Case of bilateral complete posterior dislocation of lens caused by elder abuse

We report a case of bilateral complete dislocation of lenses into the vitreous cavities due to elder abuse in a patient with senile dementia. According to the patient’s son, bilateral complete lens dislocation occurred after he hit his father in the head with socks in order to control his violent behavior. Although the patient was taken to our ophthalmological ward for a planned vitrectomy, restlessness and inability to remain in his room during the night led to his leaving the hospital. The patient has not returned but did receive a vitrectomy at another clinic. While the number of patients with senile dementia has dramatically increased, no specific remedy is currently available. When treating medical concerns of seniors with unknown backgrounds, elder abuse needs to be considered as a potential cause of such injuries

Repeated exacerbations of ocular inflammation with vitreous hemorrhage in a patient with HLA-B27 associated uveitis

HLA-B27 associated uveitis is characterized by recurrent alternating acute unilateral attacks of intraocular inflammation in the anterior chamber. The aim of this study was to report an unusual case of repeated exacerbations with vitreous hemorrhage in HLA-B27 associated uveitis. Thirty four-year-old man was diagnosed as HLA-B27 associated uveitis in his right eye. He showed repeated exacerbation of ocular inflammation with retinal vein dilation and small retinal hemorrhage following vitreous hemorrhage. Fluorescein fundus angiography a week before the appearance of vitreous hemorrhage showed no neovascularization. Oral prednisolone administration was started from 40 mg/day with gradual tapering. About 3 weeks after the onset, most of the vitreous hemorrhage disappeared and visual acuity was improved to 20/20. Through the decreased vitreous hemorrhage, Weiss ring was detected later. The vitreous hemorrhage found in this patient is a severe exacerbation, and might be a consequence of the vitritis that leads to posterior vitreous detachment

Evaluation of PTPN22 polymorphisms and Vogt-Koyanagi-Harada disease in Japanese patients

Purpose: Vogt-Koyanagi-Harada (VKH) disease is an autoimmune disorder against melanocytes. Polymorphisms of the protein tyrosine phosphatase non-receptor 22 gene (PTPN22) have recently been reported to be associated with susceptibility to several autoimmune diseases. In this study, genetic susceptibility to VKH disease was investigated by screening for single nucleotide polymorphisms (SNPs) of PTPN22. Methods: A total of 167 Japanese patients with VKH disease and 188 healthy Japanese controls were genotyped by direct sequencing methods for six SNPs (rs3811021, rs1217413, rs1237682, rs3761935, rs3789608, and rs2243471) of PTPN22 including the uncoding exons. Results: The six SNPs in PTPN22 showed no significant association with susceptibility to VKH disease or its ocular, neurologic, or dermatological manifestation. Conclusions: Further studies are needed to clarify the genetic mechanisms underlying VKH disease

Ex vivo reconstitution of fetal oocyte development in humans and cynomolgus monkeys

ヒト・サルの胎児卵巣から原始卵胞を体外で作出することに成功. 京都大学プレスリリース. 2022-08-01.New egg recipe to boost fertility research. 京都大学プレスリリース. 2022-08-14.In vitro oogenesis is key to elucidating the mechanism of human female germ-cell development and its anomalies. Accordingly, pluripotent stem cells have been induced into primordial germ cell-like cells and into oogonia with epigenetic reprogramming, yet further reconstitutions remain a challenge. Here, we demonstrate ex vivo reconstitution of fetal oocyte development in both humans and cynomolgus monkeys (Macaca fascicularis). With an optimized culture of fetal ovary reaggregates over three months, human and monkey oogonia enter and complete the first meiotic prophase to differentiate into diplotene oocytes that form primordial follicles, the source for oogenesis in adults. The cytological and transcriptomic progressions of fetal oocyte development in vitro closely recapitulate those in vivo. A comparison of single-cell transcriptomes among humans, monkeys, and mice unravels primate-specific and conserved programs driving fetal oocyte development, the former including a distinct transcriptomic transformation upon oogonia-to-oocyte transition and the latter including two active X chromosomes with little X-chromosome upregulation. Our study provides a critical step forward for realizing human in vitro oogenesis and uncovers salient characteristics of fetal oocyte development in primates

A novel biomarker TERTmRNA is applicable for early detection of hepatoma

<p>Abstract</p> <p>Backgrounds</p> <p>We previously reported a highly sensitive method for serum human telomerase reverse transcriptase (hTERT) mRNA for hepatocellular carcinoma (HCC). α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) are good markers for HCC. In this study, we verified the significance of hTERTmRNA in a large scale multi-centered trial, collating quantified values with clinical course.</p> <p>Methods</p> <p>In 638 subjects including 303 patients with HCC, 89 with chronic hepatitis (CH), 45 with liver cirrhosis (LC) and 201 healthy individuals, we quantified serum hTERTmRNA using the real-time RT-PCR. We examined its sensitivity and specificity in HCC diagnosis, clinical significance, ROC curve analysis in comparison with other tumor markers, and its correlations with the clinical parameters using Pearson relative test and multivariate analyses. Furthermore, we performed a prospective and comparative study to observe the change of biomarkers, including hTERTmRNA in HCC patients receiving anti-cancer therapies.</p> <p>Results</p> <p>hTERTmRNA was demonstrated to be independently correlated with clinical parameters; tumor size and tumor differentiation (P < 0.001, each). The sensitivity/specificity of hTERTmRNA in HCC diagnosis showed 90.2%/85.4% for hTERT. hTERTmRNA proved to be superior to AFP, AFP-L3, and DCP in the diagnosis and underwent an indisputable change in response to therapy. The detection rate of small HCC by hTERTmRNA was superior to the other markers.</p> <p>Conclusions</p> <p>hTERTmRNA is superior to conventional tumor markers in the diagnosis and recurrence of HCC at an early stage.</p

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Investigation of molecular biomarker candidates for diagnosis and prognosis of chronic periodontitis by bioinformatics analysis of pooled microarray gene expression datasets in Gene Expression Omnibus (GEO)

Abstract Background Chronic periodontitis (CP) is a multifactorial inflammatory disease. For the diagnosis of CP, it is necessary to investigate molecular biomarkers and the biological pathway of CP. Although analysis of mRNA expression profiling with microarray is useful to elucidate pathological mechanisms of multifactorial diseases, it is expensive. Therefore, we utilized pooled microarray gene expression data on the basis of data sharing to reduce hybridization costs and compensate for insufficient mRNA sampling. The aim of the present study was to identify molecular biomarker candidates and biological pathways of CP using pooled datasets in the Gene Expression Omnibus (GEO) database. Methods Three pooled transcriptomic datasets (GSE10334, GSE16134, and GSE23586) of gingival tissue with CP in the GEO database were analyzed for differentially expressed genes (DEGs) using GEO2R, functional analysis and biological pathways with the Database of Annotation Visualization and Integrated Discovery database, Protein-Protein Interaction (PPI) network and hub gene with the Search Tool for the Retrieval of Interaction Genes database, and biomarker candidates for diagnosis and prognosis and upstream regulators of dominant biomarker candidates with the Ingenuity Pathway Analysis database. Results We shared pooled microarray datasets in the GEO database. One hundred and twenty-three common DEGs were found in gingival tissue with CP, including 81 upregulated genes and 42 downregulated genes. Upregulated genes in Gene Ontology were significantly enriched in immune responses, and those in the Kyoto Encyclopedia of Genes and Genomes pathway were significantly enriched in the cytokine-cytokine receptor interaction pathway, cell adhesion molecules, and hematopoietic cell lineage. From the PPI network, the 12 nodes with the highest degree were screened as hub genes. Additionally, six biomarker candidates for CP diagnosis and prognosis were screened. Conclusions We identified several potential biomarkers for CP diagnosis and prognosis (e.g., CSF3, CXCL12, IL1B, MS4A1, PECAM1, and TAGLN) and upstream regulators of biomarker candidates for CP diagnosis (TNF and TGF2). We also confirmed key genes of CP pathogenesis such as CD19, IL8, CD79A, FCGR3B, SELL, CSF3, IL1B, FCGR2B, CXCL12, C3, CD53, and IL10RA. To our knowledge, this is the first report to reveal associations of CD53, CD79A, MS4A1, PECAM1, and TAGLN with CP

Tyrosinase gene family and Vogt-Koyanagi-Harada disease in Japanese patients.

PURPOSE: The aim of the present study was to examine the genetic background of Vogt-Koyanagi-Harada (VKH) disease in a Japanese population by analyzing the tyrosinase gene family (TYR, TYRP1, and dopachrome tautomerase (DCT)). METHODS: 87 VKH patients and 122 healthy controls were genotyped using seven microsatellite markers on the candidate loci. We analyzed microsatellite (MS) polymorphisms at regions within tyrosinase gene family loci. In addition, the haplotype frequencies were also estimated and statistical analysis was performed. HLA-DRB1 genotyping was performed by the PCR-restriction fragment length polymorphism (RFLP) method. RESULTS: No significant evidence for an association was found. HLA-DRB1*0405 showed a highly significant association with VKH disease compared with the healthy controls (Pc=0.000000079), as expected. CONCLUSIONS: We concluded that there is no genetic susceptibility or increased risk attributed to the tyrosinase gene family. Our results suggest the need for further genetic study and encourage a search for novel genetic loci and predisposing genes in order to elucidate the genetic mechanisms underlying VKH disease