaluations might be needed in early-onset patients due to the higher incidence of comorbid diseases. It is suggested that patients with AU or family history of AA make worse progress in the early-onset group than in the late-onset group.
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Alopecia em Áreas/diagnóstico , Adolescente , Adulto , Idade de Início , Alopecia/diagnóstico , Alopecia/epidemiologia , Alopecia em Áreas/epidemiologia , Criança , Pré-Escolar , Dermatite Atópica/diagnóstico , Saúde da Família , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Doenças da Unha/diagnóstico , Prognóstico , Adulto JovemRESUMO
OBJECTIVE: This study aimed to develop and verify an endometriosis self-assessment tool (ESAT). METHODS: A non-experimental, descriptive, correlational study design was used. Candidate items were developed based on a conceptual framework constructed using the results of in-depth interviews and an integrative literature review. The construct validity of the developed tool was also examined. One-hundred and forty-two participants (117 patients with endometriosis and 25 patients without endometriosis) were included in the validity and reliability tests. The data were collected between August and December 2018. Nomological validity was verified based on significant correlations between the ESAT and the quality-of-life scores. RESULTS: A 21-item ESAT was developed, and its construct validity was supported. Exploratory factor analysis indicated that the tool consisted of four components (gastrointestinal symptoms, dysmenorrhea, usual symptoms, and the amount and characteristics of menstrual bleeding) with a variance of 61.6%. The variance in quality-of-life scores, as explained by the ESAT scores, was relatively high. Receiver operator characteristics curve analysis indicated that ESAT scores significantly differentiated endometriosis from non-endometriosis with fair discriminatory power at a cut-off score of 50 (sensitivity, 0.76; specificity, 0.72; area under the curve, >0.75; P<0.001). This means that patients with ESAT scores >50 points were more likely to have endometriosis. Thus, the reliability of the ESAT was confirmed. CONCLUSION: The devised tool appears valid and reliable. This tool may allow women to determine their risk of endometriosis by distinguishing between normal and pathological menstruation-related symptoms.
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OBJECTIVE: The aim of this study was to investigate changes in objective sleep quality with hormone therapy (HT) in women with late menopausal transition. METHODS: Healthy midlife women with sleep difficulty who received HT were included. Those undergoing late menopausal transition were screened. Sleep patterns and self-reported questionnaires were collected before and 10 weeks after starting HT. RESULTS: Ten women who met the criteria (age, 50.1 ± 2.8 years) showed higher sleep efficiency and shorter wakefulness after sleep onset (WASO) 10 weeks after starting HT. However, no significant change was found in objective sleep quality after adjustment for multiple comparisons: sleep efficiency, 84.2 ± 7.7 versus 88.2% ± 4.7%, P = 0.037, adjusted P = 0.259; WASO, 59.0 ± 27.2 minutes versus 41.4 ± 17.4 minutes, P = 0.020, adjusted P = 0.140; average duration per awakening, 2.9 ± 1.0 minutes versus 2.2 ± 0.5 minutes, P = 0.033, adjusted P = 0.231. A better score of subjective sleep quality in the Pittsburgh Sleep Quality Index was observed 10 weeks after starting HT (2.0 ± 0.0 vs 1.2 ± 0.4, P = 0.006, adjusted P = 0.042), but sensitivity analysis did not show consistent results after adjustment for multiple comparisons (2.0 ± 0.0 vs 1.1 ± 0.4, P = 0.020, adjusted P = 0.140). Total scores of the Insomnia Severity Index and Menopause Rating Scale were better 10 weeks after starting HT (Insomnia Severity Index, 14.7 ± 3.0 vs 9.1 ± 3.8, P = 0.010; Menopause Rating Scale, 29.0 ± 5.2 vs 21.6 ± 3.0, P = 0.009) with consistent results in sensitivity analyses. There was no difference in the Epworth Sleepiness Scale before and after HT (7.2 ± 1.7 vs 8.6 ± 4.5, P = 0.309). The change in each objective sleep quality variable before and after HT showed strong positive or negative correlations with the change in only a few items in subjective sleep quality. CONCLUSION: Women in the late menopausal transition period showed higher sleep efficiency and shorter WASO after HT; however, multiple comparisons showed no statistically significant difference in objective sleep quality between before and after HT.
Assuntos
Distúrbios do Início e da Manutenção do Sono , Transtornos do Sono-Vigília , Feminino , Humanos , Pessoa de Meia-Idade , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Sono , Qualidade do Sono , Menopausa , HormôniosRESUMO
Iron influx increases the translation of the Alzheimer amyloid precursor protein (APP) via an iron-responsive element (IRE) RNA stem loop in its 5'-untranslated region. Equal modulated interaction of the iron regulatory proteins (IRP1 and IRP2) with canonical IREs controls iron-dependent translation of the ferritin subunits. However, our immunoprecipitation RT-PCR and RNA binding experiments demonstrated that IRP1, but not IRP2, selectively bound the APP IRE in human neural cells. This selective IRP1 interaction pattern was evident in human brain and blood tissue from normal and Alzheimer disease patients. We computer-predicted an optimal novel RNA stem loop structure for the human, rhesus monkey, and mouse APP IREs with reference to the canonical ferritin IREs but also the IREs encoded by erythroid heme biosynthetic aminolevulinate synthase and Hif-2α mRNAs, which preferentially bind IRP1. Selective 2'-hydroxyl acylation analyzed by primer extension analysis was consistent with a 13-base single-stranded terminal loop and a conserved GC-rich stem. Biotinylated RNA probes deleted of the conserved CAGA motif in the terminal loop did not bind to IRP1 relative to wild type probes and could no longer base pair to form a predicted AGA triloop. An AGU pseudo-triloop is key for IRP1 binding to the canonical ferritin IREs. RNA probes encoding the APP IRE stem loop exhibited the same high affinity binding to rhIRP1 as occurs for the H-ferritin IRE (35 pm). Intracellular iron chelation increased binding of IRP1 to the APP IRE, decreasing intracellular APP expression in SH-SY5Y cells. Functionally, shRNA knockdown of IRP1 caused increased expression of neural APP consistent with IRP1-APP IRE-driven translation.
Assuntos
Regiões 5' não Traduzidas , Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Encéfalo/metabolismo , Proteína 1 Reguladora do Ferro/metabolismo , Conformação de Ácido Nucleico , Biossíntese de Proteínas , Receptores de Superfície Celular/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/genética , Animais , Encéfalo/patologia , Linhagem Celular Tumoral , Humanos , Ferro/metabolismo , Proteína 1 Reguladora do Ferro/genética , Macaca mulatta , Camundongos , Nexinas de Proteases , Receptores de Superfície Celular/genéticaRESUMO
Single-walled carbon nanotubes (SWCNTs), multiwalled carbon nanotubes (MWCNTs), and oxidized MWCNTs (O-MWCNTs) were studied for the adsorption of ibuprofen (IBU) and triclosan (TCS) as representative types of pharmaceutical and personal care products (PPCPs) under different chemical solution conditions. A good fitting of sorption isotherms was obtained using a Polanyi-Manes model (PMM). IBU and TCS sorption was stronger for SWCNTs than for MWCNTs due to higher specific surface area. The high oxygen content of O-MWCNT further depressed PPCP sorption. The sorption capacity of PPCPs was found to be pH-dependent, and more adsorption was observed at pHs below their pK(a) values. Ionic strength was also found to substantially affect TCS adsorption, with higher adsorption capacity observed for TCS at lower ionic strength. In the presence of a reference aquatic fulvic acid (FA), sorption of IBU and TCS was reduced due to the competitive sorption of FA on carbon nanotubes (CNTs). Sorption isotherm results with SWCNTs, MWCNTs and O-MWCNTs confirmed that the surface chemistry of CNTs, the chemical properties of PPCPs, and aqueous solution chemistry (pH, ionic strength, fulvic acid) all play an important role in PPCP adsorption onto CNTs.