Awareness of Infectious Disease Screening During Early Pregnancy and Knowledge About its Vertical Transmission in Japan: A Report from the Pregnant Women Health Initiative.

OBJECTIVES: We aimed to clarify the accuracy of pregnant women's knowledge and understanding regarding infectious disease screening in early pregnancy and clarify the roles that should be played by health care providers in promoting the health of pregnant women and their children. METHODS: A cross-sectional questionnaire survey was conducted in 25 hospitals across Japan from May 2018 to September 2019. We compared the agreement rates regarding screening results for hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis, human T-cell leukemia virus-1 (HTLV-1), and cervical cytology in the medical records and understanding of their results by pregnant women. We then investigated whether participants had knowledge regarding the risk of mother-to child transmission in these diseases and factors associated with their knowledge. RESULTS: We enrolled 2,838 respondents in this study. The rates of agreement for HBV and cervical cancer screening related to human papillomavirus infection were "substantial," those for syphilis was "moderate," and those for HCV and HTLV-1 were "fair," according to the Kappa coefficient. The rate of knowledge regarding mother-to-child transmission of syphilis was highest (37.0%); this rate for the other items was approximately 30%. Increased knowledge was associated with higher educational level and higher annual income. CONCLUSIONS FOR PRACTICE: Pregnant women in Japan had generally good levels of understanding regarding their results in early-pregnancy infectious disease screening. However, they had insufficient knowledge regarding mother-to-child transmission of these diseases. Health care providers should raise awareness in infectious disease prevention among pregnant women and the general public, providing appropriate measures and implementing effective perinatal checkups and follow-ups for infectious diseases.

Case of suspected lobular endocervical glandular hyperplasia in a cervical cystic lesion during pregnancy.

Lobular endocervical glandular hyperplasia (LEGH) is characterized by clinically profuse and watery vaginal discharge. In pregnancy with LEGH, with watery fluid leakage persisting throughout pregnancy, it is often difficult to visually diagnose PROM. Adding to this difficulty, auxiliary diagnostic tests might also show positive results, complicating treatment and management.

Trends in Pregnancy-Associated Cervical Cancer in Japan between 2012 and 2017: A Multicenter Survey.

Large-scale data on maternal and neonatal outcomes of pregnancy-associated cervical cancer in Japan are scarce, and treatment strategies have not been established. This multicenter retrospective observational study investigated clinical features and trends in pregnancy-associated cervical cancer treatments at 523 hospitals in Japan. We included cervical cancer cases that were histologically diagnosed (between 1 January 2012, and 31 December 2017), and their clinical information was retrospectively collected. Of 40 patients diagnosed with pregnancy-associated cervical cancer at ≥22 gestational weeks, 34 (85.0%) were carefully followed until delivery without intervention. Of 163 diagnosed at <22 gestational weeks, 111 continued and 52 terminated their pregnancy. Ninety patients with stage IB1 disease had various treatment options, including termination of pregnancy. The 59 stage IB1 patients who continued their pregnancy were categorized by the primary treatment into strict follow-up, conization, trachelectomy, and neoadjuvant chemotherapy groups, with no significant differences in progression-free or overall survival. The birth weight percentile at delivery was smaller in the neoadjuvant chemotherapy group than in the strict follow-up group (p = 0.029). Full-term delivery rate was relatively higher in the trachelectomy group (35%) than in the other groups. Treatment decisions for pregnancy-associated cervical cancer are needed after estimating the stage, considering both maternal and fetal benefits.

Factors Predicting Rubella Vaccination and Antibody in Pregnant Women in Japan: A Report from Pregnant Women Health Initiative.

This study aimed to identify the factors predicting rubella vaccination status based on self-reported data and the presence of sufficient rubella antibody titers in pregnant women in Japan. We used the results of the nationwide questionnaire survey conducted at obstetric facilities in the Pregnant Women Health Initiative Project (PWHI), with 23 participating hospitals recruiting pregnant women from June 2018-November 2019. We extracted age, the number of deliveries, educational level, household income, pre-pregnancy smoking, and knowledge of rubella from questionnaires and medical records. We analyzed the association of rubella vaccination status and antibodies with each of these factors. We found that the number of previous deliveries, educational level, annual household income, smoking before pregnancy, and knowledge of rubella were factors predicting self-reported rubella vaccination status, while age and the number of previous deliveries were identified as factors predicting the presence of sufficient rubella antibody titers (32 folds or higher). Women considering pregnancy should be immunized against rubella to prevent congenital rubella syndrome in the future. Furthermore, social policies are needed to strongly encourage vaccination, especially for all citizens who were not given the opportunity or missed the chance to be vaccinated against rubella.

Depth Perception with a Newly Developed Microscope Stereotest.

PURPOSE: We aimed to compare the depth perception under a microscope between binocular and monocular conditions using a newly developed microscopic stereotest (M-stereotest) and examine the effect of anisometropia on depth perception under a microscope. SUBJECTS AND METHODS: Thirty young and healthy subjects were examined. A manipulator attached with a stainless wire was placed under the objective lens of a stereomicroscope. The wire was moved up manually, and the subjects were instructed to stop the knob movement once the wire reached the same height as the fixed two wires. The deviation from the height of the fixed wires was measured under a best optically corrected binocular, a best optically corrected monocular, or an anisometropic binocular [±3 diopters (D) in the dominant or nondominant eye] condition. RESULTS: The deviation was significantly smaller in the binocular condition than in the monocular dominant eye condition (0.38 ± 0.26 mm vs 1.89 ± 1.15 mm, p < 0.001) and was also significantly smaller in the best optically corrected binocular than in the anisometropic binocular condition [1.07 ± 1.00 mm (-3.0 D), p = 0.003; 0.85 ± 0.67 mm (+3.0 D), p < 0.001]. CONCLUSION: Depth perception under the microscope is more accurate under the binocular than in the monocular condition, indicating the potential role of stereopsis. Anisometropia deteriorates depth perception, suggesting that refractive error should be corrected during microscopic work, such as during ophthalmic surgery.

Factors Predicting Rubella Vaccination among Pregnant Women in Japan: an Interim Report from the Pregnant Women Health Initiative.

Following the 2018 rubella outbreak in Japan, this study aimed to assess rubella prevention measures based on the vaccination and immunization status of pregnant women in Japan. Our cohort study involved 3 local core hospitals in Yokohama City, and a total of 666 pregnant women were recruited between June 2018 and September 2019 and answered an online questionnaire. In total, 67.5% of the pregnant women had received rubella vaccination. The rate of rubella vaccination among pregnant women in the present survey was lower than that among age-matched female participants in a nationwide survey conducted in 2018. Overall, the study results showed that pregnant women in their 20s had a higher vaccination rate than those in their 40s, women who were nonsmokers before pregnancy had a higher vaccination rate than those who were smokers, and pregnant women who were aware that rubella may affect their fetuses had a higher vaccination rate than those who were unaware of this. This survey elucidated multiple predictive factors for rubella vaccination among pregnant women in Japan. Our results confirm the recommendation that women considering pregnancy should be vaccinated against rubella.

Iodine Redistribution During Trauma, Sepsis, and Hibernation: An Evolutionarily Conserved Response to Severe Stress.

OBJECTIVE: We performed these studies to learn how iodine in the form of free iodide behaves during stress. DESIGN: Prospective observational trial using samples obtained from human trauma patients and retrospective observational study using remnant samples from human sepsis patients and arctic ground squirrels. Preclinical interventional study using hind-limb ischemia and reperfusion injury in mice. SETTING: Level I trauma center emergency room and ICU and animal research laboratories. SUBJECTS: Adult human sepsis and trauma patients, wild-caught adult arctic ground squirrels, and sexually mature laboratory mice. INTERVENTIONS: Ischemia and reperfusion injury was induced in mice by temporary application of tourniquet to one hind-limb. Iodide was administered IV just prior to reperfusion. MEASUREMENTS AND MAIN RESULTS: Free iodide was measured using ion chromatography. Relative to iodide in plasma from normal donors, iodide was increased 17-fold in plasma from trauma patients and 26-fold in plasma from sepsis patients. In arctic ground squirrels, iodide increases over three-fold during hibernation. And during ischemia/reperfusion injury in mice, iodide accumulates in ischemic tissue and reduces both local and systemic tissue damage. CONCLUSIONS: Iodide redistributes during stress and improves outcome after injury. Essential functions of iodide may have contributed to its evolutionary selection and be useful as a therapeutic intervention for human patients.

Early vitrectomy to reverse macular dragging in a one-month-old boy with familial exudative vitreoretinopathy.

PURPOSE: Vitrectomy is usually only indicated for familial exudative vitreoretinopathy (FEVR) cases with progressive retinal folds or macular dragging. In this report, we present our experience reversing the progression of macular dragging by performing early eye vitrectomies in a 1-month-old male baby with FEVR. OBSERVATIONS: A 7-day-old, full-term male baby was examined by a pediatric ophthalmologist. His sister had a laser ablation treatment after being diagnosed with FEVR. The ophthalmologist found the baby had avascular retinas, fibrovascular membranes, and vitreous hemorrhages in both eyes, and performed retinal photocoagulations the next day. Although the retinal folds had not yet formed, the arcade vessels began to linearize after the procedure, strongly suggesting disease progression. Therefore, we performed lens-sparing vitrectomies in both eyes on the twenty-ninth day of life. After surgery, the macular dragging reversed, as evidenced by vascular arcade angle measurements. Three years after the surgery, the boy's visual acuity was 0.4 in both eyes. CONCLUSIONS AND IMPORTANCE: In this case, we believe the good postoperative outcomes were due to early vitrectomies before the vitreoretinal traction became severe. In addition, the retinal photocoagulation performed on the eighth day of life may have reduced disease activity, at least partially. This case highlights the importance of prompt diagnosis and appropriate treatment of FEVR.

Novel mutations in the RS1 gene in Japanese patients with X-linked congenital retinoschisis.

X-linked congenital retinoschisis (XLRS) is an inherited retinal disorder characterized by reduced central vision and schisis of the macula and peripheral retina. XLRS is caused by mutations in the RS1 gene. We have identified 37 different mutations in the RS1 gene, including 12 novel mutations, in 67 Japanese patients from 56 XLRS families. We present clinical features of these patients in relation to the associated mutations.

Iodide Improves Outcome After Acute Myocardial Infarction in Rats and Pigs.

OBJECTIVES: In this study, we tested whether iodide would reduce heart damage in rat and pig models of acute myocardial infarction as a risk analysis for a human trial. DESIGN: Prospective blinded and randomized laboratory animal investigation. SETTING: Animal research laboratories. SUBJECTS: Sexually mature rats and pigs. INTERVENTIONS: Acute myocardial infarction was induced by temporary ligation of the coronary artery followed by reperfusion. Iodide was administered orally in rats or IV in rats and pigs just prior to reperfusion. MEASUREMENTS AND MAIN RESULTS: Damage was assessed by blood cardiac troponin and infarct size; heart function was determined by echocardiography. Blood peroxide scavenging activity was measured enzymatically, and blood thyroid hormone was determined using radioimmune assay. Iodide administration preserved heart function and reduced blood cardiac troponin and infarct size by approximately 45% in pigs and approximately 60% in rats. Iodide administration also increased blood peroxide scavenging activity and maintained thyroid hormone levels. CONCLUSIONS: Iodide administration improved the structure and function of the heart after acute myocardial infarction in rats and pigs.

Diurnal variations in luminal and stromal areas of choroid in normal eyes.

AIMS: To determine the diurnal variations of the luminal and stromal areas of the choroid in normal eyes. METHODS: This was a prospective observational study of 38 eyes of 38 normal subjects. The blood pressure, heart rate, intraocular pressure and enhanced depth imaging optical coherence tomographic (EDI-OCT) images were recorded every 3 hours between 6:00 and 21:00 hours. The horizontal EDI-OCT images of the subfoveal choroid were converted to binary images. The central choroidal thickness (CCT), total cross-sectional choroidal area, the luminal areas, stromal areas and the ratio of luminal area to total choroidal area (L/C ratio) were determined. RESULTS: There were significant diurnal variations in the CCT, total choroidal area, luminal area and L/C ratio with the maximum values at 6:00 hours and the minimum values at 15:00 hours (p<0.001 for the CCT, p=0.011 for the total choroidal area, p<0.001 for the luminal area and p=0.014 for the L/C ratio). There was no significant variation in the stromal area (p=0.216). The range of fluctuation in the CCT was significantly correlated with that in the luminal area and the total choroidal area (p<0.001). However, there was no significant correlation between the fluctuation range in the CCT and that in the stromal area (p=0.095). There was no statistical relationship between the systemic parameters and the choroidal parameters. CONCLUSIONS: The changes in the luminal area are most likely responsible for the diurnal change in the CCT and subfoveal choroidal area. TRIAL REGISTRATION NUMBER: UMIN000019060, Pre-results.

A case of IgG4-related lymphadenopathy, pericarditis, coronary artery periarteritis and luminal stenosis.

Immunoglobulin G4 (IgG4)-related disease is an emerging new clinicopathological disorder that is characterized by elevation of serum IgG4 levels and histological findings of IgG4-positive plasmacytic infiltration. IgG4-related disease may appear synchronously or metachronously in a wide variety of organs. The current patient was found to have pericardial effusion and retroperitoneal fibrosis. He was subsequently diagnosed with coronary artery stenosis. (18)F-FDG positron emission tomography showed enhanced FDG uptake in lymph nodes as well as pericardial and peri-aortic tissue. Histopathology of the mediastinal lymph node showed the infiltration of numerous IgG4-positive cells, leading to the diagnosis of IgG4-related lymphadenopathy with pericardial and periarterial involvement.

Selenide Targets to Reperfusing Tissue and Protects It From Injury.

OBJECTIVES: Since blood selenium levels decrease after ischemia and reperfusion injury, and low blood selenium correlates with negative outcome, we designed and performed experiments to determine how selenium distribution is affected by ischemia reperfusion injury. Furthermore, we tested whether different chemical forms of selenium would affect outcome after ischemia and reperfusion injury. We also examined the metabolic effects of selenide administration. DESIGN: Laboratory investigation. SETTING: Animal research laboratory. SUBJECTS: Adult male C57BL/6 mice. INTERVENTIONS: To determine selenium localization, we administered tracer doses of radioactive selenium 75 in the form of selenite or selenide and measured blood and tissue selenium levels after ischemia and reperfusion injury. Anesthetized mice were subjected to myocardial ischemia reperfusion injury (coronary artery occlusion for 60 min followed by 5 min of reperfusion after occlusion was removed) or hindlimb ischemia reperfusion injury (left leg tourniquet for 90 min followed by 5 min reperfusion after tourniquet removal). To determine whether exogenous selenium administration could reduce ischemia reperfusion injury, we synthesized and administered sodium hydroselenide and sodium selenite solutions (0.05-2.4 mg/kg). Solutions were administered at the end of coronary artery occlusion but before reperfusion. In order to determine the metabolic effects of selenide administration, we exposed mice to hydrogen selenide gas (0-5 ppm) mixed into air (20.95% oxygen) for up to 3 hours. MEASUREMENTS AND MAIN RESULTS: In targeting assays, we measured blood and tissue selenium levels. We observed that blood selenium decreases after myocardial ischemia reperfusion and displays an inverse correlation with injury severity; selenium accumulation in heart correlates directly with injury severity. We also measured whether oxidized selenium, selenite, and reduced selenium, selenide, would target to injured heart tissue in myocardial ischemia reperfusion and injured leg muscle in a hindlimb model of ischemia reperfusion. Only selenide targets to injured tissue. We also measured damage after myocardial ischemia reperfusion injury using morphometry, neutrophil accumulation, blood cardiac troponin levels, and echocardiography and observed in all assays that selenide reduced damage to the heart; selenite was not effective. And finally, to assay metabolism, we measured oxygen consumption, carbon dioxide production, and body core temperature before, during, and after hydrogen selenide administration. All measurements indicate that selenide decreases metabolism. CONCLUSIONS: Selenide targets to reperfusing tissue and reduces reperfusion injury perhaps by affecting oxygen metabolism.

Binarization of enhanced depth imaging optical coherence tomographic images of an eye with Wyburn-Mason syndrome: a case report.

BACKGROUND: To report a thicker choroid and larger choroidal luminal area in an eye with Wyburn-Mason syndrome. To the best of our knowledge, this is the first report demonstrating an increase in the choroidal thickness and the luminal area in a case of Wyburn-Mason syndrome. In addition, we report the changing appearance of retinal arteriovenous malformations over a 16-year period. CASE PRESENTATION: A 27-year-old woman, who was diagnosed with Wyburn-Mason syndrome at age 11 years, visited our clinic. Her best-corrected visual acuity was 20/12.5 in the right eye and light perception in the left eye. Severely dilated, tortuous vascular loops were distributed from the optic disc over all four quadrants of the left fundus. The vascular loops in some areas were more dilated and tortuous than 16 years earlier. Optical coherence tomography (OCT) showed retinal edema with cystic changes and enlarged choroidal vessel lumens in the left eye. The subfoveal choroidal thickness was manually measured by the caliper function in the enhanced depth imaging OCT (EDI-OCT) images. Binarization of the EDI-OCT images was performed with publicly accessible ImageJ software. The examined area of the subfoveal choroid was 1,500 µm wide, and the dark areas representing the luminal areas were traced by the Niblack method. After determining the distance of each pixel, the luminal area was automatically calculated. The subfoveal choroidal thickness was 250 µm in the right eye and 462 µm in the left eye. The luminal area of the 1,500-µm-wide subfoveal choroid was computed to be 307,165.6 µm(2) in the right eye and 545,780.7 µm(2) in the left eye. CONCLUSIONS: The EDI-OCT images showed a thicker choroid, and binarization of the EDI-OCT images showed that the luminal areas were significantly larger in the affected eye, suggesting a dilatation of the choroidal vessels. The results demonstrated that conversion of EDI-OCT images to binary images was a useful method to quantify the choroidal structure.

Iodide protects heart tissue from reperfusion injury.

Iodine is an elemental nutrient that is essential for mammals. Here we provide evidence for an acute therapeutic role for iodine in ischemia reperfusion injury. Infusion of the reduced form, iodide, but not the oxidized form iodate, reduces heart damage by as much as 75% when delivered intravenously following temporary loss of blood flow but prior to reperfusion of the heart in a mouse model of acute myocardial infarction. Normal thyroid function may be required because loss of thyroid activity abrogates the iodide benefit. Given the high degree of protection and the high degree of safety, iodide should be explored further as a therapy for reperfusion injury.

Abrogation of Rbpj attenuates experimental autoimmune uveoretinitis by inhibiting IL-22-producing CD4+ T cells.

Experimental autoimmune uveoretinitis (EAU) is an organ-specific T cell-mediated disease induced by immunizing mice with interphotoreceptor retinoid binding protein (IRBP). Autoaggressive CD4(+) T cells are the major pathogenic population for EAU. We investigated the contribution of Notch signaling in T cells to EAU pathogenesis because Notch signaling regulates various aspects of CD4(+) T cell functions. Rbpj is required for Notch signaling, and Rbpj deficiency in T cells inhibited EAU disease severity. The amelioration of EAU in T cell-specific Rbpj-deficient mice correlated with low levels of IL-22 production from CD4(+) T cells, although IRBP-specific CD4(+) T cell proliferation and Th17 differentiation were unaffected. Administration of recombinant IL-22 during the late phase, but not the early phase, of EAU increased EAU clinical scores in T cell-specific Rbpj-deficient mice. Notch inhibition in mice immunized with IRBP with a γ-secretase inhibitor (GSI) suppressed EAU progression, even when GSI was administered as late as 13 days after IRBP immunization. Our data demonstrate that Rbpj/Notch-mediated IL-22 production in T cells has a key pathological role in the late phase of EAU, and suggest that Notch blockade might be a useful therapeutic approach for treating EAU.

Development of an automatic ROI setting program for input function determination in 99mTc-ECD non-invasive cerebral blood flow quantification.

Non-invasive quantitative measurements are useful for clinical study as these are simple and pain-free procedures. A new non-invasive semi-automatic quantitative measurement method, the improved brain uptake ratio (IBUR) method using (99m)Tc-ECD SPECT, has recently been reported. If an automatic ROI setting algorithm could be developed to determine the input function for the IBUR method, analysis of regional cerebral blood flow (rCBF) can be completed within a few min without recourse to complex techniques, through a fully automatic rCBF analysis program. The purpose of this study was to develop an automatic input function determination program for (99m)Tc-ECD non-invasive cerebral blood flow quantification and to confirm the feasibility of use of this program. The images of 15 consecutive patients who underwent both (99m)Tc-ECD chest RI angiography and SPECT examinations were used for development of the automatic arterial input function program. The images of 69 consecutive patients were used for validation of the program. The coincidence ratio between the ROI automatic method and the manual setting method was 98%. The mean difference in the ROI location was ±6.4 mm in the X direction and ±8.6 mm in the Y direction. Individual rCBF values obtained using these independent techniques were also reasonably well correlated (r = 0.95). The total time for the IBUR analysis using the automatic method is 2-3 min as compared to 20-30 min for the current analysis method. This technique improves the throughput of nuclear medical examinations.

Hematopoietic Fas deficiency does not affect experimental atherosclerotic lesion formation despite inducing a proatherogenic state.

The Fas death receptor (CD95) is expressed on macrophages, smooth muscle cells, and T cells within atherosclerotic lesions. Given the dual roles of Fas in both apoptotic and nonapoptotic signaling, the aim of the present study was to test the effect of hematopoietic Fas deficiency on experimental atherosclerosis in low-density lipoprotein receptor-null mice (Ldlr(-/-)). Bone marrow from Fas(-/-) mice was used to reconstitute irradiated Ldlr(-/-) mice as a model for atherosclerosis. After 16 weeks on an 0.5% cholesterol diet, no differences were noted in brachiocephalic artery lesion size, cellularity, or vessel wall apoptosis. However, Ldlr(-/-) mice reconstituted with Fas(-/-) hematopoietic cells had elevated hyperlipidemia [80% increase, relative to wild-type (WT) controls; P < 0.001] and showed marked elevation of plasma levels of CXCL1/KC, CCL2/MCP-1, IL-6, IL-10, IL-12 subunit p70, and soluble Fas ligand (P < 0.01), as well as systemic microvascular inflammation. It was not possible to assess later stages of atherosclerosis because of increased mortality in Fas(-/-) bone marrow recipients. Our data indicate that hematopoietic Fas deficiency does not affect early atherosclerotic lesion development in Ldlr(-/-) mice.