The Health History of First-Degree Relatives' Dyslipidemia Can Affect Preferences and Intentions following the Return of Genomic Results for Monogenic Familial Hypercholesterolemia.

Genetic testing is key in modern healthcare, particularly for monogenic disorders such as familial hypercholesterolemia. This Tohoku Medical Megabank Project study explored the impact of first-degree relatives' dyslipidemia history on individual responses to familial hypercholesterolemia genomic results. Involving 214 participants and using Japan's 3.5KJPN genome reference panel, the study assessed preferences and intentions regarding familial hypercholesterolemia genetic testing results. The data revealed a significant inclination among participants with a family history of dyslipidemia to share their genetic test results, with more than 80% of participants intending to share positive results with their partners and children and 98.1% acknowledging the usefulness of positive results for personal health management. The study underscores the importance of family health history in genetic-testing perceptions, highlighting the need for family-centered approaches in genetic counseling and healthcare. Notable study limitations include the regional scope and reliance on questionnaire data. The study results emphasize the association between family health history and genetic-testing attitudes and decisions.

Randomized Multicenter Clinical Trial Comparing 0.1% Brimonidine/0.5% Timolol Versus 1% Dorzolamide/0.5% Timolol as Adjuncts to Prostaglandin Analogues: Aibeta Crossover Study.

INTRODUCTION: This multicenter, randomized, comparative, and investigator-masked crossover clinical trial sought to compare the efficacy and tolerability of fixed combinations of 0.1% brimonidine/0.5% timolol (BTFC) versus 1% dorzolamide/0.5% timolol (DTFC) as adjunctive therapies to prostaglandin analogues. METHODS: A total of 110 patients with open-angle glaucoma or ocular hypertension previously treated with prostaglandin analogue monotherapy were randomized to receive either BTFC or DTFC as adjunctive therapy for 8 weeks. These patients were then crossed over to the alternative treatment arm for another 8 weeks. The reduction in intraocular pressure (IOP) (primary outcome), occurrence of adverse events, ocular discomfort after instillation, and patient preference (secondary outcomes) were recorded through patient interviews. RESULTS: BTFC instillation for 8 weeks reduced IOP by 3.55 mmHg, demonstrating non-inferiority to DTFC instillation (3.60 mmHg; P < 0.0001, mixed-effects model). Although adverse events were rare with both combinations, patients reported greater discomfort with DTFC than with BTFC (P < 0.0001). More patients preferred BTFC (P < 0.0001) over DTFC, as BTFC caused minimal or no eye irritation. CONCLUSION: As BTFC offered better tolerability than DTFC with comparable reduction in IOP, we recommend it as an alternative for patients who experience ocular discomfort with DTFC-prostaglandin analogue combination therapy. TRIAL REGISTRATION NUMBER: jRCTs051190125.

Patients with glaucoma who require further reduction in intraocular pressure while undergoing monotherapy with prostaglandin analogue ophthalmic solution have been prescribed two enhanced treatment options: 0.1% brimonidine/0.5% timolol fixed combination ophthalmic solution (BTFC) and 1% dorzolamide/0.5% timolol fixed combination ophthalmic solution (DTFC). The Aibeta Crossover Study Group in Japan compared the efficacy and tolerability of fixed combinations of BTFC versus DTFC when an additional fixed combination ophthalmic solution was prescribed in patients with open-angle glaucoma or ocular hypertension who had been treated with prostaglandin analogue monotherapy. We recruited 110 patients previously treated with prostaglandin analogue monotherapy at 20 clinical centers in Japan, then randomly assigned them to two alternative treatment groups: the BTFC to DTFC group or the DTFC to BTFC group, as an adjunctive therapy to prostaglandin analogues for total of 16 weeks. We compared the reduction in intraocular pressure, occurrence of side effects, eye discomfort after instillation, and patient preference between BTFC versus DTFC instillations. The intraocular pressure reduction of BTFC instillation was comparable to that of DTFC instillation, showing non-inferiority to DTFC (3.55 mmHg vs. 3.60 mmHg; P < 0.0001, mixed-effects model). Both eye drops caused few side effects; however, patients felt greater eye discomfort with DTFC than with BTFC (P < 0.0001). Because of less eye irritation, more patients preferred BTFC (P < 0.0001) over DTFC. We can recommend using BTFC for patients who feel eye discomfort with DTFC­prostaglandin analogue combination therapy.

Evaluation of temperature-dependent fluctuations in skin microcirculation flow using a light-emitting diode based photoacoustic imaging device.

PURPOSE: Skin microvessels maintain temperature homeostasis by contracting and dilating upon exposure to changes in temperature. Under general anesthesia, surgical invasiveness, including incisions and coagulation, and the effects of anesthetics may cause variations in the threshold temperature, leading to the constriction and dilation of cutaneous blood vessels. Therefore, studies on skin microvascular circulation are necessary to develop appropriate interventions for complications during surgery. METHODS: We visualized and quantified skin microcirculatory fluctuations associated with temperature variations using a light-emitting diode photoacoustic imaging (LED-PAI) device. The hands of ten healthy volunteers were stressed with four different water temperatures [25℃ (Control), 15℃ (Cold1), 40℃ (Warm), and 15℃ (Cold2)]. The photoacoustic images of the fingers were taken under each condition, and the microvascular flow owing to temperature stress was quantified as the area of photoacoustic signal (S) in each image. The S values were compared with the variations in blood flow (Q) measured by laser Doppler flowmetry (LDF). RESULTS: The correlation between Q and S according to the 40 measurements was r = 0.45 (p＜0.01). In addition, the values of S under each stress condition were as follows: Scontrol = 10,826 ± 3364 pixels, Scold1 = 8825 ± 2484 pixels, Swarm = 13,369 ± 3001 pixels, and Scold2 = 8838 ± 1892 pixels; the differences were significant. The LDF blood flow (Q) showed similar changes among conditions. CONCLUSION: These findings suggest that the LED-PAI device could be an option for evaluating microcirculation in association with changes in temperature.

TDP-43 N-terminal domain dimerisation or spatial separation by RNA binding decreases its propensity to aggregate.

Aggregation of the 43 kDa TAR DNA-binding protein (TDP-43) is a pathological hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). RNA binding and TDP-43 N-terminal domain dimerisation has been suggested to ameliorate TDP-43 aggregation. However, the relationship between these factors and the solubility of TDP-43 is largely unknown. Therefore, we developed new oligonucleotides that can recruit two TDP-43 molecules and interfere with their intermolecular interactions via spatial separation. Using these oligonucleotides and TDP-43-preferable UG-repeats, we uncovered two distinct mechanisms for modulating TDP-43 solubility by RNA binding: One is N-terminal domain dimerisation, and the other is the spatial separation of two TDP-43 molecules. This study provides new molecular insights into the regulation of TDP-43 solubility.

Japanese Translation and Validation of Genomic Knowledge Measure in the International Genetics Literacy and Attitudes Survey (iGLAS-GK).

Knowledge of genetics is essential for understanding the results of genetic testing and its implications. Recent advances in genomic research have allowed us to predict the risk of onset of common diseases based on individual genomic information. It is anticipated that more people will receive such estimates of risks based on their genomic data. However, currently, there is no measure for genetic knowledge that includes post-genome sequencing advancements in Japan. In this study, we translated the genomic knowledge measure in the International Genetics Literacy and Attitudes Survey (iGLAS-GK) into Japanese and validated it in a general Japanese adult population (n = 463). The mean score was 8.41 (SD 2.56, range 3-17). The skewness and kurtosis were 0.534 and 0.088, respectively, and the distribution showed a slightly positive skewness. Exploratory factor analysis proposed a six-factor model. Results for 16 of the 20 items of the Japanese version of the iGLAS-GK were comparable to those from previous studies in other populations. These results indicate that the Japanese version is reliable and can be used to measure the genomic knowledge of adults in the general population, and this version of the knowledge measure maintains the multidimensional structure for assessing genomic knowledge.

Recontact: a survey of current practices and BRCA1/2 testing in Japan.

Genetic testing advances have enabled the provision of previously unavailable information on the pathogenicity of genetic variants, frequently necessitating the recontact of former patients by clinicians. In Japan, national health insurance coverage was extended to BRCA1/2 testing for the diagnosis of hereditary breast and ovarian cancer for patients who meet certain criteria in 2020, and conditions necessitating recontact were expected to increase. Studies and discussions regarding recontact have been conducted in the U.S. and Europe; however, in Japan, the national discussion around recontact remains undeveloped. We conducted a cross-sectional study by interviewing 73 facilities accredited by the Japanese Organization of Hereditary Breast and Ovarian Cancer regarding the practice of recontacting patients at these facilities. Sixty-six facilities responded that they recontact patients, but only 17 facilities had a protocol for this. The most common reason for recontact was that it could benefit the patient. Facilities that did not recontact stated that they lacked the necessary personnel or services. Most facilities indicated that a recontact system should be implemented in their practice. The increased burden on too few medical personnel, unestablished systems, patient confusion, and the right not to know were cited as barriers to implementing recontact. Although developing recommendations on recontact would be useful for providing equitable healthcare in Japan, there is an urgent need to deepen the discussion on recontacting, as negative opinions about recontacting patients were observed.

Outcome of Nivolumab-Induced Vogt-Koyanagi-Harada Disease-Like Uveitis in a Patient Managed without Intravenous Methylprednisolone Therapy.

Background: In recent years, immune checkpoint inhibitors (ICI) have been often used for several types of cancers. Immune-related adverse events (irAEs) are autoimmune responses caused by ICI. Among the different types of irAEs, uveitis is common in ophthalmology. Moreover, there are reports on Vogt-Koyanagi-Harada (VKH) disease-like uveitis. In most cases, VKH, as in the usual VKH, is managed with intravenous methylprednisolone therapy. Case Report. A 72-year-old man was diagnosed with gastric cancer, and he was treated with nivolumab, a type of ICI. After eight cycles of nivolumab therapy, he developed fulminant type 1 diabetes mellitus and diabetic ketoacidosis. Thus, the treatment was discontinued. Subsequently, the patient was referred to our department due to bilateral blurry vision. He had decreased visual acuity in both eyes, and slit lamp examination revealed the presence of bilateral anterior chamber cells and keratic precipitates. Fundus examination showed bilateral serous retinal detachment (SRD), wavy retinal pigment epithelium (RPE), and choroidal thickening. Cerebrospinal fluid examination revealed prominent pleocytosis. Thus, we initiated eye drop therapy and subtenon injection of triamcinolone acetonide on the right eye only. After 1 month, SRD and wavy RPE disappeared, and the patient's visual acuity improved. Further, both eyes had similar improvements in visual acuity and abnormal findings. Oral prednisolone was subsequently administered for hearing loss. However, intravenous methylprednisolone was not used, and ophthalmologic findings and visual acuity did not change before and after systemic steroid therapy. One year after disease onset, SRD and wavy RPE did not relapse. Conclusion: Nivolumab-induced VKH disease-like uveitis can have good outcomes even in a patient managed without intravenous methylprednisolone therapy.

Stakeholder Perception of the Implementation of Genetic Risk Testing for Twelve Multifactorial Diseases.

Genome-wide association studies have been employed to develop numerous risk prediction models using polygenic risk scores (PRSs) for multifactorial diseases. However, healthcare providers lack confidence in their understanding of PRS risk stratification for multifactorial diseases, which underscores the need to assess the readiness of PRSs for clinical use. To address this issue, we surveyed the perceptions of healthcare providers as stakeholders in the clinical implementation of genetic-based risk prediction for multifactorial diseases. We conducted a web-based study on the need for risk prediction based on genetic information and the appropriate timing of testing for 12 multifactorial diseases. Responses were obtained from 506 stakeholders. Positive perceptions of genetic risk testing were found for adult-onset chronic diseases. As per participant opinion, testing for adult-onset diseases should be performed after the age of 20 years, whereas testing for psychiatric and allergic disorders that manifest during childhood should be performed from birth to 19 years of age. The stakeholders recognized the need for genetic risk testing for diseases that develop in adulthood, believing that the appropriate testing time is after maturity. This study contributes to the discussion on the clinical implementation of the PRS for genetic risk prediction of multifactorial diseases.

The effects of hydroxyethyl starch 130/0.4 on perioperative renal function in patients undergoing cardiac surgery: A randomised controlled trial.

Background: Acute kidney injury (AKI) after cardiac surgery increases the risk of morbidity and mortality. Hydroxyethyl starch (HES) is often used during surgery due to its plasma-volume expanding effect, but the impact of HES 130/0.4 on renal function in patients undergoing cardiac surgery remains unclear. The aim of our study is to investigate the impact of HES 130/0.4 on postoperative renal function in patients undergoing cardiac surgery using cardiopulmonary bypass. Methods: Our study was a randomised, single-center, single-blind study conducted on 60 adult patients who underwent cardiac surgery using cardiopulmonary bypass: 30 patients were intraoperatively administered with HES 130/0.4; the other 30 with Ringer's bicarbonate. The primary endpoints were occurrence of AKI within 30 days of surgery and the disease stages. Results: The mean dose of 6% HES 130/0.4 was 28 ml/kg. AKI occurred within 30 days of the operation in 8 cases (28.6%) in the HES group and 6 cases (21.4%) in the crystalloid group (no significance: p = 0.5371). Disease stages were as follows: "no AKI", "stage 1", "stage 2″ and "stage 3″, accounting for 20 cases (71.5%), 6 cases (21,4%), 2 cases (7.1%), and 0 cases, respectively, in the HES group, and 22 cases (78.6%), 6 cases (21.4%), 0 cases, and 0 cases, respectively, in the crystalloid group (no significance: p = 0.3508). Conclusion: There was no significant difference in the occurrences or stages of AKI during the 30 days following cardiac surgery with cardiopulmonary bypass between patients administered with HES 130/0.4 or Ringer's bicarbonate.

Perception of genetic testing among patients with inherited retinal disease: Benefits and challenges in a Japanese population.

Inherited retinal disease (IRD) is clinically and genetically heterogeneous. Awareness of the importance of genetic testing for IRD in the clinical setting is increasing with the recent development of new therapeutic strategies, such as gene therapy. Here, the perception of genetic testing, including its benefits and potential challenges, among patients with IRD was investigated to establish strategies for IRD genetic testing and counseling practices that can meet the requirements of the patients in Japan. An anonymous self-administered questionnaire was distributed to 275 patients with IRD who underwent genetic testing after clinical consultation and genetic counseling to investigate the motivations for genetic testing, benefits, challenges, status of communication of results to family, and attitude to timing of genetic testing. In total, 228 (82.9%) responses were analyzed. Several major motivations for genetic testing were identified, including gaining information on future treatment options and clarification of the inheritance pattern, among others. No association was found between the sharing of results with family members and the results of genetic testing. Moreover, according to patients who received positive results, the benefits of genetic testing included information on the inheritance pattern, additional information on the diagnosis, and mental preparation for the future. Even patients who received negative or inconclusive (variant of uncertain significance) results reported certain informative and psychological benefits. Altogether, these findings suggest that provisions for genetic testing and genetic counseling are necessary within a certain period after clinical diagnosis and it is necessary to facilitate appropriate family communication about genetic testing results while paying attention to the background of family relationships. Moreover, the benefits of genetic testing can be influenced by the careful interpretation and information provided on the test results during genetic counseling and consultation.

Characterization of Frond and Flower Development and Identification of FT and FD Genes From Duckweed Lemna aequinoctialis Nd.

Duckweeds (Araceae: Lemnoideae) are aquatic monocotyledonous plants that are characterized by their small size, rapid growth, and wide distribution. Developmental processes regulating the formation of their small leaf-like structures, called fronds, and tiny flowers are not well characterized. In many plant species, flowering is promoted by the florigen activation complex, whose major components are florigen FLOWERING LOCUS T (FT) protein and transcription factor FD protein. How this complex is regulated at the molecular level during duckweed flowering is also not well understood. In this study, we characterized the course of developmental changes during frond development and flower formation in Lemna aequinoctialis Nd, a short-day plant. Detailed observations of frond and flower development revealed that cell proliferation in the early stages of frond development is active as can be seen in the separate regions corresponding to two budding pouches in the proximal region of the mother frond. L. aequinoctialis produces two stamens of different lengths with the longer stamen growing more rapidly. Using high-throughput RNA sequencing (RNA-seq) and de novo assembly of transcripts from plants induced to flower, we identified the L. aequinoctialis FT and FD genes, whose products in other angiosperms form a transcriptional complex to promote flowering. We characterized the protein-protein interaction of duckweed FT and FD in yeast and examined the functions of the two gene products by overexpression in Arabidopsis. We found that L. aequinoctialis FTL1 promotes flowering, whereas FTL2 suppresses flowering.

Pyloric, pseudopyloric, and spasmolytic polypeptide-expressing metaplasias in autoimmune gastritis: a case series of 22 Japanese patients.

There are two types of pyloric gland-like metaplasia in the corpus of stomach: pyloric and pseudopyloric metaplasias. They show the same morphology as the original pyloric glands in H&E staining. Pseudopyloric metaplasia is positive for pepsinogen (PG) I immunohistochemically, whereas pyloric metaplasia is negative. Recently, spasmolytic polypeptide-expressing metaplasia (SPEM) is proposed for pyloric gland-like metaplasia mainly in animal experiments. SPEM expresses trefoil factor family 2 (TFF2) and is often considered synonymous with pseudopyloric metaplasia. We reviewed consecutive 22 Japanese patients with autoimmune gastritis (AIG) to investigate TFF2 expression in pyloric and pseudopyloric metaplasias by counting all pyloric gland-like glands in biopsy specimens taken from greater curvature of the middle corpus according to the Updated Sydney System. Pyloric metaplasia was seen in all the 22 cases, and pseudopyloric metaplasia was found in 15 cases. Of 1567 pyloric gland-like glands in all the cases, 1381 (88.1%) glands were pyloric metaplasia glands, and the remaining 186 (11.9%) glands were pseudopyloric metaplasia glands. TFF2 expression was observed in pyloric or pseudopyloric metaplasia glands in 20 cases. TFF2 expression was recognized in 409 of 1381 (26.9%) pyloric metaplasia glands and 27 of 186 (14.5%) pseudopyloric metaplasia glands (P<0.01, chi-square test). In conclusion, SPEM was not always the same as pseudopyloric metaplasia in human AIG, and the majority of metaplasia in AIG was not pseudopyloric but pyloric metaplasia.

Difference Between Day and Night Temperatures Affects Stem Elongation in Tomato (Solanum lycopersicum) Seedlings via Regulation of Gibberellin and Auxin Synthesis.

Temperature is a critical environmental factor governing plant growth and development. The difference between day temperature (DT) and night temperature (NT), abbreviated as DIF, influences plant architecture. Subjecting plants to artificial DIF treatments is an effective strategy in ornamental horticulture. For example, negative DIF (when DT - NT < 0) generally inhibits stem elongation, resulting in dwarf plants. However, the mechanisms underlying stem growth regulation by DIF remains to be completely elucidated. In this study, we aimed to analyze the growth, transcriptome, and phytohormone profiles of tomato (Solanum lycopersicum) seedlings grown under different DIF treatments. Under positive DIF (when DT - NT > 0), in contrast to the control temperature (25°C/20°C, DT/NT), high temperature (30°C/25°C) increased stem length and thickness, as well as the number of xylem vessels. Conversely, compared with the positive high temperature DIF treatment (30°C/25°C), under negative DIF treatment (25°C/30°C) stem elongation was inhibited, but stem thickness and the number of xylem vessels were not affected. The negative DIF treatment decreased the expression of gibberellin (GA)-, auxin-, and cell wall-related genes in the epicotyl, as well as the concentrations of GAs and indole-3-acetic acid (IAA). The expression of these genes and concentrations of these hormones increased under high temperature compared to those under the control temperature positive DIF. Our results suggest that stem length in tomato seedlings is controlled by changes in GA and IAA biosynthesis in response to varying day and night temperatures.

Truncating Variants Contribute to Hearing Loss and Severe Retinopathy in USH2A-Associated Retinitis Pigmentosa in Japanese Patients.

USH2A is a common causal gene of retinitis pigmentosa (RP), a progressive blinding disease due to retinal degeneration. Genetic alterations in USH2A can lead to two types of RP, non-syndromic and syndromic RP, which is called Usher syndrome, with impairments of vision and hearing. The complexity of the genotype-phenotype correlation in USH2A-associated RP (USH2A-RP) has been reported. Genetic and clinical characterization of USH2A-RP has not been performed in Japanese patients. In this study, genetic analyses were performed using targeted panel sequencing in 525 Japanese RP patients. Pathogenic variants of USH2A were identified in 36 of 525 (6.9%) patients and genetic features of USH2A-RP were characterized. Among 36 patients with USH2A-RP, 11 patients had syndromic RP with congenital hearing problems. Amino acid changes due to USH2A alterations were similarly located throughout entire regions of the USH2A protein structure in non-syndromic and syndromic RP cases. Notably, truncating variants were detected in all syndromic patients with a more severe retinal phenotype as compared to non-syndromic RP cases. Taken together, truncating variants could contribute to more serious functional and tissue damages in Japanese patients, suggesting important roles for truncating mutations in the pathogenesis of syndromic USH2A-RP.

Attitudes toward and current status of disclosure of secondary findings from next-generation sequencing: a nation-wide survey of clinical genetics professionals in Japan.

The management of secondary findings (SFs), which are beyond the intended purpose of the analysis, from clinical comprehensive genomic analysis using next generation sequencing (NGS) presents challenges. Policy statements regarding their clinical management have been announced in Japan and other countries. In Japan, however, the current status of and attitudes of clinical genetics professionals toward reporting them are unclear. We conducted a questionnaire survey of clinical genetics professionals at two time points (2013 and 2019) to determine the enforcement of the SF management policy in cases of comprehensive genetic analysis of intractable diseases and clinical cancer genome profiling testing. According to the survey findings, 40% and 70% of the respondents stated in the 2013 and 2019 surveys, respectively, that they had an SF policy in the field of intractable diseases, indicating that SF policy awareness in Japan has changed significantly in recent years. Furthermore, a total of 80% of respondents stated that their facility had established a policy for clinical cancer genome profiling testing in the 2019 survey. In both surveys, the policies included the selection criteria for genes to be disclosed and the procedure to return SFs, followed by recommendations and proposals regarding SFs in Japan and other countries. To create a better list of the genes to be disclosed, further examination is needed considering the characteristics of each analysis.

Intake frequency of vegetables or seafoods negatively correlates with disease activity of rheumatoid arthritis.

OBJECTIVE: To clarify the relationship between dietary habit and disease activity of rheumatoid arthritis (RA). METHODS: This study enrolled RA patients who met the ACR/EULAR 2010 classification criteria from Kyoto University Rheumatoid Arthritis Management Alliance (KURAMA) cohort in 2015. 22-item food frequency questionnaire (FFQ) was taken for the measurement of dietary habit in a single-institution cohort of RA (Kyoto University Rheumatoid Arthritis Management Alliance: KURAMA) in 2015. The disease activities of RA using the Disease Activity Score calculated based on the erythrocyte sedimentation rate (DAS28-ESR), Simplified Disease Activity Index (SDAI), Health Assessment Questionnaire (HAQ), and serum matrix metalloproteinase-3 (MMP-3) level, the use of disease-modifying anti-rheumatic drugs (DMARDs), disease duration, rheumatoid factor, anti-cyclic citrullinated antibody, and body mass index were also examined. All of them were combined and statistically analyzed. RESULTS: 441 RA patients (81% women; mean age 65 years; mean disease duration 15 years) were enrolled from the KURAMA cohort. Average Disease Activity Score-28 using the erythrocyte sedimentation rate (DAS28-ESR) was 2.7. Univariate analysis showed that intake frequency of vegetables had a statistically significant negative correlation with disease activity markers, such as DAS28-ESR (ρ = -0.11, p<0.01), Simplified Disease Activity Index (SDAI) (ρ = -0.16, p<0.001), matrix metalloproteinase-3 (MMP-3) (ρ = -0.21, p<0.0001), and Health Assessment Questionnaire (HAQ) (ρ = -0.13, p<0.01). Factor analysis with varimax rotation was done to simplify the relevance of disease activity to various food items. 22 foods were categorized into five dietary patterns: "seafoods", "vegetables/fruits", "meats/fried foods", "snacks", and "processed foods". The multivariate analysis adjusted for clinically significant confounders showed that "seafoods" had statistically significant negative correlations with DAS28-ESR (ß = -0.15, p<0.01), SDAI (ß = -0.18, p<0.001), MMP-3 (ß = -0.15, p<0.01), and HAQ (ß = -0.24, p<0.0001). "Vegetables/fruits" had statistically significant negative correlations with SDAI (ß = -0.11 p<0.05), MMP-3 (ß = -0.12, p<0.01), and HAQ (ß = -0.11, p<0.05). CONCLUSIONS: These results suggest that high intake frequency of vegetables/fruits and/or seafoods might correlate with low disease activity.

Ethical and professional challenges encountered by Japanese healthcare professionals who provide genetic counseling services.

It is important to identify ethical and professional challenges associated with genetic counseling services and systems to improve these services. In previous studies, specific challenges in genetic counseling were categorized into 16 domains. However, these studies were limited to a few countries, and genetic counseling differs according to national cultures or systems. Thus, additional efforts should be made to collect and analyze challenges in genetic counseling to address these issues. We interviewed 48 genetic counseling professionals in Japan (including 29 clinical geneticists, 17 genetic counselors, and 2 other professionals) about anecdotes that included ethical professional challenges. Thematic analysis was used to code the interview data, and anecdotes were categorized according to the ethical and professional challenges. The anecdotes (n = 333) were classified into the 16 previously identified domains and three unique subcategories: 'lack of understanding about genetic professionals or departments of genetic counseling by other professionals and patients', 'insufficient communication skills to carry out counseling on the part of the genetic counseling professionals', and 'lack of a system for self-improvement'. Many of the anecdotes also noted the emotional responses domain. The challenges experienced by Japanese genetic counseling professionals described herein will improve the quality of the service these professionals provide. Furthermore, the results can assist development of high-quality genetic counseling systems in countries developing these systems.

Suppression of Leaf Blade Development by BLADE-ON-PETIOLE Orthologs Is a Common Strategy for Underground Rhizome Growth.

Rhizomes are modified stems that grow horizontally underground in various perennial species, a growth habit that is advantageous for vigorous asexual proliferation. In Oryza longistaminata, a rhizomatous wild relative of cultivated rice (Oryza sativa), leaves in the aerial shoots consist of a distal leaf blade and a proximal leaf sheath [1]. Leaf blade formation is, however, suppressed in rhizome leaves. In O. sativa, BLADE-ON-PETIOLE (BOP) genes are the main regulators of proximal-distal leaf patterning [2]. During the juvenile phase of O. sativa, BOP expression is maintained at high levels by the small regulatory RNA microRNA156 (miR156), leading to formation of leaves consisting predominantly of the sheath. Here, we show that in O. longistaminata, high expression of BOPs caused by miR156 was responsible for suppression of the blade in rhizomes and that bop loss-of-function mutants produced leaves consisting of the leaf blade only. Rhizome growth in soil was also hampered in the mutants due to a severe reduction in rhizome tip stiffness. Leaf blade formation is also suppressed in the stolons of Zoysia matrella, a monocot species, and in the rhizomes of Houttuynia cordata, a dicot species, indicating that leaf blade suppression is widely conserved. We also show that strong expression of BOP homologs in both rhizome and stolon leaves rather than in aerial leaves is another conserved feature. We propose that suppression of the leaf blade by BOP is an evolutionary strategy that has been commonly recruited by both rhizomatous and stoloniferous species to establish their unique growth habit.

A case of bilateral vasculitis associated with pineal germinoma.

PURPOSE: To report a rare case of bilateral periphlebitis associated with a pineal germinoma. OBSERVATIONS: A 17-year-old male teenager presented at a local clinic complaining of blurred vision in both eyes. The treating physician identified bilateral uveitis, and prescribed the patient with a local steroid treatment. However, the inflammatory findings did not improve with the treatment, and the patient was referred to our hospital for further examination. At the first visit, his best-corrected visual acuities were 0.3 for the right eye and 0.06 for the left eye; we found no inflammation in the anterior ocular segment, but observed bilateral retinal periphlebitis and a proliferative membrane from the papilla to the macula in the ocular fundus. In addition, we found a tractional serous retinal detachment in the macula. We suspected tuberculous uveitis clinically and initiated treatment with an antituberculous drug. However, the condition of the patient did not improve. Two months after our initial examination, left optic neuritis appeared, and we initiated a steroid pulse therapy. Although the periphlebitis remained, the left optic nerve findings and the visual acuity of both eyes improved. Thus, we reduced the oral steroid dose gradually. However, two months after initiating the dose reduction, the patient suffered a consciousness disturbance, and we detected a pineal tumor by magnetic resonance imaging (MRI). The patient was diagnosed as having a germ cell tumor by pathological examination and underwent radiation and chemotherapy. We noted marked improvements in both the periphlebitis findings and in the visual acuity following the treatment for the pineal tumor. CONCLUSIONS AND IMPORTANCE: Cases of pineal tumor accompanied with retinal periphlebitis have been reported rarely. Because juvenile retinal vasculitis cases of unknown cause can be associated with pineal germinomas, we recommend brain MRI examinations for such cases.