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1.
Curr Med Sci ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34643881

RESUMO

OBJECTIVE: Filaggrin (FLG) is a protein expressed in the epidermis and involved in the maintenance of the epidermal barrier. However, the expression and localization of FLG in the upper airway remain controversial. The present study aimed to determine the significance of FLG and the effect of S100A7 on FLG expression in the upper respiratory mucosa. METHODS: Human nasal epithelial cells (HNECs) were cultured and examined for FLG expression and S100A7 effects by real-time polymerase chain reaction and Western blotting. The localization and distribution of FLG were assessed using sinonasal mucosa. RESULTS: A significant expression of FLG was detected at the mRNA and protein levels in HNECs. A moderate FLG immunoreactivity was observed in the epithelial cells, but no staining was seen in epithelial goblet cells. S100A7 increased the FLG mRNA level in HNECs in a dose-dependent manner and also up-regulated the FLG protein in a dose-dependent manner. CONCLUSION: This study significantly contributes to a better understanding of the role of FLG in the pathogenesis of airway inflammation from the viewpoint of the epithelial barrier function. FLG-related events in response to S100A7 protein may represent novel therapeutic targets for the treatment of upper airway inflammation.

3.
Nat Biomed Eng ; 5(8): 926-940, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34373601

RESUMO

Current protocols for the differentiation of human pluripotent stem cells (hPSCs) into chondrocytes do not allow for the expansion of intermediate progenitors so as to prospectively assess their chondrogenic potential. Here we report a protocol that leverages PRRX1-tdTomato reporter hPSCs for the selective induction of expandable and ontogenetically defined PRRX1+ limb-bud-like mesenchymal cells under defined xeno-free conditions, and the prospective assessment of the cells' chondrogenic potential via the cell-surface markers CD90, CD140B and CD82. The cells, which proliferated stably and exhibited the potential to undergo chondrogenic differentiation, formed hyaline cartilaginous-like tissue commensurate to their PRRX1-expression levels. Moreover, we show that limb-bud-like mesenchymal cells derived from patient-derived induced hPSCs can be used to identify therapeutic candidates for type II collagenopathy and we developed a method to generate uniformly sized hyaline cartilaginous-like particles by plating the cells on culture dishes coated with spots of a zwitterionic polymer. PRRX1+ limb-bud-like mesenchymal cells could facilitate the mass production of chondrocytes and cartilaginous tissues for applications in drug screening and tissue engineering.


Assuntos
Proteínas de Homeodomínio/genética , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Pluripotentes/citologia , Animais , Técnicas de Cultura de Células/métodos , Diferenciação Celular , Condrócitos/citologia , Condrócitos/metabolismo , Condrócitos/transplante , Condrogênese , Doenças do Colágeno/terapia , Meios de Cultura/química , Proteínas de Homeodomínio/metabolismo , Humanos , Células-Tronco Mesenquimais/citologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Células-Tronco Pluripotentes/metabolismo , Polímeros/química , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Antígenos Thy-1/metabolismo , Engenharia Tecidual
4.
Int J Cancer ; 149(8): 1593-1604, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34152598

RESUMO

Lung adenocarcinoma (LUAD) is the most common types among lung cancers generally arising from terminal airway and understanding of multistep carcinogenesis is crucial to develop novel therapeutic strategy for LUAD. Here we used human induced pluripotent stem cells (hiPSCs) to establish iHER2-hiPSCs in which doxycycline induced the expression of the oncoprotein human epidermal growth factor receptor 2 (HER2)/ERBB2. Lung progenitors that differentiated from iHER2-hiPSCs, which expressed NKX2-1/TTF-1 known as a lung lineage maker, were cocultured with human fetal fibroblast and formed human lung organoids (HLOs) comprising alveolar type 2-like cells. HLOs that overexpressed HER2 transformed to tumor-like structures similar to atypical adenomatous hyperplasia, which is known for lung precancerous lesion and upregulated the activities of oncogenic signaling cascades such as RAS/RAF/MAPK and PI3K/AKT/mTOR. The degree of morphological irregularity and proliferation capacity were significantly higher in HLOs from iHER2-hiPSCs. Moreover, the transcriptome profile of the HLOs shifted from a normal lung tissue-like state to one characteristic of clinical LUAD with HER2 amplification. Our results suggest that hiPSC-derived HLOs may serve as a model to recapitulate the early tumorigenesis of LUAD and would provide new insights into the molecular basis of tumor initiation and progression.


Assuntos
Adenocarcinoma de Pulmão/patologia , Carcinogênese , Regulação Neoplásica da Expressão Gênica , Células-Tronco Pluripotentes Induzidas/patologia , Neoplasias Pulmonares/patologia , Organoides/patologia , Receptor ErbB-2/metabolismo , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Diferenciação Celular , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Organoides/metabolismo , Receptor ErbB-2/genética , Transcriptoma , Células Tumorais Cultivadas
5.
Jpn J Ophthalmol ; 65(2): 271-281, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33411099

RESUMO

PURPOSE: To determine eye drop type and usage frequency and investigate risk factors for no eye drop use in individuals with symptomatic dry eye (DE) in Japan. STUDY DESIGN: Crowdsourced observational study. METHODS: This study was conducted using the DryEyeRhythm smartphone application between November 2016 and September 2019. Data collected included the type and frequency of eye drop use, demographics, medical history, lifestyle, and self-reported symptoms. Symptomatic DE was defined as an Ocular Surface Disease Index total score of ≥ 13. Risk factors for no eye drop use were identified using multivariate logistic regression analyses. RESULTS: Among 2619 individuals with symptomatic DE, 1876 did not use eye drops. The most common eye drop type was artificial tears (53.4%), followed by hyaluronic acid 0.1% (33.1%) and diquafosol sodium 3% (18.7%). Risk factors (odds ratio [95% confidence interval]) for no eye drop use were age (0.97 [0.97-0.98]), body mass index (1.04 [1.01-1.07]), brain disease (0.38 [0.15-0.98]), collagen disease (0.30 [0.13-0.68]), mental illness other than depression and schizophrenia (0.65 [0.45-0.93]), cataract surgery (0.12 [0.02-0.59]), ophthalmic surgery other than cataract and laser-assisted in situ keratomileusis (0.55 [0.34-0.88]), current (0.47 [0.38-0.57]) or past (0.58 [0.43-0.77]) contact lens use, >8 h screen exposure time (1.38 [1.05-1.81]), <6 h (1.24 [1.01-1.52]) and >9 h (1.34 [1.04-1.72]) sleep time, and water intake (0.97 [0.94-0.98]). CONCLUSION: Many participants with symptomatic DE did not use optimized eye drop treatment and identified risk factors for no eye drop use. The DryEyeRhythm application may help improve DE treatment.


Assuntos
Crowdsourcing , Síndromes do Olho Seco , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/epidemiologia , Humanos , Japão/epidemiologia , Lubrificantes Oftálmicos , Soluções Oftálmicas , Lágrimas
6.
Clin J Gastroenterol ; 14(1): 63-70, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32996111

RESUMO

We report a rare case of undifferentiated-type intramucosal gastric cancer that occurred in the fornix of the stomach without Helicobacter pylori infection, which consisted mainly of poorly differentiated adenocarcinoma. A 49-year-old man visited our hospital for a follow-up endoscopic examination of a small depressed lesion of the gastric fornix detected by surveillance esophagogastroduodenoscopy. On magnifying endoscopy with blue laser imaging, the depressed lesion (approximately 10 mm in diameter) was regarded as undifferentiated-type early gastric cancer that proved to be a poorly differentiated adenocarcinoma by histological examination of biopsied specimens. The cancerous lesion was successfully treated with endoscopic submucosal dissection and microscopically showed an intramucosal cancer that invaded the whole mucosal layer with predominant growth of a poorly differentiated adenocarcinoma component. The patient status was verified as Helicobacter pylori-naïve according to the strict diagnostic criteria, thereby confirming this case as an undifferentiated-type Helicobacter pylori-uninfected gastric cancer. Helicobacter pylori-uninfected intramucosal poorly differentiated adenocarcinoma occurring in the gastric fornix has not been previously reported.


Assuntos
Adenocarcinoma , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Adenocarcinoma/cirurgia , Mucosa Gástrica , Infecções por Helicobacter/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/cirurgia
7.
Intern Med ; 60(8): 1211-1215, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33229807

RESUMO

We herein report a rare case of intraductal papillary mucinous neoplasm with a pancreatogastric fistula in an elderly Japanese man admitted to our hospital. The pancreatogastric fistula was confirmed using endoscopic retrograde pancreatography via a cannulated guidewire placed in the stomach. Six months after admission, the patient was diagnosed with intraductal papillary mucinous carcinoma. A pancreatogastric fistula is generally a rare complication of intraductal papillary mucinous neoplasm. It was caused by mechanical penetration in this case. Interestingly, we also observed endoscopic and histochemical mucosal changes in the fistula.


Assuntos
Adenocarcinoma Mucinoso , Adenocarcinoma Papilar , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adenocarcinoma Mucinoso/complicações , Adenocarcinoma Mucinoso/diagnóstico , Idoso , Carcinoma Ductal Pancreático/complicações , Carcinoma Ductal Pancreático/diagnóstico , Colangiopancreatografia Retrógrada Endoscópica , Humanos , Masculino , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/diagnóstico
8.
Gene ; 767: 145285, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33144271

RESUMO

The genus Takifugu is a group of approximately 20 species of puffer fishes living in a wide range of salinity environments around East Asian countries. This group presents a broad spectrum of evolutionary stages adapted to anadromy as a result of speciation that occurred a short time (2-5 million years) ago on an evolutionary timescale. This group thus can be considered as a model for studying the evolutionary mechanisms of anadromy. We firstly conducted a transfer experiment from seawater to low-salinity waters on five Takifugu species: two anadromous species T. obscurus and T. ocellatus, two euryhaline wanderer marine species T. rubripes and T. niphobles, and a strictly marine species T. snyderi, and confirmed that the capacity for acclimation to hypotonic environments was associated with their life history strategies. Next, transcriptomes of the gill and intestine of these species in hypotonic condition were compared to those under hypertonic condition for each species using RNA-Sequencing so as to determine possible candidate transporters playing an important role on freshwater adaptation. As this analysis suggested that cftr, encoding an important ion transporter for seawater acclimation in the gill, and ncc, encoding a transporter that is suggested to play important osmoregulatory roles in the intestine, are important candidates, their expression was validated by quantitative real-time PCR analysis. Expression of cftr was downregulated in the gills of the four euryhaline species under the hypotonic condition, but no change was detected in the gill of stenohaline T. snyderi, which may be one reason for the poor hypotonic acclimation capacity of T. snyderi. Expression of ncc was clearly upregulated in the intestines of the two anadromous species under the hypotonic condition, but not in other three species. Different ion transporter expression patterns between the five species indicate that the transcriptional regulation of cftr in the gill and ncc in the intestine may be important for the improvement of hypotonic acclimation capacity and evolution of anadromy in the Takifugu species.


Assuntos
Transporte de Íons/genética , Takifugu/genética , Takifugu/metabolismo , Aclimatação/genética , Adaptação Fisiológica/genética , Animais , Água Doce , Regulação da Expressão Gênica/genética , Brânquias/metabolismo , Transporte de Íons/fisiologia , Concentração Osmolar , Salinidade , Água do Mar , ATPase Trocadora de Sódio-Potássio/metabolismo , Transcriptoma/genética , Equilíbrio Hidroeletrolítico/genética
9.
Sci Rep ; 10(1): 18106, 2020 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-33093551

RESUMO

Various symptoms of the dry eye disease (DED) interfere with the quality of life and reduce work productivity. Therefore, screening, prevention, and treatment of DED are important. We aimed to investigate the potential diagnostic ability of the maximum blink interval (MBI) (the length of time participants could keep their eyes open) with disease-specific questionnaire for DED. This cross-sectional study included 365 patients (252 with DED and 113 without DED) recruited between September 2017 and December 2019. Discriminant validity was assessed by comparing the non-DED and DED groups based on the MBI with a Japanese version of the Ocular Surface Disease Index (J-OSDI) and tear film breakup time (TFBUT) with J-OSDI classifications. The MBI with J-OSDI showed good discriminant validity by known-group comparisons. The positive and predictive values of MBI with J-OSDI were 96.0% (190/198 individuals) and 37.1% (62/167 individuals), respectively. The area under the receiver operating characteristic curve (AUC) of MBI with J-OSDI was 0.938 (95% confidence interval 0.904-0.971), the sensitivity was 75.4% (190/252 individuals), and the specificity was 92.9% (105/113 individuals), which are similar to the diagnostic ability of TFBUT with J-OSDI (AUC 0.954). In conclusion, MBI with J-OSDI may be a simple, non-invasive screening test for DED.


Assuntos
Piscadela/fisiologia , Doenças da Túnica Conjuntiva/fisiopatologia , Doenças da Córnea/fisiopatologia , Síndromes do Olho Seco/diagnóstico , Programas de Rastreamento , Qualidade de Vida , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Concentração Osmolar , Prognóstico , Curva ROC , Inquéritos e Questionários
10.
Cornea ; 39 Suppl 1: S39-S46, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33055549

RESUMO

Dry eye disease (DED) is a chronic, multifactorial ocular surface disorder with multiple etiologies that results in tear film instability. Globally, the prevalence of DED is expected to increase with an aging society and daily use of digital devices. Unfortunately, the medical field is currently unprepared to meet the medical needs of patients with DED. Noninvasive, reliable, and readily reproducible biomarkers have not yet been identified, and the current mainstay treatment for DED relies on symptom alleviation using eye drops with no effective preventative therapies available. Medical big data analyses, mining information from multiomics studies and mobile health applications, may offer a solution for managing chronic conditions such as DED. Omics-based data on individual physiologic status may be leveraged to prevent high-risk diseases, accurately diagnose illness, and improve patient prognosis. Mobile health applications enable the portable collection of real-world medical data and biosignals through personal devices. Together, these data lay a robust foundation for personalized treatments for various ocular surface diseases and other pathologies that currently lack the components of precision medicine. To fully implement personalized and precision medicine, traditional aggregate medical data should not be applied directly to individuals without adjustments for personal etiology, phenotype, presentation, and symptoms.

11.
BMC Genomics ; 21(1): 668, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993516

RESUMO

BACKGROUND: The clupeoid fishes are ecologically and commercially important fish species worldwide that exhibit a high level of population fluctuation, accompanied by alteration of reproductive traits. However, knowledge about their reproductive physiology in order to understand mechanisms underlying such population dynamics is limited. The endocrine system along with the brain-pituitary-gonadal (BPG) axis is critical for regulating reproduction. The aims of this study were to provide transcript data and genes related to the BPG axis, and to characterize the expression profiles of ovarian steroidogenesis-related genes in the Japanese sardine (Sardinops melanostictus, Clupeidae). RESULTS: RNA sequencing was performed using the sardine brain, pituitary, and gonad in both sexes. A total of 290,119 contigs were obtained and 115,173 non-redundant ORFs were annotated. The genes differentially expressed between ovary and testis were strongly associated with GO terms related to gamete production. The tissue-specific profile of the abundance of transcripts was characterized for the major regulators in the BPG axis, such as gonadotropin-releasing hormone, gonadotropin, and steroidogenic enzyme. By comparing between ovary and testis, out of eight different 17ß-hydroxysteroid dehydrogenase (Hsd17b) genes identified, higher hsd17b7 expression was found in testis, whereas higher expression of hsd17b8, hsd17b10, hsd17b12a, and hsd17b12b was found in ovary. The cDNAs encoding key endocrine factors in the ovarian steroidogenic pathway were cloned, sequenced, and quantitatively assayed. In the pituitary, follicle-stimulating hormone beta peaked during vitellogenesis, while luteinizing hormone beta peaked at the completion of vitellogenesis. In the ovary, follicle-stimulating hormone receptor and luteinizing hormone receptor were upregulated from mid- to late phase of vitellogenesis. Furthermore, three steroidogenic enzyme genes (cyp11a1, cyp17a1, and cyp19a1a) gradually increased their expression during ovarian development, accompanying a rise in serum estradiol-17ß, while 3ß-hydroxysteroid dehydrogenase and steroidogenic acute regulatory protein did not change significantly. CONCLUSIONS: This is the first report of deep RNA sequencing analysis of Japanese sardine, in which many key genes involved in the BPG axis were identified. Expression profiles of ovarian steroidogenesis-related genes provide a molecular basis of the physiological processes underlying ovarian development in the sardine. Our study will be a valuable resource for clarifying the molecular biology of clupeoid fishes.


Assuntos
Encéfalo/metabolismo , Peixes/genética , Hormônios Esteroides Gonadais/genética , Ovário/metabolismo , Hipófise/metabolismo , Transcriptoma , 11-beta-Hidroxiesteroide Desidrogenases/genética , 11-beta-Hidroxiesteroide Desidrogenases/metabolismo , Animais , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Feminino , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Hormônio Foliculoestimulante/genética , Hormônio Foliculoestimulante/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Hormônio Luteinizante/genética , Hormônio Luteinizante/metabolismo
12.
Invest Ophthalmol Vis Sci ; 61(10): 29, 2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32797198

RESUMO

Purpose: This systematic review aimed to determine currently reported clinical and prodromal ocular symptoms in patients with coronavirus disease 2019 (COVID-19). Methods: An online article search was performed in PubMed and EMBASE. Altogether 15 studies (retrospective, prospective, or case studies) involving 1533 patients with COVID-19, reporting on ocular symptoms, and with outcome data available were identified. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines were followed. Study-specific estimates (incidence rates of ocular symptoms in patients with COVID-19) of cases were combined using one-group meta-analysis in a random-effects model. Results: Of all included studies, 11.2% (95% confidence interval, 5.5-16.9; 78/1526 cases) reported ocular symptoms. The most common ocular finding was conjunctivitis. Prodromal ocular symptoms occurred in 12.5% (13/104 cases) of patients with COVID-19. Positive real-time polymerase chain reaction results were obtained for 16.7% (10/60 cases) of conjunctival samples and 0% (0/17 cases) of tear samples. Twelve ocular conjunctival swab samples tested positive for SARS-CoV-2. Ten cases were from subjects showing ocular symptoms (16.7%, 10/60 cases), and the remaining two cases were from subjects without ocular manifestation (1.8%, 2/113 cases). Limitations included the short study period, small sample size, findings were limited to the Asian population, only seven articles included ophthalmologic examination details, and there is currently no consensus on COVID-19 management. Conclusions: Ocular symptoms may occur in the presymptomatic phase as a prodromal symptom (12.5%, 13/104 cases), suggesting the possibility of viral transmission from the conjunctiva.


Assuntos
Conjuntivite Viral/epidemiologia , Infecções por Coronavirus/epidemiologia , Pandemias/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Sintomas Prodrômicos , Síndrome Respiratória Aguda Grave/diagnóstico , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico/métodos , Conjuntivite Viral/diagnóstico , Infecções por Coronavirus/diagnóstico , DNA Viral/análise , Progressão da Doença , Feminino , Humanos , Incidência , Masculino , Pandemias/prevenção & controle , Pneumonia Viral/diagnóstico , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real/métodos , Medição de Risco , Síndrome Respiratória Aguda Grave/epidemiologia
13.
Allergol Int ; 69(4): 510-518, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32651122

RESUMO

Allergic conjunctivitis affects approximately 15-20% of the global population and can permanently deteriorate one's quality of life (QoL) and work productivity, leading to societal work force costs. Although not fully understood, allergic conjunctivitis is a multifactorial disease with a complex network of environmental, lifestyle, and host contributory risk factors. To effectively enhance the quality of treatment for patients with allergic conjunctivitis, as well as other allergic diseases, the field must first comprehend the pathology underlying various individualized subjective symptoms and stratify the disease according to risk factors and presentations. Such competent stratification and societal reconstruction that targets the alleviation of the damage due to allergic diseases would greatly help ramify personalized treatments and prevent the projected increase in societal costs imposed by allergic diseases. Owing to the rapid advancements in the information and technology sector, medical big data are greatly accessible and useful to decipher the pathophysiology of many diseases. Such data collected through multi-omics and mobile health have been effective for research on chronic diseases including allergic and immune-mediated diseases. Novel big data containing vast and continuous information on individuals with allergic conjunctivitis and other allergic symptoms are being used to search for causative genes of diseases, gain insights into new biomarkers, prevent disease progression, and, ultimately, improve QoL. The individualized and holistic data accrued from new angles using technological innovations are helping the field realize the principles of P4 medicine: predictive, preventive, personalized, and participatory medicine.

14.
JMIR Form Res ; 4(6): e16880, 2020 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-32515745

RESUMO

BACKGROUND: Measuring emotional status objectively is challenging, but voice pattern analysis has been reported to be useful in the study of emotion. OBJECTIVE: The purpose of this pilot study was to investigate the association between specific sleep measures and the change of emotional status based on voice patterns measured before and after nighttime sleep. METHODS: A total of 20 volunteers were recruited. Their objective sleep measures were obtained using a portable single-channel electroencephalogram system, and their emotional status was assessed using MIMOSYS, a smartphone app analyzing voice patterns. The study analyzed 73 sleep episodes from 18 participants for the association between the change of emotional status following nighttime sleep (Δvitality) and specific sleep measures. RESULTS: A significant association was identified between total sleep time and Δvitality (regression coefficient: 0.036, P=.008). A significant inverse association was also found between sleep onset latency and Δvitality (regression coefficient: -0.026, P=.001). There was no significant association between Δvitality and sleep efficiency or number of awakenings. CONCLUSIONS: Total sleep time and sleep onset latency are significantly associated with Δvitality, which indicates a change of emotional status following nighttime sleep. This is the first study to report the association between the emotional status assessed using voice pattern and specific sleep measures.

15.
Nihon Shokakibyo Gakkai Zasshi ; 117(6): 532-541, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32565511

RESUMO

IgG4-related autoimmune hepatitis (IgG4-AIH) is characterized by hepatic inflammation and is considered an IgG4-related disease. Several inflammatory pseudotumors (IPTs) are also considered as IgG4-related diseases;however, there have been no reports of cases wherein both diseases occurred concurrently. An older adult with liver dysfunction was admitted to the hospital and was diagnosed with IgG4-AIH following a liver biopsy;IgG4-positive plasma cell infiltration in the portal tract and high serum IgG4 concentration were detected. A few months following biopsy, imaging studies revealed two IPTs in the liver. The patient was diagnosed with cryptogenic organized pneumonia several months after imaging and was treated with steroids in a different hospital. Her liver dysfunction improved, and one of the two IPTs disappeared in response to steroid treatment. The following is an account of a rare case of IgG4-AIH with IPTs of the liver.


Assuntos
Doenças Autoimunes , Granuloma de Células Plasmáticas , Hepatite Autoimune , Hepatopatias , Idoso , Feminino , Humanos , Imunoglobulina G
16.
J Med Internet Res ; 22(6): e18996, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32589162

RESUMO

BACKGROUND: Discontinuation of contact lens use is mainly caused by contact lens-associated dry eye. It is crucial to delineate contact lens-associated dry eye's multifaceted nature to tailor treatment to each patient's individual needs for future personalized medicine. OBJECTIVE: This paper aims to quantify and stratify individual subjective symptoms of contact lens-associated dry eye and clarify its risk factors for future personalized medicine using the smartphone app DryEyeRhythm (Juntendo University). METHODS: This cross-sectional study included iPhone (Apple Inc) users in Japan who downloaded DryEyeRhythm. DryEyeRhythm was used to collect medical big data related to contact lens-associated dry eye between November 2016 and January 2018. The main outcome measure was the incidence of contact lens-associated dry eye. Univariate and multivariate adjusted odds ratios of risk factors for contact lens-associated dry eye were determined by logistic regression analyses. The t-distributed Stochastic Neighbor Embedding algorithm was used to depict the stratification of subjective symptoms of contact lens-associated dry eye. RESULTS: The records of 4454 individuals (median age 27.9 years, SD 12.6), including 2972 female participants (66.73%), who completed all surveys were included in this study. Among the included participants, 1844 (41.40%) were using contact lenses, and among those who used contact lenses, 1447 (78.47%) had contact lens-associated dry eye. Multivariate adjusted odds ratios of risk factors for contact lens-associated dry eye were as follows: younger age, 0.98 (95% CI 0.96-0.99); female sex, 1.53 (95% CI 1.05-2.24); hay fever, 1.38 (95% CI 1.10-1.74); mental illness other than depression or schizophrenia, 2.51 (95% CI 1.13-5.57); past diagnosis of dry eye, 2.21 (95% CI 1.63-2.99); extended screen exposure time >8 hours, 1.61 (95% CI 1.13-2.28); and smoking, 2.07 (95% CI 1.49-2.88). The t-distributed Stochastic Neighbor Embedding analysis visualized and stratified 14 groups based on the subjective symptoms of contact lens-associated dry eye. CONCLUSIONS: This study identified and stratified individuals with contact lens-associated dry eye and its risk factors. Data on subjective symptoms of contact lens-associated dry eye could be used for prospective prevention of contact lens-associated dry eye progression.


Assuntos
Lentes de Contato/efeitos adversos , Crowdsourcing/métodos , Síndromes do Olho Seco/complicações , Aplicativos Móveis/normas , Smartphone/instrumentação , Adulto , Estudos Transversais , Feminino , Humanos , Incidência , Masculino , Estudos Prospectivos , Fatores de Risco
17.
Diagnostics (Basel) ; 10(4)2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32272589

RESUMO

The aim of this study was to compare patient-reported symptoms of dry eye disease (DED) between the Japanese version of the Ocular Surface Disease Index (J-OSDI) and the Dry Eye-Related Quality-of-Life Score (DEQS). A total of 169 participants were enrolled between September 2017 and May 2018. Patients were administered the J-OSDI and DEQS questionnaires at their first (baseline) and follow-up visits to evaluate DED-related symptoms. The correlations between the J-OSDI total score and DEQS (Frequency and Degree) scores were evaluated using Pearson's correlation coefficient, and their clinical differences were assessed using the Bland-Altman analysis. At the baseline visit, the J-OSDI score and DEQS (Frequency and Degree) were significantly correlated (r = 0.855, r = 0.897, respectively). Moreover, a significant correlation was found between the J-OSDI score and DEQS (Frequency and Degree) at the follow-up visit (r = 0.852, r = 0.888, respectively). The Bland-Altman analysis revealed a difference (bias) of 4.18 units at the baseline and 4.08 units at the follow-up between the scores of the two questionnaires. The J-OSDI and DEQS were significantly correlated with negligible score differences, suggesting that the J-OSDI can be reliably used for Japanese patients, allowing for cross-country comparisons.

18.
Ocul Surf ; 18(2): 312-319, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32113987

RESUMO

PURPOSE: Dry eye (DE) disease and depression are increasing in modern times. We investigated the association between DE and depressive symptoms using the iPhone application, DryEyeRhythm. METHODS: This large-scale crowdsourced observational study was conducted within iPhone users in Japan who downloaded DryEyeRhythm. Participants with a Zung Self-rating Depression Scale (SDS) score ≥ 40 were defined as having depressive symptoms, and those with an Ocular Surface Disease Index (OSDI) score ≥ 13 were defined as having DE symptoms (mild, 13-22; moderate, 23-32; and severe, 33-100). We compared SDS scores between participants with normal eye and mild, moderate, and severe OSDI-based DE symptoms. Logistic regression analyses were used to determine the association between DE severity and depressive symptoms after adjustment for demographic characteristics, medical history, and lifestyle habits. RESULTS: This study included 4454 participants (mean age, 27.9 ± 12.6 years; female, 66.7%). Participants with SDS scores ≥40 accounted for 58.2%, 70.9%, 79.4%, and 85.0% of normal controls and participants with mild, moderate, and severe DE symptoms, respectively (P trend < 0.001). The adjusted odds ratios (95% confidence interval) for depressive symptoms (SDS score of ≥40) were 1.62 (1.35-1.95) for mild, 2.39 (1.92-2.97) for moderate, and 3.29 (2.70-4.00) for severe DE symptoms. CONCLUSION: This large-scale crowdsourced clinical study using DryEyeRhythm suggests that depressive symptoms are more common in individuals with more severe DE symptoms. DryEyeRhythm could play a role in earlier prevention or future prospective interventions for depressive symptoms in individuals with DE symptoms.


Assuntos
Crowdsourcing , Síndromes do Olho Seco , Adolescente , Adulto , Depressão/epidemiologia , Síndromes do Olho Seco/epidemiologia , Feminino , Humanos , Japão/epidemiologia , Masculino , Inquéritos e Questionários , Adulto Jovem
19.
JAMA Ophthalmol ; 138(1): 58-68, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31774457

RESUMO

Importance: The incidence of dry eye disease has increased; the potential for crowdsource data to help identify undiagnosed dry eye in symptomatic individuals remains unknown. Objective: To assess the characteristics and risk factors associated with diagnosed and undiagnosed symptomatic dry eye using the smartphone app DryEyeRhythm. Design, Setting, and Participants: A cross-sectional study using crowdsourced data was conducted including individuals in Japan who downloaded DryEyeRhythm and completed the entire questionnaire; duplicate users were excluded. DryEyeRhythm was released on November 2, 2016; the study was conducted from November 2, 2016, to January 12, 2018. Exposures: DryEyeRhythm data were collected on demographics, medical history, lifestyle, subjective symptoms, and disease-specific symptoms, using the Ocular Surface Disease Index (100-point scale; scores 0-12 indicate normal, healthy eyes; 13-22, mild dry eye; 23-32, moderate dry eye; 33-100, severe dry eye symptoms), and the Zung Self-Rating Depression Scale (total of 20 items, total score ranging from 20-80, with ≥40 highly suggestive of depression). Main Outcomes and Measures: Multivariate-adjusted logistic regression analysis was used to identify risk factors for symptomatic dry eye and to identify risk factors for undiagnosed symptomatic dry eye. Results: A total of 21 394 records were identified in our database; 4454 users, included 899 participants (27.3%) with diagnosed and 2395 participants (72.7%) with undiagnosed symptomatic dry eye, completed all questionnaires and their data were analyzed. A total of 2972 participants (66.7%) were women; mean (SD) age was 27.9 (12.6) years. The identified risk factors for symptomatic vs no symptomatic dry eye included younger age (odds ratio [OR], 0.99; 95% CI, 0.987-0.999, P = .02), female sex (OR, 1.99; 95% CI, 1.61-2.46; P < .001), pollinosis (termed hay fever on the questionnaire) (OR, 1.35; 95% CI, 1.18-1.55; P < .001), depression (OR, 1.78; 95% CI, 1.18-2.69; P = .006), mental illnesses other than depression or schizophrenia (OR, 1.87; 95% CI, 1.24-2.82; P = .003), current contact lens use (OR, 1.27; 95% CI, 1.09-1.48; P = .002), extended screen exposure (OR, 1.55; 95% CI, 1.25-1.91; P < .001), and smoking (OR, 1.65; 95% CI, 1.37-1.98; P < .001). The risk factors for undiagnosed vs diagnosed symptomatic dry eye included younger age (OR, 0.96; 95% CI, 0.95-0.97; P < .001), male sex (OR, 0.55; 95% CI, 0.42-0.72; P < .001), as well as absence of collagen disease (OR, 95% CI, 0.23; 0.09-0.60; P = .003), mental illnesses other than depression or schizophrenia (OR, 0.50; 95% CI, 0.36-0.69; P < .001), ophthalmic surgery other than cataract surgery and laser-assisted in situ keratomileusis (OR, 0.41; 95% CI, 0.27-0.64; P < .001), and current (OR, 0.64; 95% CI, 0.54-0.77; P < .001) or past (OR, 0.45; 95% CI, 0.34-0.58; P < .001) contact lens use. Conclusions and Relevance: This study's findings suggest that crowdsourced research identified individuals with diagnosed and undiagnosed symptomatic dry eye and the associated risk factors. These findings could play a role in earlier prevention or more effective interventions for dry eye disease.


Assuntos
Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/epidemiologia , Smartphone , Adulto , Estudos Transversais , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Aplicativos Móveis , Razão de Chances , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
20.
J Pharm Biomed Anal ; 178: 112912, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31610394

RESUMO

Cortisol (CRT), the main glucocorticoid in humans, plays a crucial role in many physiological processes, therefore, the measurement of its serum level is of great clinical significance. Matrix-assisted laser desorption/ionization-tandem mass spectrometry (MALDI-MS/MS) might be an effective approach for the quantification of CRT in serum due to its attractive properties, i.e., high specificity, ease of use, ruggedness and rapid analysis. In this study, we developed a method to quantify the serum CRT by MALDI-MS/MS. This method employed the derivatization using a Girard-type reagent, 1-(hydrazinocarbonylmethyl)isoquinolinium chloride, which compensated for the lack of sensitivity. This method enabled the reproducible quantification of the serum CRT using a 20-µL sample (intra- and inter-assay relative standard deviations, 7.4% or lower), and the measurable range was 25-500 ng/mL. The serum CRT concentrations determined by the newly-developed MALDI-MS/MS method agreed well with those by liquid chromatography/electrospray ionization-MS/MS or electrochemiluminescence immunoassay. The MALDI-MS/MS method was used for the analysis of peripheral venous serum samples of healthy subjects and adrenal venous serum samples of patients with primary aldosteronism, and satisfactory results were obtained.


Assuntos
Hidrocortisona/sangue , Betaína/análogos & derivados , Betaína/química , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Espectrometria de Massas em Tandem/métodos
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